StemCell Therapy

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD). Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

Duchenne muscular dystrophy (DMD) is a genetic disease affecting approximately 1 in 3500 male live births [1]. It results in progressive degeneration of skeletal muscle causing complete paralysis, respiratory and cardiac complications, and ultimately death. Normal symptoms include the delay of motor milestones including the ability to sit and stand independently. DMD is caused by an absence of functional dystrophin protein and skeletal muscle stem cells, as well as the exhaustion of satellite cells following many rounds of muscle degeneration and regeneration [2]. The dystrophin gene is primarily responsible for connecting and maintaining the stability of the cytoskeleton of muscle fibers during contraction and relaxation. Despite the low frequency of occurrence, this disease is incurable and will cause debilitation of the muscle and eventual death in 20 to 30 year olds with recessive X-linked form of muscular dystrophy. Although there are no current treatments developed for DMD, there are several experimental therapies such as stem cell therapies.

Skeletal muscle is known to be a regenerative tissue in the body. This muscle regeneration is mediated by muscle satellite cells, a stem cell population for skeletal muscle [3, 4]. Although satellite cells exhibit some multipotential differentiation capabilities [5], their primary differentiation fate is skeletal muscle cells in normal muscle regeneration. Ex vivo expanded satellite cell-derived myoblasts can be integrated into muscle fibers following injection into damaged muscle, acting as a proof-of-concept of myoblast-mediated cell therapy for muscular dystrophies [69]. However, severe limitations exist in relation to human therapy. The number of available satellite cells or myoblasts from human biopsies is limited. In addition, the poor cell survival and low contribution of transplanted cells have hindered practical application in patients [6, 8, 9]. Human-induced pluripotent stem cells (hiPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem cell- (ESC-) like state by being forced to express genes and factors important for maintaining the defining properties of ESCs. hiPSCs can be generated from a wide variety of somatic cells [10, 11]. They have the ability to self-renew and successfully turn into any type of cells. With their ability to capture genetic diversity of DMD in an accessible culture system, hiPSCs represent an attractive source for generating myogenic cells for drug screening.

The ESC/iPSC differentiation follows the steps of embryonic development. The origin of skeletal muscle precursor cells comes from the mesodermal lineage, which give rise to skeletal muscle, cardiac muscle, bone, and blood cells. Mesoderm subsequently undergoes unsegmented presomitic mesoderm followed by segmented compartments termed somites from anterior to caudal direction. Dermomyotome is an epithelial cell layer making up the dorsal part of the somite underneath the ectoderm. Dermomyotome expresses Pax3 and Pax7 and gives rise to dermis, skeletal muscle cells, endothelial cells, and vascular smooth muscle [12]. Dermomyotome also serves as a tissue for secreted signaling molecules to the neural tube, notochord, and sclerotome [13, 14]. Upon signals from the neural tube and notochord, the dorsomedial lip of dermomyotome initiates and expresses skeletal muscle-specific transcription factors such as MyoD and Myf5 to differentiate into myogenic cells termed myoblasts. Myoblasts then migrate beneath the dermomyotome to form myotome. Eventually, these myoblasts fuse with each other to form embryonic muscle fibers. ESCs/iPSCs mimic these steps toward differentiation of skeletal muscle cells. Many studies utilize methods of overexpression of muscle-related transcription factors such as MyoD or Pax3 [15], or the addition of small molecules which activate or inhibit myogenic signaling during development. Several studies show that iPSCs retain a bias to form their cell type of origin due to an epigenetic memory [1619], although other papers indicate that such epigenetic memory is erased during the reprogramming processes [2022]. Therefore, this phenomenon is not completely understood at the moment. In light of these developments, we have recently established mouse myoblast-derived iPSCs capable of unlimited expansion [23]. Our data demonstrates that these iPSCs show higher myogenic differentiation potential compared to fibroblast-derived iPSCs. Thus, myogenic precursor cells generated from human myoblast-derived iPSCs expanded ex vivo should provide an attractive cell source for DMD therapy. However, since DMD is a systemic muscle disease, systemic delivery of myoblasts needs to be established for efficient cell-based therapy.

During developmental myogenesis, presomitic mesoderm is first formed by Mesogenin1 upregulation, which is a master regulator of presomitic mesoderm [24]. Then, the paired box transcription factor Pax3 gene begins to be expressed from presomitic mesoderm to dermomyotome [25]. Following Pax3 expression, Pax7 is also expressed in the dermomyotome [26], and then Myf5 and MyoD, skeletal muscle-specific transcription factor genes, begin to be expressed in the dorsomedial lip of the dermomyotome in order to give rise to myoblasts which migrate beneath the dermomyotome to form the myotome. Subsequently, Mrf4 and Myogenin, other skeletal muscle-specific transcription factor genes, followed by skeletal muscle structural genes such as myosin heavy chain (MyHC), are expressed in the myotome for myogenic terminal differentiation (Figure 1) [27, 28]. Pax3 directly and indirectly regulates Myf5 expression in order to induce myotomal cells. Dorsal neural tube-derived Wnt proteins and floor plate cells in neural tube and notochord-derived sonic hedgehog (Shh) positively regulate myotome formation [13, 29]. Neural crest cells migrating from dorsal neural tubes are also involved in myotome formation: Migrating neural crest cells come across the dorsomedial lip of the dermomyotome, and neural crest cell-expressing Delta1 is transiently able to activate Notch1 in the dermomyotome, resulting in conversion of Pax3/7(+) myogenic progenitor cells into MyoD/Myf5(+) myotomal myoblasts [30, 31]. By contrast, bone morphogenetic proteins (BMPs) secreted from lateral plate mesoderm are a negative regulator for the myotome formation by maintaining Pax3/Pax7(+) myogenic progenitor cells [29, 32]. Pax3 also regulates cell migration of myogenic progenitor cells from ventrolateral lip of dermomyotome to the limb bud [33]. Pax3 mutant mice lack limb muscle but trunk muscle development is relatively normal [34]. Pax3/Pax7 double knockout mice display failed generation of myogenic cells, suggesting that Pax3 and Pax7 are critical for proper embryonic myogenesis [35]. Therefore, both Pax3 and Pax7 are also considered master transcription factors for the specification of myogenic progenitor cells. Importantly, MyoD was identified as the first master transcription factor for myogenic specification since MyoD is directly able to reprogram nonmuscle cell type to myogenic lineage when overexpressed [3638]. In addition, genetic ablation of MyoD family gene(s) via a homologous gene recombination technique causes severe myogenic developmental or regeneration defects [3945]. Finally, genetic ablation of combinatory MyoD family genes demonstrates that MyoD/:Myf5/:MRF4/ mice do not form any skeletal muscle during embryogenesis, indicating the essential roles in skeletal muscle development of MyoD family genes [28, 46]. It was proven that Pax3 also possesses myogenic specification capability since ectopic expression of Pax3 is sufficient to induce myogenic programs in both paraxial and lateral plate mesoderm as well as in the neural tube during chicken embryogenesis [47]. In addition, genetic ablation of Pax3 and Myf5 display complete defects of body skeletal muscle formation during mouse embryogenesis [48]. Finally, overexpression of Pax7 can convert CD45(+)Sca-1(+) hematopoietic cells into skeletal muscle cells [49]. From these notions, overexpression of myogenic master transcription factors such as MyoD or Pax3 has become the major strategy for myogenic induction in nonmuscle cells, including ES/iPSCs.

The overexpression of MyoD approach to induce myogenic cells from mESCs was first described by Dekel et al. in 1992. This has been a standard approach for the myogenic induction from pluripotent stem cells (Table 1). Ozasa et al. first utilized Tet-Off systems for MyoD overexpression in mESCs and showed desmin(+) and MyHC(+) myotubes in vitro [50]. Warren et al. transfected synthetic MyoD mRNA in to hiPSCs for 3 days, which resulted in myogenic differentiation (around 40%) with expression of myogenin and MyHC [51]. Tanaka et al. utilized a PiggyBac transposon system to overexpress MyoD in hiPSCs. The PiggyBac transposon system allows cDNAs to stably integrate into the genome for efficient gene expression. After integration, around 70 to 90% of myogenic cells were induced in hiPSC cultures within 5 days [52]. This study also utilized Miyoshi myopathy patient-derived hiPSCs for the MyoD-mediated myogenic differentiation. Miyoshi myopathy is a congenital distal myopathy caused by defective muscle membrane repair due to mutations in dysferlin gene. The patient-derived hiPSC-myogenic cells will be able to provide the opportunity for therapeutic drug screening. Abujarour et al. also established a model of patient-derived skeletal muscle cells which express NCAM, myogenin, and MyHC by doxycycline-inducible overexpression of MyoD in DMD patient-derived hiPSCs [53]. Interestingly, MyoD-induced iPSCs also showed suppression of pluripotent genes such as Nanog and a transient increase in the gene expression levels of T (Brachyury T), Pax3, and Pax7, which belong to paraxial mesodermal/myogenic progenitor genes, upstream genes of myogenesis. It is possible that low levels of MyoD activity in hiPSCs may initially suppress their pluripotent state while failing to induce myogenic programs, which may result in transient paraxial mesodermal induction. Supporting this idea, BAF60C, a SWI/SNF component that is involved in chromatin remodeling and binds to MyoD, is required to induce full myogenic program in MyoD-overexpressing hESCs [54]. Overexpression of MyoD alone in hESC can only induce some paraxial mesodermal genes such as Brachyury T, mesogenin, and Mesp1 but not myogenic genes. Co-overexpression of MyoD and BAF60C was now able to induce myogenic program but not paraxial mesodermal gene expression, indicating that there are different epigenetic landscapes between pluripotent ESCs/iPSCs and differentiating ESC/iPSCs in which MyoD is more accessible to DNA targets than those in pluripotent cells. The authors then argued that without specific chromatin modifiers, only committed cells give rise to myogenic cells by MyoD. These results strongly indicate that nuclear landscapes are important for cell homogeneity for the specific cell differentiation in ESC/iPSC cultures. Similar observations were seen in overexpression of MyoD in P19 embryonal carcinoma stem cells, which can induce paraxial mesodermal genes including Meox1, Pax3, Pax7, Six1, and Eya2 followed by muscle-specific genes. However, these MyoD-induced paraxial mesodermal genes were mediated by direct MyoD binding to their regulatory regions, which was proven by chromatin immunoprecipitation (ChIP) assays, indicating the novel role for MyoD in paraxial mesodermal cell induction [55].

hESCs/iPSCs have been differentiated into myofibers by overexpression of MyoD, and this method is considered an excellent in vitro model for human skeletal muscle diseases for muscle functional tests, therapeutic drug screening, and genetic corrections such as exon skipping and DNA editing. Shoji et al. have shown that DMD patient-derived iPSCs were used for myogenic differentiation via PiggyBac-mediated MyoD overexpression. These myogenic cells were treated with morpholinos for exon-skipping strategies for dystrophin gene correction and showed muscle functional improvement [56]. Li et al. have shown that patient-derived hiPSC gene correction by TALEN and CRISPR-Cas9 systems, and these genetically corrected hiPSCs were used for myogenic differentiation via overexpression of MyoD [57]. This work also revealed that the TALEN and CRISPR-Cas9-mediated exon 44 knock-in approach in the dystrophin gene has high efficiency in gene-editing methods for DMD patient-derived cells in which the exon 44 is missing in the genome.

Along this line of the strategy, Darabi et al. first performed overexpression of Pax3 gene, which can be activated by treatment with doxycycline in mESCs, and showed efficient induction of MyoD/Myf5(+) skeletal myoblasts in EB cultures [15]. Upon removing doxycycline, these myogenic cells underwent MyHC(+) myotubes. However, teratoma formation was observed after EB cell transplantation into cardiotoxin-injured regenerating skeletal muscle in Rag2/:C/ immunodeficient mice [15]. This indicates that myogenic cell cultures induced by Pax3 in mESCs still contain some undifferentiated cells which gave rise to teratomas. To overcome this problem, the same authors separated paraxial mesodermal cells from Pax3-induced EB cells by FACS using antibodies against cell surface markers as PDGFR(+)Flk-1() cell populations. After cell sorting, isolated Pax3-induced paraxial mesodermal cells were successfully engrafted and contributed to regenerating muscle in mdx:Rag2/:C/ DMD model immunodeficient mice without any teratoma formations. Darabi et al. also showed successful myogenic induction in mESCs and hES/iPSCs by overexpression of Pax7 [58, 59]. Pax3 and Pax7 are not only expressed in myogenic progenitor cells. They are also expressed in neural tube and neural crest cell-derived cells including a part of cardiac cell types in developmental stage, suggesting that further purification to skeletal muscle cell lineage is crucial for therapeutic applications for muscle diseases including DMD.

Taken together, overexpression of myogenic master transcription factors such as MyoD or Pax3/Pax7 is an excellent strategy for myogenic induction in hESCs and hiPSCs, which can be utilized for in vitro muscle disease models for their functional test and drug screening. However, for the safe stem cell therapy, it is essential to maintain the good cellular and genetic qualities of hESC/hiPSC-derived myogenic cells before transplantation. Therefore, random integration sites of overexpression vectors for myogenic master transcription factors and inappropriate expression control of these transgenes may diminish the safety of using these induced myogenic cells for therapeutic stem cell transplantation.

Stepwise induction protocols utilizing small molecules and growth factors have been established as alternative myogenic induction approaches and a more applicable method for therapeutic situations. As described above, during embryonic myogenesis, somites and dermomyotomes receive secreted signals such as Wnts, Notch ligands, Shh, FGF, BMP, and retinoic acid (RA) with morphogen gradients from surrounding tissues in order to induce the formation of myogenic cells (Figure 2). The canonical Wnt signaling pathway has been shown to play essential roles in the development of myogenesis. In mouse embryogenesis, Wnt1 and Wnt3a secreted from the dorsal neural tube can promote myogenic differentiation of dorsomedial dermomyotome via activation of Myf5 [31, 32, 60]. Wnt3a is able to stabilize -catenin which associates with TCF/LEF transcription factors that bind to the enhancer region of Myf5 during myogenesis [61]. Other Wnt proteins, Wnt6 and Wnt7a, which emerge from the surface ectoderm, induce MyoD [62]. BMP functions as an inhibitor of myogenesis by suppression of some myogenic gene expressions. In the lateral mesoderm, BMP4 is able to increase Pax3 expression which delays Myf5 expression in order to maintain an undifferentiated myogenic progenitor state [63]. Therefore, Wnts and BMPs regulate myogenic development by antagonizing each other for myogenic transcription factor gene expression [64, 65]. Wnt also induces Noggin expression to antagonize BMP signals in the dorsomedial lip of the dermomyotome [66]. In this region, MyoD expression level is increased, which causes myotome formation. Notch signaling plays essential roles for cell-cell communication to specify the different cells in developmental stages. During myotome formation, Notch is expressed in dermomyotome, and Notch1 and Notch2 are expressed in dorsomedial lip of dermomyotome. Delta1, a Notch ligand, is expressed in neural crest cells which transiently interact with myogenic progenitor cells in dorsomedial lip of dermomyotome via Notch1 and 2. This contact induces expression of the Myf5 or MyoD gene in the myogenic progenitor cells followed by myotome formation. The loss of function of Delta1 in the neural crest displays delaying skeletal muscle formation [67]. Knockdown of Notch genes or use of a dominant-negative form of mastermind, a Notch transcriptional coactivator, clearly shows dramatically decrease of Myf5 and MyHC(+) myogenic cells. Interestingly, induction of Notch intracellular domain (NICD), a constitutive active form of Notch, can promote myogenesis, while continuous expression of NICD prevents terminal differentiation. Taken together, transient and timely activation of Notch is crucial for myotome formation from dermomyotome [30].

Current studies for myogenic differentiation of ESCs/iPSCs have utilized supplementation with some growth factors and small molecules, which would mimic the myogenic development described above in combination with embryoid body (EB) aggregation and FACS separation of mesodermal cells (Table 2). To induce paraxial mesoderm cells from mESCs, Sakurai et al. utilized BMP4 in serum-free cultures [68]. Three days after treatment with BMP4, mESCs could be differentiated into primitive streak mesodermal-like cells, but the continuous treatment with BMP4 turned the ESCs into osteogenic cells. Therefore, they used LiCl after treatment with BMP4 to enhance Wnt signaling, which is able to induce myogenic differentiation. After treatment with LiCl, PDGFR(+) E-cadherin() paraxial mesodermal cells were sorted by FACS. These sorted cells were cultured with IGF, HGF, and FGF for two weeks in order to induce myogenic differentiation. Hwang et al. have shown that treatment with Wnt3a efficiently promotes skeletal muscle differentiation of hESCs [69]. hESCs were cultured to form EB for 9 days followed by differentiation of EBs for additional 7 days, and then PDGFR(+) cells were sorted by FACS. These PDGFR(+) cells were cultured with Wnt3a for additional 14 days. Consequently, these Wnt3a-treated cells display significantly increased myogenic transcription factors and structural proteins at both mRNA and protein levels. An interesting approach to identify key molecules that induce myogenic cells was reported by Xu et al. [70]. They utilized reporter systems in zebrafish embryos to display myogenic progenitor cell induction and myogenic differentiation in order to identify small compounds for myogenic induction. Myf5-GFP marks myogenic progenitor cells, while myosin light polypeptide 2 (mylz2)-mCherry marks terminally differentiated muscle cells. They found that a mixed cocktail containing GSK3 inhibitor, bFGF, and forskolin has the potential to induce robust myogenic induction in hiPSCs. GSK3 inhibitors act as a canonical Wnt signaling activator via stabilizing -catenin protein, which is crucial for inducing mesodermal cells. Forskolin activates adenylyl cyclase, which then stimulates cAMP signaling. cAMP response element-binding protein (CREB) is able to stimulate cell proliferation of primary myoblasts in vitro, suggesting that the forskolin-cAMP-CREB pathway may help myogenic cell expansion [71], However the precise mechanisms for CREB-mediated myogenic cell expansion remain unclear. The adenylyl cyclase signaling cascade leads to CREB activation [71]. During embryogenesis, phosphorylated CREB has been found at dorsal somite and dermomyotome. CREB gene knockout mice display significantly decreased Myf5 and MyoD expressions in myotomes. While activation of Wnt1 or Wnt7a promotes Pax3, Myf5, and MyoD expressions, inhibition of CREB eliminates these Wnt-mediated myogenic gene expressions without altering the Wnt canonical pathway, suggesting that CREB-induced myogenic activation may be mediated through noncanonical Wnt pathways. Several groups also utilized GSK3 inhibitors for inducing mesodermal cells from ESCs and iPSCs [72, 73]. These mesodermal cell-like cells were expanded by treatment with bFGF, and then ITS (insulin/transferrin/selenite) or N2 medium were used to induce myogenic differentiation. Finally, bFGF is a stimulator for myogenic cell proliferation. Caron et al. demonstrated that hESCs treated with GSK3 inhibitor, ascorbic acid, Alk5 inhibitor, dexamethasone, EGF, and insulin generated around 80% of Pax3(+) myogenic precursor cells in 10 days [74]. Treatment with SB431542, an inhibitor of Alk4, 5, and 7, PDGF, bFGF, oncostatin, and IGF was able to induce these Pax3(+) myogenic precursor cells into around 5060% of MyoD(+) myoblasts in an additional 8 days. For the final step, treatment with insulin, necrosulfonamide, an inhibitor of necrosis, oncostatin, and ascorbic acid was able to induce these myoblasts into myotubes in an additional 8 days. Importantly, the same authors utilized ESCs from human facioscapulohumeral muscular dystrophy (FSHD) to demonstrate the myogenic characterization after myogenic induction by using the protocol described above. Hosoyama et al. have shown that hESCs/iPSCs with high concentrations of bFGF and EGF in combination with cell aggregation, termed EZ spheres, efficiently give rise to myogenic cells [75]. After 6-week culture, around 4050% of cells expressed Pax7, MyoD, or myogenin. However, the authors also showed that EZ spheres included around 30% of Tuj1(+) neural cells. Therefore, the authors discussed the utilization of molecules for activation of mesodermal and myogenic signaling pathways such as BMPs and Wnts.

Taken together, it is likely that the induced cell populations from ESCs/iPSCs may contain other cell types such as neural cells or cardiac cells because neural cells share similar transcription factor gene expression with myogenic cells such as Pax3, and cardiac cells also develop from mesodermal cells. To overcome this limitation, Chal et al. treated ESCs/iPSCs with BMP4 inhibitor, which prevents ESCs/iPSCs from differentiating into lateral mesodermal cells [76, 77]. To identify what genes are involved in myogenic differentiation in vivo, they performed a microarray analysis which compared samples of dissected fragments in mouse embryos, which are able to separate tail bud, presomitic mesoderm, and somite regions. From microarray data, the authors focused on Mesogenin1 (Msgn1) and Pax3 genes. Importantly, they utilized three lineage tracing reporters, Msgn1-repV (Mesogenin1-Venus) marking posterior somitic mesoderm, Pax3-GFP marking anterior somitic mesoderm and myogenic cells, and Myog-repV (Myogenin-Venus) marking differentiated myocytes, allowing the authors to readily detect different differentiation stages during ESC/iPSC cultures. Treatment with GSK3 inhibitors and then BMP inhibitors in ESC cultures induced Msgn1(+) somitic mesoderm with 45 to 65% efficiencies, Pax3(+) anterior somitic mesoderm with 30 to 50% efficiencies, and myogenin(+) myogenic cells with 25 to 30% efficiencies. Furthermore, the authors examined differentiation of mdx ESCs into skeletal muscle cells and revealed abnormal branching myofibers. Current protocols were also published and described more details for hiPSC differentiation [77].

Some nonmuscle cell populations such as mesoangioblasts have the potential to differentiate into skeletal muscle [6]. Mesoangioblasts were originally isolated from embryonic mouse dorsal aorta as vessel-associated pericyte-like cells, which have the ability to differentiate into a myogenic lineage in vitro and in vivo [6, 78]. Mesoangioblasts possess an advantage for the clinical cell-based treatment because they can be injected through an intra-arterial route to systemically deliver cells, which is crucial for therapeutic cell transplantation for muscular dystrophies [79]. Tedesco et al. successfully generated human iPSC-derived mesoangioblast-like stem/progenitor cells called HIDEMs by stepwise protocols without FACS sorting [80, 81]. They displayed similar gene expression profiles as embryonic mesoangioblasts. However, HIDEMs do not spontaneously differentiate into skeletal muscle cells, and thus, the authors utilized overexpression of MyoD to differentiate into skeletal muscle cells. Similar to mesoangioblasts, HIDEM-derived myogenic cells could be delivered to injured muscle via intramuscular and intra-arterial routes. Furthermore, HIDEMs have been generated from hiPSCs derived from limb-girdle muscular dystrophy (LGMD) type 2D patients and used for gene correction and cell transplantation experiments for the potential therapeutic application.

Myogenic precursor cells derived from ESCs/iPSCs by various methods may contain nonmuscle cells. Therefore, further purification is mandatory for therapeutic applications. Barberi et al. isolated CD73(+) multipotent mesenchymal precursor cells from hESCs by FACS, and these cells underwent differentiation into fat, cartilage, bone, and skeletal muscle cells [82]. Barberi et al. also demonstrated that hESCs cultured on OP9 stroma cells generated around 5% of CD73(+) adult mesenchymal stem cell-like cells [83]. After FACS, these CD73(+) mesenchymal stem cell-like cells were cultured with ITS medium for 4 weeks and then gave rise to NCAM(+) myogenic cells. After FACS sorting, these NCAM(+) myogenic cells were purified by FACS and transplanted into immunodeficient mice to show their myogenic contribution to regenerating muscle.

It has been shown that many genes are associated with myogenesis. In addition, exhaustive analysis, such as microarray, RNA-seq, and single cell RNA-seq supplies much gene information in many different stages. Chal et al. showed key signaling factors by microarray from presomitic somite, somite, and tail bud cells [76]. They found that initial Wnt signaling has important roles for somite differentiation. Furthermore, mapping differentiated hESCs by single cell RNA-seq analysis is useful to characterize each differentiated stage [84].

As shown above, cell sorting of mesodermal progenitor cells, mesenchymal precursor cells, or myogenic cells is a powerful tool to obtain pure myogenic populations from differentiated pluripotent cells. Sakurai et al. have been able to induce PDGFR(+)Flk-1() mesodermal progenitor cells by FACS followed by myogenic differentiation [85]. Chang et al. and Mizuno et al. have been able to sort SMC-2.6(+) myogenic cells from mouse ESCs/iPSCs [86, 87]. These SMC-2.6(+) myogenic cells were successfully engrafted into mouse regenerating skeletal muscle. However, this SMC-2.6 antibody only recognizes mouse myogenic cells but not human myogenic cells [86, 88]. Therefore, Borchin et al. have shown that hiPSC-derived myogenic cells differentiated into c-met(+)CXCR4(+)ACHR(+) cells, displaying that over 95% of sorted cells are Pax7(+) myogenic cells [72]. Taken together, current myogenic induction protocols utilizing small molecules and growth factors, with or without myogenic transcription factors, have been largely improved in the last 5 years. It is crucial to standardize the induction protocols in the near future to obtain sufficient myogenic cell conversion from pluripotent stem cells.

Recent work demonstrated that cells inherit a stable genetic program partly through various epigenetic marks, such as DNA methylation and histone modifications. This cellular memory needs to be erased during genetic reprogramming, and the cellular program reverted to that of an earlier developmental stage [16, 22, 89]. However, iPSCs retaining an epigenetic memory of their origin can readily differentiate into their original tissues [1619, 90100]. This phenomenon becomes a double-edged sword for the reprogramming process since the retention of epigenetic memory may reduce the quality of pluripotency while increasing the differentiation efficiency into their original tissues. DNA methylation levels are relatively low in the pluripotent stem cells compared to the high levels of DNA methylation seen in somatic cells [101]. Global DNA demethylation is required for the reprogramming process [102]. In the context of these observations, recent work demonstrates that activation-induced cytidine deaminase AID/AICDA contributing to the DNA demethylation can stabilize stem-cell phenotypes by removing epigenetic memory of pluripotent genes. This directly deaminates 5-methylcytosine in concert with base-excision repair to exchange cytosine in genomic DNA [103]. MicroRNA-155 has been identified as a key player for the retention of epigenetic memory during in vitro differentiation of hematopoietic progenitor cell-derived iPSCs toward hematopoietic progenitors [104]. iPSCs that maintained high levels of miR-155 expression tend to differentiate into the original somatic population more efficiently.

Recently, we generated murine skeletal muscle cell-derived iPSCs (myoblast-derived iPSCs) [23] and compared the efficiency of differentiation of myogenic progenitor cells between myoblast-derived iPSCs and fibroblast-derived iPSCs. After EB cultures, more satellite cell/myogenic progenitor cell differentiation occurred in myoblast-derived iPSCs than that in fibroblast-derived-iPSCs (unpublished observation and Figure 3), suggesting that myoblast-derived iPSCs are potential myogenic and satellite cell sources for DMD and other muscular dystrophy therapies (Figure 4). We also noticed that MyoD gene suppression by Oct4 is required for reprogramming in myoblasts to produce iPSCs (Figure 3) [23]. During overexpression of Oct4, Oct4 first binds to the Oct4 consensus sequence located in two MyoD enhancers (a core enhancer and distal regulatory region) [105107] preceding occupancy at the promoter in myoblasts in order to suppress MyoD gene expression. Interestingly, Oct4 binding to the MyoD core enhancer allows for establishment of a bivalent state in MyoD promoter as a poised state, marked by active (H3K4me3) and repressive (H3K27me3) modifications in fibroblasts, one of the characteristics of stem cells (Figure 3) [23, 108]. It should be investigated whether the similar bivalent state is also established in Oct4-expressing myoblasts during reprogramming process from myoblasts to pluripotent stem cells. It remains to be elucidated whether Oct4-mediated myogenic repression only relies on repression of MyoD expression or is just a general phenomenon of functional antagonism between Oct4 and MyoD on activation of muscle genes. Nevertheless, myoblast-derived iPSCs will enable us to produce an unlimited number of myogenic cells, including satellite cells that could form the basis of novel treatments for DMD and other muscular dystrophies (Figure 4).

There are pros and cons of transgene-free small molecule-mediated myogenic induction protocols. In the transgene-mediated induction protocols, integration of the transgene in the host genome may lead to risk for insertional mutagenesis. To circumvent this issue, there is an obvious advantage for transgene-free induction protocols. Some key molecules such as Wnt, FGF, and BMP have used signaling pathways to induce myogenic differentiation of ES/iPSCs. However, these molecules are also involved in induction of other types of cell lineages, which makes it difficult for ES/iPSCs to induce pure myogenic cell populations in vitro. By contrast, transgene-mediated myogenic induction is able to dictate desired specific cell lineages. In any case, it is necessary to intensively investigate these myogenic induction protocols for the efficient and safe stem cell therapy for patients.

For skeletal muscle diseases, patient-derived hiPSCs, which possess the ability to differentiate into myogenic progenitor cells followed by myotubes, can be a useful tool for drug screening and personalized medicine in clinical practice. However, there are still limitations for utilizing hiPSC-derived myogenic cells for regenerative medicine. For cell-based transplantation therapies such as a clinical situation, animal-free defined medium is essential for stem cell culture and skeletal muscle cell differentiation. Therefore, such animal-free defined medium needs to be established for optimal myogenic differentiation from hiPSCs. Gene correction in DMD patient iPSCs by TALENs and CRISPR-Cas9 systems are promising therapeutic approaches for stem cell transplantation. However, there are still problems for DNA-editing-mediated stem cell therapy such as safety and efficacy. Since iPSC-derived differentiated myotubes do not proliferate, they are not suited for cell transplantation. Therefore, a proper culture method needs to be established for hiPSCs in order to maintain cells in proliferating the myogenic precursor cell stage in vitro in order to expand cells to large quantities of transplantable cells for DMD and other muscular dystrophies. For other issues, it is essential to establish methods to separate ES/iPSC-derived pure skeletal muscle precursor cells from other cell types for safe stem cell therapy that excludes tumorigenic risks of contamination with undifferentiated cells. In the near future, these obstacles will be taken away for more efficient and safe stem cell therapy for DMD and other muscular dystrophies.

The authors declare that they have no conflicts of interest.

This work was supported by the NIH R01 (1R01AR062142) and NIH R21 (1R21AR070319). The authors thank Conor Burke-Smith and Neeladri Chowdhury for critical reading.

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Skeletal Muscle Cell Induction from Pluripotent Stem Cells

Peter J. Embi, MD1,2, Matthew E. Levy, PhD3, Allison L. Naleway, PhD4, Palak Patel, MBBS5, Manjusha Gaglani, MBBS6, Karthik Natarajan, PhD7,8, Kristin Dascomb, MD, PhD9, Toan C. Ong, PhD10, Nicola P. Klein, MD, PhD11, I-Chia Liao, MPH6, Shaun J. Grannis, MD2,12, Jungmi Han7, Edward Stenehjem, MD9, Margaret M. Dunne, MSc3, Ned Lewis, MPH11, Stephanie A. Irving, MHS4, Suchitra Rao, MBBS10, Charlene McEvoy, MD13, Catherine H. Bozio, PhD5, Kempapura Murthy, MBBS6, Brian E. Dixon, PhD12,14, Nancy Grisel, MPP9, Duck-Hye Yang, PhD3, Kristin Goddard, MPH11, Anupam B. Kharbanda, MD15, Sue Reynolds, PhD5, Chandni Raiyani, MPH6, William F. Fadel, PhD12,14, Julie Arndorfer, MPH9, Elizabeth A. Rowley, DrPH3, Bruce Fireman, MA11, Jill Ferdinands, PhD5, Nimish R. Valvi, DrPH12, Sarah W. Ball, ScD3, Ousseny Zerbo, PhD11, Eric P. Griggs, MPH5, Patrick K. Mitchell, ScD3, Rachael M. Porter, MPH5, Salome A. Kiduko, MPH3, Lenee Blanton, MPH5, Yan Zhuang, PhD3, Andrea Steffens, MPH5, Sarah E. Reese, PhD3, Natalie Olson, MPH5, Jeremiah Williams, MPH5, Monica Dickerson, MPH5, Meredith McMorrow, MD5, Stephanie J. Schrag, DPhil5, Jennifer R. Verani, MD5, Alicia M. Fry, MD5, Eduardo Azziz-Baumgartner, MD5, Michelle A. Barron, MD10, Mark G. Thompson, PhD5 and Malini B. DeSilva, MD13

1Regenstrief Institute, Indianapolis, Indiana; 2Indiana University School of Medicine, Indianapolis, Indiana; 3Westat, Rockville, Maryland; 4Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon; 5CDC COVID-19 Response Team; 6Baylor Scott & White Health, Texas A&M University College of Medicine, Temple, Texas; 7Department of Biomedical Informatics, Columbia University, New York, New York; 8New York Presbyterian Hospital, New York, New York; 9Division of Infectious Diseases and Clinical Epidemiology, Intermountain Healthcare, Salt Lake City, Utah; 10School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, Colorado; 11Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, California; 12Center for Biomedical Informatics, Regenstrief Institute, Indianapolis, Indiana; 13HealthPartners Institute, Minneapolis, Minnesota; 14Fairbanks School of Public Health, Indiana University, Indianapolis, Indiana; 15Children's Minnesota, Minneapolis, Minnesota.

Corresponding author Peter J. Embi, pembi@regenstrief.org.

All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Allison L. Naleway reports institutional support from Pfizer outside the submitted work. Anupam B. Kharbanda reports institutional support through HealthPartners to Children's Minnesota for VISION. Charlene McEvoy reports institutional support from AstraZeneca for the AZD1222 COVID-19 vaccine trial. Jill Ferdinands reports travel support from Institute for Influenza Epidemiology, funded in part by Sanofi Pasteur. Nicola P. Klein reports institutional support from Pfizer for COVID-19 vaccine clinical trials and institutional support from Pfizer, Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Sciences (now Sanofi Pasteur) outside the submitted work. Suchitra Rao reports grant support from GlaxoSmithKline and Biofire Diagnostics. No other potential conflicts of interest were disclosed.

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mRNA COVID-19 Vaccine Effectiveness in the Immunocompromised - Medscape

LYON, France--(BUSINESS WIRE)--Regulatory News:

MaaT Pharma (EURONEXT: MAAT - the Company), a French clinical-stage biotech and a pioneer in the development of microbiome-based ecosystem therapies dedicated to improving survival outcomes for patients with cancer, announced today positive interim engraftment data from the first four cohorts of the CIMON trial with MaaT033, the Companys high-richness, high-diversity, Microbiome Ecosystem Therapy for oral administration. These results represent the first confirmation of MaaT033s mechanism of action in humans. MaaT033 is the companys second product in clinical development and is intended to improve survival in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT), which represents approximately 22,000 patients every year in the 7 major markets. Its oral formulation, designed for targeted delivery in the intestine, may support long-term, ambulatory use.

In this dose-ranging study, data from four out of five intended cohorts showed satisfactory safety and good microbiome engraftment, which is characterized by the presence of microbial OTUs1 in the gut as a result of product administration and that were not present at treatment start.

Based on this positive data, the Company will close the CIMON trial to enable faster than planned completion and evaluation of the full data from the trial, in order to advance MaaT033 towards a planned Phase 2/3 trial, which could start in the second half of 2022. Complete results from the Phase 1b CIMON trial are expected in the first half of 2022.

These interim results are an important milestone for MaaT Pharma as MaaT033 is our second drug candidate and our first oral formulation, to demonstrate proof of engraftment in humans, said Herv Affagard, CEO and co-founder of MaaT Pharma. This expands the potential of our proprietary Microbiome Ecosystem Therapy (MET) platform to the ambulatory setting, after positive data achieved in aGvHD with MaaT013, an enema product for acute, hospital use. This is the first step towards treating larger patient populations that may benefit from orally-administered microbiome therapies, including patients receiving allo-HSCT, and also patients with solid tumors.

MaaT033 is intended to improve survival outcomes in hemato-oncology patients receiving allo-HSCT by protecting and restoring their gut microbiome. In these patients, intensive chemotherapy and antibiotic treatments that are administered to prepare for the allo-HSCT procedure result in a severely damaged gut microbiome. Importantly, higher gut microbiome diversity at the time of allo-HSCT has been correlated to higher survival and lower risks of complications, including incidence of graft-vs-host-disease and multi-resistant infections2.

With a very satisfactory safety profile and very promising engraftment data in the first four cohorts of this trial, we believe we have the appropriate amount of data in hand to confidently move forward with MaaT033s clinical development, without testing the highest planned dose of nine capsules a day, added John Weinberg, MD, Chief Medical Officer at MaaT Pharma. We look forward to further exploring the data from CIMON and preparing for a Phase 2/3 trial start.

The CIMON Phase 1b trial (NCT04150393) is an open-label, dose-ranging study and has enrolled to date a total of 21 patients in four cohorts (up to three capsules a day for 14 days) across six sites in France. CIMON is designed to investigate the maximum tolerated dose of MaaT033, over 7 or 14 days of therapy, that supports optimal gut microbiome colonization in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome who have undergone intensive chemotherapy. Overall, four Data and Safety Monitoring Board meetings have been conducted evaluating the safety of the trial. All concluded in support of the continuation of the study with the latest taking place in December 2021. Complete results from the trial will be submitted for a presentation at an upcoming key major conference in hemato-oncology as well as for peer-reviewed publication.

About MaaT033

MaaT033 is an oral, full-ecosystem, off-the-shelf, standardized, pooled-donor, high-richness Microbiome Ecosystem Therapy. It is manufactured at MaaT Pharmas centralized European cGMP production facility. MaaT033 is designed to restore the gut ecosystem to full functionality to improve clinical outcomes as well as to control adverse events related to conventional treatments for liquid tumors. The capsule formulation facilitates administration while maintaining the high and consistent richness and diversity of microbial species, including anti-inflammatory ButycoreTM species, which characterize MaaT Pharmas Microbiome Ecosystem Therapies.

About MaaT Pharma

MaaT Pharma, a clinical stage biotechnology company, has established a complete approach to restoring patient-microbiome symbiosis in oncology. Committed to treating cancer and graft-versus-host disease (GvHD), a serious complication of allogeneic stem cell transplantation, MaaT Pharma has already achieved proof of concept in a Phase II clinical trial in acute GvHD. Our powerful discovery and analysis platform, gutPrint, supports the development and expansion of our pipeline by determining novel disease targets, evaluating drug candidates, and identifying biomarkers for microbiome-related conditions.

The companys Microbiome Ecosystem Therapies are produced through a standardized cGMP manufacturing and quality control process to safely deliver the full diversity of the microbiome, in liquid and oral formulations. MaaT Pharma benefits from the commitment of world-leading scientists and established relationships with regulators to support the integration of the use of microbiome therapies in clinical practice.

MaaT Pharma is listed on Euronext Paris (ticker: MAAT).

Forward-looking Statements

All statements other than statements of historical fact included in this press release about future events are subject to (i) change without notice and (ii) factors beyond the Companys control. These statements may include, without limitation, any statements preceded by, followed by or including words such as target, believe, expect, aim, intend, may, anticipate, estimate, plan, project, will, can have, likely, should, would, could and other words and terms of similar meaning or the negative thereof. Forward-looking statements are subject to inherent risks and uncertainties beyond the Companys control that could cause the Companys actual results or performance to be materially different from the expected results or performance expressed or implied by such forward-looking statements.

1 OTU or Operational Taxonomic Unit is used to classify bacteria at the genus level, based on sequence similarity of the 16S marker gene. An OTU consists of a group of bacteria whose 16S marker gene shows a sequence identity of 97 percent and above.

2 Peled, J.U. & al N Engl J Med 2020;382:822-34

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MaaT Pharma Announces Positive Interim Engraftment Data for Oral Formulation MaaT033 Allowing Early Termination of Phase 1b CIMON Study - Business...

KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck & Co. (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA, Mercks anti-PD-1 therapy, as monotherapy for the adjuvant treatment of adults with renal cell carcinoma (RCC) at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. This approval is based on results from the Phase 3 KEYNOTE-564 trial, in which KEYTRUDA demonstrated a statistically significant improvement in disease-free survival (DFS), reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) after a median follow-up of 23.9 months compared to placebo, in patients at increased risk of recurrence (defined in the clinical trial protocol as intermediate-high or high risk following nephrectomy and those with resected advanced disease).

KEYTRUDA addresses a critical unmet need for treatment options that help patients reduce their risk of cancer returning following surgery, said Dr. Thomas Powles, professor of Genitourinary Oncology and director of Barts Cancer Centre at St. Bartholomews Hospital. The European Commissions approval of KEYTRUDA brings certain patients with renal cell carcinoma a long-awaited therapy that has demonstrated a statistically significant reduction in the risk of disease recurrence or death by almost a third.

KEYTRUDA is the first adjuvant therapy approved for certain patients with renal cell carcinoma in Europe, providing the option of immunotherapy earlier in the course of their treatment, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. This approval demonstrates our progress in bringing KEYTRUDA to patients with earlier stages of cancer, with the goal of helping more patients around the globe prevent disease recurrence.

This approval allows marketing of KEYTRUDA monotherapy in all 27 European Union member states plus Iceland, Lichtenstein, Norway and Northern Ireland.

Merck has a broad clinical development program exploring KEYTRUDA, as monotherapy or in combination, as well as several other investigational and approved medicines across multiple settings and stages of RCC, including adjuvant and advanced or metastatic disease.

Data Supporting the European Approval

The approval was based on data from KEYNOTE-564 (NCT03142334), a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 994 patients with increased risk of recurrence of RCC defined as intermediate-high or high risk, or M1 with no evidence of disease (NED). Patients must have undergone a partial or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion[s] in M1 NED participants) with negative surgical margins for at least four weeks prior to the time of screening. Patients with active autoimmune disease or a medical condition that required immunosuppression were excluded from the study. The primary efficacy outcome measure was investigator-assessed DFS. The secondary efficacy outcome measure was overall survival (OS). Patients with RCC with clear cell component were randomized (1:1) to receive KEYTRUDA 200 mg administered intravenously every three weeks (n=496) or placebo (n=498) for up to one year until disease recurrence or unacceptable toxicity.

At a pre-specified interim analysis with a median follow-up time of 23.9 months, KEYTRUDA demonstrated a statistically significant improvement in DFS, reducing the risk of disease recurrence or death by 32% (HR=0.68 [95% CI, 0.53-0.87]; p=0.0010) compared with placebo in patients with RCC at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Updated efficacy results with a median follow-up time of 29.7 months demonstrated KEYTRUDA reduced the risk of disease recurrence or death by 37% (HR=0.63 [95% CI, 0.50-0.80]; p<0.0001) compared with placebo. Median DFS has not been reached for either group. The trial will continue to assess OS as a secondary outcome measure.

The safety of KEYTRUDA as monotherapy has been evaluated in 7,148 patients with advanced melanoma, resected stage III melanoma (adjuvant therapy), non-small cell lung cancer, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, endometrial, gastric, small intestine, biliary, pancreatic cancer or adjuvant therapy of RCC across four doses (2 mg/kg bodyweight [bw] every three weeks, 200 mg every three weeks, or 10 mg/kg bw every two or three weeks) in clinical studies. In this patient population, the most frequent adverse reactions with KEYTRUDA were fatigue (31%), diarrhea (22%) and nausea (21%). The majority of adverse reactions reported for KEYTRUDA monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions. The incidences of immune-related adverse reactions were 36.1% for all Grades and 8.9% for Grades 3-5 for KEYTRUDA monotherapy in the adjuvant setting (n=1,480) and 24.2% for all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). No new immune-related adverse reactions were identified in the adjuvant setting.

About Renal Cell Carcinoma

Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. Worldwide, it is estimated there were more than 431,000 new cases of kidney cancer diagnosed and more than 179,000 deaths from the disease in 2020. In Europe, it is estimated there were more than 138,000 new cases of kidney cancer diagnosed and more than 54,000 deaths from the disease in 2020.

About Mercks Early-Stage Cancer Clinical Program

Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.

KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Cancer

KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).

KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Tumor Mutational Burden-High Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.

KEYTRUDA With Axitinib

First-line treatment of advanced RCC in combination therapy with axitinib (KEYNOTE-426)

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other antiPD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

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European Commission Approves Merck's KEYTRUDA (pembrolizumab) as Adjuvant Therapy for Certain Patients With Renal Cell Carcinoma (RCC) Following...

There has been a surge in demand for Global Circulating Tumor Cells (CTC) Market from 2021 to 2027 research witnessing which MarketsandResearch.biz has attempted to provide a detailed insights through its expertise on the same. Market participants can use this report to develop strategies based on the industrys performance.

Analyses quantitatively are based on a comparison of historical, base-year and forecasted market data from global and regional markets. Market evaluation provides clients with an understanding of the demand and supply trends for the forecasted period starting from 2021 to 2027.

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Accordingly, this study includes different segments, which helps to breakdown the revenue and volume prospects of the Circulating Tumor Cells (CTC) market.The performance of these segments varies depending on economic factors.

By type, the market includes:

By application, the market includes:

Further, for the purpose of a regional analysis, the market has been segmented into

Circulating Tumor Cells (CTC) market includes existing and emerging players in addition to segments. The list of player includes:

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Debu Tripathy, MD, discusses key developments that may set the stage for new directions in care of breast cancer, including several areas of the treatment landscape on the cusp of change.

Nearly 35 years ago, when Debu Tripathy, MD, was a fellow at the University of California, San Francisco, he became involved with a translational project that would help shape his career and cement his passion for research. I joined a project to turn off this new oncogene that had been discovered recently called HER2. My job in the lab was to turn it off using antisense DNA. As a control, I needed to have a good antibody that worked against HER2-positive breast cancer cells. Genentech was right down the road from us. I knew some of the [investigators] there, and they gave me this antibody that is now Herceptin [trastuzumab], he recalled.

Tripathy continued to study trastuzumab from the initial early phases1 through the latestage trials that ultimately led to the monoclonal antibodys approval. It proved to be a golden opportunity. I was a fellow going on to become junior faculty when I got to be 1 of the 3 physicians who presented the data to the FDA when Herceptin got approved in 1998. That was a really special accomplishment for me, he said.

Today, Tripathy is a professor and chair of the Department of Breast Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston. His role in the development of trastuzumab, which introduced a new era in the treatment of HER2-positive breast cancer,2 marks an early milestone in a career packed with diverse research projects. Over the years, Tripathy has continued to pursue novel drug targets and treatments along with developing models of patient-centered care and assessing complementary therapies.

He also has become a leader in the breast oncology community. In March 2022, Tripathy will again serve as a cochair of the 39th Annual Miami Breast Cancer Conference, a role he has filled since 2012. Physicians Education Resource (PER), LLC, is hosting the conference Thursday, March 3, through Sunday, March 6, as a live and virtual meeting in Miami Beach, Florida. The hybrid conference will feature a broad range of sessions, tumor board panels, multidisciplinary meet-the-expert sessions, poster talks, and debates.

Tripathy finds the impact that research can have on his patients lives especially meaningful. He recounted the story of a patient he saw early in his career when trastuzumab was still in its infancy. The patient had advanced metastatic breast cancer with significant liver involvement, and she barely met the inclusion criteria for the trastuzumab study. At first, she had a tough time with the treatment and became more ill, but she eventually improved and then kept improving to the point that Tripathy was able to clear her to go on a vacation.

She sent me this amazing picture of her scuba diving in Belize. And just a couple of months before that, she was so ill that I didnt think she would even qualify for the study. To see someone who was so ill such a short time ago be able to send me a picture from vacation was a really special moment for me, he said.

Tripathy developed a passion for science and medicine at a very early age by observing his father, who was an investigator and a physician.

When I was young, between 8 and 10 years old, I used to go to the lab with my father and help wash the glassware and do other simple tasks. I was just fascinated with all the experiments. And I also got to accompany him on house calls when he thought it was safe for me to go. So I sort of got to see the whole picture at a young age, Tripathy told OncLive in a recent interview.

Like his father, he has been able to structure his time so that he can engage in research activities as well as care for his patients in a way that allows him to maintain a personal touch. I didnt want to be trapped in just the cold science part or have a super busy clinician type of experience either, he said.

Today, he says he has the best of both worlds, maintaining 1 or 2 clinic days and then spending the remainder of his time on research, teaching, and administration. This balance has enabled him to get to know his patients and keep in tune with their needs while also participating in the cutting-edge research that is expanding their treatment options and helping move the field forward.

Trastuzumab was among the first targeted therapies approved for cancer therapy. Tripathy has continued identifying and studying new drug targets that will personalize care. In 2014, he became the global principal investigator of the phase 3 MONALEESA-7 trial (NCT02278120) assessing ribociclib (Kisqali), an orally bioavail-able, selective CDK 4/6 inhibitor, as first-line therapy for premenopausal and perimenopausal patients with advanced hormone receptorpositive, HER2-negative breast cancer. Four years later, Tripathy and colleagues reported a progression-free survival (PFS) improvement in patients with the addition of ribociclib to endocrine therapy.3

We were really excited when those data came out because we had broken the survival barrier that really hadnt been crossed in hormone receptorpositive breast cancer. Being part of that story was very exciting, he said.

MONALEESA-7 included 672 patients in the intention-to-treat (ITT) population and randomly assigned them to receive ribociclib or placebo in addition to endocrine therapy (goserelin plus a nonsteroidal aromatase inhibitor [AI] or tamoxifen).4 At 42 months, 70.2% of patients in the ribociclib arm were alive versus 46.0% of patients in the placebo arm, indicating a 29% reduction in the relative risk of death compared with placebo (HR, 0.71; 95% CI, 0.54-0.95; P = .00973). In the subgroup of 495 patients who received an AI, the overall survival (OS) benefit was consistent with that of the overall ITT population (HR for death, 0.70; 95% CI, 0.50-0.98).

In July 2018, based on favorable PFS data from the MONALEESA-7 trial, the FDA expanded ribociclibs indication for use in combination with an AI as an initial endocrine-based therapy in pre/perimenopausal women with hormone receptorpositive, HER2-negative advanced or metastatic breast cancer.5 In March 2017, ribociclib had received its initial FDA approval for use in combination with an AI as an initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptorpositive, HER2-negative advanced or metastatic breast cancer, based on data from the MONALEESA-2 study (NCT01958021).6 Ribociclib also is approved in combination with fulvestrant (Faslodex) for postmenopausal women or in men with hormone receptorpositive, HER2-negative advanced or metastatic breast cancer as initial endocrine-based therapy or following disease progression on endocrine therapy.7

Looking forward, Tripathy sees several areas of the breast cancer treatment landscape on the cusp of change. In a wide-ranging interview with OncologyLive, Tripathy discussed key developments that may set the stage for new directions in care.

The cancer treatment paradigm has traditionally been based on killing as many cancer cells as possible. Although this approach is curative for some patients, others develop resistance mechanisms that eventually stop once-beneficial treatments from working, often leaving them in a treatment void.

Just like rivers continue to flow downward under the force of gravity and form the landscape, we know that tumors do that, too, under selective pressurejust like gravity, they find a path. They are in continual evolution, and we have increasingly better tools to discern what new mutations are being acquired, to understand how that cancer is surviving, Tripathy said. He explained that an evolving concept in cancer medicine is to use the information gleaned from new technologies, such as liquid biopsies, to adapt patients treatments in real time so that they stay ahead of their tumors evolving resistance mechanisms. He believes a proactive, rather than a reactive, approach will become the new treatment paradigm.

If we can understand the mechanisms of resistance and be able to monitor patients in real time, then we will be able to turn many cases of cancer into chronic diseases. Hopefully, [they will be] chronic conditions that allow patients to experience a generally good quality of life, he said.

To adapt a patients treatment requires an understanding of the nature of that patients tumor profile, including whether they have any beneficial, harmful, or neutral mutations so that therapies targeting potentially actionable mutations can be identified and used for treatment planning. Recently, mutations in the ESR1 gene, which encodes for an estrogen receptor (ER), have been found to be a common cause of acquired resistance to endocrine therapy in patients with metastatic ER-positive breast cancer. This discovery spurred the development of novel therapies to target these mutations, including potent selective ER degraders (SERDs) or modulators (SERMs) such as lasofoxifene, which Tripathy is studying. The SERD elacestrant was shown be more effective than the current standard, fulvestrant, especially in cases with ESR1 mutations, in findings of the EMERALD trial (NCT03778931) presented at the 2021 San Antonio Breast Cancer Symposium (SABCS 2021).8

Lasofoxifene is being investigated in combination with the CDK4/6 inhibitor abemaciclib (Verzenio) in the phase 2 ELAINEII trial (NCT04432454) in patients with advanced or metastatic ER-positive, HER2-negative breast cancer whose tumors harbor an ESR1 mutation. The trial completed enrollment in June 2021, and initial data are expected in the first half of 2022.9

Tripathy noted that the National Cancer Institute (NCI) Molecular Analysis for Therapy Choice (MATCH) Screening Trial (NCT02465060) is providing significant assistance in advancing adaptive therapy. It is one of the first trials to match patients with cancer to a treatment based on genetic changes in their tumors rather than their cancer type. NCI-MATCH plans to enroll more than 6000 patients with advanced refractory solid tumors, lymphomas, or myelomas who have progressed on standard treatment and harbor certain genetic changes into 1 of more than 35 subprotocol studies, with most arms planning to enroll approximately 35 patients.10 Ten substudies in NCI-MATCH are currently open for enrollment.

Findings from various NCI-MATCH substudies have confirmed that targeting genetic changes in tumors, such as mutations, amplifications, and fusions, is an effective strategy and that genomic sequencing in patients with advanced cancers may be beneficial in guiding treatment decision- making.11 Were sequencing everyone at MD Anderson with metastatic breast cancer because we may find a rare mutation thats got a drug approved for it or in clinical trials, regardless of where the tumor originated, Tripathy said.

NCI-MATCH data have led to plans for other large NCI basket trials such as ComboMATCH, which will test genomically directed combination regimens; MyeloMATCH, which will assign therapy for patients with acute myeloid leukemia and myelodysplastic syndromes based on genetic changes in their cancer cells; and ImmunoMATCH, which will use immune profiling to channel patients to treatments based on tumor mutational burden and interferon signature.11,12 Tripathy expressed excitement about the PI3K/AKT pathway, a signal transduction pathway that was successfully targeted in the NCI-MATCH trial.

The PI3K/AKT pathway is one of the most frequently altered pathways in cancer, including genetic changes such as aberrant signaling, overexpression, sequence variations, and somatic copy number alterations. In the EAY131-Y subprotocol of the NCI-MATCH trial, 35 patients with AKT1 E17K-mutated metastatic tumors of various histologies were treated with capivasertib, an AKT inhibitor, at 480 mg orally twice daily for 4 days on and 3 days off weekly in 28-day cycles until disease progression or unacceptable toxicity. In patients with metastatic breast cancer who continued hormone therapy, capivasertib was reduced to 400 mg.13

The most prevalent cancers treated included patients with breast (n = 18) and gynecologic (n = 11) malignancies. The overall response rate across cancer types was 28.6% (95% CI, 15%-46%). One patient with endometrioid endometrial adenocarcinoma achieved a complete response and was still receiving treatment at 35.6 months. Nine patients had partial responses and continued to receive treatment at 28.8 months, which included 7 patients with hormone receptorpositive/ERBB2-negative breast cancer, 1 with uterine leiomyosarcoma, and 1 with oncocytic parotid gland carcinoma.13 Several trials are open at MD Anderson that target different components of this critical pathway both for breast and other cancers.

Tripathy expects data for several key trials focused on the AKT pathway to be released in 2022, including a follow-up trial of the EAY131-Y subprotocol with capivasertib. He also anticipates follow-up data from the phase 1/2 FAKTION trial (NCT01992952). The initial FAKTION trial data showed a nearly 6-month PFS improvement when capivasertib vs placebo was added to fulvestrant in women with advanced ER-positive/HER2negative breast cancer (median PFS, 10.3 vs 4.8 months, respectively).14

Based on these promising initial data, the phase 3 trial CAPItello-291 trial (NCT04305496) is currently recruiting patients. Investigators plan to enroll more than 800 patients with locally advanced or metastatic hormone receptorpositive/HER2-negative breast cancer in the study, which has an estimated primary completion date of May 2022. Additionally, capivasertib is being studied as first-line therapy for women with locally advanced or metastatic triple-negative breast cancer in the randomized, double-blinded, phase 3 CAPItello-290 trial (NCT03997123), where capivasertib vs placebo is being added to paclitaxel. This trial is seeking to enroll more than 900 patients and has an estimated primary completion date of March 2023.

For a tumor to be considered positive for a targetable biomarker, it must express a certain quantity of that biomarker, which is usually set at fairly high levels. It has been discovered, however, that such tumors may still express very low levels of the targetable biomarker, which may render them vulnerable to a treatment targeting that biomarker if a potent enough treatment is found.

This is the story that is now unfolding with HER2-positive breast cancers. Although patients with HER2-positive breast cancers historically have had a lower likelihood of cure and survival, this changed with the advent of HER2-targeted therapies, including trastuzumab. Until recently, however, only patients with strong HER2 expression could be treated with such agents, but Tripathy said that may soon change.

He noted the development of fam-trastuzumab deruxtecan-nxki (Enhertu), a HER2-directed antibody-drug conjugate currently approved for patients with previously treated unresectable or metastatic breast cancer and for those with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received prior therapy. In the pivotal DESTINY-Breast01 trial (NCT03248492), HER2 positivity was defined as an immunohistochemistry (IHC) 3+ score or a positive result on in situ hybridization (ISH+), with testing conducted on tissue.15

Thats probably one of the most potent drugs we have against HER2 cancers. And it turns out that it may also work in HER2-low cancer, Tripathy said.

At SABCS 2021, investigators presented the results of the phase 2 DAISY study (NCT04132960), which tested trastuzumab deruxtecan in patients with previously treated advanced breast cancer in 3 biomarker-defined cohorts: HER2-overexpressing (HER2 IHC3+ or HER2 IHC2+/ISH+); HER2 low-expressing (IHC1+ or IHC2+/ISH-); and HER2 nonexpressing (IHC0+). Trastuzumab deruxtecan demonstrated a best objective response (BOR) rate of 37.5% in patients with low HER2 expression and 29.7% in patients with no detectable HER2 expression.16 In contrast, the BOR among patients with HER2 overexpression was 70.6%, which was comparable to the confirmed objective response rate (ORR) of 79.7% reported with trastuzumab deruxtecan as second-line therapy in the phase 3 DESTINYBreast03 study (NCT03529110).17

The findings in low HER2-expressing tumors from the DAISY study support those previously reported in 2020 in a subgroup analysis of a first-inhuman, phase 1b study (NCT02564900) assessing trastuzumab deruxtecan, which showed an ORR of 37.0% among heavily pretreated patients with HER2 low-expressing advanced or metastatic breast cancers.18 The finding of a nearly 30% BOR in the DAISY trial among individuals with no detectable HER2 expression, however, has led to some questions, including whether those individuals may have HER2 expression levels below what current assays are able to detect. Another presentation from SABCS 2021 may lend support to that theory.19 According to an analysis of data from 1400 global laboratories, current standard assays measuring HER2 expression were not able to efficiently differentiate between HER2 expression levels of IHC0 and IHC1+. More studies are under way to understand the distinct biology in HER2-low breast cancers.

The blood-brain barrier has long been difficult to cross. However, some newer agents are able to pass through this barrier and are potent enough to exert their effects on brain metastases, Tripathy said. In patients with HER2-positive breast cancer with brain metastases, one such agent is tucatinib (Tukysa).

In the HER2CLIMB trial (NCT02614794), 612 patients with HER2-positive breast cancer with and without brain metastases were randomized to receive tucatinib or placebo in combination with trastuzumab and capecitabine. Overall, 47.5% (n = 291) of the total population had brain metastases or a history of brain metastases at baseline, according to pivotal findings reported by Rashmi K. Murthy, MD, MBE, of MD Anderson and colleagues.20

The median PFS was 7.8 months for patients who received the regimen containing tucatinib compared with 5.6 months for those who received placebo (HR for disease progression or death, 0.54; 95% CI, 0.42-0.71; P < .001). Findings were similar for patients with brain metastases; the median PFS was 7.6 months with tucatinib vs 5.4 months with placebo (HR, 0.48; 95% CI, 0.34-0.69; P < .001).20 In April 2020, the FDA approved the tucatinib regimen for patients with previously treated advanced unresectable or metastatic HER2-positive breast cancer based on findings from the study.21

New data presented at SABCS 2021 from an exploratory analysis of HER2CLIMB results showed that adding tucatinib to trastuzumab and capecitabine in patients with active and stable brain metastases improved the median OS by 9.1 months vs trastuzumab and capecitabine alone (21.6 months vs 12.5 months, respectively; HR, 0.60; 95% CI, 0.44-0.81).22

Meanwhile, updated data from the DESTINYBreast03 study presented at SABCS 2021 also showed impressive response rates in patients with brain metastases. For participants with stable brain metastases at baseline (n = 82), the median PFS was 15.0 months with trastuzumab deruxtecan compared with 3.0 months with ado-trastuzumab emtansine (Kadcyla; T-DM1), which translated into a 75% reduction in the risk of progression (HR, 0.25; 95% CI, 0.310.45). Additionally, the ORR for patients with stable brain metastases at baseline was 67.4% for patients who received trastuzumab deruxtecan vs 20.5% for those treated with T-DM1.23

Were at the point now where [individuals] with brain metastases can live for many years. Now the next barrier to cross is going to be treating nonHER2-positive brain metastases, Tripathy said.

He noted that several agents are being examined that may provide benefit to patients with brain metastases without HER2-positive tumors, including sacituzumab govitecan-hziy (Trodelvy). The FDA, which initially approved the drug on an accelerated basis in April 2020, granted regular approval the following year for patients with unresectable locally advanced or metastatic triple-negative breast cancer previously treated with 2 or more prior systemic therapies, at least 1 of which was for metastatic disease.24

The regular approval was based on data from the phase 3 ASCENT trial (NCT02574455), which included patients with and without brain metastases. Among all randomized patients, median PFS in the sacituzumab govitecan plus chemotherapy arm was 4.8 months (95% CI, 4.1-5.8) compared with 1.7 months (95% CI, 1.5-2.5) in those receiving chemotherapy alone (HR, 0.43; 95% CI, 0.35-0.54; P < .0001). Median OS was 11.8 months (95% CI, 10.5-13.8) and 6.9 months (95% CI, 5.9-7.6), respectively (HR, 0.51; 95% CI, 0.41-0.62; P < .0001).24 Studies assessing sacituzumab govitecan in CNS metastases are under way.

Cancer stem cells (CSCs) were discovered in leukemia in the mid-1990s.25 Since their discovery, they have been considered a promising therapeutic target. Most cells have the capacity to move back into their stem state, and cancer cells do that to escape treatment, Tripathy explained, adding that this leads to the cancer becoming less immunogenic.

Tripathy is working on a project exploring epithelial-mesenchymal transition (EMT), a complex gene expression program that enables cancer cells to suppress their epithelial features and change into mesenchymal/CSC-like ones, giving the cell mobility and the capacity to migrate from its primary site, which can lead to metastases. Using a proprietary platform called ApoStream that isolates circulating tumor cells (CTCs) for research use, Tripathy and colleagues were able to detect chemotherapy-resistant micrometastatic disease expressing an EMT-like or CSC-like phenotype in the neoadjuvant setting. The presence of EMT-CTCs or CSC-CTCs was not predictive, however, of tumor response to neoadjuvant chemotherapy.26

Cancer cells are highly metabolic and programmed to focus their functions primarily on growth, which requires more energy, Tripathy said. This understanding has given rise to the field of cancer energetics, which focuses on understanding how cancer cells derive their energy so that their metabolic pathways may become targets for anticancer therapies.

Several important observations have been made in cancer energetics since the 1920s when Otto Warburg, a German physician and Nobel laureate, observed that cancer cells consume more glucose and produce more lactate than normal cells and suggested that cancer cells rely on adenosine triphosphate (ATP) production via the glycolytic pathway to satisfy their energy requirements.27,28 More recent observations suggest a metabolic symbiosis, with glycolytic and oxidative tumor cells mutually regulating their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate. Oxygenated cancer cells then use that lactate as fuel.

Our bodies also have their own macro level type of energy generation that has a lot to do with our quality of life and whether we gain or lose weight and our energy levels or sleep states. So at that level, understanding the biology of energetics has a whole different meaning, Tripathy said. At MD Anderson teams are working on both the macro and micro sides of cancer energetics, which is an area of research that he also is actively involved with and one that he sees leading to promising developments in the near future.

Much of the cancer metabolism research is being done in the Gan Laboratory.29 Areas of focus include the role and mechanisms of ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death involving lipid peroxidation, cellular metabolism, tumor suppression, and cancer therapy, as well as cystine metabolism-induced nutrient dependency and its implication in cancer therapy. The hope is that a better understanding of ferroptosis and nutrient dependency will translate into novel efficacious cancer therapies. In June 2021, investigators from the Gan Laboratory published preclinical findings pointing to a possible target, dihydroorotate dehydrogenase (DHODH), with DHODH inhibitors in GPX4low cancers being a potential strategy to inhibit ferroptosis and lead to cancer cell death.30

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Targeted Therapy Innovator Foresees New Paradigms in Breast Cancer - OncLive

Biotechnology is a wide discipline that harnesses cellular and biomolecular processes to develop technologies that help in improving the health and lives of the people.

Biotechnology is the field that exploits living organisms to make technological advances in various fields for the sustainable development of mankind. It has its applications in the medical as well as agricultural sectors. The biological processes of living organisms have been used for more than 6000 years to make essential products such as bread, cheese, alcohol, etc.

Let us have a look at the various types and applications of biotechnology in various fields.

Also Read: Biotechnology Principles

Biotechnology is divided into the following types:

Medical biotechnology involves the use of living cells to develop technologies for the improvement of human health. It involves the use of these tools to find more efficient ways of maintaining human health. It also helps in the study of DNA to identify the causes of genetic disorders and methods to cure them.

Vaccines and antibiotics have been developed with the help of medical biotechnology that is essential for human health. Several plants are genetically engineered to produce antibodies with the help of biotechnology.

This field deals with the development of genetically modified plants by introducing the gene of interest in the plant. This, in turn, helps in increasing the crop yield.

Various pest-resistant crops such as Bt-cotton and Bt-brinjal are created by transferring the genes from Bacillus thuringiensis into the plants.

The animals with the most desirable characteristics are bred together to obtain the offspring with the desired traits.

Also Read: Biotechnology Principles and Processes

Following are the important applications of biotechnology:

Nutrients can be infused into food in situations of aid. e.g., Golden rice is prepared by the infusion of beta-carotene into the rice.

Biotechnology helps in the production of crops that can handle abiotic stress such as cold, drought, salinity, etc. In the regions with extreme climatic conditions, such crops have proved beneficial in withstanding the harsh climate.

Biotechnology involves the production of alcohol, detergents, cosmetic products, etc. It involves the production of biological elements and cellular structures for numerous purposes.

Spider webs have materials with the strongest tensile strength. The genes from the spiders have been picked up through biotechnological techniques and infused in goats to produce silk proteins in their milk. This helps in the production of silk easily.

Biotechnology is widely used in energy production. Due to the depletion of natural resources, there is a need to find an alternative source. Such fuels are produced by using biotechnology tools. These are environment friendly and do not release any greenhouse gas.

Biotechnology is applied in the development of pharmaceuticals that had proven problematic when produced through conventional means due to purity concerns.

Also Read: Applications Of Biotechnology

This is how biotechnology is a boon to society. To know more about biotechnology class 12 topics such as what is biotechnology, its types and applications, keep visiting BYJUS website or download BYJUS app for further reference.

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Biotechnology - Types And Applications Of Biotechnology

SUMMARY: Simon Anderson (22) combines advanced physical science and competencies necessary to help people of different backgrounds, capacities, and beliefs.

Simon Anderson is building an Independent Scholars major around disparities in health and healthcare that stem from broader issues of diversity, equity, and inclusion. His major emphasizes coursework in biology and the medical humanities. Simon is also pursuing a degree in Biotechnology, with minors in Honors Interdisciplinary Studies and Pre-Medicine. Simon is a prime example of a Biotech student at JMU--passionate, determined, engaged, and innovative, says Dr. Stephanie Stockwell, past director of the Biotechnology program. By combining a wide array of interests and talents, Simon is paving the way for a lifetime of success and positive impact.

Simon is a graduate of South County High School in Fairfax County, Virginia, where he completed a demanding set of AP courses that nurtured his passions for math, biology, and chemistry. He also participated in the Governors School for Medicine and Health Sciences at Virginia Commonwealth University in the summer of 2017. During this program he worked with other students to examine case studies from three perspectives: Person (in-person interviews with the patient), Scientist (lab tests and results), and Community (implications of the ailment for the surrounding people)before splitting into smaller groups and analyzing a case study from all three perspectives simultaneously. In the area I grew up in, sickness and injury were the main reasons people went to the hospital, not for treatments related to opioid abuse, Simon remembers. But I learned that opioid abuse was also becoming a huge problem. Later, at JMU, he learned about the importance of local and county remote access clinics. Its not just in cities where people lack healthcare services, says Simon. If youre in a rural area you may also not have access.

Simon took a Viral Discovery (ISAT 203) course with ISAT professor Dr. Louise Temple in his freshman semester. In that class, Simon had his first real encounter with laboratory research. Viral Discovery is an exploratory experiential science class designed for incoming freshmen. Students learn about the life cycle and ecology of viruses infecting bacteria, collect soil samples, and practice techniques for isolation and purification of viruses from the soil. Dr. Temple is an expert in bacterial pathogenesis and bacterial virus discovery and genomic analysis. Isolated viruses are visualized in her lab using electron microscopy, and the genomic material is isolated and prepared for nucleic acid sequencing. Dr. Temples class built confidence in my ability to assess a problem and come up with solutions in a setting where theres flexible structure and no right answer, Simon recalls. He wanted to keep on with the work he had invested in phages, and so joined Dr. Temples lab. Simon has learned a number of valuable techniques related to DNA isolation and annotation, and is writing a paper about phages.

More recently, Simon enrolled in Cancer Genetics (BIO 477) with Dr. Tim Bloss, associate professor of biology. The course is cross-listed as a graduate-level course (BIO 577). I really enjoyed learning about how cancer develops and progresses, he says. Learning about molecular malfunctions in cancer helps me think about how I might create and test treatments in the future. Simon notes that Dr. Bloss is gifted at explaining genetics to students at both a basic and advanced level.

Simon is also a teaching assistant for JMUs General Chemistry laboratory courses (CHEM 131L and CHEM 132L). The course is designed to acquaint students with basic procedures and techniques encountered in the chemical laboratory. The experiments illustrate these techniques and supplement lectures. Simon gives instruction to students and assists with in-class procedures. He also digitally comments on students lab plans, data, and reports. It was a difficult, hybrid year of lab instruction due to the COVID pandemic. At first professors filmed experiments in the lab themselves, and then trialed virtual lab simulation software. This spring, Simon and other assistants returned to the labs to teach students. Proper use of pipette filler bulbs is one lesson we teach, notes Simon, People seem to have a lot of trouble with them.

Simon joined Independent Scholars to extend and broaden his undergraduate education. He understood that medical schools want to see students prepare themselves with an education in both science and the humanities. Simon found the Medical Humanities minor in the JMU catalog, and realized that he might build a major around it. Simons major is entitled Social Responsibility in Healthcare. It combines physical science and competencies necessary to help people of different backgrounds, capacities, and beliefs.

I wanted to take more classes across a wider range of subjects, says Simon. The Independent Scholars major made it possible to take a bunch of science courses that built a broader base around medical humanities. Simon hopes that the Independent Scholars major will give him exposure to a little bit of everything:biology, chemistry, bioinformatics, sociology, anthropology, psychology, and philosophy. I am just beginning to realize the connections between everything, he says. I want to understand how my research into biology and chemistry intersects with disparities in healthcare and beyond.

Simon says he likes the Independent Scholars approach to learning: I develop my questions, and then look for courses and experiences that can help me answer those questions. I wanted something different, to choose an area of study where the questions arent well established, or the answers known. Simon has written about the complexities of healthcare for the Independent Scholars e-zine on multiple occasions. In his essays, Simon seeks answers to enduring questions: What does it mean to be a doctor in our globalized world? How do institutions treat people of different backgrounds differently? What is healthy, and who gets to decide what healthy is? What are the impacts of structural and institutional prejudices? he asks. Simon is currently studying and writing about how person-oriented perspectives characterized by a holistic approach to patient management that embraces the physical, psychological, and social aspects of health and disease are becoming essential to undergraduate pre-medical education. His essays may be accessed here.

Independent Scholars students complete a culminating capstone project. Simons project has implications for the mitigation of racial disparities in health. He notes that, despite having roughly equal rates of breast cancer as non-Hispanic white women, African-American women are 40% more likely to die from the disease than white women, experience the highest breast cancer mortality of any racial group, and have an increasing rate of incidence of breast cancer. African American women are also more likely to have hormone-dependent breast cancers, which are deadlier than hormone-independent tumors.

Researchers have shown that delivering the protein HES-1 to hormone-dependent breast cancers has the effect of decreasing a nuclear protein called PCNA (found in dividing cells), which inhibits proliferation of the tumor, explains Simon. Were attempting to show that oxidative stress will prompt production of the GFP encoded behind an hlh-29 promoter to increase green fluorescent protein expression in all cells. If Simons project can provide evidence that oxidative stress is capable of increasing cells levels of proteins like HES-1, then they will have also laid the groundwork for potential clinical applications. One such application could be the induction of localized oxidative stress in tumors in an attempt to stall their proliferation, which would provide other therapies with an opportunity to shrink and kill the cancer.

Simon was a member of JMUs Huber Residential Learning Community (RLC) for freshmen in 2018-2019. The Huber RLC (which no longer operates) required two classes, one in each of the students first semesters. These classes focused on how different fields of medicine coexist, and gave a place for analysis and discussion of the social determinants of health. In the second semester, each student was required to volunteer with health- and education-related services in Rockingham County and Harrisonburg. Simon volunteered with the Virginia Personal Responsibility Education Program Innovative Strategies (VPREIS) project through JMUs Institute for Innovation in Health and Human Services (IIHHS). His volunteer work included working through the units of VPREISs Vision of Youa program for teen sexual and social health education, currently being administered to at-risk youth as part of a randomized controlled study in decreasing teen pregnancy in Virginia. Simon also volunteered at the ECHO (Ecumenical Community Helping Others) food pantry in Springfield, Virginia during the COVID-19 pandemic.

In the summer of 2021, Simon participated in a virtual summer research internship with the Pediatric Oncology Branch of the National Cancer Institute. During the experience, he worked on three projects that identified novel potential molecular targets in neuroblastoma, devised assembly schemes for designing new chimeric antigen receptors, and reviewed transcripts, patient data, and trial design documents for new psychological health programs. He also attended daily interactive seminars on many topics, including pediatric bone and neural cancers, cancer predisposition syndromes, lab mouse genetics, translation of basic science into therapies, and patient advocacy. Outside of the POB, he participated in an immunotherapy journal club, and two workshops on health disparities and social injustice in health research.

Simon also nurtures interests in how things are made. He enjoys watching videos about how the Disney and Universal theme parks create their engineered attractions, and builds models of landmarks and machinery from around the world. In the summer of 2019, Simon taught LEGO Robotics classes to young people in the Fairfax Collegiate Summer Program, based in Herndon.

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Health Disparities Research and Biotechnology - JMU - James Madison University

Prophecy Market Insights recently presented Pharmaceutical and Biotechnology market report which provides reliable and sincere insights related to the various segments and sub-segments of the market. The market study throws light on the various factors that are projected to impact the overall dynamics of the Pharmaceutical and Biotechnology market over the forecast period (2019-2029).

The Pharmaceutical and Biotechnology research study contains 100+ market data Tables, Pie Chat, Graphs & Figures spread through Pages and easy to understand detailed analysis. This Pharmaceutical and Biotechnology market research report estimates the size of the market concerning the information on key retailer revenues, development of the industry by upstream and downstream, industry progress, key highlights related to companies, along with market segments and application. This study also analyzes the market status, market share, growth rate, sales volume, future trends, market drivers, market restraints, revenue generation, opportunities and challenges, risks and entry barriers, sales channels, and distributors.

Base Year

Estimated Year

Forecast Year

2019

2020

2019-2029

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Global Pharmaceutical and Biotechnology market 2020-2030 in-depth study accumulated to supply latest insights concerning acute options. The report contains different predictions associated with Pharmaceutical and Biotechnology market size, revenue, CAGR, consumption, profit margin, price, and different substantial factors. Along with a detailed manufacturing and production analysis, the report also includes the consumption statistics of the industry to inform about Pharmaceutical and Biotechnology market share. The value and consumption analysis comprised in the report helps businesses in determining which strategy will be most helpful in expanding their Pharmaceutical and Biotechnology market size. Information about Pharmaceutical and Biotechnology market traders and distributors, their contact information, import/export and trade analysis, price analysis and comparison is also provided by the report. In addition, the key company profiles/players related with Pharmaceutical and Biotechnology industry are profiled in the research report.

The Pharmaceutical and Biotechnology market is covered with segment analysis and PEST analysis for the market. PEST analysis provides information on a political, economic, social and technological perspective of the macro-environment from Pharmaceutical and Biotechnology market perspective that helps market players understand the factor which can affect businesss accomplishments and performance-related with the particular market segment.

Segmentation Overview:

By Product Type(Vaccines (Recombinant Vaccines, Conventional Vaccines, Recombinant Enzymes, Cell and Gene Therapies and Other Product Types) and Synthetic Immuno-modulators (Cytokines, Interferones, Interleukins and Tumor Necrosis Factor))

By Therapeutic Application (Oncology, Inflammatory and Infectious Diseases, Autoimmune Disorders, Metabolic Disorders, Hormonal Disorders, Disease Prevention, Cardiovascular Diseases, Neurological Diseases and Other Diseases)

By Region (North America, Europe, Asia Pacific, Latin America, and Middle East & Africa)

Competitive landscape of the Pharmaceutical and Biotechnology market is given presenting detailed insights into the company profiles including developments such as merges & acquisitions, collaborations, partnerships, new production, expansions, and SWOT analysis.

Pharmaceutical and Biotechnology Market Key Players:

Pfizer

Roche

Johnson-Johnson

Sanofi

Merck, Novartis

Amgen Abbott Laboratories,

Agilent Technologies, Ely Lily

Biogen Scientific

Bio-Rad Laboratories

Danaher, F. Hoffmann-La Roche

Illumina

Merck

PerkinElmer, Qiagen

Thermo Fisher Scientific.

The research scope provides comprehensive market size, and other in-depth market information details such as market growth-supporting factors, restraining factors, trends, opportunities, market risk factors, market competition, product and services, product advancements and up-gradations, regulations overview, strategy analysis, and recent developments for the mentioned forecast period.

The report analyzes various geographical regions like North America, Europe, Asia-Pacific, Latin America, Middle East, and Africa and incorporates clear market definitions, arrangements, producing forms, cost structures, improvement approaches, and plans. Besides, the report provides a key examination of regional market players operating in the specific market and analysis and outcomes related to the target market for more than 20 countries.

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The report responds to significant inquires while working on Global Pharmaceutical and Biotechnology Market. Some important Questions Answered in Pharmaceutical and Biotechnology Market Report are:

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Regional Strategic Analysis of Pharmaceutical and Biotechnology Market during the Forecasted Period 2020-2030 Construction News Portal - Construction...

The latest research report provides a complete assessment of the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market for the forecast year 2022-2031, which is beneficial for companies regardless of their size and revenue. This Survey report covers the major market insights and industry approach towards COVID-19 (Omicron) in the upcoming years. The Chromatography Resin for Pharmaceuticals & Biotechnology Application Market report presents data and information on the development of the investment structure, technological improvements, market trends and developments, capabilities, and comprehensive information on the key players of the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market. The worldwide market strategies undertaken, with respect to the current and future scenario of the industry, have also been listed in the study.

The report begins with a brief presentation and overview of the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market, about the current market landscape, market trends, major market players, product type, application, and region. It also includes the impact of COVID-19 (Omicron) on the global Chromatography Resin for Pharmaceuticals & Biotechnology Application Market trends, future forecasts, growth opportunities, end-user industries, and market players. It also provides historical data, current market scenario and future insights on Chromatography Resin for Pharmaceuticals & Biotechnology Application Market. This study provides a comprehensive understanding of market value with the product price, demand, gross margin, and supply of the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market. The competitive perspective section of the report presents a clear insight into the market share analysis of the major players in the industry.

See how the research methodology work for the report | request sample report:https://market.us/report/chromatography-resin-for-pharmaceuticals-biotechnology-application-market/request-sample/

*** NOTE: Our team of industry researchers are studying Covid-19 (Omicron) and its impact on the growth of the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market and where necessary we will consider the Covid-19 footmark for better analysis of the market and industries. Contact us cogently for more detailed information.***

Figure:

Competitive Spectrum Top Companies Participating in the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market are:

Mitsubishi CorpThermo Fisher Scientific Inc.Danaher CorporationMerck KGaATosoh CorporationAvantor Inc.Bio-Rad Laboratories Inc.Sartorius Stedim Biotech SAPuroliteBio-Works TechnologiesOthers

Chromatography Resin for Pharmaceuticals & Biotechnology Application Market research report will be sympathetic for:

1. New Investors

2. Propose investors and private equity companies

3. Cautious business organizers and analysts

4. Intelligent network security Suppliers, Manufacturers and Distributors

5. Government and research organizations

6. Speculation / Business Research League

7. End-use industries And much more

Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Segments Evaluated in the Report:

Product Overview:

Based on Product Type

Natural PolymersSynthetic PolymersInorganic Media

Classified Applications of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market :

Based on Technique

Ion Exchange (IEX) ChromatographyAffinity ChromatographyHydrophobic Interaction Chromatography (HIC)Size Exclusion Chromatography (SEC)Multimodal ChromatographyOther Techniques

Do You Have Any Query Or Specific Requirement? Ask Our Industry Expert@https://market.us/report/chromatography-resin-for-pharmaceuticals-biotechnology-application-market/#inquiry

Key regions divided during this report:

The Middle East and Africa Chromatography Resin for Pharmaceuticals & Biotechnology Application Market (Saudi Arabia, United Arab Emirates, Egypt, Nigeria, South Africa)

North America Chromatography Resin for Pharmaceuticals & Biotechnology Application Market (United States, Canada, Mexico)

Asia Pacific Chromatography Resin for Pharmaceuticals & Biotechnology Application Market (China, Japan, Korea, India, Southeast Asia)

South America Chromatography Resin for Pharmaceuticals & Biotechnology Application Market (Brazil, Argentina, Colombia)

Europe Chromatography Resin for Pharmaceuticals & Biotechnology Application Market (Germany, UK, France, Russia, Italy)

The Chromatography Resin for Pharmaceuticals & Biotechnology Application Market research is sourced for experts in both primary and developed statistics and includes qualitative and quantitative details. The analysis is derived Manufacturers experts work around the clock to recognize current circumstances, such as COVID-19, the possible financial reversal, the impact of a trade slowdown, the importance of the limitation on export and import, and all the other factors that may increase or decrease market growth during the forecast period.

TOC Highlights:

Chapter 1. Introduction

The Chromatography Resin for Pharmaceuticals & Biotechnology Application Market research work report covers a brief introduction to the global market. this segment provides opinions of key participants, an audit of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market industry, outlook across key regions, financial services and various challenges faced by Chromatography Resin for Pharmaceuticals & Biotechnology Application Market. This section depends on the Scope of the Study and Report Guidance.

Chapter 2. Outstanding Report Scope

This is the second most important chapter, which covers market segmentation along with a definition of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market. It defines the entire scope of the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market report and the various facets it is describing.

Chapter 3. Market Dynamics and Key Indicators

This chapter includes key dynamics focusing on drivers[ Includes Globally Growing Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Prevalence and Increasing Investments in Chromatography Resin for Pharmaceuticals & Biotechnology Application Market, Key Market Restraints [High Cost of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market], opportunities [Emerging Markets in Developing Countries] and also presented in detail the emerging trends [Consistent Launch of New Screening Products] growth challenges, and influence factors shared in this latest report.

Chapter 4. Type Segments

This Chromatography Resin for Pharmaceuticals & Biotechnology Application Market report shows the market growth for various types of products marketed by the most comprehensive companies.

Chapter 5. Application Segments

The examiners who wrote the report have fully estimated the market potential of key applications and recognized future opportunities.

Chapter 6. Geographic Analysis

Each regional market is carefully scrutinized to understand its current and future growth, development, and demand scenarios for this market.

Chapter 7. Impact of COVID-19(Omicron)Pandemic on Global Chromatography Resin for Pharmaceuticals & Biotechnology Application Market

7.1 North America: Insight On COVID-19 (Omicron) Impact Study 2021

7.2 Europe: Serves Complete Insight On COVID-19 (Omicron) Impact Study 2021

7.3 Asia-Pacific: Potential Impact of COVID-19 (Omicron)

7.4 Rest of the World: Impact Assessment of COVID-19 (Omicron) Pandemic

Chapter 8. Manufacturing Profiles

The major players in the Chromatography Resin for Pharmaceuticals & Biotechnology Application Market are detailed in the report based on their market size, market served, products, applications, regional growth, and other factors.

Chapter 9. Pricing Analysis

This chapter provides price point analysis by region and other forecasts.

Chapter 10. North America Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Analysis

This chapter includes an assessment on Chromatography Resin for Pharmaceuticals & Biotechnology Application Market product sales across major countries of the United States and Canada along with a detailed segmental outlook across these countries for the forecasted period 2022-2031.

Chapter 11. Latin America Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Analysis

Major countries of Brazil, Chile, Peru, Argentina, and Mexico are assessed apropos to the adoption of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market.

Chapter 12. Europe Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Analysis

Market Analysis of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market report includes insights on supply-demand and sales revenue of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market across Germany, France, United Kingdom, Spain, BENELUX, Nordic and Italy.

Chapter 13. Asia Pacific Excluding Japan (APEJ) Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Analysis

Countries of Greater China, ASEAN, India, and Australia & New Zealand are assessed and sales assessment of Chromatography Resin for Pharmaceuticals & Biotechnology Application Market in these countries is covered.

Chapter 14. Middle East and Africa (MEA) Chromatography Resin for Pharmaceuticals & Biotechnology Application Market Analysis

This chapter focuses on Chromatography Resin for Pharmaceuticals & Biotechnology Application Market scenario across GCC countries, Israel, South Africa, and Turkey.

Chapter 15. Research Methodology

The research methodology chapter includes the following main facts,

15.1 Coverage

15.2 Secondary Research

15.3 Primary Research

Chapter 16. Conclusion

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Chromatography Resin for Pharmaceuticals & Biotechnology Application Market 2022 Size, Share, Revenue, Growth Opportunities, Trends and Demand by...

SHANGHAI, Jan. 28, 2022 /PRNewswire/ -- HanBio Therapeutics ("HanBio"), a biotechnology company committed to researching and developing next generation transformative medicines, today announced that it has completed a US$40 million Series A financing to advance the preclinical and clinical development of its series of innovative antibodies and other biologics products. This round of financing was jointly led by OrbiMed and Hankang Capital, followed by Yonghua Investment and Elikon Investment. Before the completion of this round of financing, HanBio was an early product research and development company incubated by Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd. ("Sunshine Guojian"). The company's current pipeline includes three bispecific antibodies in the IND and pre-IND stages, and a variety of early-stage antibodies and other biologics products.

Dr. Zhenping Zhu, Founder, Chairman and Chief Executive Officer of HanBio, said, "We highly appreciate OrbiMed and Hankang Capital and the other investors for their recognition of HanBio's R&D capability, its innovative pipeline and overall development strategy. This round of funds will be used for preclinical research and clinical trials of our multiple antibody and bispecific antibody products, as well as the establishment of an efficient company management and R&D team. We expect to submit IND applications to the regulatory agencies in both China and the United States for three innovative bispecific antibody products in 2022. On the research front we will focus on exploring new therapeutic targets and modalities, and developing innovative medicines with better safety and efficacy profiles to the current standard treatment options."

Dr. Zhu has extensive experience and an excellent track record in the biopharmaceutical industrial field, including more than 28 years of research and management experience in several world-renowned pharmaceutical companies. Prior to founding HanBio, Dr. Zhu served as the President of R&D and Chief Scientific Officer of 3SBio Group. Before joining 3SBio, Dr. Zhu has served as Executive Vice President at Kadmon Holdings, Vice President and Global Head of Protein Sciences at Novartis Biologics, and Vice President of Research at ImClone Systems. Dr. Zhu has contributed greatly to the discovery and development of a number of therapeutic antibody products approved by the US FDA, European EMA and China NMPA; he is the patent inventor of both ramucirumab (CyramzaR) and necitumumab (PortrazzaR), and one of the main contributors to cetuximab (ErbituxR). Dr. Zhu has published more than 200 peer-reviewed scientific papers in international journals, and has applied for or obtained more than 150 patents in China, United States and other international territories.

Dr. Jing Lou, Chairman of Sunshine Guojian, said, "I am very glad that HanBio, as an early product R&D company incubated by Sunshine Guojian, is recognized by leading biotech investors. Sunshine Guojian is committed to working with the investors to fully support HanBio for the rapid development of the company's innovative products that will benefit cancer patients in China and around the world."

Dr. Steven Dasong Wang, Partner at OrbiMed, said, "Dr. Zhu is one of the pioneers and leaders in the global biopharmaceutical industry. Several antibody products he invented or greatly contributed to, including ramucirumab (CyramzaR) and cetuximab (ErbituxR), have become ones of the most prescribed biologics in the treatment of gastric and colorectal cancers, with total global annual sales nearing 3 billion US dollars. HanBio led by Dr. Zhu has impressed us with its holistic approach to target selection, antibody discovery and design, and clinical translation strategy with special focus on cancers of the human digestive system. We look forward to supporting the company in advancing product clinical development and achieving breakthroughs in the treatment of cancers with high prevalence in China."

Mr. Quanhong Yuan, Partner at Hankang Capital, said, "PD1/PDL1 antibodies have reshaped the landscape of cancer treatment, but they also face the problem of limited response rate. Combination therapies and bispecific antibodies represent a new wave of therapeutic modalities, and are expected to provide a breakthrough solution to the treatment of PD1/PD1 resistant tumors. Dr. Zhu and his team at HanBio have rich experience and excellent track record in the field of antibody drug R&D and tumor immunotherapy. We expect HanBio to achieve great success in the field of cancer treatment."

About HanBio Therapeutics

"Transformative Medicines by Innovation."HanBio Therapeutics is an innovative biotechnology company committed to researching and developing next generation transformative medicines to treat patients with serious diseases.

For more information, please contact:Zhenping Zhu, MD, PhDEmail:[emailprotected][emailprotected]

Tel:+1 347 327 0705 (USA) +011 86 186 1234 0399 (China)

SOURCE HanBio Therapeutics

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HanBio Therapeutics Announces the Completion of a US$40 Million Series A Financing Led by OrbiMed and Hankang Capital - PRNewswire

Biotechnology Reagents Market report offers one of the best solutions to know the trends and opportunities in healthcare industry. The industry analysis report offers broader perspective of the market place with its comprehensive market insights and analysis. This market research report contains lot of features to offer for healthcare industry which includes general market conditions, trends, inclinations, key players, opportunities, and geographical analysis. What is more, global Biotechnology Reagents market document provides superior market perspective in terms of product trends, marketing strategy, future products, new geographical markets, future events, sales strategies, customer actions or behaviors.

The first class Biotechnology Reagents business report contains top to bottom analysis and estimation of various market related factors that are incredibly crucial for better decision making. Competitive analysis has been carried out in this business report for the major players in the market which supports businesses take better moves for enhancing their product and sales. Besides, Biotechnology Reagents market survey report takes into consideration several industry verticals such as company profile, contact details of manufacturer, product specifications, geographical scope, production value, market structures, recent developments, revenue analysis, market shares and possible sales volume of the company.

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Key Market Players mentioned in this report:Abbott, Agilent Technologies Inc., Danaher, BD, Bio-Rad Laboratories Inc., General Electric, bioMrieux SA, LONZA, F. Hoffmann-La Roche Ltd., Thermo Fisher Scientific Inc., Hoefer, Inc., Meridian Bioscience, Inc., PerkinElmer

Market Analysis and Insights: Global Biotechnology Reagents Market:

The biotechnology reagents market is expected to gain market growth in the forecast period of 2022 to 2027. Data Bridge Market Research analyses that the market is growing with the CAGR of 11.7% in the forecast period of 2022 to 2027 and is expected to reach USD 10.37 billion by 2027. The growing number of clinical trials will help in escalating the growth of the biotechnology reagents market.

This Biotechnology Reagents market report provides details of new recent developments, trade regulations, import export analysis, production analysis, value chain optimization, market share, impact of domestic and localised market players, analyses opportunities in terms of emerging revenue pockets, changes in market regulations, strategic market growth analysis, market size, category market growths, application niches and dominance, product approvals, product launches, geographic expansions, technological innovations in the market. To gain more info on Data Bridge Market Research Biotechnology Reagents market contact us for an Analyst Brief, our team will help you take an informed market decision to achieve market growth.

To know more details, visit in depth study Report @ https://www.databridgemarketresearch.com/reports/global-biotechnology-reagents-market?aZ

Biotechnology Reagents Market Country Level Analysis:

The Biotechnology Reagents market is segmented on the basis of product type, application and end user.

The countries covered in the Biotechnology Reagents market report are the U.S., Canada, and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of the Middle East and Africa (MEA) as a part of the Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America.

Competitive Landscape and Biotechnology Reagents Market Share Analysis:

The Biotechnology Reagents market competitive landscape provides details by competitor. Details included are company overview, company financials, revenue generated, market potential, investment in research and development, new market initiatives, global presence, production sites and facilities, production capacities, company strengths and weaknesses, product launch, product width and breadth, application dominance. The above data points provided are only related to the companies focus related to Biotechnology Reagents market.

Table Of Contents: Global Biotechnology Reagents Market

1 Introduction2 Market Segmentation3 Market Overview4 Executive Summary5 Premium Insights6 Global Biotechnology Reagents Market, By Type7 Global Biotechnology Reagents Market, By Tumor Type8 Global Biotechnology Reagents Market, By Application9 Global Biotechnology Reagents Market, By End User10 Global Biotechnology Reagents Market, By Geography11 Global Biotechnology Reagents Market, Company Landscape12 Company Profiles13 Related Reports

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The key questions answered in Biotechnology Reagents Market report are:

Key points covered in the report:

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Biotechnology Reagents Trends, Market Share, Industry Size, Growth, Opportunities and Forecast to 2028 The Oxford Spokesman - The Oxford Spokesman

One of the next big shifts in patient care will be precision medicine will be"an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment and lifestyle for each person," as the Precision Medicine Initiative describes it.

For physicians and researchersthis means predicting more accurately which treatment and prevention strategies for a particular disease will work in particular groups of people.

This is completely different from the traditional one-size-fits-all approach, in which treatment and prevention strategies are developed for the average person, with less consideration for the differences between individuals.

What does this mean for healthcare and health IT? A lot of new challenges. Because precision medicine and genomics generate massive volumes of varied and granular data, new approaches to data storage and exchangeand new designs for electronic health records,for example, may be required. Physician education and patient communication are two other areas that will demand attention

Some advanced healthcare provider organizations, such as large academic medical centers,are already well-advanced in their precision medicine efforts. But most providers are still early in the journey, if they're attempting it at all. But many are preparing today for what many think will be the next step in the evolution of healthcare.

This story, focused on precision medicine and other emerging technologies, is the sixth and final installment in Healthcare IT News' feature series, "Health IT Investment: The Next Five Years."

The series offers interviews with primarily CIOs to learn from them the path forward through the priorities they set with their investments in six categories: AI and machine learning; interoperability; telehealth, connected health and remote patient monitoring; cybersecurity; electronic health records and population health; and precision medicine and other emerging technologies. Click here to access all the features.

The six health IT leaders discussing their plans for the next five years in this sixth and final installment in the series include:

Precision medicine has been an organizational priority for UPMC for more than a decade, and it has an ambitious vision of using it to provide better, more personalized care and improved outcomes for patients.

"Through these efforts, we aim to create new insights into the drivers of health and disease to allow the discovery of innovative therapies and models of care, while also lowering the cost of care by avoiding diagnostic delays and therapeutic dead ends," said Kleinz of UPMC.

"As one of the largest integrated healthcare delivery and insurance organizations, UPMC has the scale, capabilities and ambition to lead the discovery, assessment and clinical deployment of impactful precision medicine approaches," he continued.

Dr. Matthias J. Kleinz, UPMC Enterprises

"Our efforts are led by the Institute for Precision Medicine, which was established in 2014 in collaboration with our academic research partner, the University of Pittsburgh."

The mission for the institute is to accelerate translational and clinical research in precision medicine and to deliver the most advanced prediction and treatment of disease, tailored to an individual's unique circumstances, history and condition.

"In this context, we have and will continue to make significant investments in established molecular and genomic tests [and]emerging proteomic, metabolomic, and microbiome assay technology, and drive the discovery of highly personalized precision therapeutic approaches, including cell, gene and regenerative medicines," Kleinz explained.

Investment in deployment and development of novel technologies is an important pillar inunlocking the value of precision medicine.

UPMC has made a number of significant initial investments in the following areas, Kleinz noted, and is continuing to evaluate new opportunities:

"UPMC's leadership strongly supports this vision and already has invested heavily in the implementation of precision medicine," he said. "The appropriate use of precision medicine approaches benefits first and foremost our patients, but also supports our providers as they deliver care across the UPMC system.

"The tangible benefits are streamlined clinical workflows, improved patient outcomes, and the potential to optimize resource allocation and reduce the long-term cost of care," he continued.

"We are dedicated to continuing the aggressive rollout of precision medicine, both through internal efforts and increasingly through creative partnerships with industry, such as our partnership with proteomics company Somalogic."

Sanford Health believes precision medicine will be the future of healthcare, so it continues to make significant investments in this space.

"Leveraging machine learning and high computational power to analyze data sets containing genetic, clinical and socioeconomic data will not only help design the best personalized treatment for our patients, but also will help identify those patients or patient populations that would benefit most from early screening and interventions to prevent disease," said Hocks of Sanford Health.

Matt Hocks, Sanford Health

"Precision medicine will allow us to concentrate our efforts on prevention and early screening, diagnosis, and care that will help keep our patients healthy and thriving for generations to come," he added. "Cancer care and chronic disease management are burdensome to patients, communities and health systems. Concentrating resources to prevent these conditions will benefit us all."

Mobile health is an area of health IT that has been emerging in recent years. The same with remote patient monitoring, which has especially gained ground during the COVID-19 pandemic. Virginia Hospital Center is on top of both.

"Virginia Hospital Center does not view itself as cutting-edge when it comes to technology," Mistretta said. "It considers itself more of a fast, early adopter of new technology it believes may provide an advantage to its patients.

"We are extremely patient-focused, so many of our investments moving forward are going to be in that realm," he continued. "We will be investing in hospital-at-home and remote patient monitoring features in depth, along with other patient engagement functions to empower our population and maintain low-touch care to minimize costs."

Mike Mistretta, Virginia Hospital Center

Mobility is in demand by patients, so connecting through web and app technologies will be a high priority, he added.

"We need to make care convenient for patients and provide care on their terms," he observed. "In our Northern Virginia/D.C. market, we hear about this frequently due to traffic and distance considerations."

Thus the development of pilot programs like the organization's OB Connect, where patients followed for maternity care are issued home equipment, post resultsand are able to skip the office if everything is within expected limits. Mistretta believes this kind of technology will permeate the market.

"These types of technologies will be required to sustain significant growth for health systems," he said. "Combined with the effective use of data to produce appropriate metrics, we should be able to pinpoint more specific markets and what treatments produce more effective outcomes.

"It also is the only way we will be able to meet the significant demands that will be placed on the care system with the shortage of nursing and primary care resources predicted to hit in the coming years," he added. "We simply will not be able to continue to experience the same results and levels of treatment enjoyed today as the population grows and ages without providing increased care outside the walls of our traditional organizational structures."

Leadership buy-in on a different approach will take some time, but with successes along the way (and supporting data to reinforce), healthcare organizations will be able to achieve what will be needed, he said.

Providence pledged to invest $50 million over five years in health equity. Here is a recap of how it invested in year one.

Elsewhere, Moore is concerned with the internet of things.

"The internet of things is it it's smart devices," he said. "We may give our patients smart devices that sit in our care delivery environments, and have the telemetry information, and go into our big data model. Because that's how we're really going to make these machine learning and artificial intelligence models shine.

B.J. Moore, Providence

"We in healthcare say big data, but until you're working with streams of data, it's not really big data, it's just large data warehouses," he continued. "So getting that remote care delivery data is important, like a temperature four times a day, or real-time streaming of oxygen or heart data."

Moore believes the IoT and the streams of data it can provide are things healthcare executives should be talking about more. "It's all about data volumes: The bigger the volume, the better," he said.

Regenstrief is in the process of developing tools and processes to identify bias in algorithms to improve health equity, said Grannis of Regenstrief Institute.

"As AI becomes more ubiquitous, researchers, clinicians, health systems, industry, government and others must be wary of unintended consequences," he stated. "Our research scientists are working on best practices as well as novel analytical tools to regularly monitor for bias in algorithms, a process Regenstrief and CEO Dr. Peter Emb have coined "algorithmovigilance."

"Over the next five years, Regenstrief will be working with individuals and organizations around the world to implement," he added.

Dr. Shaun Grannis, Regenstrief Institute

Regenstrief also is investing in the broader ecosystem required to sustain advanced AI and machine learning methods. In the same way that clinical decision-makers, including physicians and other care providers, undergo regular training updates and certification due to healthcare's evolving nature and potential for bias, advanced algorithms will need frequent updates and certification to minimize bias and or errors, Grannis said.

Frameworks for overseeing algorithms and analytics are nascent.Developing and evaluating approaches to accurately and efficiently monitor AI and machine learning will become increasingly important in the future of healthcare analytics, he added.

"We also are investing in patient ergonomics the application of human factors,engineering and psychology to the design and evaluation of patient-facing technology to enhance delivery of healthcare," he explained.

"Institute scientists are using user-centered design to create apps that help informal caregivers provide care for their loved ones with Alzheimer's and other chronic conditions. Other apps are exploring the benefits of specific diets and brain-stimulating games."

Babachicos of South Shore Health believes tools that assist patients with care navigation will allow for a more improved and directed patient experience.

"These tools combined with the next-generation call centers also known as patient access centers can be accessed 24/7 by patients looking for care options and direct patients to the right place at the right time for their care needs," she explained. "These patient access centers will use multichannel options such as text, voice and chat while allowing patients to perform many self-service functions, as well.

Cara Babachicos, South Shore Health

"These patient access centers might also be staffed by care navigators for a more human connection when necessary," she concluded. "The same centers could potentially deliver virtual visits/consults, as well as potentially manage patient medications and vitals for subscribed patients in the community."

Twitter:@SiwickiHealthITEmail the writer:bsiwicki@himss.orgHealthcare IT News is a HIMSS Media publication.

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CIOs' 5-year plans for precision medicine and emerging technologies - Healthcare IT News

MONTPELLIER, France--(BUSINESS WIRE)--SeqOne Genomics, provider of next genomic analysis solutions for personalized medicine today announced a Series A funding round of 20M.

The round, led by Omnes, Merieux Equity Partners, together with the Software Club and existing investors, Elaia and IRDI Capital Investissement, will enable SeqOne Genomics to accelerate its international sales and the development of new collaborative genomic analysis tools to facilitate communications between different disciplines in the medical team, in order to improve patient outcomes in cancer and hereditary disease.

The company will intensify investments in the development of its genomic-aware data lake to improve the use of big data and machine learning approaches in genomic analysis with the aim of better addressing the fast-evolving needs of molecular biology labs that provide genomic analysis in clinical routine environments, as well as to biopharma companies developing new therapies.

SeqOnes cloud-based solution manages the entire genomic analysis process from raw data to final report presented to clinicians. The solutions end-to-end approach affords better analytic performance, high levels of traceability and improved operational efficiency and has already been adopted by a score of hospitals and central labs and biopharmas as well as spawning partnerships with leading manufacturers of genomics analysis hardware and reagents.

Nicolas Philippe, Ph.D., Co-founder and CEO of SeqOne Genomics stated We are extremely happy to have closed this round with leading investors who bring extensive experience in deep-tech, healthcare and biotherapy and who share our vision of building SeqOne into a global leader in personalized medicine. The funding will give us the resources we need to enhance and commercialize our solution to make genomic analysis more accessible and affordable so that each patient can benefit from personalized medicine recommandations.

The genomics analysis market is experiencing exponential growth driven by the needs of personalized medicine. With the rapid expansion in the available genomic-linked treatments, the complexity of treatment interactions, and the staggering volume of biological and medical data to be factored into each medical decision, biologists and doctors must have access to reliable and actionable analyses in real-time, stated Fabien Collangettes, Director at Omnes. We were particularly impressed by SeqOnes innovative technological approach that enables improved accuracy of genomic test while reducing turnaround time and cost, thus delivering a key competitive advantage in this fast-growing market.

With the closing of this round, SeqOnes board of directors will be: Sacha Loiseau, Ph.D. independent board member and Chairman of the Board, Fabien Collangettes, Director at Omnes, Yoann Bonnamour, Investment Manager at Merieux Equity Partners, Marc Rougier, Partner at Elaia, Nicolas Philippe, co-founder and CEO of SeqOne Genomics and Jean-Marc Holder, Co-founder and Chief Strategy and Innovation officer of SeqOne Genomics.

This new funding round brings the total amount raised by SeqOne Genomics since its founding in 2017 to 23M.

The company currently employs over 40 staff, primarily experts in genomic medicine, data science, bioinformatics, software development and regulatory compliance / quality assurance. It plans to double its staff within the year to execute its ambitious plans.

Advisors:

Legal:Anthony Beauquier - LSF AdvisoryJones Day - Jean-Gabriel Griboul and Hortense FouillandMarket intelligence : Clara Niarfeix Alcimed

Intellectual property: Claire Verschelde, PhD ICOSA

Financial due diligence : Crowe HAF Maxime Hazim and Julien Latrubesse

About SeqOne Genomics

SeqOne Genomics offers high performance genomic analysis solutions for healthcare providers treating patients suffering from cancer, rare and hereditary diseases as well as pharmaceutical companies developing new therapies. The solution leverages advanced machine learning coupled with the company's proprietary GeniOS genomics operating system to dramatically reduce turnaround times and costs while delivering a comprehensive and actionable insights for personalised medicine. The company has won numerous awards including the iLab award and the ARC cancer foundations Hlne Stark prize.Investors include Elaia, IRDI Capital Investissement, Merieux Equity Partners, Omnes and Software Club.

Web: https://seqone.com Direct link to this release: https://seqone.com/seriesa

About Elaia

For more information: http://www.elaia.com @Elaia_Partners

About IRDI Capital Investissement

Learn more: https://www.irdi.fr/

About Merieux Equity Partners

For more precision: http://www.merieux-partners.com

About Omnes

For more precision: http://www.omnescapital.com

About Software Club

For more precision: softwareclub.io

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SeqOne Genomics Closes 20M Series a to Accelerate the Deployment of Its Genomic Medicine Platform - Business Wire

BUFFALO, N.Y. A joint study conducted by researchers at the University at Buffalo and the University of California, Los Angeles is revealing for the first time that behavioral self-management of irritable bowel syndrome (IBS), a painful and common gastrointestinal disorder, can fundamentally change the gut microbiome. It is the first to show how cognitive behavioral therapy can teach patients information-processing skills that address the biological roots of their GI symptoms.

This work demonstrates that teaching people how to think more flexibly in specific situations can reduce the physical tension and stress that can disrupt brain-gut interactions and crank up symptoms, said Jeffrey M. Lackner, PsyD, co-senior author on the paper, professor in the Department of Medicine and chief of the Division of Behavioral Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB.

Published late last year in the journal Microbiome, this study, conceived by an interdisciplinary UB team, shows how a non-drug, non-dietary treatment for IBS induces changes in brain function and in the microbiome by normalizing ways of processing information, Lackner explained.

These results will have a dramatic impact on understanding a gastrointestinal disease that has a significant public health burden, he said. This is paradigm-shifting for how we understand the role of the microbiome and therapeutics that can modify its composition to treat and prevent disease.

Emeran A. Mayer, MD, an internationally known expert on the interactions between the digestive and nervous systems, is co-senior author on the paper. He is a professor in the David Geffen School of Medicine at UCLA and executive director of the G. Oppenheimer Center for Neurobiology of Stress and Resilience.

"Dr. Lackners collaborative project with UCLA is an important breakthrough in the understanding of how cognitive behavioral therapy can alter brain-gut interaction to provide relief for IBS patients, saysAllison Brashear, MD, UBs vice president for health sciences and dean of theJacobs School. This studys translational research provides new hope for those afflicted with this debilitating disease.

The study was funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases to Lackner and Mayer, UBs Office of the Vice President for Research and Economic Development and UBs Genome, Environment and Microbiome (GEM) Community of Excellence.

The findings are the first to demonstrate that a specific type of cognitive behavioral therapy developed at UB that teaches information-processing skills can modulate key components of the brain-gut-microbiome axis in some of the most severe IBS patients, said Lackner.

Learning-based treatments

We know that the gut microbiome is a key to regulating brain-gut interactions and plays a role in overall human health from metabolism to immunity. We also know learning-based treatments like cognitive behavioral therapy are some of the most robust treatments of any kind for what is the most prevalent GI (gastrointestinal) disease, even when they are home-based delivered with minimal doctor involvement, said Lackner.

What we didnt know is how those two facts interact, said Lackner. We didnt know whether symptom relief following CBT depends on the microbiome environment to achieve its effects.

This study is important because it reveals a precise microbiome signature that distinguishes patients who respond positively to a drug-free treatment and those who dont, and that signature corresponds with objective changes in brain function, he added.

The fact that we see patient-reported GI symptom improvements that correspond with objective biological changes in the microbiome and brain function is pretty remarkable given that we focused on a low-intensity, home-based behavioral treatment and not medical therapies like probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation known to manipulate our microbiome, Lackner said.

Eighty-four IBS patients were recruited from the parent CBT trial the Irritable Bowel Syndrome Outcome Study, a landmark, National Institutes of Health-funded clinical trial led by Lackner that has transformed the way IBS is understood and treated.

The 84 participants underwent neuroimaging and detailed clinical assessment at clinical sites at UB and Northwestern University. UB also collected microbiome data through fecal sampling from 34 of the patients.

Eligible patients were randomized to receive 10 sessions of clinic-based CBT or four sessions of largely home-based CBT with minimal therapist contact over a 10-week acute phase. Both treatments were developed at UB.

Boundary-breaking translational research

This trial was enormously complex in that we collected symptom data across different sites at pre-treatment and post-treatment, said Lackner, who sees patients at the Behavioral Medicine Clinic at UBMD Internal Medicine. Because we were also collecting biological data at multiple times, it required a high level of precision and project management unique among major research centers. It really speaks to our divisions capacity to support boundary-breaking, novel translational research with high impact potential.

UB partnered with the David Geffen School of Medicine at UCLA and the G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA.

All that data had to be expertly analyzed and that is where we were able to draw from the expertise of our long-standing collaborators at UCLA, experts in microbiome and imaging research, Lackner says.

UB developed the treatment, delivered it and collected data, while UCLA analyzed gut microbiome and neuroimaging data.

It is a great example of team science between two outstanding research facilities with unique synergies, Lackner says. Theres a lot of reasons why this type of study hasnt been done up to now, but we were able to leverage our unique clinical expertise and our clinical research infrastructure and UCLAs expertise.

Of the 84 participants in the trial, 58 were classified as CBT responders and 26 were classified as non-responders.

While there were small pre-treatment differences between brain network connectivity for responders and non-responders, the significant difference was how much the connectivity changed after treatment.

Responders showed greater baseline connectivity than non-responders between the central autonomic network and the emotional regulation network, according to the study.

Lackner said that the findings raise the possibility that CBT-responsive IBS patients can be identified in clinical practice using microbial biomarkers, before less effective treatments are initiated at great expense to the patient and health care system.

The pattern of data may explain normal versus abnormal gut function and just how the brain-gut can influence symptoms and the relief of them, Lackner says. Larger studies are needed to characterize the functional correlates of gut microbial changes and to identify distinct subtypes of IBS patients for whom brain- and gut-directed therapies are most effective.

This is an example of science moving away from a one-size-fits-all brand of medicine toward a more personalized medicine approach driven by translational research.

Jonathan P. Jacobs, MD, PhD, and Arpana (Annie) Gupta, PhD, both of the David Geffen School of Medicine at UCLA and the G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, are the studys co-first authors.

Co-authors from the Jacobs Schools Division of Behavioral Medicine are:

Rebecca S. Firth, division administrator and research coordinator.

Gregory D. Gudleski, PhD, research assistant professor.

Other co-authors are from the following institutions:

David Geffen School of Medicine at UCLA.

G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA.

Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine at University of Southern California.

Read more here:
Study: In IBS patients, cognitive behavioral therapy modulates the brain-gut microbiome and helps relieve symptoms - UB News Center

[93 Pages Report] Digital Genome Market Insights 2022 This report contains market size and forecasts of Digital Genome in United States, including the following market information:

United States Digital Genome Market Revenue, 2016-2021, 2022-2027, (USD millions)

United States top five Digital Genome companies in 2020 (%)

The global Digital Genome market size is expected to growth from USD 6963.3 million in 2020 to USD 10930 million by 2027; it is expected to grow at a CAGR of 6.2% during 2021-2027.

The United States Digital Genome market was valued at USD million in 2020 and is projected to reach USD million by 2027, at a CAGR of % during the forecast period.

The Research has surveyed the Digital Genome Companies and industry experts on this industry, involving the revenue, demand, product type, recent developments and plans, industry trends, drivers, challenges, obstacles, and potential risks.

Get a Sample PDF of report https://www.360researchreports.com/enquiry/request-sample/19492806

Leading key players of Digital Genome Market are

Digital Genome Market Type Segment Analysis (Market size available for years 2022-2027, Consumption Volume, Average Price, Revenue, Market Share and Trend 2015-2027): Sequencing Services, Sequencing Instruments, Sequencing Consumables, Bioinformatics, Sample Preparation Kits and Reagents

Regions that are expected to dominate the Digital Genome market are North America, Europe, Asia-Pacific, South America, Middle East and Africa and others

If you have any question on this report or if you are looking for any specific Segment, Application, Region or any other custom requirements, then Connect with an expert for customization of Report.

Get a Sample PDF of report https://www.360researchreports.com/enquiry/request-sample/19492806

For More Related Reports Click Here :

Automobile Speakers Market In 2022

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(New Report) Digital Genome Market In 2022 : The Increasing use in Diagnostics, Agriculture & Animal Research, Personalized Medicine, Drug...

News Release

Monday, January 24, 2022

NIH-funded preclinical study identifies potential therapeutic approach to treat ALS.

Using an experimental drug, researchers were able to suppress a mutated amyotrophic lateral sclerosis (ALS) gene. Studies in mice demonstrate that the therapy could show promise in treating rare, aggressive forms of ALS caused by mutations in the fused in sarcoma (FUS) gene. The study, published in Nature Medicine, was funded in part by the National Institute for Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

The study models how promising gene-targeting therapies can move expeditiously from pre-clinical development to clinical testing, said Amelie Gubitz, Ph.D., program director at NINDS. There is a desperate need for innovative approaches to treating ALS.

ALS, also known as Lou Gehrigs disease, is a fatal neurological disorder that causes the degeneration of motor neurons in the brain and spinal cord. People with ALS rapidly lose muscle strength and eventually their ability to move, swallow, and breathe. Most cases of ALS are sporadic, but at least 10% of cases are familial, or due to mutations in various genes. Mutations in the gene FUS cause severe forms of ALS, referred to as FUS-ALS, including a rare type that begins in adolescence or young adulthood.

In the study, Neil Shneider, M.D., Ph.D., the Claire Tow Associate Professor of Motor Neuron Disorders and Director of the Eleanor and Lou Gehrig ALS Center at Columbia University, New York City, and his team delayed the onset of motor neuron degeneration in mice by using an antisense oligonucleotide drug designed to silence FUS by blocking cells from making specific proteins. Following encouraging results, they administered the drug to a patient with ALS.

Compared to normal mice, mice with a mutated FUS gene had higher levels of insoluble FUS and other ALS-related proteins in their brains and spinal cords. Mice with higher doses of mutant FUS in motor neurons experienced rapid neurodegeneration that began early in life, much like FUS-ALS patients.

The study establishes a mouse model that is highly disease-relevant, said Dr. Shneider. In mice, we found that FUS toxicity was due to a gain of function and was dose-dependent, suggesting that we could treat FUS-ALS by silencing the FUS gene.

In 2019 Dr. Shneider met an individual with ALS in search of therapies that may help her disease. Inspired by her story, Dr. Shneider teamed up with a pharmaceutical company to develop a personalized therapy designed to target the FUS mutation.

In mice, injecting a single dose of the drug into the ventricles, fluid-filled spaces surrounding the brain, delayed the onset of inflammation and motor neuron degeneration by six months. The drug also knocked down levels of FUS by 50% to 80% in the brain and spinal cord. Following drug administration, insoluble forms of other ALS-associated proteins were also cleared.

Under a compassionate use protocol reviewed by the U.S. Food and Drug Administration, Dr. Shneider administered the drug to the patient it had been designed for. The patient received repeated infusions of the drug into her spinal canal for 10 months. During the treatment, the patients rate of motor function deterioration slowed. The patient tolerated the treatment well and there were no medically adverse effects.

The study is an example of a precision medicine, bench-to-bedside effort, said Dr. Shneider. We began with the mouse model to establish a rationale for the drug, conducted efficacy studies in the mouse, moved the drug into a human, and collected valuable data that was ultimately used to support a larger Phase 3 clinical trial.

Treatment began more than six months after clinical onset, by which time the disease had already significantly advanced. As is typical with juvenile-onset FUS-ALS, the disease progressed rapidly, and the patient died from complications of the disease.

By studying the patients brain and spinal cord tissue, researchers found that the drug silenced FUS throughout the nervous system and reversed the toxic nature of FUS and other disease-related proteins. Compared to tissue from untreated FUS-ALS patients and healthy controls, FUS protein aggregatesa pathological hallmark of this form of ALSwere sparse, suggesting that they may have been cleared by the drug. Tissue samples were provided by the New York Brain Bank of Columbia University.

The protein made from the FUS gene has been shown to be important for various cellular processes. Prior studies in mice suggest that FUS mutations result in the production of an abnormal protein that forms clumps, or aggregates, leading to motor neuron damage. By targeting the faulty gene in a way that suppresses toxic FUS activity, gene silencing products like the antisense oligonucleotide drug could potentially reduce or prevent disease progression.

The results were used to support a clinical trial testing the drug in patients with FUS-ALS (NCT04768972).

This study was supported by grants from the NIH (NS106236), Nancy Perlman, Tom Klingenstein, and the Judith and Jean Pape Adams Charitable Foundation.

NINDSis the nations leading funder of research on the brain and nervous system.The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Korobeynikov, V.A., et al. Antisense oligonucleotide silencing of FUS expression as a therapeutic approach in amyotrophic lateral sclerosis. Nature Medicine, January 24, 2022. DOI: 10.1038/s41591-021-01615-z

###

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Silencing a faulty gene may uncover clues to rare forms of ALS - National Institutes of Health

The Soyuz MS-19 crew ship and the Prichal docking module attached to the Nauka multipurpose laboratory module are pictured during an orbital sunset.

The Expedition 66 crew split its research schedule between space botany and life science aboard the International Space Station today.

NASA Flight Engineer Thomas Marshburn started Thursday watering plants growing for the Veggie PONDS study that explores ways to reliably grow vegetables in microgravity. Afterward, the three-time space station visitor verified the operability of the two robotics workstations, located in the U.S. Destiny laboratory module and the cupola, that control the Canadarm2 robotic arm.

Matthias Maurer, flight engineer from ESA (European Space Agency), printed samples from a handheld bioprinter for analysis back on Earth. The samples were printed to investigate how to develop tissues in microgravity to advance personalized medicine on Earth and in space.

The three other NASA Flight Engineers aboard the orbiting lab, Raja Chari, and Kayla Barron, Mark Vande Hei, worked throughout the day on a variety of life support and science maintenance tasks. Chari was on plumbing duty draining and transferring fluids in station tanks. Barron serviced the labs exercise cycle before replacing components in the waste and hygiene compartment, the stations bathroom. Vande Hei processed samples for DNA analysis for the Food Physiology experiment that documents how diet affects a crew members health during a long-term space mission.

The stations commander, Anton Shkaplerov of Roscosmos, was back on exercise research on Thursday exploring how to maximize the effectiveness of working out in weightlessness. Russian Flight Engineer Pyotr Dubrov cleaned up the Zvezda and Poisk modules, returning them to a post-spacewalk configuration following his excursion with Shkaplerov on Jan. 19.

Learn more about station activities by following thespace station blog,@space_stationand@ISS_Researchon Twitter, as well as theISS FacebookandISS Instagramaccounts.

Get weekly video highlights at:http://jscfeatures.jsc.nasa.gov/videoupdate/

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Plants, Bioprinting and Orbital Plumbing Fill Crew's Thursday Schedule - NASA

Tackling Seasonal Affective Disorder

MIAMI (PRWEB) January 28, 2022

ClarityX, providers of genetic testing to empower both consumers and physicians, today announced that its at-home genetic tests can aid in finding the appropriate medications for patients combating Seasonal Affective Disorder (SAD). Their testing is able to reveal an individuals genetic profile in order to take the guesswork out of prescribing.

Recent clinical research has shown that depression spikes at the beginning of the new year, with over 10 million Americans struggling with seasonal depression. Seasonal Affective Disorder (SAD) is a type of depression that relates to changes in the seasons. Although the exact cause of SAD is unknown, treatments include light therapy, talk therapy, Vitamin D and antidepressant medications. Unfortunately, the sheer amount of these drugs available on the market make it difficult for healthcare providers to determine which medication will be the most effective for each patient. Additionally, incorrect dosing may interact negatively within a patient.

ClarityX offers genetic test kits that are able to reliably predict a persons response to medication. Pharmacogenetic testing is a type of DNA testing that examines genes for variations that may affect how patients metabolize certain drugs. The insight helps when having to choose between different antidepressants as well as providing physicians information to help with optimal dosing.

Additionally, ClarityX's Mindwell Test is designed to provide answers on how a patient responds to various antidepressants, antipsychotics, anxiolytics, SSNRIs and SSRIs based on their DNA. As genes do not change over time, an individuals Mindwell test results and treatment plan will remain valid and accurate for life. The Mindwell Test covers genetic testing for depression, anxiety, bipolar, ADHD/ADD, OCD, PTSD medications.

Whether someone is experiencing mild SAD or is facing debilitating depression, its important to confront the symptoms. When left untreated, the condition can worsen and infiltrate every aspect of life causing patients to lose interest in their favorite activities, stop maintaining social relationships and neglect their daily obligations, said Andres Benzaquen, President of ClarityX. However, getting the right depression medication is a process of trial and error that can take months. ClarityX helps cut the guesswork out of the process - especially as more and more patients are searching for personalized, precise medication healthcare. In the near future, you won't be prescribed medications without a pharmacogenetic test.

Testing happens in a quick three step process. First, the patient clicks the "Get Started" button torequest a ClarityX test. Once a patient has received and activated their kit, they perform a simple cheek swab. The sample is then returned in the provided pre-paid envelope. Patients receive their personalized report online in their ClarityX patient portal and the results can easily be shared with their doctors.

The days of going back and forth to your physician just to find the right medications are over. "Were at the beginning of a growing shift towards the at-home medically actionable, test market., adds Benzaquen. . In a time when mental Health is a growing problem - and has been exacerbated during Covid - precision medicine is the future of healthcare. Our genetic tests can help to take the guesswork out of your medications,

Whether patients are looking for a new medication or have been recently diagnosed with SAD, pharmacogenetics can help find the optimal treatment to empower people to take control of their health, happiness and overall well-being.

For more information, please visit http://www.clarityxdna.com, Email: abenz@clarityxdna.comor call 800-921-8957 for more information.

ClarityX believes in taking the guesswork out of your healthcare. We Believe that one size does not fit all, when it comes to your medication or treatments. Individualized personal medicine is the future of healthcare.

ClarityX direct to consumer genetic testing empowers both patients and physicians. We deliver on that promise everyday by helping patients with convenient, easily accessible in-home testing options.

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DUBLIN--(BUSINESS WIRE)--The "High Performance Computing Market by Component, Infrastructure, Services, Price Band, HPC Applications, Deployment Types, Industry Verticals, and Regions 2022 - 2027" report has been added to ResearchAndMarkets.com's offering.

The High Performance Computing market includes computation solutions provided either by supercomputers or via parallel processing techniques such as leveraging clusters of computers to aggregate computing power.

HPC is well-suited for applications that require high performance data computation and analysis such as high frequency trading, autonomous vehicles, genomics-based personalized medicine, computer-aided design, deep learning, and more. Specific examples include computational fluid dynamics, simulation, modeling, and seismic tomography.

This report evaluates the HPC market including companies, solutions, use cases, and applications. Analysis includes HPC by organizational size, software and system type, server type, price band, and industry verticals.

The report also assesses the market for integration of various artificial intelligence technologies in HPC. It also evaluates the exascale-level HPC market including analysis by component, hardware type, service type, and industry vertical.

Select Report Findings:

High Performance Computing (HPC) may be provided via a supercomputer or via parallel processing techniques such as leveraging clusters of computers to aggregate computing power. HPC is well-suited for applications that require high performance data computation such as certain financial services, simulations, and various R&D initiatives.

The market is currently dominated on the demand side by large corporations, universities, and government institutions by way of capabilities that are often used to solve very specific problems for large institutions. Examples include financial services organizations, government R&D facilities, universities research, etc.

However, the cloud-computing based "as a Service" model allows HPC market offerings to be extended via HPC-as-a-Service (HPCaaS) to a much wider range of industry verticals and companies, thereby providing computational services to solve a much broader array of problems. Industry use cases are increasingly emerging that benefit from HPC-level computing, many of which benefit from split processing between localized devices/platforms and HPCaaS.

In fact, HPCaaS is poised to become much more commonly available, partially due to new on-demand supercomputer service offerings, and in part as a result of emerging AI-based tools for engineers. Accordingly, up to 54% of revenue will be directly attributable to the cloud-based business model via HPCaaS, which makes High-Performance Computing solutions available to a much wider range of industry verticals and companies, thereby providing computational services to solve a much broader array of problems.

One of the challenge areas identified is low utilization but (ironically) also high wait times for most supercomputers. Scheduling can be a challenge in terms of workload time estimation. About 23% of jobs are computationally heavy and 37% of jobs cannot be defined very well in terms of how long jobs will take (within a 3-minute window at best). In many instances, users request substantive resources and don't actually use computing time.

Key Topics Covered:

High Performance Computing Market Dynamics

High Performance Computing Market Analysis and Forecasts

High Performance Computing Company Analysis

High Performance Computing Market Use Cases

Conclusions and Recommendations

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/fim7bo

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Global High Performance Computing Market 2022-2027: AI, IoT, and 5G will be Major Drivers for HPC Growth as they Facilitate the Need to Process Vast...