StemCell Therapy

Research funded by grantsPFAS linked with liver injury in children

Exposure to per- and polyfluoroalkyl substances (PFAS) in the womb may increase liver injury risk in children, according to NIEHS-funded researchers. This study is the first to examine the impact of early life exposures to a PFAS mixture on child liver injury. PFAS, a large group of synthetic chemicals found in a variety of consumer products, have been linked to immune dysfunction, altered metabolism, brain development, and certain cancers.

The study used data from 1,105 mothers and their children enrolled in the Human Early-Life Exposome, or HELIX, study in Europe. Using computational modeling, the scientists found that higher exposures to PFAS during pregnancy were associated with higher levels of liver enzymes in children. High liver enzyme levels may point to nonalcoholic fatty liver disease (NAFLD). The researchers also identified a profile for children at high risk for liver injury, characterized by high prenatal PFAS exposures.

Citation: Stratakis N, Conti DV, Jin R, Margetaki K, Valvi D, Siskos AP, Maitre L, Garcia E, Varo N, Zhao Y, Roumeliotaki T, Vafeiadi M, Urquiza J, Fernandez-Barres S, Heude B, Basagana X, Casas M, Fossati S, Grazuleviciene R, Andrusaityte S, Uppal K, McEachan RRC, Papadopoulou E, Robinson O, Haug LS, Wright J, Vos MB, Keun HC, Vrijheid M, Berhane KT, McConnell R, Chatzi L. 2020. Prenatal exposure to perfluoroalkyl substances associated with increased susceptibility to liver injury in children. Hepatology 72(5):17581770. (Synopsis(https://factor.niehs.nih.gov/2020/10/papers/dert/index.htm#a1))

In an NIEHS-funded study, researchers uncovered a previously unknown way that genes code for proteins. Rather than directions going one way from DNA through messenger RNA (mRNA) to proteins, the study showed that RNA can modify how DNA is transcribed into mRNA and translated to produce proteins.

Using mouse stem cells, the scientists found that mRNA modifies how DNA is transcribed using a reversible chemical reaction called methylation, which can change the activity of a DNA segment without changing the sequence. The researchers identified and characterized several proteins that recognized the methylated mRNA. They also discovered a group of RNAs called chromosome-associated regulatory RNAs (carRNAs) that used the same methylation process and controlled how DNA was stored and transcribed. The team found that a specific methylation modification, N6-methyladenosine, served as a switch to control carRNA levels, which regulated DNA transcription.

Citation: Liu J, Dou X, Chen C, Chen C, Liu C, Xu MM, Zhao S, Shen B, Gao Y, Han D, He C. 2020. N 6-methyladenosine of chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367(6477):580586. (Synopsis(https://factor.niehs.nih.gov/2020/4/papers/dert/index.htm#a1))

Loss of the enzyme topoisomerase 1 (TOP1) leads to DNA damage in neurons and neurodegeneration, according to an NIEHS-funded study. TOP1 plays an important role in facilitating the expression of long genes that are important for neuronal function. The data suggest that TOP1 maintains proper gene function in the central nervous system.

The researchers deleted TOP1 in mouse neurons and examined behavior, development, and underlying indicators of neurodegeneration, such as inflammation. Mice lacking TOP1 showed signs of early neurodegeneration, with brains 3.5-times smaller at postnatal day 15 compared with controls. Although neurons developed normally, mice without TOP1 showed motor deficits, exhibited lower levels of nicotinamide adenine dinucleotide (NAD-plus) a compound critical in energy metabolism and died prematurely. However, when these mice received supplemental NAD-plus, they lived 30% longer, had less inflammation, and showed improved neuronal survival.

Citation: Fragola G, Mabb AM, Taylor-Blake B, Niehaus JK, Chronister WD, Mao H, Simon JM, Yuan H, Li Z, McConnell MJ, Zylka MJ. 2020. Deletion of topoisomerase 1 in excitatory neurons causes genomic instability and early onset neurodegeneration. Nat Commun 11(1):1962. (Synopsis(https://factor.niehs.nih.gov/2020/6/papers/dert/index.htm#a4))

NIEHS grantees found that a protein known as XPA bends DNA and pauses in response to DNA damage, revealing the location of damaged DNA and potentially promoting the recruitment of DNA repair proteins. Using single molecule experiments and imaging techniques, the researchers observed the biochemistry of a living cell.

The researchers used a new method to calculate the molecular weight of small proteins bound to DNA and tracked proteins involved in DNA repair in 3D using real-time single molecule imaging. XPA cycled through three distinct states on DNA: rapidly hopping over long distances of the DNA strand; slowly sliding over short ranges of DNA while bending local DNA regions; and pausing and forming complexes with bent DNA. XPA paused more frequently in the presence of more DNA damage. The work provided insight into a new damage sensor role for XPA.

Citation: Beckwitt EC, Jang S, Detweiler IC, Kuper J, Sauer F, Simon N, Bretzler J, Watkins SC, Carell T, Kisker C, Van Houten B. 2020. Single molecule analysis reveals monomeric XPA bends DNA and undergoes episodic linear diffusion during damage search. Nat Commun 11(1):1356. (Synopsis(https://factor.niehs.nih.gov/2020/5/papers/dert/index.htm#a2))

NIEHS grantees found that individual cells in a population respond differently to estrogen stimulation at both the level of single cells and alleles, which are other possible forms of a gene. These differences were not explained by estrogen receptor levels in the cells or receptor activation status.

The researchers treated human breast cancer cells with estrogen and examined two genes, GREB1 and MYC, whose activities are regulated by estrogen. Unexpectedly, individual cells exhibited large differences in the level of gene activation, even between alleles within the same cell. The scientists used automated high-throughput technologies to test small molecule inhibitors of the estrogen receptor regulators. One inhibitor, called MS049, markedly increased the response of individual alleles to estrogen. The researchers altered estrogenic response by inhibiting estrogen receptor regulators, establishing a previously unrecognized regulation path for estrogen to activate genes at the single cell level.

Citation: Stossi F, Dandekar RD, Mancini MG, Gu G, Fuqua SAW, Nardone A, De Angelis C, Fu X, Schiff R, Bedford MT, Xu W, Johansson HE, Stephan CC, Mancini MA. 2020. Estrogen-induced transcription at individual alleles is independent of receptor level and active conformation but can be modulated by coactivators activity. Nucleic Acids Res 48(4):18001810. (Synopsis(https://factor.niehs.nih.gov/2020/4/papers/dert/index.htm#a3))

NIEHS grantees showed that mice exposed to e-cigarette smoke (ECS) were more likely to develop lung adenocarcinomas, a type of lung cancer. They also found that exposed mice had higher levels of bladder urothelial hyperplasia, an abnormal increase in epithelial cells that can precede development of bladder tumors.

The researchers exposed one group of mice to ECS aerosols generated from e-juice containing nicotine and compared them to a second group of mice exposed to a control aerosol without ECS. A third group of mice was exposed only to filtered air. Of the ECS mice, 22.5% developed lung adenocarcinomas and 57.5% developed urothelial hyperplasia. Mice with ECS-induced lung adenocarcinomas were not more prone to developing urothelial hyperplasia, which suggested that the two outcomes were divergent events and might involve different mechanisms.

Citation: Tang MS, Wu XR, Lee HW, Xia Y, Deng FM, Moreira AL, Chen LC, Huang WC, Lepor H. 2019. 2019. Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc Natl Acad Sci U S A 116(43):2172721731. (Synopsis(https://factor.niehs.nih.gov/2020/1/papers/dert/index.htm#a1))

NIEHS grantees identified a novel pathway that controls the metabolic response of astrocytes, which are brain and spinal cord cells essential to maintaining central nervous system (CNS) health. Although astrocytes perform various functions, such as providing nerve cells with nutrients, they have been linked to CNS inflammation and multiple sclerosis (MS).

Using a mouse model of MS, researchers found that during the progressive phase of the disease, brain astrocytes switched on metabolic pathways that activated a protein called the mitochondrial antiviral signaling (MAVS) protein. It led to activation of several proinflammatory genes, triggering inflammation in the brain and spinal cord. If the scientists gave the mice the drug miglustat before the onset of MS, they were able to suppress MAVS activation and subsequent inflammation. The findings suggest a new role for MAVS in CNS inflammation and a potential therapeutic target for MS.

Citation: Chao CC, Gutierrez-Vazquez C, Rothhammer V, Mayo L, Wheeler MA, Tjon EC, Zandee SEJ, Blain M, de Lima KA, Takenaka MC, Avila-Pacheco J, Hewson P, Liu L, Sanmarco LM, Borucki DM, Lipof GZ, Trauger SA, Clish CB, Antel JP, Prat A, Quintana FJ. 2019. Metabolic control of astrocyte pathogenic activity via cPLA2-MAVS. Cell 179(7):14831498.e22. (Synopsis(https://factor.niehs.nih.gov/2020/2/papers/dert/index.htm#a3))

NIEHS-funded researchers found that a mutation in the ultraviolet irradiation resistanceassociated gene (UVRAG), which is involved in cell regulation, can disrupt autophagy in mice. Autophagy is the process of removing damaged cells so the body can regenerate newer cells. The scientists say the UVRAG mutation causes increased inflammatory response and tumor development. The study provides the first genetic evidence connecting UVRAG suppression to autophagy regulation, inflammation, and cancer predisposition.

The researchers generated mice that expressed UVRAG with a frameshift mutation, which is a deletion or insertion in DNA that shifts the way the sequence is read. After inducing sepsis or intestinal colitis, they found that mice with the UVRAG mutation displayed increased inflammatory responses in both conditions and increased spontaneous tumor development compared with wild-type mice. The results indicate UVRAG could be one reason people are more susceptible to cancers as they age.

Citation: Quach C, Song Y, Guo H, Li S, Maazi H, Fung M, Sands N, O'Connell D, Restrepo-Vassalli S, Chai B, Nemecio D, Punj V, Akbari O, Idos GE, Mumenthaler SM, Wu N, Martin SE, Hagiya A, Hicks J, Cui H, Liang C. 2019. A truncating mutation in the autophagy gene UVRAG drives inflammation and tumorigenesis in mice. Nat Commun 10(1):5681. (Synopsis(https://factor.niehs.nih.gov/2020/2/papers/dert/index.htm#a4))

Exposure to polybrominated biphenyl (PBB) 153, a type of brominated flame retardant, alters DNA methylation in sperm, according to NIEHS grantees. DNA methylation refers to heritable changes in gene expression that occur with no alteration in the DNA sequence. Because PBB153 is toxic to living organisms following direct exposure, the study suggests it may also harm future generations.

The results of a Michigan PBB study showed that PBB153 was associated with gene methylation events in mens sperm. Based on this information, the research team conducted sperm studies and determined that exposure to PBB153 decreased methylation at regions of DNA that control imprinted genes, which are essential for fetal growth and play an important role in other aspects of development. These effects could explain some of the endocrine-related health effects that have been observed among children of PBB-exposed parents.

Citation: Greeson KW, Fowler KL, Estave PM, Thompson SK, Wagner C, Edenfield RC, Symosko KM, Steves AN, Marder EM, Terrell ML, Barton H, Koval M, Marcus M, Easley CA 4th. 2020. Detrimental effects of flame retardant, PBB153, exposure on sperm and future generations. Sci Rep 10(1):8567. (Synopsis(https://factor.niehs.nih.gov/2020/7/papers/dert/index.htm#a4))

NIEHS grantees determined that in mice, air pollution may play a role in the development of cardiometabolic diseases, such as diabetes, with effects comparable to eating a high-fat diet (HFD). They also established that effects were reversed when exposure to air pollution stopped.

The scientists divided male mice into three categories: those that received clean filtered air; those exposed to concentrated particulate matter 2.5 air pollution; and those that received clean filtered air and were fed an HFD. After 14 weeks, team members measured insulin resistance and glucose levels and assessed epigenetic changes, or chemical tags, that attach to DNA and affect gene expression.

Air pollution exposure was comparable to eating an HFD. Mice in the air pollution and HFD groups had impaired insulin resistance, high glucose, and reduced metabolism. After removing air pollution from the environment, health and epigenetic changes reversed within eight weeks.

Citation: Rajagopalan S, Park B, Palanivel R, Vinayachandran V, Deiuliis JA, Gangwar RS, Das LM, Yin J, Choi Y, Al-Kindi S, Jain MK, Hansen KD, Biswal S. 2020. Metabolic effects of air pollution exposure and reversibility. J Clin Invest 130(11):60346040. (Synopsis(https://factor.niehs.nih.gov/2020/10/papers/dert/index.htm#a3))

NIEHS researchers learned that mineralocorticoid receptors (MRs) control the gene profiles of neurons within the CA2 brain region, which is associated with learning and memory. MRs are a type of steroid receptor activated by corticosteroid hormones. The findings revealed the essential roles of MRs in the development and maintenance of CA2 neurons, as well as CA2-related behaviors.

In response to environmental stress, the body secretes corticosteroids that bind to MRs or glucocorticoid receptors and that induce gene expression changes in the brain. The CA2 region of the mouse and human hippocampus is enriched with MRs. Neuronal deletion of MRs at embryonic, early postnatal development, or adulthood stages in mice led to significantly reduced expression of CA2 molecular markers. Mice with CA2-targeted deletion of MRs showed disrupted social behavior and altered responses to novel objects. Therefore, MRs control both the identity and function of CA2 neurons.

Citation: McCann KE, Lustberg DJ, Shaughnessy EK, Carstens KE, Farris S, Alexander GM, Radzicki D, Zhao M, Dudek SM. 2019. Novel role for mineralocorticoid receptors in control of a neuronal phenotype. Mol Psychiatry; doi: 10.1038/s41380-019-0598-7 [Online 19 November 2019]. (Synopsis(https://factor.niehs.nih.gov/2020/1/papers/dir/index.htm#a2))

NIEHS researchers discovered a novel symbiotic interaction between mammalian cells and bacteria that boosts nicotinamide adenine dinucleotide biosynthesis in host cells. NAD is a cofactor that exists in all cell types and is necessary for life. Decreased levels of NAD are associated with aging, and elevated levels of its biosynthesis are important to sustain the higher metabolic needs of tumors.

The researchers showed that cancer cell lines infected with Mycoplasma hyorhinis were protected against toxicity by nicotinamide phosphoribosyl transferase (NAMPT) inhibitors, which halt NAD biosynthesis. This same effect was observed in vivo, when infected versus noninfected cancer cells were injected in mice. Using a variety of screens and techniques, they showed that this resistance was the result of bacteria providing alternative NAD precursors to mammalian cells through the bacterial nicotinamidase PncA, bypassing the NAMPT-dependent pathway.

Citation: Shats I, Williams JG, Liu J, Makarov MV, Wu X, Lih FB, Deterding LJ, Lim C, Xu X, Randall TA, Lee E, Li W, Fan W, Li J-L, Sokolsky M, Kabanov AV, Li L, Migaud ME, Locasale JW, Li X. 2020. Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway. Cell Metab 31(3):564579.e7. (Synopsis(https://factor.niehs.nih.gov/2020/5/papers/dir/index.htm#a3)) (Story)

New insights into how the liver adapts to an HFD may lead to novel treatments for obesity-related diseases such as NAFLD, according to a study by NIEHS researchers. They found that long-term consumption of a diet high in saturated fat led to dramatic reprogramming of gene regulation in the mouse liver.

NAFLD involves the buildup of excessive fat in the liver of an individual who is not a heavy user of alcohol, increasing the risk of liver damage. When the scientists fed mice an HFD, the mice became obese and showed other changes similar to metabolic syndrome in humans. Moreover, their livers became fatty and showed wide-ranging abnormalities at both molecular and cellular levels. The livers adaptation to the fat-rich diet was mediated by a protein called hepatocyte nuclear factor 4 alpha.

Citation: Qin Y, Grimm SA, Roberts JD, Chrysovergis K, Wade PA. 2020. Alterations in promoter interaction landscape and transcriptional network underlying metabolic adaptation to diet. Nat Commun 11(1):962. (Synopsis(https://factor.niehs.nih.gov/2020/4/papers/dir/index.htm#a3)) (Story)

An NIEHS study reported a concerning rise in the prevalence of antinuclear antibodies (ANAs), which are commonly used biomarkers for autoimmunity. ANAs, which are produced by a persons own immune system, bind to and sometimes attack healthy cells. This study is the first to evaluate ANA changes over time in a representative sampling of the U.S. population. The findings may indicate an increase in autoimmune diseases.

Team members used the National Health and Nutrition Examination Survey to analyze serum ANAs in 14,211 participants aged 12 years and older from three time periods. ANA prevalence increased as follows.

The researchers found the largest ANA increases in adolescents, males, non-Hispanic whites, and adults older than 50 years compared with other subgroups.

Citation: Dinse GE, Parks CG, Weinberg CR, Co CA, Wilkerson J, Zeldin DC, Chan EKL, Miller FW. 2020. Increasing prevalence of antinuclear antibodies in the United States. Arthritis Rheumatol 72(6):10261035. (Synopsis(https://factor.niehs.nih.gov/2020/6/papers/dir/index.htm#a4)) (Story)

Ubiquitin (Ub) stimulates the removal of topoisomerase 2 DNA-protein crosslinks (TOP2-DPCs) by tyrosyl-DNA phosphodiesterase 2 (TDP2) according to NIEHS researchers and their collaborators in Spain. The team also reported that TDP2 single nucleotide polymorphisms can disrupt the TDP2-Ub interface. Because TDP2 works with a protein called ZATT to remove dangerous DNA-protein crosslinks, the work is important for understanding how cells handle this type of DNA damage.

Using X-ray crystallography and small angle X-ray scattering analysis, the scientists examined how Ub-dependent links and TDP2 function as they relate to DNA repair and other cellular pathways. Previous studies hypothesized that TDP2 interacts with K48-Ub chains to promote recruitment to TOP2-DPCs that are repaired using a proteasome-mediated TOP2 degradation pathway. However, the authors showed that TDP2 preferentially binds to K63-linked Ub3 and associates with K27 and K63 poly-Ub chains.

Citation: Schellenberg MJ, Appel CD, Riccio AA, Butler LR, Krahn JM, Liebermann JA, Cortes-Ledesma F, Williams RS. 2020. Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2. Nucleic Acids Res 48(11):63106325. (Synopsis(https://factor.niehs.nih.gov/2020/7/papers/dir/index.htm#a4))

NIEHS researchers and their collaborators concluded that a protein called tankyrase serves a critical role in mammalian embryonic genome activation (EGA). Using an in vitro culture system, the researchers identified and characterized tankyrase, a factor that allows EGA to occur. The characterization of tankyrase during the oocyte-to-embryo transition fills a gap in knowledge about how factors are activated in mammalian oocytes and early embryos and may lead to improved strategies for treating infertility.

Using a mouse model, the scientists depleted tankyrase from the embryos and observed that they could not perform EGA and stopped developing. They also found that tankyrase is necessary for gene transcription, protein translation, DNA damage repair, and modulation of beta-catenin in the early embryo. This study found a new role for tankyrase during normal development, revealing an essential function of this protein during the oocyte-to-embryo transition.

Citation: Gambini A, Stein P, Savy V, Grow EJ, Papas BN, Zhang Y, Kenan AC, Padilla-Banks E, Cairns BR, Williams CJ. 2020. Developmentally programmed tankyrase activity upregulates beta-catenin and licenses progression of embryonic genome activation. Dev Cell 53(5):545560.e7. (Synopsis(https://factor.niehs.nih.gov/2020/7/papers/dir/index.htm#a3)) (Story)

NIEHS researchers showed that an enzyme called CLP1 plays an important role in transfer RNA (tRNA) processing by regulating the ligation of tRNAs. They also demonstrated that mature, functional tRNAs are generated from pre-tRNAs through a process called TSEN, or (tRNA splicing endonuclease)mediated splicing of introns. Mutations in CLP1 and the TSEN complex often lead to severe neurological disorders.

Using a technique that allowed Escherichia coli to produce several proteins at once, the scientists expressed and reconstituted the TSEN protein complex, which cleaved tRNA. TSEN complex alone was sufficient for removing tRNA introns, but CLP1, a binding partner for TSEN, was needed to correctly regulate the ligation step that generates mature tRNAs and tRNA intronic circular RNAs (tricRNAs). Genetic knockdown of CLP1 led to increases in mature tRNAs and tricRNAs, which suggested that CLP1 acts as a negative modulator of tRNA processing.

Citation: Hayne CK, Schmidt CA, Haque MI, Matera AG, Stanley RE. 2020. Reconstitution of the human tRNA splicing endonuclease complex: insight into the regulation of pre-tRNA cleavage. Nucleic Acids Res 48(14):76097622. (Synopsis(https://factor.niehs.nih.gov/2020/8/papers/dir/index.htm#a2))

Researchers at NIEHS and the National Toxicology Program developed the Tox21BodyMap to predict which organs in the human body may be affected by a chemical. The tool will help scientists generate novel hypotheses to test, prioritize chemicals for toxicity testing, and identify knowledge gaps.

To identify organs that could potentially be affected by a chemical, Tox21BodyMap used data from 971 high-throughput screening assays that evaluated approximately 10,000 unique chemicals. Specifically, it combined information about which gene an assay targets, how highly expressed that gene is in a human organ, and at what tested concentrations a chemical generated a positive assay result. The result was an overall picture of chemical bioactivity. The Tox21BodyMap provided multiple visualizations of the data, highlighting target organs on a map of the body, as well as showing a web of network connections and providing downloadable data.

Citation: Borrel A, Auerbach SS, Houck KA, Kleinstreuer NC. 2020. Tox21BodyMap: a webtool to map chemical effects on the human body. Nucleic Acids Res 48(W1):W472W476. (Synopsis(https://factor.niehs.nih.gov/2020/8/papers/dir/index.htm#a4))

In pregnant women, polyunsaturated fatty acids and their metabolic derivatives called eicosanoids are associated with infant size at delivery, according to NIEHS scientists and their collaborators. This work also provides novel longitudinal characterization of eicosanoids in blood plasma during different gestational ages of pregnancy. The results link inflammatory eicosanoids with adverse fetal growth outcomes.

The blood plasma concentration of polyunsaturated fatty acids, including omega-3 and omega-6, in study participants was found to be higher in cases of low birth weight and lower in cases of higher birth weight. Lower and higher birth weights were defined as equal to or less than the 10th percentile and equal to or greater than the 90th percentile for gestational age, respectively. In addition, certain eicosanoids, which are known to derive from inflammatory processes from these fatty acids, were found to be exclusively higher in pregnancy cases, which resulted in low birth weight.

Citation: Welch BM, Keil AP, van't Erve TJ, Deterding LJ, Williams JG, Lih FB, Cantonwine DE, McElrath TF, Ferguson KK. 2020. Longitudinal profiles of plasma eicosanoids during pregnancy and size for gestational age at delivery: a nested case-control study. PLoS Med 17(8):e1003271. (Synopsis(https://factor.niehs.nih.gov/2020/10/papers/dir/index.htm#a2))

Researchers at NIEHS and collaborators at the National Institute of Diabetes and Digestive and Kidney Diseases uncovered the neural basis behind the drive to select calorie-rich foods over nutritionally balanced diets. The findings partly explain the difficulty of dieting.

One group of mice received a standard diet (SD) consisting of regular chow, and another group ate an HFD. When the HFD mice were switched to a SD, they refused to eat. Even after fasting to stimulate their appetites, HFD mice preferred fatty food, rather than regular chow.

However, whenHFD mice were switched to a SD, regular chow no longer fully alleviated the response. The authors also saw that dopamine signaling, which is responsible for the pleasurable feelings from eating, were significantly diminished in the SD mice following HFD exposure.

Citation: Mazzone CM, Liang-Guallpa J, Li C, Wolcott NS, Boone MH, Southern M, Kobzar NP, Salgado IA, Reddy DM, Sun F, Zhang Y, Li Y, Cui G, Krashes MJ. 2020. High-fat food biases hypothalamic and mesolimbic expression of consummatory drives. Nat Neurosci 23(10):12531266. (Synopsis(https://factor.niehs.nih.gov/2020/10/papers/dir/index.htm#a4))

To uncover novel deletion patterns in mitochondrial DNA (mtDNA), NIEHS researchers and their collaborators developed LostArc, an ultrasensitive method for quantifying deletions in circular mtDNA molecules. The team used the technique to reveal links between mitochondrial DNA replication, aging, and mitochondrial disease.

A mutation in POLG, a nuclear gene responsible for maintaining the mitochondrial genome, is known to be the most common cause of mitochondrial disease, a condition in which the mitochondria fail to produce enough energy for the body to function properly.

The scientists analyzed mtDNA from skeletal muscle biopsies of 41 patients with mitochondrial disease with wild-type and mutated POLG. They used LostArc to detect loss of mtDNA segments by mapping split-reads in the samples to a normal mtDNA reference. Thirty-five million deletion segments were detected in the biopsies. They spanned more than 470,000 unique segments, 99% of which were novel.

Citation: Lujan SA, Longley MJ, Humble MH, Lavender CA, Burkholder A, Blakely EL, Alston CL, Gorman GS, Turnbull DM, McFarland R, Taylor RW, Kunkel TA, Copeland WC. 2020. Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging. Genome Biol 21(1):248. (Synopsis(https://factor.niehs.nih.gov/2020/11/papers/dir/index.htm#a3))

Individual heterogeneity, or genetic variability among samples, can substantially affect reprogramming of somatic cells into induced pluripotent stem cells (iPSCs), according to NIEHS scientists and their collaborators. iPSCs are stem cells that are derived from differentiated cells, such as fibroblasts, and they can both self-renew and are pluripotent, meaning they can be differentiated into other cell types. In a previous publication, the research team obtained fibroblasts from healthy diverse donors and observed that each persons fibroblasts had consistent differences in the ability to be reprogrammed to iPSCs. Ancestry was identified as a large contributing factor.

Using 72 dermal fibroblast-iPSCs from self-identified African Americans and White Americans, the researchers found ancestry-dependent and ancestry-independent genes associated with reprogramming efficiency. They also added 36 new genomic profiles of African American fibroblast-iPSCs pairs to publicly available databases, which will help address the underrepresentation of genomic data from non-European groups.

Citation: Bisogno LS, Yang J, Bennett BD, Ward JM, Mackey LC, Annab LA, Bushel PR, Singhal S, Schurman SH, Byun JS, Napoles AM, Perez-Stable EJ, Fargo DC, Gardner K, Archer TK. 2020. Ancestry-dependent gene expression correlates with reprogramming to pluripotency and multiple dynamic biological processes. Sci Adv 6(47):eabc3851. (Synopsis(https://factor.niehs.nih.gov/2021/1/papers/dir/index.htm#a2))

Researchers in the Division of the National Toxicology Program (DNTP) at NIEHS successfully compiled a rich resource to explore data on polycyclic aromatic compound (PACs) toxicity. This data-driven approach to contextualizing PAC hazard characterization allows researchers to predict eight different toxicity profiles of various PACs and other classes of compounds.

PACs are a structurally diverse class of human-made toxicants found widely in the environment. Unfortunately, information about human exposure and health effects of PACs is limited. To facilitate greater understanding of PAC toxicity in a cost-effective manner, DNTP researchers created an automated approach to identify PAC structures using computer workflows, algorithms, and clusters. Using existing data on similar compounds, the scientists categorized PACs based on structure and hazard characterization. The analysis results are available and searchable through an interactive web application.

Citation: Hsieh JH, Sedykh A, Mutlu E, Germolec DR, Auerbach SS, Rider CV. 2020. Harnessing in silico, in vitro, and in vivo data to understand the toxicity landscape of polycyclic aromatic compounds (PACs). Chem Res Toxicol; doi:10.1021/acs.chemrestox.0c00213 [Online 16 October 2020]. (Synopsis(https://factor.niehs.nih.gov/2020/12/papers/dir/index.htm#a1))

DNTP scientists and their collaborators used computational modeling to probe databases and to identify existing drugs that could be repurposed to fight SARS-CoV-2, the virus that causes COVID-19.

Proteases are enzymes that break down proteins. An essential step in the formation of infectious viral particles is the breakdown of precursor viral proteins by viral proteases. A class of antiviral drugs called protease inhibitors block the activity of viral proteases. The main protease (Mpro) of SARS-CoV-2 is a proposed target for COVID-19 drugs. The structure and activity of Mpro is highly conserved across the coronavirus family. In this study, previous data on drug interactions with SARS-CoV Mpro were used to develop quantitative structure-activity relationship models, which the team used to virtually screen all drugs in the DrugBank database. They identified 42 drugs that could be repurposed against SARS-CoV-2 Mpro.

Citation: Alves VM, Bobrowski T, Melo-Filho CC, Korn D, Auerbach S, Schmitt C, Muratov EN, Tropsha A. 2020. QSAR modeling of SARS-CoV Mpro inhibitors identifies sufugolix, cenicriviroc, proglumetacin, and other drugs as candidates for repurposing against SARS-CoV-2. Mol Inform; doi:10.1002/minf.202000113 [Online 28 July 2020]. (Synopsis(https://factor.niehs.nih.gov/2020/10/papers/dir/index.htm#a1))

DNTP scientists evaluated a high-throughput transcriptomics approach using liver and kidney tissue from 5-day assays in male rats to estimate the toxicological potency of chemicals.

Toxicity and carcinogenicity are typically assessed by the resource intensive two-year cancer bioassay. In the 5-day assays, the authors determined toxicological potency based on the most sensitive sets of genes active in the liver and kidney. For most chemicals, the results approximated the toxicological potency derived from the most sensitive histopathological effects independent of target tissue or organ observed in male rats in long-term assays. Notably, these approximations were similar in female rats, as well as in male and female mice. The findings suggest that estimates of transcriptomics-based potency from short-term in vivo assays can, in the absence of other data, provide a rapid and effective estimate of toxicological potency.

Citation: Gwinn WM, Auerbach SS, Parham F, Stout MD, Waidyanatha S, Mutlu E, Collins B, Paules RS, Merrick BA, Ferguson S, Ramaiahgari S, Bucher JR, Sparrow B, Toy H, Gorospe J, Machesky N, Shah RR, Balik-Meisner MR, Mav D, Phadke DP, Roberts G, DeVito MJ. 2020. Evaluation of 5-day in vivo rat liver and kidney with high-throughput transcriptomics for estimating benchmark doses of apical outcomes. Toxicol Sci 176(2):343354. (Synopsis(https://factor.niehs.nih.gov/2020/8/papers/dir/index.htm#a1))

Researchers from DNTP studied the effects of gestational and postnatal boron exposure on developing rat pups. The team was the first to show that pups exposed to boric acid, an oxidized form of boron commonly found in the environment, gained significantly less weight during postnatal development.

Pregnant rats were exposed to varying concentrations of boric acid once daily by oral gavage dosing, a technique that administered it directly to the stomach. Food intake, body weight, boron blood plasma levels, and any signs of morbidity were evaluated during gestation. After birth, the pups received boric acid at the same concentration as their mothers, and the scientists monitored the same parameters in the pups for the next 28 days. The team observed that the pups that received the highest dose of boric acid had a 23% reduction in weight gain.

Citation: Watson ATD, Sutherland VL, Cunny H, Miller-Pinsler L, Furr J, Hebert C, Collins B, Waidyanatha S, Smith L, Vinke T, Aillon K, Xie G, Shockley KR, McIntyre BS. 2020. Postnatal effects of gestational and lactational gavage exposure to boric acid in the developing Sprague Dawley rat. Toxicol Sci 176(1):6573. (Synopsis(https://factor.niehs.nih.gov/2020/7/papers/dir/index.htm#a1))

When scientists from DNTP analyzed the entire genetic code of tumors in rodent cancer studies, they determined that most rodent tumors whether arising spontaneously or induced by chemicals had DNA mutation signatures resembling those seen in human cancers.

Tumors can form as a result of DNA damage or they can arise spontaneously when physiological processes do not function properly. To understand the mechanism of cancer formation, members of the research team sequenced lung and liver tumor DNA from mice exposed to 20 carcinogens. They compared the sequences to those from tumors that formed spontaneously and from normal tissue. DNA signatures from exposure to 17 of the chemicals were similar to those from spontaneous tumors in mice. The finding suggests chemicals promote tumor formation through mechanisms that build on existing cancer processes.

Citation: Riva L, Pandiri AR, Li YR, Droop A, Hewinson J, Quail MA, Iyer V, Shepherd R, Herbert RA, Campbell PJ, Sills RC, Alexandrov LB, Balmain A, Adams DJ. 2020.The mutational signature profile of known and suspected human carcinogens in mice. Nat Genet 52(11):11891197. (Story)

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January 2021: 2020 Papers of the Year - Environmental Factor Newsletter

In 2007, scientists developed a method to determine the sexes of Atlantic walruses using only their jaws' size and shape. Researchers have now put that sexing (identification of an organism's sex) method to the test with Pacific walruses.

There was some doubt about whether this technique would work for one, Pacific walruses are significantly larger than their Atlantic counterparts. This size difference shows even in individual body parts, including the mandibles.

Yet, the team, led by Nathan Taylor at the University of Alaska, Fairbanks, persisted in applying the sex identification strategy since, if successful, it would significantly reduce the time and financial commitment needed for researching preserved, unidentified walrus specimens. To distinguish between male and female Pacific walruses, they measured the length and height of the jawbone, the minimum jawbone depth (from about the middle point of the jaw to the back), and jaw thickness.

A female Pacific walrus and a calf

USFWS via Wikimedia

The scientists had to be mindful of whether the jawbones were "not fully fused" (not fully developed, unique to juvenile walruses) or "fused" (fully developed, the sign of a mature walrus). Walruses with partially fused mandibles were likely to yield misleading results.

For example, jaws from male walruses that had not yet fully fused were similar in dimensions to mature females' jaws. To ensure the results were accurate, they could only include fully matured, fused specimens.

After measuring 67 modern specimens (33 of which were male, 24 belonging to females, and ten unknown) and 11 archaeological samples, the researchers concluded that jaw size is indeed a reliable body part to distinguish between male and female walruses. The most significant differences were jaw length and thickness, with females notably smaller in both categories.

A male Pacific walrus

Joel Garlich-Miller, USFWS, via Wikimedia

With the original sexing method now confirmed to work for Pacific walruses, scientists will be better prepared to perform several types of analyses, including measuring stable isotopes, trace elements, and hormones in study animals, with greater confidence and less risk of misidentification.

This is a crucial finding, given the insufficient data on Pacific walrus populations, and will hopefully push conservation efforts for this species forward.

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Ozone in the air is bad for birds - Massive Science

In 2007, scientists developed a method to determine the sexes of Atlantic walruses using only their jaws' size and shape. Researchers have now put that sexing (identification of an organism's sex) method to the test with Pacific walruses.

There was some doubt about whether this technique would work for one, Pacific walruses are significantly larger than their Atlantic counterparts. This size difference shows even in individual body parts, including the mandibles.

Yet, the team, led by Nathan Taylor at the University of Alaska, Fairbanks, persisted in applying the sex identification strategy since, if successful, it would significantly reduce the time and financial commitment needed for researching preserved, unidentified walrus specimens. To distinguish between male and female Pacific walruses, they measured the length and height of the jawbone, the minimum jawbone depth (from about the middle point of the jaw to the back), and jaw thickness.

A female Pacific walrus and a calf

USFWS via Wikimedia

The scientists had to be mindful of whether the jawbones were "not fully fused" (not fully developed, unique to juvenile walruses) or "fused" (fully developed, the sign of a mature walrus). Walruses with partially fused mandibles were likely to yield misleading results.

For example, jaws from male walruses that had not yet fully fused were similar in dimensions to mature females' jaws. To ensure the results were accurate, they could only include fully matured, fused specimens.

After measuring 67 modern specimens (33 of which were male, 24 belonging to females, and ten unknown) and 11 archaeological samples, the researchers concluded that jaw size is indeed a reliable body part to distinguish between male and female walruses. The most significant differences were jaw length and thickness, with females notably smaller in both categories.

A male Pacific walrus

Joel Garlich-Miller, USFWS, via Wikimedia

With the original sexing method now confirmed to work for Pacific walruses, scientists will be better prepared to perform several types of analyses, including measuring stable isotopes, trace elements, and hormones in study animals, with greater confidence and less risk of misidentification.

This is a crucial finding, given the insufficient data on Pacific walrus populations, and will hopefully push conservation efforts for this species forward.

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How good are the COVID-19 vaccines? - Massive Science

Dublin, Dec. 30, 2020 (GLOBE NEWSWIRE) -- The "Companion Diagnostics Market - Growth, Trends, and Forecasts (2020 - 2025)" report has been added to ResearchAndMarkets.com's offering.

The growth of the global companion diagnostics market can be attributed to the rising focus on personalized medicine and the co-development of drug and diagnostic technologies. Additionally, rising cases of adverse drug reactions related to drugs, due to the lack of efficacy, drive the need for companion diagnostics.

One of the major factors driving the growth of the companion diagnostics market is the increasing demand for personalized medicines and awareness about the same, among the population. With companies increasing their collaborations for better biomarkers and diagnostics, in order to focus on cost regulations, there has been a significant number of opportunities for its applications in indications, like cancer, cardiovascular, and neurological disorders.

Key Market Trends

Application in Lung Cancer is expected to Dominate the Market over the Forecast Period

Companion diagnostic tests (CDXs) are considered mandatory in decision-making for treatment with targeted therapies in lung cancer. The emergence of immunotherapy has also given rise to the development of CDXs. Therascreen EGFR RGQ PCR Kit (Qiagen) and Cobas EGFR Mutation Test v2 (Roche Molecular Systems) are some of the many companion diagnostics available for lung cancer therapies.

Moreover, lung cancer is the most common form of cancer, and causes most cancer-related deaths, globally, as per the 2018 report by the World Health Organization. This translates to more demand for lung cancer companion diagnostics, which is expected to help the market growth.

North America Captured the Largest Market Share and is Expected to Retain its Dominance

North America dominated the overall companion diagnostics market, with the United States emerging as the major contributor to the market. The use of companion diagnostics is considered as an important treatment decision tool for a number of oncology drugs, which is also reflected in the way the FDA classifies these assays, in relation to risk.

In the United States, companion diagnostic assays are classified as IVD class III products, which represents a high-risk category, and consequently, the highest level of regulatory control. Hence, owing to high healthcare technology adoption rates and increasing demand for personalized medicine, the US companion diagnostics market is expected to register a substantial growth rate, during the forecast period.

Competitive Landscape

The presence of major market players, such as Abbott Laboratories, Agilent Technologies Inc., F Hoffmann-La Roche Ltd, Biomerieux SA, and Qiagen NV, is increasing the overall competitive rivalry of the market studied.

However, the issues associated with the high development cost and poor reimbursement are affecting the market negatively. Moreover, the rising focus of companies toward personalized medicine, co-development activities, and increased cases of adverse drug reactions is expected to boost the competitive rivalry in the market studied.

Key Topics Covered:

1 INTRODUCTION1.1 Study Deliverables1.2 Study Assumptions1.3 Scope of the Study

2 RESEARCH METHODOLOGY

3 EXECUTIVE SUMMARY

4 MARKET DYNAMICS4.1 Market Overview4.2 Market Drivers4.2.1 Companies Promoting Personalized Medicine and Targeted Therapy as a New Treatment Option4.2.2 Increasing Cases of Adverse Drug Reactions4.2.3 Co-development of Drug and Diagnostic Technology4.3 Market Restraints4.3.1 High Cost of Drug Development and Associated Clinical Trials4.3.2 Reimbursement Issues among Many Countries4.4 Industry Attractiveness - Porter's Five Forces Analysis

5 MARKET SEGMENTATION5.1 By Technology5.1.1 Immunohistochemistry (IHC)5.1.2 Polymerase Chain Reaction (PCR)5.1.3 In-situ Hybridization (ISH)5.1.4 Real-time PCR (RT-PCR)5.1.5 Gene Sequencing5.1.6 Other Technologies5.2 By Indication5.2.1 Lung Cancer5.2.2 Breast Cancer5.2.3 Colorectal Cancer5.2.4 Leukemia5.2.5 Melanoma5.2.6 Other Indications5.3 By Geography

6 COMPETITIVE LANDSCAPE6.1 Company Profiles6.1.1 Abbott Laboratories6.1.2 Agilent Technologies Inc.6.1.3 F Hoffmann-La Roche Ltd6.1.4 Biomerieux SA6.1.5 Qiagen NV6.1.6 Siemens Healthcare6.1.7 Thermo Fisher Scientific Inc.6.1.8 Danaher Corporation (Beckman Coulter Inc.)

7 MARKET OPPORTUNITIES AND FUTURE TRENDS

For more information about this report visit https://www.researchandmarkets.com/r/7z4nt2

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Global Companion Diagnostics Market Growth, Trends, and Forecasts Report 2020-2025: Companies Promoting Personalized Medicine and Targeted Therapy as...

Dublin, Dec. 31, 2020 (GLOBE NEWSWIRE) -- The "Research Antibodies and Reagents Market by Product {Antibodies [Type (Primary, Secondary), Production, Source, Research Area (Oncology, Neurology)], Reagents}, Technology (ELISA, Western Blot), Application, End User (Pharma, Academia) - Global Forecast to 2027." report has been added to ResearchAndMarkets.com's offering.

The research antibodies and reagents market is expected to grow at a CAGR of 5.6% from 2020 to 2027 to reach USD 6.32 billion by 2027.

Factors such as rising demand for protein therapeutics & personalized medicine, increasing investment in stem cell research, and rising need for biomarker identification represent high-growth opportunities for players during the forecast period. However, factors such as high cost and time related to identifying and developing potential antibodies are expected to hinder the growth of this market.

In 2020, based on type, the antibodies segment is projected to account for the largest share of this market. The large share of this segment is mainly attributed to increasing demand for antibodies for biomedical research, growing focus on protein and cell-based research, and increasing number of biomarker discovery.

On the basis of technology, in 2020, the flow cytometry segment is poised to command the largest share of the research antibodies and reagents market. The raising biomedical research for better diagnosis and therapy, initiatives for rising biomarker discovery, and growing cell & molecular-based research are the factors driving this growth of this segment.

In 2020, the proteomics segment is expected to command the largest share of the research antibodies and reagents market. Growing focus on protein-based research and the rising need for effective drugs using various protein-based disease profiling are the factors driving the growth of this segment.

The pharmaceutical and biotechnology industry is widely adopting research antibodies and reagents for proteomics research and drug discovery and development.

An in-depth analysis of the geographical scenario of the research antibodies and reagents market provides detailed qualitative and quantitative insights for the five major geographies (North America, Europe, Asia-Pacific, Latin America, and the Middle East & Africa) along with the coverage of major countries in each region. In 2020, North America is estimated to command the largest share of the research antibodies and reagents market, followed by Europe, Asia-Pacific, Latin America, and the Middle East & Africa.

Key Topics Covered:

1. Introduction1.1. Market Ecosystem1.1.1. Research Antibodies and Reagents Market1.1.2. Research Antibodies and Reagents Market, by Product1.2. Currency and Limitations1.3. Key Stakeholders

2. Research Methodology2.1. Research Process2.1.1. Secondary Research2.1.2. Primary Research

3. Executive Summary

4. Market insights4.1. Introduction4.2. Market Dynamics4.2.1. Drivers4.2.1.1. Rising Proteomics and Genomics Research Studies4.2.1.2. Increase in the Funding for Research Activities4.2.1.3. Growing Industry-Academia Collaboration4.2.2. Restraint4.2.2.1. High Cost and Time Related to Identification and Development of Potential Antibodies4.2.3. Opportunities4.2.3.1. Rising Demand for Protein Therapeutics and Personalized Medicines4.2.3.2. Rising Investment and Focus on Stem-Cell Research4.2.3.3. Rising Need for New Biomarker Identification4.2.3.4. Significant Opportunities from Emerging Asia-Pacific and Latin-American Markets4.2.4. Challenges4.2.4.1. Issues Related to Quality and Stability of Research Antibodies4.2.4.2. Intense Pricing Pressure on Leading Players

5. Research Antibodies and Reagents Market, by Product5.1. Introduction5.2. Antibodies5.2.1. Antibodies Market, by Type5.2.1.1. Primary Antibodies5.2.1.2. Secondary Antibody5.2.2. Antibodies Market, by Production Type5.2.2.1. Monoclonal Antibody5.2.2.2. Polyclonal Antibody5.2.2.3. Antibody Fragments5.2.3. Antibody Market, by Source5.2.3.1. Mouse5.2.3.2. Rabbit5.2.3.3. Other Sources5.2.4. Antibodies Market, by Research Area5.2.4.1. Oncology5.2.4.2. Infectious Diseases5.2.4.3. Cardiovascular Disease5.2.4.4. Immunology5.2.4.5. Neurology5.2.4.6. Stem Cell Research5.2.4.7. Other Research Areas5.3. Reagents5.3.1. Sample Preparation Reagents5.3.1.1. Media and Serum5.3.1.2. Stains and Dyes5.3.1.3. Probes5.3.1.4. Buffers5.3.1.5. Solvents5.3.2. Antibody Production Reagents5.3.2.1. Enzymes5.3.2.2. Proteins5.3.3. Other Research Reagents

6. Research Antibodies and Reagents Market, by Technology6.1. Introduction6.2. Flow Cytometry6.3. Immunofluorescence6.4. Enzyme-Linked Immunosorbent Assay6.5. Immunoprecipitation (IP)6.6. Multiplex Immunosorbent Assay6.7. Immunohistochemistry6.8. Western Blot6.9. Other Technologies

7. Research Antibodies and Reagents Market, by Application7.1. Introduction7.2. Proteomics7.3. Drug Discovery and Development7.4. Genomics

8. Research Antibodies and Reagents Market, by End User8.1. Introduction8.2. Pharmaceutical and Biotechnology Industry8.3. Academic and Research Institutes8.4. Contract Research Organizations

9. Research Antibodies and Reagents Market, by Geography

10. Competitive Landscape10.1. Introduction10.2. Key Growth Strategies10.3. Competitive Benchmarking10.4. Market Share Analysis

11. Company Profiles11.1. Business Overview11.2. Financial Overview11.3. Product Portfolio

For more information about this report visit https://www.researchandmarkets.com/r/q5a7ww

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

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Global Research Antibodies and Reagents Market Report 2020-2027: Significant Opportunities from Emerging Asia-Pacific and Latin-American Markets -...

WEST PALM BEACH, FL, Dec. 30, 2020 (GLOBE NEWSWIRE) -- USA EQUITIES CORP. (OTCQB: USAQ) (the Company, we, or our) announced today that its revenues for the fourth quarter of 2020 would be approximately $120,000 and that its revenues would exceed $300,000 in the first quarter of 2021.

We introduced our QHSLab, Software as a Service (SaaS) platform, to 159 medical practices in June 2020. Through September, physicians in these practices provided 374 allergy patients with a QHSLab-generated allergen immunotherapy prescription, generating an estimated $664,608 in revenue for these physicians practices. In November, building on the capabilities of our QHSLab, we began shipping allergy diagnostic related products and immunotherapy treatments to these physicians in response to their requests based upon courses of treatment recommended for their patients by QHSLab. Our revenue in the fourth quarter will be $120,000 as a result of these sales. Based upon orders in hand and reasonably anticipated, revenues from our allergy diagnostic test kits and treatment programs should exceed $300,000 in the first quarter of 2021. Revenues from this program should continue to increase thereafter as we increase the number of physicians and medical practices utilizing QHSLab.

Based on our QHSLab allergy treatment systems success, we intend to increase our revenues by charging physicians a monthly subscription fee for the use of QHSLab. USAQ plans to introduce these physicians to additional point of care diagnostic, digital medicine, and treatments that our physician clients can use and prescribe. They will be paid under existing government and private insurance programs, based upon analyses conducted utilizing QHSLab.

The revenues we generated in the fourth quarter of 2020 and anticipated revenue in the first quarter of 2021 far exceed the revenue levels assumed by the equity research firm, Litchfield Hills Research, when it released its first analyst coverage report on USAQ. Litchfield Hills continue to rate our stock as a buy under its three-tiered rating system, with a target price of $5.00 per share.

About USA Equities Corp (OTCQB: USAQ)

On December 20, 2019 USA Equities Corp completed a share exchange whereby it acquired Medical Practice Income, Inc. (MPI). The Company is focused on value-based healthcare solutions, clinical informatics and algorithmic personalized medicine including digital therapeutics, behavior based remote patient monitoring, chronic care and preventive medicine. The Companys products are intended to allow the general practice physician to increase his revenues by cost effectively diagnosing and treating chronic diseases generally referred to specialists. The Companys products and information service portfolio are directed towards prevention, early detection, management, and reversal of cardio-metabolic and other chronic diseases. Our principal objectives are to develop proprietary software tools, devices, and approaches, providing more granular, timely, and specific clinical decision-making information for practicing physicians and other health care providers to address todays obese, diabetic and cardiovascular disease population. The Company is located in West Palm Beach, Florida. For more information, visit http://www.MedicalPracticeIncome.com/discover.

Forward-Looking Statements

Certain matters discussed in this press release are 'forward-looking statements' intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. In particular, the Company's statements regarding trends in the marketplace, future revenues, future products and potential future results and acquisitions, are examples of such forward-looking statements. Forward-looking statements are generally identified by words such as may, could, believes, estimates, targets, expects, or intends and other similar words that express risks and uncertainties. These statements are subject to numerous risks and uncertainties, including, but not limited to, the timing of the introduction of new products, the inherent discrepancy in actual results from estimates, projections and forecasts made by management, regulatory delays, changes in government funding and budgets, and other factors, including general economic conditions, not within the Company's control. The factors discussed herein and expressed from time to time in the Company's filings with the Securities and Exchange Commission could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances.

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USA Equities Corp (USAQ), Announces Revenues of $120000 for the 4th Quarter of 2020 and Projects Revenues in excess of $300000 for the 1st Quarter of...

PHOENIX, Dec. 29, 2020 /PRNewswire/ --(OTC-CELZ)Creative Medical Technology Holdings Inc. announced today novel data and patent filing No. 63131261 describing the ability of ImmCelz to reverse liver failure in the carbon tetrachloride preclinical model of hepatocyte necrosis.

These findings are the basis for a patent filing covering various means of generating the ImmCelz product in a hepatoprotective specific manner. The Company has previously reported that ImmCelz is capable of treating animal models of stroke,1 as well as inducing "immunological tolerance" in a model of autoimmune rheumatoid arthritis.2

The work is an extension of previously published findings of Dr. Thomas E. Ichim, in which mesenchymal stem cells were capable of inhibiting progression of liver failure.3

"I am proud of the work the team at Creative Medical Technologies is conducting in advancing the concept of immunologically-mediated regeneration,"said Dr. Ichim, Co-inventor of the patent. "ImmCelz is an advancement on our previous liver failure work due to the fact that we have shown transfer of regenerative activity from the stem cell to the immune cell. Immune cells possess ability to home to injured tissues faster than stem cells due to their smaller size. Additionally, immune cells possess immunological memory, which we believe may be applied to the concept of regeneration."

"While stem cell therapeutics are recognized as the future of medicine, I believe it is important to realize that many activities of stem cells are mediated by changes to the immune system," said Dr. Amit Patel, Board Member of the Company and Co-Inventor of the Patent Application. "ImmCelz represents a fundamental advancement in regenerative medicine in that instead of administering stem cells in the body to induce immune modulation, we actually optimize the immune modulation in the laboratory before injecting immune cells into the patient."

Being at the forefront in identifying novel regenerative treatment options, the Company possesses numerous issued patents in the area of cellular therapy, including patent no. 10,842,815 covering use of T regulatory cells for spinal disc regeneration, patent no. 9,598,673 covering stem cell therapy for disc regeneration, patent no. 10,792,310 covering regeneration of ovaries using endothelial progenitor cells and mesenchymal stem cells, patent no. 8,372,797 covering use of stem cells for erectile dysfunction, and patent no. 7,569,385 licensed from the University of California covering a novel stem cell type.

"Liver failure represents a significant unmet medical need and I am extremely excited that ImmCelz has the potential to help the numerous patients on the liver transplant waiting list who currently have no other option.

With growing validation and acceptance of such technologies, the company intends to continue to broaden its intellectual property portfolio by compiling research data and filing patents, in order to record early filing dates and increase the likelihood of our receiving patent issue.

We continue to welcome opportunities with collaborators and Key Opinion Leaders as we are dedicated to accelerating the further development of our technology."

About Creative Medical Technology Holdings

Creative Medical Technology Holdings, Inc. is a commercial stage biotechnology company specializing in stem cell technology in the fields of urology, neurology and orthopedics and trades on the OTC under the ticker symbol CELZ. For further information about the company, please visitwww.creativemedicaltechnology.com.

Forward Looking Statements

OTC Markets has not reviewed and does not accept responsibility for the adequacy or accuracy of this release. This news release may contain forward-looking statements including but not limited to comments regarding the timing and content of upcoming clinical trials and laboratory results, marketing efforts, funding, etc. Forward-looking statements address future events and conditions and, therefore, involve inherent risks and uncertainties. Actual results may differ materially from those currently anticipated in such statements. See the periodic and other reports filed by Creative Medical Technology Holdings, Inc. with the Securities and Exchange Commission and available on the Commission's website atwww.sec.gov.

Creativemedicaltechnology.comwww.StemSpine.comwww.Caverstem.comwww.Femcelz.com

1 Creative Medical Technology Holdings Identifies Mechanism of Action of ImmCelz Stroke Regenerative Activity (prnewswire.com)2 Creative Medical Technology Holdings Reports Positive Preclinical Data on ImmCelz Immunotherapy Product in Rheumatoid Arthritis Model | BioSpace 3 Human endometrial regenerative cells alleviate carbon tetrachloride-induced acute liver injury in mice | Journal of Translational Medicine | Full Text (biomedcentral.com)

SOURCE Creative Medical Technology Holdings, Inc.

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Creative Medical Technology Holdings Announces Reversion of Liver Failure Using ImmCelz Personalized Cellular Immunotherapy in Preclinical Model -...

Santiago Quirce,1 Enrico Heffler,2 Natalia Nenasheva,3 Pascal Demoly,4 Andrew Menzies-Gow,5 Ana Moreira-Jorge,6 Francis Nissen,7 Nicola A Hanania8

1Department of Allergy, La Paz University Hospital, IdiPAZ and Universidad Autnoma de Madrid, Madrid, Spain; 2Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, MI, Italy; 3Department of Allergology and Immunology of Russian Medical Academy for Continuous Medical Education, Moscow, Russian Federation; 4Department of Pulmonology, Division of Allergy, Hpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France; 5Department of Respiratory Medicine, Royal Brompton Hospital, London, UK; 6Novartis Farmaceutica, S.A., Barcelona, Spain; 7London School of Hygiene and Tropical Medicine, London, UK; 8Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA

Correspondence: Santiago QuirceHospital Universitario La Paz, P. La Castellana, 261, Madrid, 28046 SpainEmail squirce@gmail.com

Abstract: The Global Initiative for Asthma (GINA) 2020 defines late-onset asthma (LOA) as one of the clinical phenotypes of asthma wherein patients, particularly women, present with asthma for the first time in adult life, tend to be non-allergic and often require higher doses of inhaled corticosteroids (ICS) or are relatively refractory to corticosteroid treatment. In this review, we examine the published literature improve the understanding of the following aspects of LOA: 1) the age cut-off for its diagnosis; 2) its distinct clinical phenotypes, characteristics and risk factors; and 3) its association with allergic comorbidities and conditions. Overall, our review reveals that clinicians and researchers have used multiple age cut-offs to define LOA, with cut-off ages ranging from > 12 years to 65 years. LOA has also been classified into several distinct phenotypes, some of which drastically differ in their clinical characteristics, course and prognosis. Although LOA has traditionally been considered non-allergic in nature, our review indicates that it is commonly associated with allergic features and comorbidities. Our findings suggest that there is an urgent need for the development of more clear clinical practice guidelines that can provide more clarity on the definition and other aspects of LOA. In addition, the association of LOA and allergy needs to be re-examined to frame a more optimal treatment strategy for patients with LOA.

Keywords: asthma, diagnosis, age of onset, allergy, allergic asthma, asthma phenotypes

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Revisiting Late-Onset Asthma: Clinical Characteristics and Association | JAA - Dove Medical Press

On 1 January 2020, I published my very first Ex Machina article of the year. Since it was also the beginning of a new decade, I made my own modest attempt at predicting the technological changes we could hope to expect in the coming years. I wrote about the promise of artificial intelligence, speech recognition and augmented reality, and how they would come together to let us speak to computers in novel ways. I argued that technology would transform our commute, eventually leading to a future of shared autonomous vehicles that would completely eliminate the need to own personal cars, etc. Finally, I spoke of personalized medicine and a future in which treatments could be calibrated to individual requirements, instead of being focused on discovering drugs that need to work on the entire human population.

What I did not predict was that in a couple of months, a global pandemic would bring the entire world to a grinding halt.

Much of what I had thought would happen will likely still come to passalthough in a slightly different way from what I had imagined. Now that companies have realized how easy it is to support working from home, many businesses are re-thinking their investments in commercial real estatecommitting themselves instead to enabling employees to work from wherever they might be at a given point in time.

In addition to all that I had anticipated, I believe this new mindset will eventually contribute to a fundamental alteration of our commute and be another catalyst for some of the urban mobility solutions. I had anticipated. And while autonomous transportation may not become a reality anytime soon, I am excited by the immediate promise that platform solutions of the likes of Beckn have to offer.

I had suggested in my article that computers might soon be able to speak coherently with us, but even I did not imagine wed get there so soon. The remarkable language abilities of OpenAIs Generative Pre-trained Transformer Ver 3 (GPT-3) technology took the world by storm this year. But while initial reports suggested that it would make computer communications indistinguishable from human speech, closer study revealed flaws in its output, as also practical limitations in working with very large data-sets. That said, I was heartened by the emergence of new techniques of artificial intelligence such as few-shot learning, and the promise that it could hold for data-starved countries like India.

But the technology breakthrough that everyone was focused on for all of 2020 was in medicine. On this front, my prediction at the beginning of the year fell well short of the mark. As hopeful as I still am for a future in which medicine will be personalized, the covid pandemic made it clear that there will always be a need for medical solutions that can be rolled out rapidly and at scale to the entire global population.

I am thankful that our investments in genetic technologies, the global interconnectedness of the scientific community and the manufacturing capabilities of pharmaceutical companies came together so well this past year to enable us to produce multiple vaccines for covid-19 in record time. I hope these demonstrations of success encourage us to invest in platform vaccine technologies, so that we are better placed to deal with such challenges that we will, no doubt, continue to face in the future.

But, more than anything else, the pandemic demonstrated the central role that technology now plays in society. From the contact-tracing apps that were all the rage in the early months of the diseases outbreak, to the remote-working solutions that brought us together even though we were far apart, it is clear that all aspect of our lives today are dependent on technology.

Our recent experiences will hopefully serve as the impetus we need to make sure that small businesses and ordinary citizens in this country get greater access to the internet, so that they can all partake in this future.

Early in the lockdown, the department of telecommunications relaxed the work-from-home restrictions that applied to technology companies registered as Other Service Providers (OSP)a relaxation that was made permanent before the end of the year with a radical overhaul of the entire OSP framework. Later in the year, the Union cabinet approved the Prime Minister Wi-Fi Access Network Interface, or PM Wani , a new regulation system for wifi that will encourage the rapid proliferation of digital technologies in India.

As good as these regulatory measures might be, we still need key technology legislation to bring us on par with the rest of the world. It was good to see that despite the constraints imposed by the pandemic, the meetings of the Joint Parliamentary Committee on data protection proceeded apace. Equally interesting was the governments interest in regulating non-personal data, making India the first country to attempt governing the entire data landscape.

As gruesome as the year has been, it has forced us to reconsider our relationship with technologyand to engage with it in different ways.

Rahul Matthan is a partner at Trilegal and also has a podcast by the name Ex Machina. His Twitter handle is @matthan

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The technological transformations that marked 2020 - Mint

NEW YORK, Dec. 29, 2020 (GLOBE NEWSWIRE) -- Predictive Oncology (NASDAQ: POAI) (the Company), a knowledge-driven company focused on applying artificial intelligence (AI) to personalized medicine and drug discovery, today announced that its Board of Directors has decided to cancel its Special Meeting of Stockholders that was originally scheduled for December 1, 2020. On that date, the meeting was adjourned to December 30, 2020 because a quorum was not reached. As of December 30, 2020, approximately 47% of the outstanding shares as of the record date have been voted, and therefore a quorum has still not been reached. The Board of Directors has determined that it is not practical to incur the expense of adjourning the meeting further to continue to solicit proxies, because approval of the reincorporation proposal would require the affirmative vote of a majority of the Companys outstanding shares (not simply a majority of the shares voted).

The Board notes that, of the shares that were voted at the Special Meeting, nearly 88% of the shares were voted FOR the reincorporation from Delaware to Nevada. In the future, the Board intends to continue to seek stockholder approval for reincorporation, due in part to the oppressive franchise taxes charged by Delaware.

About Predictive Oncology Inc.

Predictive Oncology (NASDAQ: POAI) operates through three segments (Skyline, Helomics and Soluble Biotech), which contain four subsidiaries: Helomics, TumorGenesis, Skyline Medical and Soluble Biotech.

Helomics applies artificial intelligence to its rich data gathered from patient tumors to both personalize cancer therapies for patients and drive the development of new targeted therapies in collaborations with pharmaceutical companies. TumorGenesis Inc. specializes in media that help cancer cells grow and retain their DNA/RNA and proteomic signatures, providing researchers with a tool to expand and study cancer cell types found in tumors of the blood and organ systems of all mammals, including humans. Skyline Medical markets its patented and FDA cleared STREAMWAY System, which automates the collection, measurement and disposal of waste fluid, including blood, irrigation fluid and others, within a medical facility, through both domestic and international divisions. Soluble Biotech is a provider of soluble and stable formulations for proteins including vaccines, antibodies, large and small proteins and protein complexes.

Forward-Looking Statements

Certain matters discussed in this release contain forward-looking statements. These forward-looking statements reflect our current expectations and projections about future events and are subject to substantial risks, uncertainties and assumptions about our operations and the investments we make. All statements, other than statements of historical facts, included in this press release regarding our strategy, future operations, future financial position, future revenue and financial performance, projected costs, prospects, plans and objectives of management are forward-looking statements. The words anticipate, believe, estimate, expect, intend, may, plan, would, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Our actual future performance may materially differ from that contemplated by the forward-looking statements as a result of a variety of factors including, among other things, factors discussed under the heading Risk Factors in our filings with the SEC. Except as expressly required by law, the Company disclaims any intent or obligation to update these forward-looking statements.

Investor Relations Contact:

Hayden IRJames Carbonara(646)-755-7412

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Predictive Oncology Announces Cancellation of Special Meeting in December 2020Reincorporation Proposal Received Overwhelming Support Among Shares...

The "Global Microbiome Sequencing Services Market (2020-2025) by Technology, Application, Research Type, Laboratory Type, End-Users, Geography and the Impact of Covid-19 with Ansoff Analysis" report has been added to ResearchAndMarkets.com's offering.

The Global Microbiome Sequencing Services Market is estimated to be USD 1.02 billion in 2020 and is expected to reach USD 2.31 billion by 2025, growing at a CAGR of 17.8%.

Microbiomes are a group of micro-organisms living on a human body. They live on the skin, eyes, saliva, mouth, and the gastrointestinal tract. The human microbiome contains thousands of bacterial species/microbes in diverse communities, along with their genes, proteins, and metabolites. An imbalance of these microbes can lead to life-threatening diseases. The study of Microbiome sequencing and its techniques relates to the study of the microbial composition of the human gut and to understand the resulting impact on health and disease development.

Microbiome sequencing is usually done to understand this microflora residing on the human body and further study human microbes and their role in related diseases. This study can also be helpful while analyzing the patient's response to a particular treatment. Effective understanding and application of microbiome sequencing services would help in the commercialization of personalized medicine and diet. Hence, the market is extensively driven by research-based communities, especially in the developed economies like the US, which has the presence of NHGRI (National Human Genome Research Institute) supporting the growth of the market.

Due to advancements in technology, there has been a rise in the NGS (Next-Gen Sequencing) to generate microbiome data. Besides, techniques such as novel high-throughput sequencing and new software tools are transforming microbiome studies by providing service at high quality, speed, and high cost. Many companies are additionally concentrating on novel exome sequencing and RNA sequencing applications in niche market segments.

Story continues

Specific factors that have led to the growth of this market are the rising use of microbiome in genomics, along with the reduced cost of sequencing. However, other factors such as the lack of expertise in the data analysis for the microbiomes with advanced tools shall hinder the growth of this market.

Market Dynamics

Drivers

Increased Focus on Human Microbiome Therapy

Reduction in the Cost of Sequencing

Human Microbiome as a New Validated Target for Drug Development

Human Microbiome Used as an Aid for Early Disease Detection and Diagnosis

Increasing Demand for NGS

Restraints

Lack of Skilled Professionals for Microbiome Sequencing Services

Lack of Awareness Among Physicians and Scientist about Advanced Tools for Data Analysis

Barriers in Proving the Causal Link Between Dysbiosis and Disease

Opportunities

Investigational New Drug (IND) Requirements for Fecal Microbiota

Increasing Collaborations Create Growth Opportunities

Increasing Research Investments and Technological Advancements

Why Buy this report?

The report offers a comprehensive evaluation of the Global Microbiome Sequencing Services Market. - The report includes in-depth qualitative analysis, verifiable data from authentic sources and projections about market size. The projections are calculated using proven research methodologies.

The report has been compiled through extensive primary and secondary research. The primary research is done through interviews, surveys and observation of renowned personnel in the industry.

The report includes in-depth market analysis using Porter's 5 force model and the Ansoff Matrix. The impact of Covid-19 on the market is also featured in the report.

The report also contains a competitive analysis using IGR Positioning Quadrants, Infogence's Proprietary competitive positioning tool.

Companies Mentioned

Baseclear B.V.

Clinical-Microbiomics A/S

Molzym GmbH & Co. Kg

Zymo Research Corp.

Rancho Biosciences

Microbiome Therapeutics, LLC.

Microbiome Insights Inc.

Openbiome

Resphera Biosciences, LLC.

MR DNA (Molecular Research LP)

Shanghai Realbio Technology Co., Ltd

Diversigen, Inc.

Merieux Nutrisciences Corporation

Metabiomics Corp.

Second Genome

LOCUS BIOSCIENCES, INC,

BioSpherex LLC

For more information about this report visit https://www.researchandmarkets.com/r/6xv3hj

View source version on businesswire.com: https://www.businesswire.com/news/home/20201229005159/en/

Contacts

ResearchAndMarkets.comLaura Wood, Senior Press Managerpress@researchandmarkets.com For E.S.T Office Hours Call 1-917-300-0470For U.S./CAN Toll Free Call 1-800-526-8630For GMT Office Hours Call +353-1-416-8900

Originally posted here:
Worldwide Industry for Microbiome Sequencing Services to 2025 - Increased Focus on Human Microbiome Therapy is Driving Growth - ResearchAndMarkets.com...

The day comes for all of us, and the day Im speaking of is that day when our once loose jeans and baggy shirt become a bit tighter around the waste. Its at that time we decide to get down to business, hit the gym, and skip the cookie aisle at the supermarket, because the diet starts now.

COVID hits and its not that easy to get our work out on. Still we wake every morning and go for a run, even buy weights, do the research and plan out are meals. After chugging down a protein shake, suddenly losing those extra pounds feels easy. However, then, with the runners high wearing off, a bag of Cheetos, a few beers, and more than one off-day later, and you realize that this is going to be an uphill battle.

Israeli startup Newt and its founder and CEO Gil Kerbs understand the struggle of maintaining a healthy diet and schedule. The company developed an AI-powered platform that uses your daily habits to generate a personalized regiment to keep your nutritional goals on track. Or as Gil puts it Our product interacts with users daily to understand and aggregate all information needed for health / nutrition based decisions, and then provides daily support to start shifting their behavior towards healthier habits.

With the year of COVID coming to a hopeful end, it was definitely a great year for remote technology, from medicine to fitness, the global pandemic did change the way people interact virtually. So how has personalized nutrition gained such popularity? GIl says that It's kind of the 'perfect storm'. We are so focused on our health and wellbeing due to the pandemic - we finally REALLY know that actively staying fit and healthy can help prevent harsh impacts from sickness, such as with COVID. We are also witnessing the rise of AI, allowing for true personalization - a personal fitness coach that is really 'personal', and now with Newt, a personal nutritionist that really tailors everything for you.

Gil explains that he sees preventative care as the future of personalized medicine, not only giving you the 'right' medicine when you need it but rather helping you make the right daily decisions that eventually shape your long term health.

Yeah, this is probably not the first fitness/nutrition app youve heard of, but Newt does things a little different, actually putting your habits in the center to better motivate you. But how is it done? In one word - "behavioral personalization". We are not aiming for a quick perfect, but for the closest to optimal that you can sustain for the long run. Our Behavioral expertise stretches from Prof. Adam Grant (Wharton, world leading motivation expert), and Stanford Mind&Body lab who focus on use of psychology for wellbeing. Our goal is to make not only the best clinical knowledge available, but rather to combine it with cutting edge psychology/behavior knowledge that makes behavior and diet change a real possibility in the long run."

Gils attachment to the subject comes from his years in the medical industry as part of Medtronic China, where he notes that it was very rewarding to help add 1-2 years to people's lives, but I wanted more - 20-30 more years, with better quality - and this could not be done when the patient is already in the OR. So, I got into preventative medicine, and there's nothing bigger for your long term health than your nutrition... All of us at Newt have this motivation - helping people keep healthy, by harnessing the strongest force available to everyone - daily nutrition."

He adds that although intervention healthcare isnt going anywhere and will maintain an important part of medical care but preventative can be better for humanity as a whole, Take cancer - surgery's solution is to take it out or 'kill it' (radiation), but not to solve what caused it, yet. This is a short term solution due to the limitations of our knowledge. Think about it this way - 5 year survival rates for various cancers are still very low, despite utilizing cutting edge technology to treat them. Preventative healthcare is much less 'high-tech', we don't need robots - nor huge amounts of dollars - it's rather cheap - and it really helps dramatically reduce chances of getting sick. The real problem is that it's a marathon, and not just a sprint intervention, making it psychologically harder. That's why we at Newt focus on behavior so much.

Founded in 2019, Newt has received backing from Welltech1 - a wellness microfund, and angel investors. And according to Gil, the company has a few partnerships in the works. Cool idea and all but why the name Newt? We wanted something short that sounds like nutrition, but is also a name of a character. We see Newt as a personal guide for nutrition. It's also a really cute animal, said Kerbs.

Ok, last thing, even though its been a weird year, were sure people will keep in the tradition of failing at their New Years resolutions (myself a victim), so we asked Gil to take from his nutritional expertise and offer some advice: ...In general I'd advise people that next time they 'fail' with a resolution, they should not beat themselves up about it, but rather think how to better approach it next time. Usually, there's a fun, easier way to achieve success and give you great results in the long run.

Excerpt from:
After accepting virtual trainers, AI-powered nutrition is the next step in keeping a healthy lifestyle - Geektime

Heres the wild part, the most 2020 thing about 2020: That schismthat conflict between public health and private well-being, between personal liberties and communal gainis as old as pandemics. The germ of the idea was, in fact, the idea of the germ.

In the mid-1800s, physicians and scientists were starting to come around to the long-gestating idea that diseases could be caused by wee, invisible critters that jumped from person to persona contagium animatum, as 16th-century thinkers put it. They didnt know what viruses or bacteria were, but they knew something was carrying illness.

The contagionists had their opposite number: scientists who in 1948 the researcher Edwin Ackerknecht famously called anticontagionists. Oh, they believed that some diseases spread by some agent, person-to-person. Smallpox and syphilis, maybe. Those were contagious. But they werent epidemicsyellow fever, cholera, or the plague, things that seemed to spread seasonally, or in specific places, or only among specific kinds of people. Nobody knew how. They didnt know anything about food- and waterborne pathogens, about differences between viruses and bacteria, about surface-borne fomites that transmitted disease in some cases, while exhaled droplets and aerosols might in others. Absent any of that? Well, maybe it was something atmospherica cloud of illness, a miasma, maybe even the filth of poverty and pre-sanitation cities. (Its telling that scientists are still fighting over the idea of an airborne contagium animatum, even today.)

But the anticontagionists knew one thing for sure. Those big three epidemicswith typhus thrown in sometimes, toowere the things that had, since the 14th century, caused governments to take population-scale measures to control them. That meant quarantines, travel restrictions, business closureswhat today we might call lockdowns. And that made the anticontagionists nuts. They said that lockdowns, then as now, were bad for business; losses incurred as a result outweighed those caused by the epidemic itself. In the midst of the 19th centurys Industrial Revolution, anything that inhibited business was an inhibition of freedom itself. Quarantines meant, to the rapidly growing class of merchants and industrialists, a source of losses, a limitation to expansion, a weapon of bureaucratic control that it was no longer willing to tolerate, Ackerknecht wrote. Contagionism would, through its associations with the old bureaucratic powers, be suspect to all liberals, trying to reduce state interference to a minimum. Anticontagionists were thus not simply scientists, they were reformers, fighting for the freedom of the individual and commerce against the shackles of despotism.

Also, by saying that disease came from lack of sanitation and poor hygiene, the pro-filth contingent was sometimes quietly and sometimes loudly associating disease with ethnicity and socioeconomic status. It was immunological social Darwinism; if poor and nonwhite people got sick first, or more often, that proved to some reformers that those people made bad personal choices (rather than indicating a failure of the systems around them). In that light, identifying filth as the generator of epidemics paved the way for the hygiene movement, showed the moral and physical superiority of unpoor whites, and provided a rationale for slum clearance and residential zoning laws. Squint at redlining and you see not just the geography of racism but also a colonial cordon sanitaire.

To be fair, as one historian notes, the (paltry) science of miasmas did suggest that quarantines would actually make epidemic diseases worse, because they amplified the confinement and lousy conditions that spread the disease. And if you read miasma as the conditions that make a disease spread, well, thats also the point Im trying to make, so yeah. These were good-faith scientific arguments that also happened to be politically motivated economic and philosophical ones, tinged by racism.

More here:
The Error of Fighting a Public Health War With Medical Weapons - WIRED

The Guardian

Republicans say they will reject presidential electors from states where Trump campaign contested results unless audit completedTed Cruz of Texas, Ron Johnson of Wisconsin and nine other Republican US senators or senators-elect said on Saturday they will reject presidential electors from states where Donald Trump has contested his defeat by Joe Biden, unless and until [an] emergency 10-day audit of such results is completed.The move is largely symbolic and unlikely to overturn the presidential election. Nonetheless, it adds to a sense of deepening crisis affecting US democracy.Trump has refused to concede, though Biden won more than 7m more votes nationally and took the electoral college by 306-232, a margin Trump called a landslide when he won it over Hillary Clinton in 2016.The Trump campaign has lost the vast majority of more than 50 lawsuits it has mounted in battleground states, alleging electoral fraud, and before the supreme court.On Friday, a federal judge dismissed a suit lodged by a House Republican which attempted to give the vice-president, Mike Pence, who will preside over the certification of the electoral college result on Wednesday, the power to overturn it.Nonetheless, the senators and senators-elect who issued a statement on Saturday followed Senator Josh Hawley of Missouri in committing to challenging the result.Objections are also expected from a majority of House Republicans. Objections must be debated and voted on but as Democrats control the House and the Senate majority leader, Mitch McConnell, and other senior Republicans have voiced opposition, the attempt to disenfranchise a majority of Americans seems doomed to fail.On Saturday, Senator Lisa Murkowski of Alaska said she would vote to certify the results, writing: The oath I took at my swearing-in was to support and defend the constitution of the United States, and that is exactly what I will do. Pat Toomey of Pennsylvania, a state where Trump has sued, said he would vigorously defend our form of government by opposing this effort to disenfranchise millions of voters in my state and others.But Cruz and Johnson were joined by Senators James Lankford (Oklahoma), Steve Daines (Montana), John Kennedy (Louisiana), Marsha Blackburn (Tennessee) and Mike Braun (Indiana). Senators-elect Cynthia Lummis (Wyoming), Roger Marshall (Kansas), Bill Hagerty (Tennessee) and Tommy Tuberville (Alabama) also signed on.The election of 2020, they said, like the election of 2016, was hard fought and, in many swing states, narrowly decided. The 2020 election, however, featured unprecedented allegations of voter fraud, violations and lax enforcement of election law, and other voting irregularities.No hard evidence for such claims has been presented. Federal officials including former attorney general William Barr and Christopher Krebs, a cyber security chief fired by Trump, have said the election was secure.Regardless, the senators said Congress should immediately appoint an electoral commission, with full investigatory and fact-finding authority, to conduct an emergency 10-day audit of the election returns in the disputed states. Once completed, individual states would evaluate the commissions findings and could convene a special legislative session to certify a change in their vote, if needed.The senators made reference to the contested election of 1876, which ended in the appointment of such a commission.We should follow that precedent, they said. Most well-informed observers would suggest otherwise, given that process put an end to post-civil war Reconstruction and led to the institution of racist Jim Crow laws across the formerly slave-owning south.In August, the Pulitzer-winning historian Eric Foner told the Guardian: The election of 1876 would not have been disputed at all if there hadnt been massive violence in the south to prevent black people from voting and voter suppression like we have today. Now, voter suppression is mostly legal.Presciently, given baseless claims that voting under a pandemic was abused by Democrats, he added: Today, I can certainly see the Trump people challenging these mail-in ballots: Theyre all fraudulent, they shouldnt be counted. Challenging peoples voting.Cruz, like Hawley, is prominent among Republicans expected to run for president in 2024, and thus eager to appeal to supporters loyal to Trump. On Saturday, Christine Pelosi, daughter of House speaker Nancy Pelosi and a member of the Democratic National Committee, referred to the bitter 2016 primary when she tweeted: Ted Cruz is defending Trumps assaults on democracy with more energy than he defended his own family against Trumps assaults on his wife and father.The Democratic strategist Max Burns wrote: The exact same Senate GOP that refused to allow a single witness during President Trumps impeachment trial now wants to call a bunch of witnesses to investigate Joe Bidens 2020 victory.Biden did not immediately comment. In Congress, the Connecticut senator Richard Blumenthal branded the statement pathetic, un-American and an attack on our democracy. Amy Klobuchar, from Minnesota, said Biden will be inaugurated on 20 January, and no publicity stunt will change that.Trump did not immediately comment but his campaign tweeted: THANK YOU! The Arizona congressman Paul Gosar hailed the senators as patriots.But there was also criticism from the right. Joe Walsh, a former congressman who ran against Trump in 2020, wrote: They cite ZERO evidence of voter fraud Donald Trumps single greatest legacy is the destruction of truth.Walsh added: These Republicans know this is bad for the country. But they dont care. They believe its good for them politically. They are placing their own interests before the countrys interests.With unintended irony or simple bad faith the senators and senators-elect said their allegations are not believed just by one individual candidate. Instead, they are widespread. Reuters/Ipsos polling, tragically, shows 39% of Americans believe the election was rigged. That belief is held by Republicans (67%), Democrats (17%), and Independents (31%). Whether or not our elected officials or journalists believe it, that deep distrust of our democratic processes will not magically disappear. It should concern us all. And it poses an ongoing threat to the legitimacy of any subsequent administrations.Marc Elias, a leading Democratic elections lawyer, said of the senators: History will remember and curse them for their cowardice and treachery.

Read more here:
Moderna, Pfizer vaccine trials were the highest of quality: vaccine expert - Yahoo Money

The Telegraph

Donald Trump was dealt a stinging rebuke by Republican senators last night as Congress overrode his veto of a sweeping defence bill. It was the first time in Mr Trump's four years as president that Congress had blocked his veto power. Many Republican senators joined Democrats in an 81-13 vote to override, well over the two thirds majority required. As a result the annual $740 billion National Defense Authorization Act to fund the military in 2021 will become law. Mr Trump had called the result, which was expected, a "disgraceful act of cowardice" and the Republican leadership in Congress "weak". The bill will provide a three per cent pay raise for US troops and included elements relating to defence policy, troop levels, weapons systems and military construction. Mr Trump had vetoed it, arguing it allowed for the renaming of military bases that honour Confederate generals, and that it limited his ability to bring troops home from Afghanistan and Germany. He also tried to link passage of the bill to measures targeting social media companies. Throughout Mr Trump's term Republican senators had been highly reluctant to break so publicly with him. He had vetoed eight previous bills and none were overridden. But with less than three weeks left in office Mr Trump's influence with Republican senators appeared to have receded markedly. Mitch McConnell, the Republican leader in the Senate, said: "It's time for us to deliver this bill. It's our chance to remind brave service members and their families that we have their backs." It came as Republicans also faced a deepening split over Mr Trump's last ditch attempt to overturn the US presidential election result. Over 140 Republicans in the House of Representatives may be ready to back a move not to certify the outcome at a joint session of Congress on Jan 6, it emerged. But even with that level of support the attempt to block the result still had no chance of success. Mr McConnell privately urged colleagues to accept the election result, and called his own vote on Jan 6 the "most consequential I have ever cast". In an open letter Ben Sasse, the Republican senator from Nebraska, accused colleagues of "playing with fire". He said: "Lets be clear what is happening here. We have a bunch of ambitious politicians who think theres a quick way to tap into the presidents populist base without doing any real, long-term damage. But theyre wrong. "Adults dont point a loaded gun at the heart of legitimate self-government." The move to oppose the election results was ignited by Josh Hawley, a Republican senator from Missouri. He will object, forcing a two-hour debate, followed by a vote in the Senate, and in the House of Representatives. The session in Congress will take place a day after two run-off races in Georgia, which will determine whether Republicans or Democrats control the Senate. David Perdue, one of two Republican candidates, announced he would spend the final days of the campaign in quarantine after possible exposure to the coronavirus. Meanwhile, it emerged that staffing changes were to be made to the Secret Service's presidential detail when Joe Biden takes office on Jan 20. Mr Biden's camp was said to have expressed concerns that current agents might be politically supportive of Mr Trump. Mr Trump cut short a trip to Florida and headed back to Washington on New Year's Eve. In a New Year video message he hailed "historic victories" on the economy and fighting the pandemic. He said: "We have to be remembered for what's been done." In the final weeks of his term the president was also facing an ongoing battle with Republicans in Congress, including Mr McConnell, after he called for an increase in stimulus cheques to Americans. He also faced growing friction with Iran.

See original here:
Celebrate the new year with this New Year's Eve fireworks show in SF - Yahoo News

The Guardian

Republicans say they will reject presidential electors from states where Trump campaign contested results unless audit completedTed Cruz of Texas, Ron Johnson of Wisconsin and nine other Republican US senators or senators-elect said on Saturday they will reject presidential electors from states where Donald Trump has contested his defeat by Joe Biden, unless and until [an] emergency 10-day audit of such results is completed.The move is largely symbolic and unlikely to overturn the presidential election. Nonetheless, it adds to a sense of deepening crisis affecting US democracy.Trump has refused to concede, though Biden won more than 7m more votes nationally and took the electoral college by 306-232, a margin Trump called a landslide when he won it over Hillary Clinton in 2016.The Trump campaign has lost the vast majority of more than 50 lawsuits it has mounted in battleground states, alleging electoral fraud, and before the supreme court.On Friday, a federal judge dismissed a suit lodged by a House Republican which attempted to give the vice-president, Mike Pence, who will preside over the certification of the electoral college result on Wednesday, the power to overturn it.Nonetheless, the senators and senators-elect who issued a statement on Saturday followed Senator Josh Hawley of Missouri in committing to challenging the result.Objections are also expected from a majority of House Republicans. Objections must be debated and voted on but as Democrats control the House and the Senate majority leader, Mitch McConnell, and other senior Republicans have voiced opposition, the attempt to disenfranchise a majority of Americans seems doomed to fail.On Saturday, Senator Lisa Murkowski of Alaska said she would vote to certify the results, writing: The oath I took at my swearing-in was to support and defend the constitution of the United States, and that is exactly what I will do. Pat Toomey of Pennsylvania, a state where Trump has sued, said he would vigorously defend our form of government by opposing this effort to disenfranchise millions of voters in my state and others.But Cruz and Johnson were joined by Senators James Lankford (Oklahoma), Steve Daines (Montana), John Kennedy (Louisiana), Marsha Blackburn (Tennessee) and Mike Braun (Indiana). Senators-elect Cynthia Lummis (Wyoming), Roger Marshall (Kansas), Bill Hagerty (Tennessee) and Tommy Tuberville (Alabama) also signed on.The election of 2020, they said, like the election of 2016, was hard fought and, in many swing states, narrowly decided. The 2020 election, however, featured unprecedented allegations of voter fraud, violations and lax enforcement of election law, and other voting irregularities.No hard evidence for such claims has been presented. Federal officials including former attorney general William Barr and Christopher Krebs, a cyber security chief fired by Trump, have said the election was secure.Regardless, the senators said Congress should immediately appoint an electoral commission, with full investigatory and fact-finding authority, to conduct an emergency 10-day audit of the election returns in the disputed states. Once completed, individual states would evaluate the commissions findings and could convene a special legislative session to certify a change in their vote, if needed.The senators made reference to the contested election of 1876, which ended in the appointment of such a commission.We should follow that precedent, they said. Most well-informed observers would suggest otherwise, given that process put an end to post-civil war Reconstruction and led to the institution of racist Jim Crow laws across the formerly slave-owning south.In August, the Pulitzer-winning historian Eric Foner told the Guardian: The election of 1876 would not have been disputed at all if there hadnt been massive violence in the south to prevent black people from voting and voter suppression like we have today. Now, voter suppression is mostly legal.Presciently, given baseless claims that voting under a pandemic was abused by Democrats, he added: Today, I can certainly see the Trump people challenging these mail-in ballots: Theyre all fraudulent, they shouldnt be counted. Challenging peoples voting.Cruz, like Hawley, is prominent among Republicans expected to run for president in 2024, and thus eager to appeal to supporters loyal to Trump. On Saturday, Christine Pelosi, daughter of House speaker Nancy Pelosi and a member of the Democratic National Committee, referred to the bitter 2016 primary when she tweeted: Ted Cruz is defending Trumps assaults on democracy with more energy than he defended his own family against Trumps assaults on his wife and father.The Democratic strategist Max Burns wrote: The exact same Senate GOP that refused to allow a single witness during President Trumps impeachment trial now wants to call a bunch of witnesses to investigate Joe Bidens 2020 victory.Biden did not immediately comment. In Congress, the Connecticut senator Richard Blumenthal branded the statement pathetic, un-American and an attack on our democracy. Amy Klobuchar, from Minnesota, said Biden will be inaugurated on 20 January, and no publicity stunt will change that.Trump did not immediately comment but his campaign tweeted: THANK YOU! The Arizona congressman Paul Gosar hailed the senators as patriots.But there was also criticism from the right. Joe Walsh, a former congressman who ran against Trump in 2020, wrote: They cite ZERO evidence of voter fraud Donald Trumps single greatest legacy is the destruction of truth.Walsh added: These Republicans know this is bad for the country. But they dont care. They believe its good for them politically. They are placing their own interests before the countrys interests.With unintended irony or simple bad faith the senators and senators-elect said their allegations are not believed just by one individual candidate. Instead, they are widespread. Reuters/Ipsos polling, tragically, shows 39% of Americans believe the election was rigged. That belief is held by Republicans (67%), Democrats (17%), and Independents (31%). Whether or not our elected officials or journalists believe it, that deep distrust of our democratic processes will not magically disappear. It should concern us all. And it poses an ongoing threat to the legitimacy of any subsequent administrations.Marc Elias, a leading Democratic elections lawyer, said of the senators: History will remember and curse them for their cowardice and treachery.

Original post:
The movie industry will strengthen again around April or May: Screenvision CEO - Yahoo Money

The Telegraph

Donald Trump was dealt a stinging rebuke by Republican senators last night as Congress overrode his veto of a sweeping defence bill. It was the first time in Mr Trump's four years as president that Congress had blocked his veto power. Many Republican senators joined Democrats in an 81-13 vote to override, well over the two thirds majority required. As a result the annual $740 billion National Defense Authorization Act to fund the military in 2021 will become law. Mr Trump had called the result, which was expected, a "disgraceful act of cowardice" and the Republican leadership in Congress "weak". The bill will provide a three per cent pay raise for US troops and included elements relating to defence policy, troop levels, weapons systems and military construction. Mr Trump had vetoed it, arguing it allowed for the renaming of military bases that honour Confederate generals, and that it limited his ability to bring troops home from Afghanistan and Germany. He also tried to link passage of the bill to measures targeting social media companies. Throughout Mr Trump's term Republican senators had been highly reluctant to break so publicly with him. He had vetoed eight previous bills and none were overridden. But with less than three weeks left in office Mr Trump's influence with Republican senators appeared to have receded markedly. Mitch McConnell, the Republican leader in the Senate, said: "It's time for us to deliver this bill. It's our chance to remind brave service members and their families that we have their backs." It came as Republicans also faced a deepening split over Mr Trump's last ditch attempt to overturn the US presidential election result. Over 140 Republicans in the House of Representatives may be ready to back a move not to certify the outcome at a joint session of Congress on Jan 6, it emerged. But even with that level of support the attempt to block the result still had no chance of success. Mr McConnell privately urged colleagues to accept the election result, and called his own vote on Jan 6 the "most consequential I have ever cast". In an open letter Ben Sasse, the Republican senator from Nebraska, accused colleagues of "playing with fire". He said: "Lets be clear what is happening here. We have a bunch of ambitious politicians who think theres a quick way to tap into the presidents populist base without doing any real, long-term damage. But theyre wrong. "Adults dont point a loaded gun at the heart of legitimate self-government." The move to oppose the election results was ignited by Josh Hawley, a Republican senator from Missouri. He will object, forcing a two-hour debate, followed by a vote in the Senate, and in the House of Representatives. The session in Congress will take place a day after two run-off races in Georgia, which will determine whether Republicans or Democrats control the Senate. David Perdue, one of two Republican candidates, announced he would spend the final days of the campaign in quarantine after possible exposure to the coronavirus. Meanwhile, it emerged that staffing changes were to be made to the Secret Service's presidential detail when Joe Biden takes office on Jan 20. Mr Biden's camp was said to have expressed concerns that current agents might be politically supportive of Mr Trump. Mr Trump cut short a trip to Florida and headed back to Washington on New Year's Eve. In a New Year video message he hailed "historic victories" on the economy and fighting the pandemic. He said: "We have to be remembered for what's been done." In the final weeks of his term the president was also facing an ongoing battle with Republicans in Congress, including Mr McConnell, after he called for an increase in stimulus cheques to Americans. He also faced growing friction with Iran.

View original post here:
Congress overrides Donald Trump's veto of a defense policy bill in the first such rebuke of his presidency - Yahoo News

This article was originally published here

Adv Exp Med Biol. 2021 Jan 1. doi: 10.1007/5584_2020_613. Online ahead of print.

ABSTRACT

COVID-19 is the current day pandemic that has claimed around 1,054,604 lives globally till date. Moreover, the number of deaths is going to increase over the next few months until the pandemic comes to an end, and a second wave has also been reported in few countries. Most interestingly, the death rate among certain populations from the same COVID-19 infection is highly variable. For instance, the European populations show a very high death rate, in contrast to the populations from Chinese ethnicities. Amongst all the closed cases with an outcome (total recovered + total died), the death rate in Italy is 13%, Iran is 6%, China is 5%, Brazil is 3%, The United States of America is 2%, India 2%, Israel is 1% as of October 08, 2020. However, the percentage was higher during the early phase of the pandemic. Moreover, the global death rate amongst all the patients with an outcome is 4%. Here we have reviewed virus-transmitted various respiratory tract infections and postulated a better understanding of SARS-CoV2 using lung stem cell organoids in vitro. Hence, here we propose the strategies of understanding first the infectivity/severity ratio of COVID-19 infections using various ethnicity originated induced pluripotent stem cell-derived lung stem cell organoids in vitro. The greater the infectivity to severity ratio, the better the disease outcome with the value of 1 being the worst disease outcome. This strategy will be useful for understanding the infectivity/severity ratio of virus induced respiratory tract infections for a possible betterment of community-based disease management. Also, such a strategy will be useful for screening the effect of various antiviral drugs/repurposed drugs for their efficacy in vitro.

PMID:33385178 | DOI:10.1007/5584_2020_613

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Induced Pluripotent Stem Cell Derived Human Lung Organoids to Map and Treat the SARS-CoV2 Infections In Vitro - DocWire News

Indore: After being jolted by governments decision to shift State Organ and Tissue Transplant Organisation (SOTTO) to Bhopal, Indore Organ Donation Society headed by divisional commissioner and MGM Medical College dean have restarted the organ donation drive in the city as an attempt to bring back the centre in city.

They have asked private hospitals to inform them about the brain stem cell death patients. Moreover, hospitals have also been directed to send monthly data on deaths that took place in the ICU of their hospitals in given format, which mentioned the reason of death, brain stem cell death declaration, and counselling of family members.

We have taken measures to restart organ donation drive in the city, which has hit Covid hurdle. We have asked hospitals to immediately inform about brain stem cell death of patients so that their families can be counselled and lives of others can be saved, MGM Medical College dean Dr Sanjay Dixit said.

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Madhya Pradesh: Organ donation drive pushed further in Indore, hospitals directed to inform about brain stem cell death patients immediately - Free...

Indore:

After being jolted by the governments decision to shift the State Organ and Tissue Transplant Organisation (SOTTO) to Bhopal, Indore Organ Donation Society and the appropriate authorities have started initiatives to restart the organ donation drive as an attempt to bring back the centre to the city.

Following the same, Dean and Appropriate Authority of Mahatma Gandhi Memorial Medical College has directed all the private hospitals to necessarily inform about the brain stem cell death patients.

Moreover, hospitals have also been directed to send monthly data on the deaths that take place in the ICU of their hospitals, brain stem cell death declaration, and counselling of the family members.

Instructions have been passed to 35 hospitals of the city including Bombay Hospital, Apollo Hospital, Medanta Hospital, CHL Hospital, Choithram Hospital, and others.

Hospitals have to send the signed scanned copy and soft copy in a given format on the first week of every month so that the authorities can learn about the deaths in ICUs of hospitals and identify the reason as to why brain stem cell death couldnt be identified or informed.

Yes, we have been taking various measures to restart the organ donation drive in the city which has hit a hurdle due to the Covid crisis. We have asked the hospitals to immediately inform about the brain stem cell death of patients so that their families can be counselled and the lives of others could be saved, Dean of MGM Medical College Dr Sanjay Dixit said.

Meanwhile, various organisations and NGOs continued their protest against the government decision of shifting SOTTO to Bhopal from Indore and said that Indore is leading city in Central India and shifting SOTTO would hit Indores ongoing drive for organ donation.

As many as 39 green corridors were formed in the city since 2015 to transport vital organs in the city and to different states to save the lives of many people.

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Indore: In a bid to push organ donation, h ospitals directed to intimate about brain stem cell deaths - Free Press Journal