tbuckley/cabot-search huggingface dataset:
Erratum. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care 2021;44:390–398
Authors: Anita Jeyam, Helen Colhoun, Stuart McGurnaghan, Luke Blackbourn, Timothy J. McDonald, Colin N.A. Palmer, John A. McKnight, Mark W.J. Strachan, Alan W. Patrick, John Chalmers, Robert S. Lindsay, John R. Petrie, Sandeep Thekkepat, Andrew Collier, Sandra MacRury, Paul M. McKeigue
Journal: Diabetes Care (2021)

The authors report that the following errors occurred in transcribing the results of the statistical computations into the abstract and text. In the Abstract, “insulin dose at …
Discrepancies on the Role of Oxygen Gradient and Culture Condition on Mesenchymal Stem Cell Fate
Authors: Jay R. K. Samal, Vignesh K. Rangasami, Sumanta Samanta, Oommen P. Varghese, Oommen P. Oommen
Journal: Advanced Healthcare Materials (2021)

Over the past few years, mesenchymal stem (or stromal) cells (MSCs) have garnered enormous interest due to their therapeutic value especially for their multilineage differentiation potential leading to regenerative medicine applications. MSCs undergo physiological changes upon in vitro expansion resulting in expression of different receptors, thereby inducing high variabilities in therapeutic efficacy. Therefore, understanding the biochemical cues that influence the native local signals on differentiation or proliferation of these cells is very important. There have been several reports that in vitro culture of MSCs in low oxygen gradient (or hypoxic conditions) upregulates the stemness markers and promotes cell proliferation in an undifferentiated state, as hypoxia mimics the conditions the progenitor cells experience within the tissue. However, different studies report different oxygen gradients and culture conditions causing ambiguity in their interpretation of the results. In this progress report, it is aimed to summarize recent studies in the field with specific focus on conflicting results reported during the application of hypoxic conditions for improving the proliferation or differentiation of MSCs. Further, it is tried to decipher the factors that can affect characteristics of MSC under hypoxia and suggest a few techniques that could be combined with hypoxic cell culture to better recapitulate the MSC tissue niche.
The pleiotropic neuroprotective effects of resveratrol in cognitive decline and Alzheimer’s disease pathology: From antioxidant to epigenetic therapy
Authors: Christian Griñán-Ferré, Aina Bellver-Sanchis, Vanessa Izquierdo, Rubén Corpas, Joan Roig-Soriano, Miguel Chillón, Cristina Andres-Lacueva, Milán Somogyvári, Csaba Sőti, Coral Sanfeliu, Mercè Pallàs
Journal: Ageing Research Reviews (2021)

While the elderly segment of the population continues growing in importance, neurodegenerative diseases increase exponentially. Lifestyle factors such as nutrition, exercise, and education, among others, influence ageing progression, throughout life. Notably, the Central Nervous System (CNS) can benefit from nutritional strategies and dietary interventions that prevent signs of senescence, such as cognitive decline or neurodegenerative diseases such as Alzheimer's disease and Parkinson's Disease. The dietary polyphenol Resveratrol (RV) possesses antioxidant and cytoprotective effects, producing neuroprotection in several organisms. The oxidative stress (OS) occurs because of Reactive oxygen species (ROS) accumulation that has been proposed to explain the cause of the ageing. One of the most harmful effects of ROS in the cell is DNA damage. Nevertheless, there is also evidence demonstrating that OS can produce other molecular changes such as mitochondrial dysfunction, inflammation, apoptosis, and epigenetic modifications, among others. Interestingly, the dietary polyphenol RV is a potent antioxidant and possesses pleiotropic actions, exerting its activity through various molecular pathways. In addition, recent evidence has shown that RV mediates epigenetic changes involved in ageing and the function of the CNS that persists across generations. Furthermore, it has been demonstrated that RV interacts with gut microbiota, showing modifications in bacterial composition associated with beneficial effects. In this review, we give a comprehensive overview of the main mechanisms of action of RV in different experimental models, including clinical trials and discuss how the interconnection of these molecular events could explain the neuroprotective effects induced by RV.
Polycystic ovary syndrome is transmitted via a transgenerational epigenetic process
Authors: Nour El Houda Mimouni, Isabel Paiva, Anne-Laure Barbotin, Fatima Ezzahra Timzoura, Damien Plassard, Stephanie Le Gras, Gaetan Ternier, Pascal Pigny, Sophie Catteau-Jonard, Virginie Simon, Vincent Prevot, Anne-Laurence Boutillier, Paolo Giacobini
Journal: Cell Metabolism (2021)

Polycystic ovary syndrome (PCOS) is the most common reproductive and metabolic disorder affecting women of reproductive age. PCOS has a strong heritable component, but its pathogenesis has been unclear. Here, we performed RNA sequencing and genome-wide DNA methylation profiling of ovarian tissue from control and third-generation PCOS-like mice. We found that DNA hypomethylation regulates key genes associated with PCOS and that several of the differentially methylated genes are also altered in blood samples from women with PCOS compared with healthy controls. Based on this insight, we treated the PCOS mouse model with the methyl group donor S-adenosylmethionine and found that it corrected their transcriptomic, neuroendocrine, and metabolic defects. These findings show that the transmission of PCOS traits to future generations occurs via an altered landscape of DNA methylation and propose methylome markers as a possible diagnostic landmark for the condition, while also identifying potential candidates for epigenetic-based therapy.
Abstract PO030: Understanding the influence of adiposity on the endometrium using human primary endometrial organoids
Authors: Alina R. Murphy, J. Julie Kim
Journal: Clinical Cancer Research (2021)

Abstract Endometrial cancer is the most commonly diagnosed type of gynecological cancer, and obesity is a major risk factor for this disease. Despite rising rates of obesity and endometrial cancer, it is still unclear how obesity alters the benign endometrium and the endometrial hormonal response to promote carcinogenesis. We used an endometrial organoid model to investigate how adiposity predisposes women to develop endometrial cancer. We hypothesized that increased adiposity would directly alter endometrial gene expression and diminish the protective progesterone response of the benign endometrium. Scaffold-free, three-dimensional endometrial organoids consisting of both epithelial and stromal cells from benign endometrial tissue were generated. Organoids were cocultured with different numbers of adipocyte spheroids to represent different levels of adiposity and were treated with a menstrual cycle level of hormones (E2 + P4 +T) over 14 days. Endometrial organoid gene expression was investigated using RNA-seq. Coculturing endometrial organoids with 30 adipocyte spheroids in the presence of E2, P4, and T caused significant differential expression of pathways involved in metabolism, angiogenesis, chromatin modification, and metal ion response, compared to endometrial organoids cultured without adipocyte spheroids. We investigated the metal ion response pathways that were altered and found that many of the most significantly differentially regulated genes in the metal ion response pathways belonged to the metallothionein (MT) family of genes. The expression of MT1A, MT1M, MT1X, and MT2A decreased approximately 50% in endometrial organoids cocultured with 30 adipocyte spheroids. Furthermore, although the results were not statistically significant, we observed a downregulation of the progesterone-responsive genes HSD17B2, IGFBP1, PAEP, PRL, FOXO1, and SPP1 in the endometrial organoids cultured with 30 adipocyte spheroids. Our results show that culturing endometrial organoids in conditions of increased adiposity alters endometrial gene expression and may change the way the endometrium responds to progesterone. Metallothioneins, which are downregulated in the presence of adipocyte spheroids, are important modulators of zinc and copper ions and reactive oxygen species in the cell. Progesterone plays an important protective role against endometrial cancer. In summary, our data show that adipocytes may influence the progesterone response of the benign endometrium. Further investigation into the role of progesterone-driven metallothioneins in the endometrium is currently underway. Citation Format: Alina R. Murphy, J. Julie Kim. Understanding the influence of adiposity on the endometrium using human primary endometrial organoids [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PO030.
Racial Differences in Rates of Traumatic Lumbar Puncture—Reply
Authors: Scott C. Howard, Alberto J. de Armendi, Ching-Hon Pui
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Model-based multi-parameter mapping
Authors: Yaël Balbastre, Mikael Brudfors, Michela Azzarito, Christian Lambert, Martina F. Callaghan, John Ashburner
Journal: Medical Image Analysis (2021)

Quantitative MR imaging is increasingly favoured for its richer information content and standardised measures. However, computing quantitative parameter maps, such as those encoding longitudinal relaxation rate (R1), apparent transverse relaxation rate (R2*) or magnetisation-transfer saturation (MTsat), involves inverting a highly non-linear function. Many methods for deriving parameter maps assume perfect measurements and do not consider how noise is propagated through the estimation procedure, resulting in needlessly noisy maps. Instead, we propose a probabilistic generative (forward) model of the entire dataset, which is formulated and inverted to jointly recover (log) parameter maps with a well-defined probabilistic interpretation (e.g., maximum likelihood or maximum a posteriori). The second order optimisation we propose for model fitting achieves rapid and stable convergence thanks to a novel approximate Hessian. We demonstrate the utility of our flexible framework in the context of recovering more accurate maps from data acquired using the popular multi-parameter mapping protocol. We also show how to incorporate a joint total variation prior to further decrease the noise in the maps, noting that the probabilistic formulation allows the uncertainty on the recovered parameter maps to be estimated. Our implementation uses a PyTorch backend and benefits from GPU acceleration. It is available at https://github.com/balbasty/nitorch.
Emerging views of statin pleiotropy and cholesterol lowering
Authors: Dongbo Yu, James K Liao
Journal: Cardiovascular Research (2021)

Abstract Over the past four decades, no class of drugs has had more impact on cardiovascular health than the 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors or statins. Developed as potent lipid-lowering agents, statins were later shown to reduce morbidity and mortality of patients who are at risk for cardiovascular disease. However, retrospective analyses of some of these clinical trials have uncovered some aspects of their clinical benefits that may be additional to their lipid-lowering effects. Such ‘pleiotropic’ effects of statins garnered intense interest and debate over its contribution to cardiovascular risk reduction. This review will provide a brief background of statin pleiotropy, assess the available clinical evidence for and against their non-lipid-lowering benefits, and propose future research directions in this field.
The Effect of Benralizumab On Allergen-Induced Responses In Subjects With Mild Allergic Asthma
Authors: Gail Gauvreau, Roma Sehmi, J. FitzGerald, Richard Leigh, Donald Cockcroft, Beth Davis, Irvin Mayers, Louis-Philippe Boulet, Brittany Salter, Ruth Cusack, Imran Satia, Kieran Killian, Patrick Mitchell, Viktoria Werkstrom, Tomasz Durzynski, Kathryn Shoemaker, Rohit Katial, Maria Jison, Paul Newbold, Paul O'Byrne
Journal: Journal of Allergy and Clinical Immunology (2021)
COVID-19 vaccination for people with severe mental illness: why, what, and how?
Authors: Victor Mazereel, Kristof Van Assche, Johan Detraux, Marc De Hert
Journal: The Lancet Psychiatry (2021)

Psychiatric disorders, and especially severe mental illness, are associated with an increased risk of severe acute respiratory syndrome coronavirus 2 infection and COVID-19-related morbidity and mortality. People with severe mental illness should therefore be prioritised in vaccine allocation strategies. Here, we discuss the risk for worse COVID-19 outcomes in this vulnerable group, the effect of severe mental illness and psychotropic medications on vaccination response, the attitudes of people with severe mental illness towards vaccination, and, the potential barriers to, and possible solutions for, an efficient vaccination programme in this population.
Prospective Development and Validation of the Computerized Adaptive Screen for Suicidal Youth
Authors: Cheryl A. King, David Brent, Jacqueline Grupp-Phelan, T. Charles Casper, J. Michael Dean, Lauren S. Chernick, Joel A. Fein, E. Melinda Mahabee-Gittens, Shilpa J. Patel, Rakesh D. Mistry, Susan Duffy, Marlene Melzer-Lange, Alexander Rogers, Daniel M. Cohen, Allison Keller, Rohit Shenoi, Robert W. Hickey, Margaret Rea, Mary Cwik, Kent Page, Taylor C. McGuire, Jiebiao Wang, Robert Gibbons, Dale Woolridge, Marie Kay, Michelle Robinson, Casey Evans, Heather Gramse
Journal: JAMA Psychiatry (2021)

The rate of suicide among adolescents is rising in the US, yet many adolescents at risk are unidentified and receive no mental health services. To develop and independently validate a novel computerized adaptive screen for suicidal youth (CASSY) for use as a universal screen for suicide risk in medical emergency departments (EDs). Study 1 of this prognostic study prospectively enrolled adolescent patients at 13 geographically diverse US EDs in the Pediatric Emergency Care Applied Research Network. They completed a baseline suicide risk survey and participated in 3-month telephone follow-ups. Using 3 fixed Ask Suicide-Screening Questions items as anchors and additional items that varied in number and content across individuals, we derived algorithms for the CASSY. In study 2, data were collected from patients at 14 Pediatric Emergency Care Applied Research Network EDs and 1 Indian Health Service hospital. Algorithms were independently validated in a prospective cohort of adolescent patients who also participated in 3-month telephone follow-ups. Adolescents aged 12 to 17 years were consecutively approached during randomly assigned shifts. Presentation at an ED. A suicide attempt between ED visit and 3-month follow-up, measured via patient and/or parent report. The study 1 CASSY derivation sample included 2075 adolescents (1307 female adolescents [63.0%]; mean [SD] age, 15.1 [1.61] years) with 3-month follow-ups (72.9% retention [2075 adolescents]). The study 2 validation sample included 2754 adolescents (1711 female adolescents [62.1%]; mean [SD] age, 15.0 [1.65] years), with 3-month follow-ups (69.5% retention [2754 adolescents]). The CASSY algorithms had excellent predictive accuracy for suicide attempt (area under the curve, 0.89 [95% CI, 0.85-0.91]) in study 1. The mean number of adaptively administered items was 11 (range, 5-21). At a specificity of 80%, the CASSY had a sensitivity of 83%. It also demonstrated excellent accuracy in the study 2 validation sample (area under the curve, 0.87 [95% CI, 0.85-0.89]). In this study, the CASSY had a sensitivity of 82.4% for prediction of a suicide attempt at the 80% specificity cutoff established in study 1. In this study, the adaptive and personalized CASSY demonstrated excellent suicide attempt risk recognition, which has the potential to facilitate linkage to services.
Integrated Patterning Programs During <i>Drosophila</i> Development Generate the Diversity of Neurons and Control Their Mature Properties
Authors: Anthony M. Rossi, Shadi Jafari, Claude Desplan
Journal: Annual Review of Neuroscience (2021)

During the approximately 5 days of Drosophila neurogenesis (late embryogenesis to the beginning of pupation), a limited number of neural stem cells produce approximately 200,000 neurons comprising hundreds of cell types. To build a functional nervous system, neuronal types need to be produced in the proper places, appropriate numbers, and correct times. We discuss how neural stem cells (neuroblasts) obtain so-called area codes for their positions in the nervous system (spatial patterning) and how they keep time to sequentially produce neurons with unique fates (temporal patterning). We focus on specific examples that demonstrate how a relatively simple patterning system (Notch) can be used reiteratively to generate different neuronal types. We also speculate on how different modes of temporal patterning that operate over short versus long time periods might be linked. We end by discussing how specification programs are integrated and lead to the terminal features of different neuronal types.
Maximizing Fit for Cloth and Medical Procedure Masks to Improve Performance and Reduce SARS-CoV-2 Transmission and Exposure, 2021
Authors: John T. Brooks, Donald H. Beezhold, John D. Noti, Jayme P. Coyle, Raymond C. Derk, Francoise M. Blachere, William G. Lindsley
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Universal masking is one of the prevention strategies recommended by CDC to slow the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1). As of February 1, 2021, 38 states and the District of Columbia had universal masking mandates. Mask wearing has also been mandated by executive order for federal property* as well as on domestic and international transportation conveyances.
Recent Mumps-Measles-Rubella Vaccination Probably Reduces COVID-19 Severity: A Proposed Strategy For Close-Contacts Of Patients
Authors: Desiree Larenas - Linnemann, Fernanda Rodríguez Monroy
Journal: Journal of Allergy and Clinical Immunology (2021)

several of the proteins produced by the SARS-CoV-2 virus inhibit interferon (IFN) and IFN gene responses, thus abating the innate immune response during the initial infection. Several US and European investigators have reported in the past trained immunity after BCG or measles vaccination: an enhanced non-specific (innate) immune response to non-related pathogens, which for BCG can last a year. However, BCG might be too strong a stimulus which we preferred not to use in the light of the cytokine storm-like syndrome in some patients with advanced COVID-19. during the measles-outbreak Feb-March 2020 we administered the Mumps-Measles-Rubella (MMR) vaccine, of three live-attenuated viruses, to our allergic patients, but with the trained immunity concept in mind, specifically to seemingly healthy, close-contacts of our COVID-19 patients. We asked them to contact the office in case of any COVID-19 symptoms or positive tests. If so, we asked them to monitor thrice daily vital signs, peak expiratory flow rate and pulse oximetry. We used a simplified, out-patient scoring to rate their final COVID-19 severity 382 subjects have received the MMR vaccine, 52 got COVID-19. 12% were 50-59, 12% were 60-75 years old. 18/52 (35%) had one or more risk-factors (-morbid-obesity, diabetes, hypertension) and 3/52 asthma. All had a mild-moderate course; none required supplementary oxygen. One exeption was a 72yo female with previous interstitial lung-disease and 7-day hospitalization due to pneumonia in 2016, who finally deceased due to respiratory insufficiency, but without any other organ impairment. MMR vaccination possibly reduces COVID-19 severity.
Quantitative systems pharmacology model predictions for efficacy of atezolizumab and nab-paclitaxel in triple-negative breast cancer
Authors: Hanwen Wang, Huilin Ma, Richard J Sové, Leisha A Emens, Aleksander S Popel
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immune checkpoint blockade therapy has clearly shown clinical activity in patients with triple-negative breast cancer, but less than half of the patients benefit from the treatments. While a number of ongoing clinical trials are investigating different combinations of checkpoint inhibitors and chemotherapeutic agents, predictive biomarkers that identify patients most likely to benefit remains one of the major challenges. Here we present a modular quantitative systems pharmacology (QSP) platform for immuno-oncology that incorporates detailed mechanisms of immune–cancer cell interactions to make efficacy predictions and identify predictive biomarkers for treatments using atezolizumab and nab-paclitaxel. Methods A QSP model was developed based on published data of triple-negative breast cancer. With the model, we generated a virtual patient cohort to conduct in silico virtual clinical trials and make retrospective analyses of the pivotal IMpassion130 trial that led to the accelerated approval of atezolizumab and nab-paclitaxel for patients with programmed death-ligand 1 (PD-L1) positive triple-negative breast cancer. Available data from clinical trials were used for model calibration and validation. Results With the calibrated virtual patient cohort based on clinical data from the placebo comparator arm of the IMpassion130 trial, we made efficacy predictions and identified potential predictive biomarkers for the experimental arm of the trial using the proposed QSP model. The model predictions are consistent with clinically reported efficacy endpoints and correlated immune biomarkers. We further performed a series of virtual clinical trials to compare different doses and schedules of the two drugs for simulated therapeutic optimization. Conclusions This study provides a QSP platform, which can be used to generate virtual patient cohorts and conduct virtual clinical trials. Our findings demonstrate its potential for making efficacy predictions for immunotherapies and chemotherapies, identifying predictive biomarkers, and guiding future clinical trial designs.
Children With Atopic Dermatitis (AD) Have a High Burden of Atopic Comorbidities: Results From a Large Worldwide Survey
Authors: Jonathan Silverberg, Eric Simpson, Stephan Weidinger, Sébastien Barbarot, Lysel Brignoli, Tarek Mnif, Grece Saba, Laurent Eckert, Ana Rossi, Dimittri Delevry, Puneet Mahajan
Journal: Journal of Allergy and Clinical Immunology (2021)