tbuckley/cabot-search huggingface dataset:
Features of the hemostasis system in patients with non-alcoholic fatty liver disease
Authors: V.I. Didenko, S.L. Melanich, V.B. Yagmur, K.A. Ruban
Journal: GASTROENTEROLOGY (2021)

Background. Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. In recent years, disorders in the hemostasis system, their role in the progression of liver diseases and the development of cardiovascular complications in NAFLD have been actively studied. The purpose was to investigate the features of the hemostasis system in patients with non-alcoholic fatty liver disease. Materials and methods. We examined 36 individuals with NAFLD (20 women and 16 men) aged 29–73 years. All patients underwent an anthropometric, general clinical, biochemical study of blood serum with the determination of platelets, prothrombin time ratio, international normalized ratio, fibrinogen, ultrasound examination of the abdominal cavity organs with elastometry, followed by statistical data processing. Results. Among patients with NAFLD, class 2 obesity and overweight (30.6% each), class 1 obesity (27.8%) prevailed. At the same time, according to the controlled attenuation parameter, 38.9% of people had a severe degree of steatosis, 33.3%— moderate and 27.8%— mild. Regarding the indicators of hemostasis, a significant increase in the level of fibrinogen up to (4.9±0.5) g/l was detected in 44.4% of patients, its severity tended to grow with an increase in the degree of hepatic steatosis. Conclusions. In 44.4% of NAFLD patients, with an increase in the degree of hepatic steatosis, the tendency to hypercoagulability has grown with an increase in fibrinogen content by 1.6 times (p&lt;0.001). Changes in the international normalized ratio, prothrombin time ratio and platelets were determined in isolated cases: more than 83.3% of patients with NAFLD didn’t have violations of these parameters.
Novel microarchitecture of human endometrial glands: implications in endometrial regeneration and pathologies
Authors: Nicola Tempest, Christopher J Hill, Alison Maclean, Kathleen Marston, Simon G Powell, Hannan Al-Lamee, Dharani K Hapangama
Journal: Human Reproduction Update (2021)

Abstract BACKGROUND Human endometrium remains a poorly understood tissue of the female reproductive tract. The superficial endometrial functionalis, the site of embryo implantation, is repeatedly shed with menstruation, and the stem cell-rich deeper basalis is postulated to be responsible for the regeneration of the functionalis. Two recent manuscripts have demonstrated the 3D architecture of endometrial glands. These manuscripts have challenged and replaced the prevailing concept that these glands end in blind pouches in the basalis layer that contain stem cells in crypts, as in the intestinal mucosa, providing a new paradigm for endometrial glandular anatomy. This necessitates re-evaluation of the available evidence on human endometrial regeneration in both health and disease in the context of this previously unknown endometrial glandular arrangement. OBJECTIVE AND RATIONALE The aim of this review is to determine if the recently discovered glandular arrangement provides plausible explanations for previously unanswered questions related to human endometrial biology. Specifically, it will focus on re-appraising the theories related to endometrial regeneration, location of stem/progenitor cells and endometrial pathologies in the context of this recently unravelled endometrial glandular organization. SEARCH METHODS An extensive literature search was conducted from inception to April 2021 using multiple databases, including PubMed/Web of Science/EMBASE/Scopus, to select studies using keywords applied to endometrial glandular anatomy and regeneration, and the references included in selected publications were also screened. All relevant publications were included. OUTCOMES The human endometrial glands have a unique and complex architecture; branched basalis glands proceed in a horizontal course adjacent to the myometrium, as opposed to the non-branching, vertically coiled functionalis glands, which run parallel to each other as is observed in intestinal crypts. This complex network of mycelium-like, interconnected basalis glands is demonstrated to contain endometrial epithelial stem cells giving rise to single, non-branching functionalis glands. Several previous studies that have tried to confirm the existence of epithelial stem cells have used methodologies that prevent sampling of the stem cell-rich basalis. More recent findings have provided insight into the efficient regeneration of the human endometrium, which is preferentially evolved in humans and menstruating upper-order primates. WIDER IMPLICATIONS The unique physiological organization of the human endometrial glandular element, its relevance to stem cell activity and scarless endometrial regeneration will inform reproductive biologists and clinicians to direct their future research to determine disease-specific alterations in glandular anatomy in a variety of endometrial pathological conditions.
WITHDRAWN: Describing the unvaccinated as the main driver of the current COVID-19 situation in Germany should not be based on analyzing pre-pandemic patterns of contacts
Authors: Günter Kampf
Journal: The Lancet Regional Health - Europe (2021)

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been withdrawn at the request of the editor and publisher. The publisher regrets that an error occurred which led to the premature publication of this paper. This error bears no reflection on the content of the article or its author. The publisher apologizes to the author and the readers for this unfortunate error.
Hamstring injury patterns in professional male football (soccer): a systematic video analysis of 52 cases
Authors: Thomas Gronwald, Christian Klein, Tim Hoenig, Micha Pietzonka, Hendrik Bloch, Pascal Edouard, Karsten Hollander
Journal: British Journal of Sports Medicine (2021)

To closely describe the injury inciting events of acute hamstring injuries in professional male football (soccer) using systematic video analysis.Video footage from four seasons (2014-2019) of the two highest divisions in German male football was searched for moderate and severe (ie, time loss of >7 days) acute non-contact and indirect contact match hamstring injuries. Two raters independently categorised inciting events using a standardised procedure to determine specific injury patterns and kinematics.52 cases of hamstring injuries were included for specific pattern analysis. The pattern analysis revealed 25 sprint-related (48%) and 27 stretch-related hamstring injuries (52%). All sprint-related hamstring injuries occured during linear acceleration or high-speed running. Stretch-related hamstring injuries were connected with closed chain movements like braking or stopping with a lunging or landing action and open chain movements like kicking. The kinematic analysis of stretch-related injuries revealed a change of movement involving knee flexion to knee extension and a knee angle of <45° at the assumed injury frame in all open and closed chain movements. Biceps femoris was the most affected muscle (79%) of all included cases.Despite the variety of inciting events, rapid movements with high eccentric demands of the posterior thigh are likely the main hamstring injury mechanism. This study provides important data about how hamstring injuries occur in professional male football and supports the need for demand-specific multicomponent risk reduction programmes.
5. Facilitating Behavior Change and Well-being to Improve Health Outcomes:<i>Standards of Medical Care in Diabetes—2022</i>
Journal: Diabetes Care (2021)

The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
Front Cover: Nuclear Aurora kinase A triggers programmed death‐ligand 1‐mediated immune suppression by activating MYC transcription in triple‐negative breast cancer
Authors: Shulan Sun, Wei Zhou, Xiaoxi Li, Fei Peng, Min Yan, Yajing Zhan, Fan An, Xiaoyan Li, Yunyong Liu, Quentin Liu, Haozhe Piao
Journal: Cancer Communications (2021)

The cover image is based on the Original Article Nuclear Aurora-A triggers programmed death ligand 1 mediated immune suppression by activating MYC transcription in triple-negative breast cancer by Quentin Liu et al., https://doi.org/10.1002/cac2.12190.
Biomarkers of Angiogenesis and Clinical Outcomes to Cabozantinib and Everolimus in Patients with Metastatic Renal Cell Carcinoma from the Phase III METEOR Trial
Authors: Thomas Denize, Subrina Farah, Alessia Cimadamore, Abdallah Flaifel, Emily Walton, Maura A. Sticco-Ivins, Chris Labaki, David A. Braun, Maxine Sun, Evelyn Wang, Wanling Xie, Toni K. Choueiri, Sabina Signoretti
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Antiangiogenic VEGF receptor (VEGFR) inhibitors are approved for metastatic clear cell renal cell carcinoma (mccRCC) and their efficacy is higher in high angiogenic tumors. As cabozantinib inhibits multiple tyrosine kinase receptors, including VEGFRs, we tested whether markers of angiogenesis, including microvascular density (MVD) and mast cell density (MCD), could predict benefit from cabozantinib versus everolimus, using RCC samples from the METEOR (NCT01865747) trial. Experimental Design: MVD and MCD were studied in 430 patients (cabozantinib = 216, everolimus = 214) by double immunohistochemistry for CD31 (vascular marker) and tryptase (mast cell marker) coupled with automated image analysis. Results from evaluable cases (MVD = 360, MCD = 325) were correlated with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Results: MVD was positively correlated with MCD. In the whole cohort, high MVD and high MCD were associated with longer PFS; improved PFS was most evident in patients with high levels of both MCD and MVD. Cabozantinib was associated with improved PFS, OS, and ORR compared with everolimus, irrespective of MVD levels. Cabozantinib was also associated with improved ORR compared with everolimus, irrespective of MCD levels. For PFS and OS, the treatment effect for cabozantinib versus everolimus tended to be greater in tumors with low MCD. Conclusions: High MVD and high MCD are associated with improved outcome in mccRCC but do not predict efficacy to cabozantinib versus everolimus. The high efficacy of cabozantinib in low angiogenic tumors allows us to speculate that its antitumor activity is not exclusively mediated by VEGFR inhibition.
Prediction models in CMI
Authors: Leonard Leibovici, Jesús Rodríguez-Baño, Roy F. Chemaly, Sally Cutler, Angela Huttner, Andre C. Kalil, Mariska Leeflang, Gerard Lina, Mical Paul, Luigia Scudeller, Panayotis T. Tassios, Erlangga Yusuf
Journal: Clinical Microbiology and Infection (2021)
118TiP A multicenter, randomized, double-blind, placebo-controlled phase III trial of camrelizumab plus chemotherapy with or without radiation therapy (RT) as first-line treatment for patients with brain metastatic non-small cell lung cancer (BM-NSCLC; CTONG2003): Trial in progress
Authors: J. Yang, Y. Pan, F. Ning, L. Lin, X. Hu, S. Ma, Q. Yu, C. Wang, X. Wang, R. Ma, X. Zhang, G. Lin, J. Zhao, Y. Chen, J. Cui, G. Wu, N. Yang, Y-L. Wu
Journal: Annals of Oncology (2021)
Abortion Safety and Use with Normally Prescribed Mifepristone in Canada
Authors: Laura Schummers, Elizabeth K. Darling, Sheila Dunn, Kimberlyn McGrail, Anastasia Gayowsky, Michael R. Law, Tracey-Lea Laba, Janusz Kaczorowski, Wendy V. Norman
Journal: New England Journal of Medicine (2021)

In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017.
Race/Ethnicity, Spirometry Reference Equations, and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study
Authors: Arielle Elmaleh-Sachs, Pallavi Balte, Elizabeth C. Oelsner, Norrina B. Allen, Aaron Baugh, Alain G. Bertoni, John L. Hankinson, Jim Pankow, Wendy S. Post, Joseph E. Schwartz, Benjamin M. Smith, Karol Watson, R. Graham Barr
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Normal values for FEV1 and FVC are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. Objectives: To determine whether race/ethnicity-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared with race/ethnicity-neutral equations. Methods: The MESA Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry from 2004 to 2006. Predicted values for spirometry were calculated using race/ethnicity-based equations following guidelines and, alternatively, race/ethnicity-neutral equations without terms for race/ethnicity. Participants were followed for events through 2019. Measurements and Main Results: The mean age of 3,344 participants was 65 years, and self-reported race/ethnicity was 36% White, 25% Black, 23% Hispanic, and 17% Asian. There were 181 incident CLRD-related events and 547 deaths over a median of 11.6 years. There was no evidence that percentage predicted FEV1 or FVC calculated using race/ethnicity-based equations improved the prediction of CLRD-related events compared with those calculated using race/ethnicity-neutral equations (difference in C statistics for FEV1, -0.005; 95% confidence interval [CI], -0.013 to 0.003; difference in C statistic for FVC, -0.008; 95% CI, -0.016 to -0.0006). Findings were similar for mortality (difference in C statistics for FEV1, -0.002; 95% CI, -0.008 to 0.003; difference in C statistics for FVC, -0.004; 95% CI, -0.009 to 0.001). Conclusions: There was no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.
Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox
Authors: David Y. Oh, Lawrence Fong
Journal: Immunity (2021)

Cytotoxic T cells are important effectors of anti-tumor immunity. While tumor killing is ascribed to CD8+ T cell function, pre-clinical and clinical studies have identified intra-tumoral CD4+ T cells that possess cytotoxic programs and can directly kill cancer cells. Cytotoxic CD4+ T cells are found in other disease settings including infection and autoimmunity. Here, we review the phenotypic and functional characteristics of cytotoxic CD4+ T cells in non-cancer and cancer contexts. We conduct a comparative examination of cytolytic mechanisms of cytotoxic CD4+ T cells across disease states and synthesize features that define these cells independent of context. We discuss regulatory mechanisms driving ontogeny and effector function and evidence for the clinical relevance of cytotoxic CD4+ T cells in cancer. In this context, we highlight important gaps in understanding in the biology of cytotoxic CD4+ T cells as well as the potential use of these cells in immunotherapies for specific cancers.
Acute Inferior Myocardial Infarction or Not?
Authors: Desmond B. Jay, Timothy D. Henry, Scott W. Sharkey
Journal: JAMA Internal Medicine (2021)

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A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease
Authors: Hieu T. Nim, Louis Dang, Harshini Thiyagarajah, Daniel Bakopoulos, Michael See, Natalie Charitakis, Tennille Sibbritt, Michael P. Eichenlaub, Stuart K. Archer, Nicolas Fossat, Richard E. Burke, Patrick P. L. Tam, Coral G. Warr, Travis K. Johnson, Mirana Ramialison
Journal: Genome biology (2021)

Abstract Background Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. Results We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis -regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14 , RpS24 , and Rpn8 are associated with heart phenotypes. Conclusions Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis -regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.
Abstract 13071: Supraglottic Airway Devices Are Associated With Asphyxial Physiology Upon Arrival for ECPR in Patients With Refractory OHCA Treated With Prolonged CPR
Authors: Jason Bartos, Arianne Agdamag, Rajat Kalra, Lindsay Nutting, Ralph J Frascone, Aaron M Burnett, Nik Vuljaj, Charles Lick, Peter J Tanghe, Paul Nystrom, Ryan Quinn, Nick Simpson, Bjorn Peterson, Kari Haley, Kevin Sipprell, Demetris Yannopoulos
Journal: Circulation (2021)

Introduction: Multiple clinical trials have failed to show significant differences in survival between use of endotracheal intubation (ETI) and supraglottic airway devices (SGA) in patients with out-of-hospital cardiac arrest (OHCA). However, treatment in these trials was limited to standard ACLS, which favors short duration of CPR. We sought to compare the physiological effect of ETI versus SGA use in patients treated with prolonged CPR and extracorporeal pulmonary resuscitation (ECPR) for refractory ventricular fibrillation/ventricular tachycardia (VT/VF) by the Minnesota Mobile Resuscitation Consortium (MMRC). Methods: Consecutive refractory VT/VF OHCA patients transported by the MMRC to the University of Minnesota for ECPR between 2015 and 2021 were included in this retrospective analysis. Patients were considered ineligible for ECPR if they failed specific arterial blood gas metabolic criteria (lactic acid &gt;18 mmol/L, PaO2 &lt;50 mmHg, and ETCO2 &lt;10 mmHg). Metabolic parameters at presentation and survival were compared between patients receiving ETI and SGA. Results: Among 260 patients (58.0±11.8 years), 46.5% received ETI and 53.5% received SGA. During the index hospitalization, 78/260 (30%) achieved neurologically favorable survival. Compared to those receiving ETI, patients receiving SGA had lower PaO2 (116.8±118.7 versus 135.8±128.3 mmHg, p=0.03), higher PaCO2 (69.7±28.9 versus 60.7±25.6 mmHg, p=0.01), and lower pH (7.00±0.19 versus 7.06±0.21, p=0.008). Significantly more patients who received SGA had PaO2 &lt;50mmHg (29.1% versus 16.9%, respectively; p=0.02) and ≥1 ECPR exclusion criteria (33.1% versus 20.7%, respectively; p=0.03). Among patients excluded for PaO2 &lt;50 mmHg, the presenting PaO2 was 35.5±11.0 mmHg and the presenting PaCO2 was 94.5±26.2 mmHg, suggestive of absence of effective ventilation (asphyxia) at presentation. Survival with CPC 1-2 was 34.7% versus 25.9% for ETI versus SGA, respectively (p=0.12). Conclusion: Use of SGA, during prolonged CPR in refractory VT/VF OHCA, was associated with a significant increase in the proportion of patients presenting with significant hypoxemia and asphyxial physiology, thus increasing ineligibility for ECPR.
Long COVID in children
Authors: Deepti Gurdasani, Athena Akrami, Valerie C Bradley, Anthony Costello, Trisha Greenhalgh, Seth Flaxman, Martin McKee, Susan Michie, Christina Pagel, Sarah Rasmussen, Gabriel Scally, Christian Yates, Hisham Ziauddeen
Journal: The Lancet Child & Adolescent Health (2021)
Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium
Authors: Yong Zhang, Jiayao Chen, Haijun Fu, Shuhong Kuang, Feng He, Min Zhang, Zongshan Shen, Wei Qin, Zhengmei Lin, Shuheng Huang
Journal: International Journal of Oral Science (2021)

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.