tbuckley/cabot-search huggingface dataset:
Effects of physical education interventions on cognition and academic performance outcomes in children and adolescents: a systematic review and meta-analysis
Authors: Antonio García-Hermoso, Robinson Ramírez-Vélez, David Revalds Lubans, Mikel Izquierdo
Journal: British Journal of Sports Medicine (2021)

Objective To determine the effects of interventions aimed at optimising the quantity and quality of physical education (PE) on cognition and academic performance in children and adolescents. Design A systematic review and meta-analysis. Data sources Studies from electronic databases from inception to 3 January 2021 were identified. Eligibility criteria for selecting studies Experimental studies that assessed the effect of quantity-based (ie, increasing the amount of curriculum time allocated to PE) or quality-based (ie, increasing students’ participation in physical activity during PE) PE interventions, or both, on changes in cognition and/or academic performance in youth (aged 5–18 years) were included. Results 19 trials comprising 8676 youth (46.5% girls) were included. Individual quality-based PE interventions increased cognition performance (Hedges’ g=0.38, 95% CI 0.15 to 0.60; I 2 =83.70%), mainly in primary education settings (g=0.48, 95% CI 0.07 to 0.89; I 2 =90.43%). Academic performance, principally mathematics-related skills, was also increased by quality-based PE interventions (g=0.15, 95% CI 0.06 to 0.24; I 2 =41.75%). Among these interventions, teaching strategies favoured similar results, but without heterogeneity in the results (g=0.12, 95% CI 0.05 to 0.18; I 2 =0%). In contrast, quantity-based PE interventions had a very small and non-significant effect on academic performance (g=0.09, 95% CI −0.05 to 0.24; Q=11.65; I 2 =48.48%). Finally, there were no differences between the three PE interventions (ie, quantity, quality, and combined PE interventions) in regard to academic performance. Conclusion Improving the quality of PE classes may improve students’ cognition and academic performance in children and adolescents. Importantly, allocating more time for PE does not seem to compromise this performance.
Exploring the Refractory Period of an Active Stand in Females With Initial Orthostatic Hypotension
Authors: Nasia A. Sheikh, Shaun Ranada, Karolina Kogut, Kate M. Bourne, Lucy Y. Lei, Robert S. Sheldon, Derek V. Exner, Aaron A. Phillips, Mary Runte, Satish R. Raj
Journal: Journal of the American College of Cardiology (2021)
Abstract 352: The Effect of the Extracellular Matrix of Failing Hearts on Cardiac Stem Cells
Authors: Dawn A Delfín, Joshua DeAguero, Elizabeth N McKown
Journal: Circulation Research (2016)

Objective: Stem cell therapy to repair cardiac damage, caused by the pathological remodeling that occurs in cardiovascular disease, represents a cutting edge therapeutic option toward preventing and treating heart failure. There is a paucity of information on how the phenotypes of stem cells are altered in the “hostile” environment of pathologically remodeled hearts. The objective of this study was to (a) determine the phenotypes of cardiac stem cells cultured on failing versus normal human heart tissue, and (b) to characterize pathology of failing human heart samples. Methods: We isolated the extracellular matrix (ECM) from end-stage failing human hearts (compared to control human hearts) and used the isolated ECM to coat tissue culture plates. The ECM represents the scaffold of the heart in which stem cells will integrate, proliferate, and differentiate. We then cultured induced pluripotent stem cell-derived cardiac progenitor cells on the cardiac-ECM plates and analyzed their phenotypes (morphology, differentiation into cardiomyocytes, and gene expression). We also performed analysis of the failing cardiac tissue itself to determine the extent of fibrosis and expression of various ECM and matricellular proteins. Results: Cells cultured on failing heart ECM showed important differences compared to those on control heart ECM, including reduced cell-matrix adhesion and altered responses to beta-adrenergic stimulation. The failing heart shows increased fibrosis and differential expression of specific ECM and matricellular proteins. Significance: We will use these data to determine how best to direct cardiac stem cells used for tissue generation in severely damaged hearts toward differentiation into functioning cardiomyocytes.
Information technology aspects of large-scale implementation of automated surveillance of healthcare-associated infections
Authors: Michael Behnke, John Karlsson Valik, Sophie Gubbels, Daniel Teixeira, Brian Kristensen, Mohamed Abbas, Stephanie M. van Rooden, Petra Gastmeier, Maaike S.M. van Mourik, Maaike S.M. van Mourik, Stephanie M. van Rooden, Mohamed Abbas, Olov Aspevall, Pascal Astagneau, Marc J.M. Bonten, Elena Carrara, Aina Gomila-Grange, Sabine C. de Greeff, Sophie Gubbels, Wendy Harrison, Hilary Humphreys, Anders Johansson, Mayke B.G. Koek, Brian Kristensen, Alain Lepape, Jean-Christophe Lucet, Siddharth Mookerjee, Pontus Naucler, Zaira R. Palacios-Baena, Elisabeth Presterl, Miquel Pujol, Jacqui Reilly, Christopher Roberts, Evelina Tacconelli, Daniel Teixeira, Thomas Tängdén, John Karlsson Valik, Michael Behnke, Petra Gastmeier
Journal: Clinical Microbiology and Infection (2021)

Healthcare-associated infections (HAI) are a major public health concern. Monitoring of HAI rates, with feedback, is a core component of infection prevention and control programmes. Digitalization of healthcare data has created novel opportunities for automating the HAI surveillance process to varying degrees. However, methods are not standardized and vary widely between different healthcare facilities. Most current automated surveillance (AS) systems have been confined to local settings, and practical guidance on how to implement large-scale AS is needed.This document was written by a task force formed in March 2019 within the PRAISE network (Providing a Roadmap for Automated Infection Surveillance in Europe), gathering experts in HAI surveillance from ten European countries.The document provides an overview of the key e-health aspects of implementing an AS system of HAI in a clinical environment to support both the infection prevention and control team and information technology (IT) departments. The focus is on understanding the basic principles of storage and structure of healthcare data, as well as the general organization of IT infrastructure in surveillance networks and participating healthcare facilities. The fundamentals of data standardization, interoperability and algorithms in relation to HAI surveillance are covered. Finally, technical aspects and practical examples of accessing, storing and sharing healthcare data within a HAI surveillance network, as well as maintenance and quality control of such a system, are discussed.With the guidance given in this document, along with the PRAISE roadmap and governance documents, readers will find comprehensive support to implement large-scale AS in a surveillance network.
Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer
Authors: Claudia Enriquez, Valeria Cancila, Renata Ferri, Roberta Sulsenti, Irene Fischetti, Matteo Milani, Paola Ostano, Ilaria Gregnanin, Maurizia Mello-Grand, Enrico Berrino, Marco Bregni, Giuseppe Renne, Claudio Tripodo, Mario P. Colombo, Elena Jachetti
Journal: Cancer Research (2021)

Fatal neuroendocrine differentiation (NED) of castration-resistant prostate cancer is a recurrent mechanism of resistance to androgen deprivation therapies (ADT) and antiandrogen receptor pathway inhibitors (ARPI) in patients. The design of effective therapies for neuroendocrine prostate cancer (NEPC) is complicated by limited knowledge of the molecular mechanisms governing NED. The paucity of acquired genomic alterations and the deregulation of epigenetic and transcription factors suggest a potential contribution from the microenvironment. In this context, whether ADT/ARPI induces stromal cells to release NED-promoting molecules and the underlying molecular networks are unestablished. Here, we utilized transgenic and transplantable mouse models and coculture experiments to unveil a novel tumor-stroma cross-talk that is able to induce NED under the pressure of androgen deprivation. Castration induced upregulation of GRP78 in tumor cells, which triggers miR29-b-mediated downregulation of the matricellular protein SPARC in the nearby stroma. SPARC downregulation enabled stromal cells to release IL6, a known inducer of NED. A drug that targets GRP78 blocked NED in castrated mice. A public, human NEPC gene expression dataset showed that Hspa5 (encoding for GRP78) positively correlates with hallmarks of NED. Finally, prostate cancer specimens from patients developing local NED after ADT showed GRP78 upregulation in tumor cells and SPARC downregulation in the stroma. These results point to GRP78 as a potential therapeutic target and to SPARC downregulation in stromal cells as a potential early biomarker of tumors undergoing NED. SIGNIFICANCE: Tumor-stroma cross-talk promotes neuroendocrine differentiation in prostate cancer in response to hormone therapy via a GRP78/SPARC/IL6 axis, providing potential therapeutic targets and biomarkers for neuroendocrine prostate cancer.
Oncolytic Reovirus Sensitizes Multiple Myeloma Cells to Anti-PD-L1 Therapy
Authors: Kevin R Kelly, Claudia M Espitia, Weiguo Zhao, Kaijin Wu, Valeria Visconte, Faiz Anwer, Christine M Calton, Jennifer S. Carew, Steffan T. Nawrocki
Journal: Blood (2017)
Deubiquitinases Modulate ACE2 in SARS-CoV-2 ARDS
Authors: J. S. Bednash, J. D. Londino, R. K. Mallampalli
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency. Respiratory failure and the acute respiratory distress syndrome (ARDS) are primary drivers of mortality in COVID-19. Currently, therapeutic options to treat COVID-19 and prevent development of ARDS are limited. To address this issue, we will examine the role of deubiquitinases (DUBs), key enzymes that remove ubiquitin from proteins, in SARS-CoV-2 ARDS. Ubiquitination marks proteins for degradation or modulates function. The role of DUBs in ARDS, and specifically SARS-CoV-2 ARDS, has not been examined. Our hypothesis is that DUBs play a central role in SARS-CoV-2 ARDS pathogenesis, through regulation of host innate immune responses and specific targeting of ACE2, a membrane protein required for SARS-CoV-2 entry. To facilitate these studies, we have established a biorepository containing human samples from COVID-19+ patients with and without ARDS. We have performed RNA sequencing of peripheral blood mononuclear cell (PBMC) samples and note differential expression of several putative DUB targets that may drive ARDS pathogenesis in SARS-CoV-2. We demonstrate that ACE2 is ubiquitinated and identify key amino acids that regulate ubiquitination. Finally, we establish a novel interaction between a DUB protein and ACE2. These studies investigate novel mechanisms of ARDS pathogenesis in SARS-CoV-2 infection. Ultimately, we aim to identify potential targets in SARS-CoV-2 infection and for future novel coronaviridae.
CAR-HEMATOTOX: a model for CAR T-cell–related hematologic toxicity in relapsed/refractory large B-cell lymphoma
Authors: Kai Rejeski, Ariel Perez, Pierre Sesques, Eva Hoster, Carolina Berger, Liv Jentzsch, Dimitrios Mougiakakos, Lisa Frölich, Josephine Ackermann, Veit Bücklein, Viktoria Blumenberg, Christian Schmidt, Laurent Jallades, Boris Fehse, Christoph Faul, Philipp Karschnia, Oliver Weigert, Martin Dreyling, Frederick L. Locke, Michael von Bergwelt-Baildon, Andreas Mackensen, Wolfgang Bethge, Francis Ayuk, Emmanuel Bachy, Gilles Salles, Michael D. Jain, Marion Subklewe
Journal: Blood (2021)
Two novel strategies to overcome the resistance to ALK tyrosine kinase inhibitor drugs: Macrocyclic inhibitors and proteolysis‐targeting chimeras
Authors: Xiaoling Song, Hui Zhong, Xiaojuan Qu, Linsong Yang, Biao Jiang
Journal: MedComm (2021)

Lung cancer is the most malignant tumor in the worldwide. About 3%-5% non-small cell lung cancer (NSCLC) patients carry anaplastic lymphoma kinase (ALK) gene fusions and receive great benefits from ALK-targeted therapy. However, drug resistance inevitably occurs even with the most potent inhibitor drug lorlatinib. About half of the resistance are caused by alteration in ALK proteins for earlier ALK TKI drugs and near one-third of loratinib resistant cases are caused by compound mutations without current effective treatment strategy in clinic. Novel strategies are in great need to overcome drug resistance. Lately, two novel strategies have been developed and attracted great attentions for their potentials to overcome drug resistance problems: (1) developed small compact macrocyclic ALK kinase inhibitors and (2) developed ALK targeted proteolysis-targeting chimera (PROTAC) drugs. The macrocyclic molecules are small and compact in size, brain barrier permeable, and highly potent against lorlatinib-resistant compound mutations. Developed ALK targeted PROTAC molecules could degrade oncogenic ALK driver proteins. Some showed superiority in killing ALK positive cancer cells and inhibiting the growth of cells expressing G1202R resistant ALK proteins comparing to inhibitor drugs. The update on these two treatment strategies was reviewed.
On the Mechanisms of Biliary Flux
Authors: Nachiket Vartak, Dirk Drasdo, Fabian Geisler, Tohru Itoh, Ronald P J Oude Elferink, Stan F J van de Graaf, John Chiang, Verena Keitel, Michael Trauner, Peter Jansen, Jan G Hengstler
Journal: Hepatology (2021)

Since the late 1950s, transport of bile in the liver has been described by the “osmotic concept,” according to which bile flows into the canaliculi toward the ducts, countercurrent to the blood flow in the sinusoids. However, because of the small size of canaliculi, it was so far impossible to observe, let alone to quantify this process. Still, “osmotic canalicular flow” was a sufficient and plausible explanation for the clearance characteristics of a wide variety of choleretic compounds excreted in bile. Imaging techniques have now been established that allow direct flux analysis in bile canaliculi of the intact liver in living organisms. In contrast to the prevailing osmotic concept these analyses strongly suggest that the transport of small molecules in canalicular bile is diffusion dominated, while canalicular flow is negligibly small. In contrast, with the same experimental approach, it could be shown that in the interlobular ducts, diffusion is augmented by flow. Thus, bile canaliculi can be compared to a standing water zone that is connected to a river. The seemingly subtle difference between diffusion and flow is of relevance for therapy of a wide range of liver diseases including cholestasis and NAFLD. Here, we incorporated the latest findings on canalicular solute transport, and align them with extant knowledge to present an integrated and explanatory framework of bile flux that will undoubtedly be refined further in the future.
Covid-19: US doctors suggest new ways to target vaccine hesitancy
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

President Biden admitted on 22 June that the US would miss the target of vaccinating 70% of adults by the 4 July holiday, but he continued his push to increase the vaccination rate. Experts at Johns Hopkins Bloomberg School of Public Health suggested ways to vaccinate people who were hesitant, such as allowing family groups to be vaccinated at the same time rather than by age.

Although covid-19 is killing more people worldwide this year than in 2020, vaccine hesitancy in the US means that fewer people are receiving the vaccine every day—only about 300 000 per day compared with nearly 2 million a day in early April.1 Nearly 66% of people aged 18 or older—over 178 million—have received at least one dose of the vaccine, including more than …
Secukinumab for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis: Physical and pharmacological properties underlie the observed clinical efficacy and safety
Authors: Frank Kolbinger, Franco Di Padova, Atul Deodhar, Jason E. Hawkes, Christine Huppertz, Torsten Kuiper, Iain B. McInnes, Christopher T. Ritchlin, David Rosmarin, Georg Schett, José M. Carballido, Peter Häusermann, Claudio Calonder, Beate Vogel, Jean-Michel Rondeau, Gerard Bruin
Journal: Pharmacology & Therapeutics (2021)

Psoriasis, psoriatic arthritis, and axial spondyloarthritis are systemic inflammatory diseases, each commonly manifesting as a spectrum of symptoms, complications, and comorbidities that arise differently in individual patients. Drugs targeting inflammatory cytokines common to the pathogenesis of each of these conditions have been developed, although their specific actions in the different tissues involved are variable. For a drug to be effective, it must be efficiently delivered to and locally bioactive in disease-relevant tissues. Detailed clinical data shed light on the therapeutic effects of individual biologics on specific domains or clinical manifestations of disease and assist in guiding treatment decisions. Pharmacologic, molecular, and functional properties of drugs strongly impact their observed safety and efficacy, and an understanding of these properties provides complementary insight. Secukinumab, a fully human monoclonal IgG1/κ antibody selectively targeting interleukin (IL)-17A, has been in clinical use for >6 years in the treatment of moderate to severe psoriasis, psoriatic arthritis, and both radiographic (also known as ankylosing spondylitis) and nonradiographic axial spondyloarthritis. In this review, we discuss pharmacokinetic and pharmacodynamic data for secukinumab to introduce clinicians to the pharmacological properties of this widely used drug. Understanding how these properties affect the observed clinical efficacy, safety, and tolerability of this drug in the treatment of IL-17A-mediated systemic inflammatory diseases is important for all physicians treating these conditions.
The Cell in Development and Inheritance.
Journal: JAMA (1900)

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Abstract 400: Advanced Cardiac Life Support Taught in a Transitional Medical School Course Improves Retention: A Prospective Cohort Study
Authors: Lindsey R Mitrani, Lauren J Sanderson, Rachel J Gordon, Julia E Iyasere
Journal: Circulation (2019)

Introduction: Advanced cardiac life support (ACLS) is taught in a two-day course. Studies show decay in retention of ACLS starting at 3 months, while repeat simulation may improve performance. Hypothesis: We hypothesize that teaching ACLS using a low-dose, spaced curriculum will improve retention of knowledge and skills. Methods: In March and April 2018, we collaborated with the AHA to incorporate ACLS training into Ready 4 Residency (R4R), a month-long course for 4 th year medical students meeting course completion requirements for ACLS. In September 2018, we consented interns, who completed traditional ACLS or ACLS in R4R. Interns completed 20 multiple-choice questions, two minutes of compressions, and one minute of ventilations for a 20-dollar gift card. Student’s t-test, chi-squared, and Fisher’s exact tests were used for statistical analyses. Results: Of 28 participants, 18 had completed traditional ACLS, and 10 had completed ACLS in R4R. For the 20-question exam, the results were 13.90 +/- 2.81 in ACLS in R4R compared to 13.83 +/- 2.38 in traditional ACLS (p = 0.95). Interns who completed ACLS in R4R performed an average rate of compressions at 111 +/- 10.3 compared to traditional ACLS for a rate of 122.89 +/- 11.05 (p=0.013), table 1. For interns who completed ACLS in R4R, 50% completed rescue breaths in range compared to 0% interns who completed traditional ACLS (p = 0.002), table 2. Conclusions: Integration of low-dose, spaced ACLS training for 4 th year medical students may improve retention of skills. Since interns are frequently ‘first-responders’ during in-hospital arrest, improved ACLS skills may improve resuscitation outcomes.
Abstract 211: ATF6 and the Adaptive ER Stress Response Enhances Proliferation and Viability in Mouse Cardiac Stem Cells
Authors: Winston T Stauffer, Shirin Doroudgar, Haley N Stephens, Brandi Bailey, Christopher C Glembotski
Journal: Circulation Research (2016)

Rationale: Cardiac stem cells (CSCs) are beneficial when administered to infarcted mouse or rat hearts. Though the mechanism of these benefits is unknown, CSC vitality likely plays a major role. Thus, investigating the factors governing CSC survival in the ischemic heart may lead to more effective therapeutic strategies. Our previous studies showed that misfolded proteins accumulate in the sarco/endoplasmic reticulum (SR/ER) of the ischemic heart. The transcription factor, ATF6, is a key component of the adaptive ER stress response because it induces genes that reduce the accumulation of misfolded proteins, improving myocyte survival during ischemic stress. While our lab has shown that, in cardiac myocytes, ATF6 is cardioprotective in the ischemic heart, neither the ER stress response nor ATF6 have been examined in CSCs. We hypothesize that ATF6 and the adaptive ER stress response are critical for optimal survival of CSCs. Objective/Methods: To gauge the relevance of the ER stress response in CSCs, we used MTT assays to compare the viabilities of mouse CSCs to neonatal rat ventricular myocytes (NRVM) subjected to treatments that mimic ischemic ER stress in the heart. We also assessed the effect of inhibiting ATF6 on both the ER stress response and CSC viability by using chemical inhibition of ATF6 activation or siRNA-mediated ATF6 knock down. Results: We found that, compared to NRVM, CSCs exhibited lower levels of adaptive ER stress response gene expression and decreased viability in response to ER stress. Thus, relative to NRVM, the adaptive ER stress response is not fully developed in CSCs. We also found that either chemical inhibition of ATF6 activation or ATF6 knock down decreased adaptive ER stress response gene expression. Strikingly, ATF6 inhibition or knockdown decreased CSC viability and cell number by as much as 70%. Conclusions: Thus, compared to cardiac myocytes, CSCs exhibit a reduced adaptive ER stress response and are more sensitive to ER stress, suggesting that enhancement of the ATF6-mediated adaptive ER stress response in CSCs may be a viable therapeutic approach for enhancing stem cell-mediated myocardial repair.
Vericiguat in patients with atrial fibrillation and heart failure with reduced ejection fraction: insights from the <scp>VICTORIA</scp> trial
Authors: Piotr Ponikowski, Wendimagegn Alemayehu, Ali Oto, M. Cecilia Bahit, Ebrahim Noori, Mahesh J. Patel, Javed Butler, Justin A. Ezekowitz, Adrian F. Hernandez, Carolyn S.P. Lam, Christopher M. O'Connor, Burkert Pieske, Lothar Roessig, Adriaan A. Voors, Cynthia Westerhout, Paul W. Armstrong
Journal: European Journal of Heart Failure (2021)