Medicine and Health Sciences Commons^™

Tenapanor Improves Abdominal Symptoms Irrespective Of Changes In Complete Spontaneous Bowel Movement Frequency In Adults With Irritable Bowel Syndrome With Constipation, Darren M Brenner, Gregory S Sayuk, Brooks D Cash, Lucinda A Harris, Nitin K Ahuja, Jill K Deutsch, Yang Yang, Suling Zhao, David P Rosenbaum, Anthony J Lembo

2020-Current year OA Pubs

INTRODUCTION: Tenapanor is a first-in-class, minimally absorbed intestinal sodium/hydrogen exchanger isoform 3 inhibitor approved by the US Food and Drug Administration for adults with irritable bowel syndrome with constipation (IBS-C). Pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies examined the effects of tenapanor on abdominal symptoms independent of tenapanor's effect on complete spontaneous bowel movement (CSBM) frequency in adults with IBS-C.

METHODS: This post hoc analysis was performed for patients with no CSBMs in ≥6 of the first 12 weeks of treatment (no-CSBM subgroup). The three-item abdominal score (AS3; the average of …

Genomic Analysis Of 11,555 Probands Identifies 60 Dominant Congenital Heart Disease Genes, Michael C Sierant, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes in 11,555 CHD probands. The results identified 60 genes with a significant burden of heterozygous damaging variants. Variants in these genes accounted for CHD in 10.1% of probands with similar contributions from de novo and transmitted variants in parent-offspring trios that showed incomplete penetrance. DNMs in these genes accounted for 58% of the signal from DNMs. Thirty-three genes were linked to a single CHD subtype while 12 genes were associated with 2 to …

Acute Trem2 Inhibition Depletes Mafb-High Microglia And Hinders Remyelination, Jinchao Hou, Roberta Magliozzi, Yun Chen, Junjie Wu, John Wulf Ii, Gregory Strout, Xiangming Fang, Marco Colonna

2020-Current year OA Pubs

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration in the brain. TREM2 is a receptor that activates microglia, which are crucial for clearing myelin debris and promoting remyelination. Previous studies in a mouse model of demyelination induced by the copper-chelating agent Cuprizone (CPZ) have shown that stimulation of TREM2 with a monoclonal antibody reduces demyelination, while deleting the

Bcl-Xl Protects Ass1-Deficient Cancers From Arginine Starvation-Induced Apoptosis, Prashanta Kumar Panda, Ana Carolina Paschoalini Mafra, Alliny C S Bastos, Li Cao, Maria Serra Bonet, Caitlyn B Brashears, Ethan Yang Chen, Heather M Benedict-Hamilton, William Ehrhardt, John Bomalaski, Carina Dehner, Leonard C Rogers, Toshinao Oyama, Brian A Van Tine

2020-Current year OA Pubs

PURPOSE: Argininosuccinate synthetase 1 (ASS1) silencing in carcinomas and sarcomas leads to a dependence on extracellular arginine for survival. Arginine deprivation therapies, such as PEGylated arginine deiminase (ADI-PEG20), have shown limited effectiveness, which may be due to underlying mechanisms that inhibit apoptosis.

EXPERIMENTAL DESIGN: The effects of ADI-PEG20 on cell-cycle regulation, apoptosis, and BCL-XL-mediated survival pathways in ASS1-deficient cancer cells were determined. The mechanism of cell death protection was determined by assessing caspase and PARP cleavage, CDK2 activity, MCL1 expression, and the interactions among BCL-XL, BAX, and BAK. In vitro synergy was determined, and in vivo efficacy was modeled.

RESULTS: …

Engineering Adhesive Hydrogels For Hemostasis And Vascular Repair, Juya Jeon, Shri Venkatesh Subramani, Kok Zhi Lee, Santiago Elizondo-Benedetto, Mohamed Adel Zayed, Fuzhong Zhang

2020-Current year OA Pubs

Adhesive hydrogels with tunable mechanical properties and strong adhesion to wet, dynamic tissues have emerged as promising materials for tissue repair, with potential applications in wound closure, hemorrhage control, and surgical adhesives. This review highlights the key design principles, material classifications, and recent advances in adhesive hydrogels designed for vascular repair. The limitations of existing adhesive hydrogels, including insufficient mechanical durability, suboptimal biocompatibility, and challenges in targeted delivery, are critically evaluated. Furthermore, innovative strategies-such as incorporating self-healing capabilities, developing stimuli-responsive systems, integrating functional nanocomposites, and employing advanced fabrication techniques like 3D bioprinting-are discussed to enhance adhesion, mechanical stability, and vascular …

In Vivo Manipulation Of Human Gut Bacteroides Fitness By Abiotic Oligosaccharides, Darryl A Wesener, Zachary W Beller, Megan F Hill, Han Yuan, David B Belanger, Cheryl Frankfater, Nicolas Terrapon, Bernard Henrissat, Dmitry A Rodionov, Semen A Leyn, Andrei Osterman, Johan E T Van Hylckama Vlieg, Jeffrey I Gordon

2020-Current year OA Pubs

Synthetic glycans (SGs) containing glycosidic linkages and structures not identified in nature offer a means for deliberately altering microbial community properties. Here pools of SG oligosaccharides were generated via polymerization of monosaccharides and screened for their ability to increase saccharolytic Bacteroides in ex vivo cultures of human fecal samples. A lead SG preparation was orally administered to gnotobiotic mice harboring a consortium of 56 cultured, phylogenetically diverse human gut bacteria and fed a Western diet. The abundances of 3 of 15 Bacteroides strains increased, most prominently B. intestinalis. Underlying mechanisms were characterized by analyzing in vivo expression of the carbohydrate …

Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Julie Choi, Zitian Tang, Wendy Dong, Jenna Ulibarri, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin

2020-Current year OA Pubs

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants …

Hospital-Onset Bacteremia In The Neonatal Intensive Care Unit: Strategies For Risk Adjustment, Erica C Prochaska, Shaoming Xiao, Elizabeth Colantuoni, Nora Elhaissouni, Reese H Clark, Julia Johnson, Sagori Mukhopadhyay, Ibukunoluwa C Kalu, Danielle M Zerr, Patrick J Reich, Jessica Roberts, Dustin D Flannery, Aaron M Milstone, Cdc Prevention Epicenters Program

2020-Current year OA Pubs

OBJECTIVE: To quantify the impact of patient- and unit-level risk adjustment on infant hospital-onset bacteremia (HOB) standardized infection ratio (SIR) ranking.

DESIGN: A retrospective, multicenter cohort study.

SETTING AND PARTICIPANTS: Infants admitted to 284 neonatal intensive care units (NICUs) in the United States between 2016 and 2021.

METHODS: Expected HOB rates and SIRs were calculated using four adjustment strategies: birthweight (model 1), birthweight and postnatal age (model 2), birthweight and NICU complexity (model 3), and birthweight, postnatal age, and NICU complexity (model 4). Sites were ranked according to the unadjusted HOB rate, and these rankings were compared to rankings based …

A Scoping Review Of Interventions To Address Financial Toxicity In Pediatric And Adult Patients And Survivors Of Cancer, Christina Ping, D Carolina Andrade, Ashley Housten, Michelle Doering, Eliana Goldstein, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Financial toxicity (FT) is a common and significant challenge for people with cancer, impacting immediate clinical outcomes such as treatment adherence, as well as long-term outcomes such as quality of life and mortality. Multiple studies have tested interventions to address FT and develop recommendations for their implementation.

METHODS: In this scoping review, we analyzed thirty-six studies across 35,405 participants examining institution-based interventions for FT in both pediatric and adult patients and survivors of cancer in the U.S.

RESULTS: Common interventions included: financial navigation (n = 15), direct financial/medical assistance (n = 8), financial counseling or coaching (n = 5), …

Model For End Stage Liver Disease Excluding International Normalized Ratio Predicts Severe Right Ventricular Failure After Heartmate 3 Implantation In A Contemporary Cohort, David S Lambert, Ana María Picó, Justin D Vincent, Elena Deych, Erin Coglianese, Joel D Schilling, Justin M Vader, Bin Q Yang

2020-Current year OA Pubs

BACKGROUND: Right ventricular failure (RVF) after left ventricular assist devices is associated with significant morbidity and mortality. Therefore, identifying patients at risk for severe RVF is important for clinical decision-making. Current risk prediction models were not developed in contemporary populations with left ventricular assist devices and have limited clinical applicability. In this study, we sought to evaluate whether the Model for End Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) can predict severe RVF after HeartMate 3 implantation.

METHODS: We retrospectively analyzed all adult patients who received HeartMate 3 left ventricular assist devices as initial implantation at 2 academic medical …

Systemic Inflammation Is Associated With Worse Outcomes From Sars-Cov-2 Infection But Not Neutralizing Antibody, Christopher W Farnsworth, Brittany Roemmich, John Prostko, Gerard Davis, Gillian Murtagh, Laurel Jackson, Christopher Jacobson, Nicolette Jeanblanc, Timothy Griffiths, Edwin Frias, David J Daghfal

2020-Current year OA Pubs

Systemic inflammation is associated with COVID-19 mortality rates, but the impact of inflammation on neutralizing antibodies to severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and on outcomes is poorly understood. This study aimed to determine the association between neutralizing antibody responses, inflammation, and clinical outcomes in hospitalized patients with COVID-19. Two hundred and eight patients presenting to the ED with symptomatic SARS-CoV-2 were included. Neutralization was assessed using the architect angiotensin-converting enzyme-2 (ACE2) binding inhibition assay, and inflammation was assessed using C reactive protein (CRP) and interleukin 6 (IL-6). Medical records were examined for 30-day mortality and 10-day intubation. Correlation …

Severe Aortic Stenosis And Chronic Myeloid Leukemia: Considerations For Valve Management, Rebecca Cunningham, Sang Gune K Yoo, Alexander A Brescia, Karolyn A Oetjen, Iskra Pusic, Joshua D Mitchell

2020-Current year OA Pubs

No abstract provided.

Preparing To Implement Shared Decision Making In Anaesthesia For Hip Fracture Surgery: A Qualitative Interview Study, Eliana C Goldstein, Mark D Neuman, Viktoria Vonder Haar, Aaron C Li, Carlos E Guerra-Londono, Glyn Elwyn, Stacie G Deiner, Adnan Hussain, Joshua W Sappenfield, Christopher J Edwards, Sabry Ayad, James H Baraldi, Karah Whatley, Mary C Politi

2020-Current year OA Pubs

BACKGROUND: Shared decision making is rarely used in anaesthesia consultations. Because either spinal or general anaesthesia can be appropriate for many patients undergoing surgery to repair a hip fracture, this is an appropriate context to implement and test shared decision making and associated resources for anaesthesia decisions. Conversation aids can facilitate shared decision making between clinicians, patients, and caregivers about treatment choices.

METHODS: We conducted semi-structured qualitative interviews at seven sites from April to September 2024 to prepare for implementation of a conversation aid about anaesthesia choices for hip fracture surgery. Interviews elicited feedback on shared decision making and a …

Associations Of Cerebrospinal Fluid Orexin-A, Alzheimer Disease Biomarkers, And Cognitive Performance, Ruijin Lu, Krish Shah, Cristina D Toedebusch, Ashley Hess, Rachel Richardson, Emmanuel Mignot, Suzanne E Schindler, Tammie L S Benzinger, Shaney Flores, Jason Hassenstab, Chengjie Xiong, John C Morris, David M Holtzman, Brendan P Lucey

2020-Current year OA Pubs

OBJECTIVE: Cerebrospinal fluid (CSF) orexin-A has been suggested to be a biomarker of Alzheimer disease (AD). In both cognitively unimpaired healthy older adults and individuals with symptomatic AD, CSF orexin-A is positively associated with CSF Aβ42, p-tau181, and total tau (t-tau) concentrations. However, a recent systematic review and meta-analysis did not support differences in orexin-A between AD and controls. In this study, we tested the association between CSF orexin-A concentrations, AD biomarkers, and cognitive performance in older adults with and without symptomatic AD.

METHODS: Two hundred and seventy community-dwelling older adults underwent standardized cognitive assessments, sleep monitoring with a single-channel …

Multi-Omic Analysis Of Biological Aging Biomarkers In Long-Term Calorie Restriction And Endurance Exercise Practitioners: A Cross-Sectional Study, Giovanni Fiorito, Valeria Tosti, Silvia Polidoro, Beatrice Bertozzi, Nicola Veronese, Edda Cava, Francesco Spelta, Laura Piccio, Dayna S Early, Daniel Raftery, Paolo Vineis, Luigi Fontana

2020-Current year OA Pubs

Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of …

Parent-Child Agreement On Fatigue In Pediatric Otolaryngology Patients, Amy E Ensing, Amy L Zhang, Rebecca Z Lin, Emma K Landes, Henok Getahun, Judith E C Lieu

2020-Current year OA Pubs

OBJECTIVES: To investigate parent-child agreement on fatigue reporting in pediatric otolaryngology patients and whether agreement might vary by diagnosis and other patient factors.

STUDY DESIGN: Cross-sectional survey.

METHODS: Patients ages 5-18 years old being evaluated for hearing loss (HL) or obstructive sleep apnea (OSA) were recruited from a pediatric otolaryngology clinic and sleep center. Children and parents completed the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL MFS).

RESULTS: Responses of 42 patients with HL, 49 with OSA, 10 with sleep-disordered breathing (SDB), and 34 controls were analyzed. Parent and child PedsQL MFS scores were strongly correlated (Pearson

CONCLUSION: …

Social Determinants Of Health And Health Literacy In Emergency Patients With Diabetic Ketoacidosis, Daniel F Suarez, Ryan M Schneider, Margo Girardi, Gina Larossa, Julianne Yeary, Taylor Kaser, Rachel Ancona, Paulina Cruz Bravo, Richard T Griffey

2020-Current year OA Pubs

INTRODUCTION: Social determinants of health (SDoH) and health literacy have been demonstrated to significantly impact health outcomes. As part of a study of diabetic ketoacidosis (DKA) treatment from the emergency department (ED), we assessed the burden of SDoH and health literacy among patients with DKA to identify potentially modifiable risk factors in the development of DKA.

METHODS: This was an exploratory, prospective, cross-sectional study of adult patients with DKA in a large urban academic ED from March 2023-March 2024. We administered the Centers for Medicare & Medicaid Services Accountable Health Communities Health-Related Social Needs Screening Tool (SNST) and the Brief …

Patient Selection, Ventricular Tachycardia Substrate Delineation, And Data Transfer For Stereotactic Arrhythmia Radioablation: A Clinical Consensus Statement Of The European Heart Rhythm Association Of The European Society Of Cardiology And The Heart Rhythm Society, Katja Zeppenfeld, Clifford Robinson, Et Al.

2020-Current year OA Pubs

Stereotactic arrhythmia radioablation (STAR) is a novel, non-invasive, and promising treatment option for ventricular arrhythmias (VAs). It has been applied in highly selected patients mainly as bailout procedure, when (multiple) catheter ablations, together with anti-arrhythmic drugs, were unable to control the VAs. Despite the increasing clinical use, there is still limited knowledge of the acute and long-term response of normal and diseased myocardium to STAR. Acute toxicity appeared to be reasonably low, but potential late adverse effects may be underreported. Among published studies, the provided methodological information is often limited, and patient selection, target volume definition, methods for determination and …

The Emergence Of Human Primordial Germ Cell-Like Cells In Stem Cell-Derived Gastruloids, Jitesh Neupane, Gabriele Lubatti, Theresa Gross-Thebing, Mayra Luisa Ruiz Tejada Segura, Richard Butler, Sargon Gross-Thebing, Sabine Dietmann, Antonio Scialdone, M Azim Surani

2020-Current year OA Pubs

Most advances in early human postimplantation development depend on animal studies and stem cell-based embryo models. Here, we present self-organized three-dimensional human gastruloids (hGs) derived from embryonic stem cells. The transcriptome profile of day 3 hGs aligned with Carnegie stage 7 human gastrula, with cell types and differentiation trajectories consistent with human gastrulation. Notably, we observed the emergence of nascent primordial germ cell-like cells (PGCLCs), but without exogenous bone morphogenetic protein (BMP) signaling, which is essential for the PGCLC fate. A mutation in the

Independent Origins And Non-Parallel Selection Signatures Of Triclabendazole Resistance In Fasciola Hepatica, Young-Jun Choi, Bruce A Rosa, Martha V Fernandez-Baca, Rodrigo A Ore, John Martin, Pedro Ortiz, Cristian Hoban, Miguel M Cabada, Makedonka Mitreva

2020-Current year OA Pubs

Triclabendazole (TCBZ) is the primary treatment for fascioliasis, a global foodborne zoonosis caused by Fasciola hepatica. Widespread resistance to TCBZ (TCBZ-R) in livestock and a rapid rise in resistant human infections are significant concerns. To understand the genetic basis of TCBZ-R, we sequenced the genomes of 99 TCBZ-sensitive (TCBZ-S) and 210 TCBZ-R adult flukes from 146 bovine livers in Cusco, Peru. We identify genomic regions of high differentiation (F

Tumor Treating Fields Therapy In Platinum-Resistant Ovarian Cancer: Results Of The Engot-Ov50/Gog-3029/Innovate-3 Pivotal Phase 3 Randomized Study, Ignace Vergote, Premal H Thaker, Et Al.

2020-Current year OA Pubs

PURPOSE: Tumor Treating Fields (TTFields) are electric fields that disrupt processes critical for cancer cell viability and tumor progression. The pivotal, phase 3 ENGOT-ov50/GOG-3029/INNOVATE-3 study evaluated efficacy and safety of TTFields therapy with paclitaxel (PTX) vs PTX in patients with platinum-resistant ovarian cancer (PROC).

PATIENTS AND METHODS: Adult patients with PROC with ≤ 5 total prior lines of therapy (LOT), including ≤ 2 prior LOT for platinum-resistant disease, and ECOG PS of 0-1 were randomized 1:1 to receive TTFields (200 kHz; ≥ 18 h/day) + PTX (80 mg/m

RESULTS: Between March 2019 and November 2021, 558 patients (ECOG PS 0, …

Pmp2+ Schwann Cells Maintain The Survival Of Large-Caliber Motor Axons, Mikolaj M Kozlowski, Amy Strickland, Ana Morales Benitez, Robert E Schmidt, A Joseph Bloom, Jeffrey Milbrandt, Aaron Diantonio

2020-Current year OA Pubs

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons. While much of this cell type selectivity may be driven by intrinsic differences among the neuron subpopulations, neuron-extrinsic mechanisms such as the selective malfunction of glial support cells may also play a role. Recently, we identified a population of Schwann cells (SCs) expressing

Molecular Basis For Human Respiratory Syncytial Virus Transcriptional Regulator Ns1 Interactions With Med25, Parismita Kalita, Oam Khatavkar, Grace Uwase, Yulia Korshunova, Yuying Hu, Nicole D Wagner, Jian Xu, Jiehong Pan, Jay C Nix, Michael L Gross, Steven L Brody, Dominika Borek, Gaya K Amarasinghe, Jacqueline E Payton, Daisy W Leung

2020-Current year OA Pubs

The Mediator complex facilitates interactions between transcription factors and RNA polymerase II, a process that is required for host gene transcription, including in response to viral infections. Among the many subunits in the Mediator complex, the MED25 subunit has been shown to be a target for viral activators during infection. Here we provide the molecular basis for the interaction between human respiratory syncytial virus (hRSV) nonstructural 1 protein (NS1) and the activator interaction domain (ACID) of MED25. The X-ray crystal structure of the complex revealed that NS1 straddles and binds two faces of MED25 ACID. This interaction is distinct from …

Tissue-Resident Ccr2+ Macrophage Trem-1/3 Signaling Is Necessary For Monocyte And Neutrophil Recruitment To Injured Hearts, Yuriko Terada, Wenjun Li, Junedh M Amrute, Amit I Bery, Charles R Liu, Venkatrao Nunna, Christian Corbin Frye, Hao Dun, Andrew L Koenig, Hannah P Luehmann, Gyu Seong Heo, Macee C Owen, Alexander N Wein, Yongjian Liu, Jon H Ritter, Sumanth D Prabhu, Ruben G Nava, Andrew E Gelman, Marina Cella, Marco Colonna, Kory J Lavine, Daniel Kreisel

2020-Current year OA Pubs

Triggering receptor expressed on myeloid cells 1 (TREM-1) has been shown to amplify inflammatory signals, such as Toll-like receptor signaling, after infection and sterile injury. While previous studies have demonstrated that TREM-1 activation in circulating immune cells promotes injury, the role of TREM-1 signaling in tissue-resident cells in the context of sterile inflammation remains poorly understood. Here, we used a cardiac transplantation model to dissect how Trem1/3 expression on heart-resident cells regulates sterile inflammation. TREM-1 is expressed in heart-resident C-C chemokine receptor 2 (CCR2)

Multicilia Dynamically Transduce Sonic Hedgehog Signaling To Regulate Choroid Plexus Functions, Suifang Mao, Michael J Holtzman, Et Al.

2020-Current year OA Pubs

The choroid plexus is a major site for cerebrospinal fluid (CSF) production, characterized by a multiciliated epithelial monolayer that regulates CSF production. We demonstrate that defective choroid plexus ciliogenesis or intraflagellar transport yields neonatal hydrocephalus, at least in part due to increased water channel Aqp1 and ion transporter Atp1a2 expression. We demonstrate choroid plexus multicilia as sensory cilia, transducing both canonical and non-canonical Sonic Hedgehog (Shh) signaling. Interestingly, it is the non-canonical Shh signaling that represses Aqp1 and Atp1a2 expression by the Smoothened (Smo)/Gαi/cyclic AMP (cAMP) pathway. Choroid plexus multicilia exhibit unique ciliary ultrastructure, carrying features of both primary and …

A Network Correspondence Toolbox For Quantitative Evaluation Of Novel Neuroimaging Results, Ru Kong, Evan M Gordon, Et Al.

2020-Current year OA Pubs

The brain can be decomposed into large-scale functional networks, but the specific spatial topographies of these networks and the names used to describe them vary across studies. Such discordance has hampered interpretation and convergence of research findings across the field. We have developed the Network Correspondence Toolbox (NCT) to permit researchers to examine and report spatial correspondence between their novel neuroimaging results and multiple widely used functional brain atlases. We provide several exemplar demonstrations to illustrate how researchers can use the NCT to report their own findings. The NCT provides a convenient means for computing Dice coefficients with spin test …

Cell-Matrix Feedback Controls Stretch-Induced Cellular Memory And Fibroblast Activation, Yuan Hong, Xiangjun Peng, Haomin Yu, Delaram Shakiba, Yuxuan Huang, Chengqing Qu, Aliza Mujahid, Yin-Yuan Huang, Jacob A Sandler, Kenneth M Pryse, Justin M Sacks, Elliot L Elson, Guy M Genin, Et Al.

2020-Current year OA Pubs

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell-extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship …

American Society Of Hematology Living Guidelines On Use Of Anticoagulation For Thromboprophylaxis For Patients With Covid-19: Executive Summary, Deborah M Siegal, Kristen M Sanfilippo, Yazan Al Jabiri, Et Al.

2020-Current year OA Pubs

BACKGROUND: COVID-19-related critical and acute illness is associated with an increased risk of venous thromboembolism (VTE). These evidence-based recommendations of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about using anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness; patients with COVID-19-related acute illness; and those being discharged from the hospital, who do not have suspected or confirmed VTE.

METHODS: ASH formed a multidisciplinary panel, including patient representatives. The Michael G. DeGroote Cochrane Canada and MacGRADE Centres at McMaster University supported guideline development, including performing systematic reviews (up to …

Metagenomic Signatures Of Extraintestinal Bacterial Infection In The Febrile Term Infant Gut Microbiome, Anna L Deveaux, Carla Hall-Moore, Nurmohammad Shaikh, Meghan Wallace, Carey-Ann D Burnham, David Schnadower, Nathan Kuppermann, Prashant Mahajan, Octavio Ramilo, Phillip I Tarr, Gautam Dantas, Drew J Schwartz

2020-Current year OA Pubs

BACKGROUND: Extraintestinal bacterial infections (EBIs), e.g., urinary tract infection, bacteremia, and meningitis, occur in approximately 10% of febrile infants younger than 60 days. Although many EBI-causing species commonly reside in the infant gut, proof that the digestive system is a pre-infection habitat remains unestablished.

RESULTS: We studied a cohort of febrile term infants <  60 days old who presented to one of thirteen US emergency departments in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Forty EBI cases and 74 febrile controls matched for age, sex, and race without documented EBIs were selected for analysis. Shotgun sequencing was performed of the gut microbiome and of strains cultured from the gut and extraintestinal site(s) of EBI cases, including blood, urine, and/or cerebrospinal fluid. Using a combination of EBI isolate genomics and fecal metagenomics, we detected an intestinal strain presumptively isogenic to the EBI pathogen (> 99.999% average nucleotide identity) in 63% of infants with EBIs. Although there was no difference in gut microbiome diversity between cases and controls, we observed significantly increased Escherichia coli relative abundance in the gut microbiome of infants with EBIs caused by E. coli. Infants with E. coli …

Integrating Mrna Vaccines Into The Attitudes Toward Genomics And Precision Medicine Scale: A Validation Study With A Sample Of 4939 Adults In The Usa, Jenine K Harris, Erin D Solomon, Kari Baldwin, Lauren L Baker, Eu Gene Chin, James M Dubois

2020-Current year OA Pubs

The attitudes toward genomics and precision medicine (AGPM) measure examines attitudes toward activities such as genetic testing, gene editing, and biobanking. This is a useful tool for research on the ethical, legal, and social implications of genomics, a major program within the National Institutes of Health. We updated the AGPM to explore controversies over mRNA vaccines. This brief report examines the factor structure of the updated AGPM using a sample of 4939 adults in the USA. The updated AGPM's seven factors include health benefits, knowledge benefits, and concerns about the sacredness of life, privacy, gene editing, mRNA vaccines, and social …