tbuckley/cabot-search huggingface dataset:
Higher Germline Mutagenesis of Genes with Stronger Testis Expressions Refutes the Transcriptional Scanning Hypothesis
Authors: Haoxuan Liu, Jianzhi Zhang
Journal: Molecular Biology and Evolution (2020)

Why are more genes expressed in the testis than in any other organ in mammals? The recently proposed transcriptional scanning hypothesis posits that transcription alleviates mutagenesis through transcription-coupled repair so has been selected in the testis to modulate the germline mutation rate in a gene-specific manner. Here, we show that this hypothesis is theoretically untenable because the selection would be too weak to have an effect in mammals. Furthermore, the analysis purported to support the hypothesis did not control known confounding factors and inappropriately excluded genes with no observed de novo mutations. After remedying these problems, we find the human germline mutation rate of a gene to rise with its testis expression level. This trend also exists for inferred coding strand-originated mutations, suggesting that it arises from transcription-associated mutagenesis. Furthermore, the testis expression level of a gene robustly correlates with its overall expression in other organs, nullifying the need to explain the testis silencing of a minority of genes by adaptive germline mutagenesis. Taken together, our results demonstrate that human testis transcription increases the germline mutation rate, rejecting the transcriptional scanning hypothesis of extensive gene expressions in the mammalian testis.
Postresuscitation Management and Survival After Cardiac Arrest—The Whole Package
Authors: Joseph E. Tonna
Journal: JAMA Network Open (2020)

Saket Girotra, MD, SM; Brahmajee K. Nallamothu, MD, MPH; Yuanyuan Tang, PhD; Paul S. Chan, MD, MSc; for the American Heart Association Get With The Guidelines–Resuscitation Investigators
cis-3, 4’, 5-trimethoxy-3’-aminostilbene is a colchicine site microtubule inhibitor and can be used as a vascular disrupting agent
Authors: David Durrant, Frank Corwin, Daniele Simoni, Ming Zhao, Michelle Rudek, Fadi Salloum, Rakesh Kukreja, Panos Fatouros, Ruey-min Lee
Journal: Cancer Research (2008)

1413  Targeting tumor vasculature is a new approach in cancer therapy. Colchicine site inhibitors (CSIs) of microtubule such as combretastatin A4 (CA4) and ZD6126 can directly damage tumor endothelium to induce tumor hypoxia and necrosis. However, both CA4 and ZD6126 were shown to have cardiovascular side effects presumably due to injury of normal cardiovascular endothelium. It is therefore important to develop new agents to avoid this major problem. Here we investigate another CSI, cis-3, 4’, 5-trimethoxy-3’-aminostilbene (stilbene 5c), which can effectively induce cell cycle arrest at G2/M phase with an IC50 20 nM. Stilbene 5c does not suppress mouse bone marrow and is tolerated by mice up to 100 mg/kg. Determination of tumor vascular perfusion by dynamic contrast-enhanced (DCE) MRI studies shows that stilbene 5c can selectively suppress tumor perfusion without damaging normal organ perfusion. Histological sections of normal organs from mice treated with stilbene 5c do not reveal any major toxicity in H & E staining. Microvascular density determined by CD34 staining is unchanged in normal organs, but significantly decreased in tumor after stilbene 5c treatment. Mice treated with 5 days of stilbene 5c 25 mg/kg maintain a normal left ventricular ejection fraction, suggesting that stilbene 5c has minimal cardiac toxicity. Pharmacokinetic study reveals that stilbene has a half-life of 1.8 hours in mice. Biodistribution of stilbene 5c is not detectable in heart and lung, but is present at a high level in brain, liver, kidney and tumor at 1 hour after intravenous injection. At 3 hours after injection, the level of stilbene 5c in brain, liver and kidney becomes undetectable, but remains high in tumor, suggesting preferential accumulation of stilbene 5c in tumor. Investigation of the in vivo efficacy of stilbene 5c with ovarian cancer xenograft model shows that stilbene 5c can suppress tumor growth by only 40% compared with control. However, its effect is dramatically improved when combined with anti-angiogenic therapy bevacizumab. We conclude that stilbene 5c is a useful vascular disrupting agent and its combination with bevacizumab could be a promising therapy for cancer.
P-235 Management of constipation associated with advanced cancers, chemotherapy and opioid-induced constipation by oral herbal supplement in heterogeneous group of gastrointestinal, hepatobiliary and pancreatic cancers
Authors: D. Bendale, D. Bendale, D. Patil, D. Kadam, D. Birari-Gawande, D. Patil
Journal: Annals of Oncology (2020)
The commensal skin microbiota triggers type I IFN–dependent innate repair responses in injured skin
Authors: Jeremy Di Domizio, Cyrine Belkhodja, Pauline Chenuet, Anissa Fries, Timothy Murray, Paula Marcos Mondéjar, Olivier Demaria, Curdin Conrad, Bernhard Homey, Sabine Werner, Daniel E. Speiser, Bernhard Ryffel, Michel Gilliet
Journal: Nature Immunology (2020)
P-36 Prognostic value of tumor laterality and recurrence risk in patients with stage III colon cancer treated with adjuvant chemotherapy
Authors: A. Monteiro, T. Cunha Pereira, R. Félix Soares, F. Macedo, J. Paulo, M. Marques, N. Bonito, P. Jacinto, J. Ribeiro, G. Sousa
Journal: Annals of Oncology (2020)
SO-2 Prevalence and prognostic role of inherited germline mutations in cancer predisposing genes in unselected patients with pancreatic cancer
Authors: E. Fountzilas, A. Eliades, G. Koliou, A. Achilleos, D. Pectasides, J. Sgouros, P. Papakostas, A. Psyrri, C. Papadimitriou, G. Oikonomopoulos, K. Ferentinos, A. Koumarianou, G. Zarkavelis, C. Dervenis, G. Aravantinos, P. Kosmidis, M. Theochari, G. Rigakos, A. Nikolaidi, A. Christopoulou, G. Fountzilas, P. Patsalis
Journal: Annals of Oncology (2020)
Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice
Authors: Yuto Nakamura, Shunbun Kita, Yoshimitsu Tanaka, Shiro Fukuda, Yoshinari Obata, Tomonori Okita, Hiroyuki Nishida, Yuki Takahashi, Yusuke Kawachi, Yuri Tsugawa-Shimizu, Yuya Fujishima, Hitoshi Nishizawa, Yoshinobu Takakura, Shigeru Miyagawa, Yoshiki Sawa, Norikazu Maeda, Iichiro Shimomura
Journal: Molecular Therapy (2020)
An expert consensus document on the management of cardiovascular manifestations of Fabry disease
Authors: Aleš Linhart, Dominique P. Germain, Iacopo Olivotto, Mohammed M. Akhtar, Aris Anastasakis, Derralynn Hughes, Mehdi Namdar, Maurizio Pieroni, Albert Hagège, Franco Cecchi, Juan R. Gimeno, Giuseppe Limongelli, Perry Elliott
Journal: European Journal of Heart Failure (2020)

Fabry disease (FD) is an X‐linked lysosomal storage disorder caused by pathogenic variants in the α‐galactosidase A ( GLA ) gene that leads to reduced or undetectable α‐galactosidase A enzyme activity and progressive accumulation of globotriaosylceramide and its deacylated form globotriaosylsphingosine in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD‐related heart disease and expert consensus recommendations for its management.
Changed Primary Outcome Between Trial Registration and Publication
Authors: Robert A. Kleinman, Michael J. Ostacher
Journal: JAMA Internal Medicine (2020)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Vaccines, convalescent plasma, and monoclonal antibodies for covid-19
Authors: Herb F Sewell, Raymond M Agius, Denise Kendrick, Marcia Stewart
Journal: BMJ (2020)

The devastating pandemic caused by the SARS-CoV-2 coronavirus appears to be a prime candidate for traditional prevention (vaccines) and passive immunity approaches.Passive immunity, using convalescent plasma from recovered patients or monoclonal antibodies with high levels of neutralising antiviral activity, have potential for both therapy and prevention.Worldwide, many covid-19 vaccines are at various phases of development. 1Trials are also investigating convalescent plasma as a containment option or supportive therapy for patients with covid-19. 2Understandably, there is great public expectation that these efforts will be successful, but caution is necessary with respect to both vaccines and passive immunity.
P-71 Prognostic biomarkers of therapy by hepatic radioembolization with yttrium-90 spheres in colorectal liver metastases
Authors: A. Rodríguez-Fernández, E. Triviño-Ibáñez, J. Ciampi-Dopazo, P. Pardo-Moreno, C. Ramos-Font, E. González-Flores
Journal: Annals of Oncology (2020)
VE-PTP inhibition elicits eNOS phosphorylation to blunt endothelial dysfunction and hypertension in diabetes
Authors: Mauro Siragusa, Alberto Fernando Oliveira Justo, Pedro Felipe Malacarne, Anna Strano, Akshay Buch, Barbara Withers, Kevin G Peters, Ingrid Fleming
Journal: Cardiovascular Research (2020)

Abstract Aims Receptor-type vascular endothelial protein tyrosine phosphatase (VE-PTP) dephosphorylates Tie-2 as well as CD31, VE-cadherin, and vascular endothelial growth factor receptor 2 (VEGFR2). The latter form a signal transduction complex that mediates the endothelial cell response to shear stress, including the activation of the endothelial nitric oxide (NO) synthase (eNOS). As VE-PTP expression is increased in diabetes, we investigated the consequences of VE-PTP inhibition (using AKB-9778) on blood pressure in diabetic patients and the role of VE-PTP in the regulation of eNOS activity and vascular reactivity. Methods and results In diabetic patients AKB-9778 significantly lowered systolic and diastolic blood pressure. This could be linked to elevated NO production, as AKB increased NO generation by cultured endothelial cells and elicited the NOS inhibitor-sensitive relaxation of endothelium-intact rings of mouse aorta. At the molecular level, VE-PTP inhibition increased the phosphorylation of eNOS on Tyr81 and Ser1177 (human sequence). The PIEZO1 activator Yoda1, which was used to mimic the response to shear stress, also increased eNOS Tyr81 phosphorylation, an effect that was enhanced by VE-PTP inhibition. Two kinases, i.e. abelson-tyrosine protein kinase (ABL)1 and Src were identified as eNOS Tyr81 kinases as their inhibition and down-regulation significantly reduced the basal and Yoda1-induced tyrosine phosphorylation and activity of eNOS. VE-PTP, on the other hand, formed a complex with eNOS in endothelial cells and directly dephosphorylated eNOS Tyr81 in vitro. Finally, phosphorylation of eNOS on Tyr80 (murine sequence) was found to be reduced in diabetic mice and diabetes-induced endothelial dysfunction (isolated aortic rings) was blunted by VE-PTP inhibition. Conclusions VE-PTP inhibition enhances eNOS activity to improve endothelial function and decrease blood pressure indirectly, through the activation of Tie-2 and the CD31/VE-cadherin/VEGFR2 complex, and directly by dephosphorylating eNOS Tyr81. VE-PTP inhibition, therefore, represents an attractive novel therapeutic option for diabetes-induced endothelial dysfunction and hypertension.
Black phosphorus-based 2D materials for bone therapy
Authors: Liang Cheng, Zhengwei Cai, Jingwen Zhao, Fei Wang, Min Lu, Lianfu Deng, Wenguo Cui
Journal: Bioactive Materials (2020)

Since their discovery, Black Phosphorus (BP)-based nanomaterials have received extensive attentions in the fields of electromechanics, optics and biomedicine, due to their remarkable properties and excellent biocompatibility. The most essential feature of BP is that it is composed of a single phosphorus element, which has a high degree of homology with the inorganic components of natural bone, therefore it has a full advantage in the treatment of bone defects. This review will first introduce the source, physicochemical properties, and degradation products of BP, then introduce the remodeling process of bone, and comprehensively summarize the progress of BP-based materials for bone therapy in the form of hydrogels, polymer membranes, microspheres, and three-dimensional (3D) printed scaffolds. Finally, we discuss the challenges and prospects of BP-based implant materials in bone immune regulation and outlook the future clinical application.
Economic evaluation of cognitive behavioural therapy for insomnia (CBT-I) for improving health outcomes in adult populations: A systematic review
Authors: Andrea N. Natsky, Andrew Vakulin, Ching L. Chai-Coetzer, Leon Lack, R.D. McEvoy, Nicole Lovato, Alexander Sweetman, Christopher J. Gordon, Robert J. Adams, Billingsley Kaambwa
Journal: Sleep Medicine Reviews (2020)
Provision of Pediatric Immunization Services During the COVID-19 Pandemic: an Assessment of Capacity Among Pediatric Immunization Providers Participating in the Vaccines for Children Program — United States, May 2020
Authors: Tara M. Vogt, Fan Zhang, Michelle Banks, Carla Black, Bayo Arthur, Yoonjae Kang, Paul Lucas, Brock Lamont
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Recent reports suggest that routine childhood immunization coverage might have decreased during the coronavirus disease 2019 (COVID-19) pandemic (1,2).To assess the capacity of pediatric health care practices to provide immunization services to children during the pandemic, a survey of practices participating in the Vaccines for Children (VFC) program was conducted during May 12-20, 2020.Data were weighted to account for the sampling design; thus, all percentages reported are weighted.Among 1,933 responding practices, 1,727 (89.8%) were currently open; 1,397 (81.1%) of these reported offering immunization services to all of their patients.When asked whether the practice would likely be able to accommodate new patients to assist with provision of immunization services through August, 1,135 (59.1%) respondents answered affirmatively.These results suggest that health care providers appear to have the capacity to deliver routinely recommended childhood vaccines, allowing children to catch up on vaccines that might have been delayed as a result of COVID-19-related effects on the provision of or demand for routine well child care.Health care providers and immunization programs should educate parents on the need to return for well-child and immunization visits or refer patients to other practices, if they are unable to provide services (3).The VFC program* is an entitlement program that provides federally purchased vaccines to eligible children aged ≤18 years at no cost.Approximately half of U.S. children are eligible to participate in the VFC program, mostly based on Medicaid enrollment or lack of insurance coverage, and an estimated 86% of U.S. pediatricians provide care in a VFC-enrolled practice (4,5).VFC provider practices include many types of health care providers; all serve at least some pediatric patients.Contact information for VFC program points of contact in VFCenrolled practices and total number of federally purchased vaccine doses ordered are recorded in two CDC systems: the
Sex Differences in Patients Receiving Left Ventricular Assist Devices for End-Stage Heart Failure
Authors: Jadry Gruen, Cesar Caraballo, P. Elliott Miller, Megan McCullough, Catherine Mezzacappa, Neal Ravindra, Clancy W. Mullan, Samuel W. Reinhardt, Makoto Mori, Eric Velazquez, Arnar Geirsson, Tariq Ahmad, Nihar R. Desai
Journal: JACC Heart Failure (2020)
Zika virus RNA and IgM persistence in blood compartments and body fluids: a prospective observational study
Authors: Mars Stone, Sonia Bakkour, Marion C Lanteri, Donald Brambilla, Graham Simmons, Roberta Bruhn, Zhanna Kaidarova, Tzong-Hae Lee, Jose Orlando Alsina, Phillip C Williamson, Susan A Galel, Lisa L Pate, Jeffrey M Linnen, Steve Kleinman, Michael P Busch
Journal: The Lancet Infectious Diseases (2020)
OM-028. EGFR AND EGFRvIII EXPRESSION IN GLIOBLASTOMA
Authors: Claire Faulkner, Abigail Palmer, Hannah Williams, Chris Wragg, Harry Haynes, Maggie Williams, Kirsten Hopkins, Kathreena Kurian
Journal: Neuro-Oncology (2013)

INTRODUCTION: Up to half of primary glioblastomas (GBM) show Epidermal Growth Factor Receptor (EGFR) (7p12) amplification, overexpression and/or mutations. EGFR activation promotes cellular proliferation via activation of MAPK and PI3K-Akt pathways. EGFR inhibitor therapy is under investigation for
Trends in Emergency Department Visits for Contact Sports–Related Traumatic Brain Injuries Among Children — United States, 2001–2018
Authors: Dana Waltzman, Lindsay S. Womack, Karen E. Thomas, Kelly Sarmiento
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

During 2010-2016, there were an average of 283,000 U.S. emergency department (ED) visits each year among children for sports and recreation-related traumatic brain injuries (SRR-TBIs); approximately 45% of these SRR-TBIs were associated with contact sports (1).Although most children with an SRR-TBI are asymptomatic within 4 weeks, there is growing concern about potential long-term effects on a child's developing brain (2).This has led to calls to reduce the risk for traumatic brain injuries (TBIs) among child athletes, resulting in the introduction of state policies and the institution of safety rules (e.g., age and contact restrictions) for some sports programs.To assess changes in the incidence of ED-related SRR-TBI among children, CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) for the period 2001-2018.After more than a decade of increasing rates, the rate of contact sportsrelated TBI ED visits declined 32% from 2012 to 2018.This reduction was primarily the result of a decline in footballrelated SRR-TBI ED visits during 2013-2018.Decreased participation in tackle football (3) and implementation of contact limitations (4) were likely contributing factors to this decline.Public health professionals should continue to expand efforts to address SRR-TBIs in football, which is the sport with the highest incidence of TBI, and identify effective prevention strategies for all sports to reduce TBIs among children.NEISS-AIP is operated by the U.S. Consumer Product Safety Commission and each year houses data on approximately 500,000 initial injury-related visits for patients treated in hospital EDs.Data are drawn from a nationally representative sample of hospitals that have been selected as a stratified probability sample (1).Data are weighted by the inverse probability of selection to provide national estimates.SRR-TBIs included TBIs among children aged ≤17 years that occurred during organized and unorganized SRR activities.Children were classified as having a TBI if the primary body part injured was the head and the principal diagnosis was concussion or internal organ injury.Each case was initially classified into one of 39 mutually exclusive sports and recreation-related groups on the basis of an algorithm that considered both the consumer products involved (e.g., bicycles, swing sets, and inline skating equipment) and the narrative description of the incident obtained from the medical record.SRR activities were collapsed into categories (i.e.
Eltanexor (KPT-8602), a Second-Generation Selective Inhibitor of Nuclear Export (SINE) Compound, in Patients with Refractory Multiple Myeloma
Authors: Robert Frank Cornell, Adriana C. Rossi, Rachid Baz, Craig C Hofmeister, Chaim Shustik, Joshua R Richter, Christine I Chen, Dan T. Vogl, Erkan Baloglu, William Senapedis, Joel Ellis, Tony Williams, Sharon Shacham, Michael G. Kauffman
Journal: Blood (2017)
Covid-19: What do we know about “long covid”?
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: What do we know about "long covid"?As recognition grows that many patients have long lasting effects, Elisabeth Mahase examines the evidence and the response Elisabeth Mahase clinical reporter What is it?"Long covid" is a term being used to describe illness in people who have either recovered from covid-19 but are still report lasting effects of the infection or have had the usual symptoms for far longer than would be expected.Many people, including doctors who have been infected, have shared their anecdotal experiences on social media, in the traditional media, and through patients' groups.
Abstract 14584: Oral Anticoagulation Therapy in Patients Hospitalized With Non-Valvular Atrial Fibrillation: A Nationwide Cohort Study
Authors: Kuan Ken Lee, Rong Bing, Federica Astengo, Jesus Perez, Atul Anand, Nathan Hill, Nicholas Bloor, Steven Lister, David McAllister, Nicholas L Mills, Anoop S Shah
Journal: Circulation (2019)

Background: Direct oral anticoagulants (DOACs) have a favorable efficacy and safety profile compared to vitamin K antagonists (VKAs) for patients with non-valvular atrial fibrillation (NVAF). In a ...
P-282 Long-term outcomes after neoadjuvant chemoradiotherapy and R0 resection in ESCC using: A propensity-matched analysis of PF versus CROSS regimen
Authors: K. Lam, Y. Wong, L. Wong, W. Chan, B. Law, R. Zhang, T. So, K. Chan, S. Chan, D. Kwong, S. Law
Journal: Annals of Oncology (2020)
Abstract 10271: Alteration of Cardiac Performance and Serum B-type Natriuretic Peptide Level in Healthy Aging; Speckle-tracking Echocardiographic Study
Authors: Yuriko Yoshida, Koki Nakanishi, Masao Daimon, Jumpei Ishiwata, Naoko Sawada, Megumi Hirokawa, Hidehiro Kaneko, Tomoko Nakao, Yoshiko Mizuno, Hiroyuki Morita, Marco Di Tullio, Shunichi Homma, Issei Komuro
Journal: Circulation (2019)

Introduction: The impact of aging on cardiac function is not fully elucidated. Speckle-tracking echocardiography can unmask subclinical cardiac dysfunction. This study aimed to investigate the impa...