tbuckley/cabot-search huggingface dataset:
Cycloserine did not increase depression incidence or severity at standard dosing for multidrug-resistant tuberculosis
Authors: Jeffrey A. Tornheim, Zarir F. Udwadia, Prerna R. Arora, Ishita Gajjar, Nikhil Gupte, Samridhi Sharma, Megha Karane, Namrata Sawant, Nisha Kharat, Alexander J. Blum, Shri Vijay Bala Yogendra Shivakumar, Jai B. Mullerpattan, Lancelot M. Pinto, Tester F. Ashavaid, Amita Gupta, Camilla Rodrigues
Journal: European Respiratory Journal (2021)

<b>In a longitudinal cohort of MDR-TB patients receiving individualised, DST-based treatment, neither the inclusion of cycloserine in a multidrug regimen nor the dose used (up to 750 mg daily) significantly increased incidence of depression during treatment</b>https://bit.ly/3GtQmOH
Abstract 11269: Recombinant Soluble Thrombomodulin in Prolonged Porcine Cardiac Arrest
Authors: Boya Zhang, Brendan McCracken, Danielle Leander, Carmen Colmenero, Nicholas Greer, Cindy H Hsu, James Cranford, Mohamad Tiba, Robert W Neumar, Colin Greineder
Journal: Circulation (2021)

Introduction: Sudden Cardiac Arrest (CA) affects more than 400,000 people per year in the United States. Although a third of these patients survive to hospital admission, another 60-70% go on to die due to failed recovery of vital organ function. Microvascular thrombosis has been suggested as a potential contributor to prolonged organ dysfunction, but no antithrombotic therapies have been shown to be beneficial and coagulofibrinolytic abnormalities in prolonged CA remain poorly understood. Objectives: To establish key biomarkers of porcine coagulation and fibrinolysis in the setting of prolonged CA and cardiopulmonary resuscitation (CPR) and test the ability of ART-123 (recombinant human thrombomodulin alpha) to reverse these abnormalities. Methods: 15 pigs (n=5 per group) underwent 8 minutes of no-flow CA followed by 50 minutes of mechanical CPR. Animals were randomized to receive saline or ART-123 (~1mg/kg) pre-arrest (5 minutes prior to ventricular fibrillation) or post-arrest (2 minutes after initiation of CPR). Results: Robust and ongoing activation of coagulation and fibrinolysis were detected throughout the resuscitation. After 50 minutes of CPR, plasma tests suggested consumptive coagulopathy, while whole blood testing (thromboelastography) indicated a persistent hypercoagulable state. ART-123 had a clear anticoagulant effect irrespective of timing (TAT complexes 381±25 vs. 238±18 vs. 226±12, p&lt;0.01, and d-dimer 4.86±0.54 vs. 2.39±0.2 vs. 2.46±0.21 for vehicle, pre-arrest, post-arrest, p = 0.05). A pro-fibrinolytic effect was also observed, but only when the drug was given before no-flow, with a significant increase in levels of free endogenous tPA (1.2±0.12 vs. 3.29±0.29 vs. 1.72±0.3, p &lt; 0.001) and corresponding suppression of free PAI-1 (0.59±0.15 vs. 0.14±0.01 vs. 0.41±0.09, p &lt; 0.001). Conclusion: Our porcine CA model provides an excellent platform for evaluating antithrombotic interventions. Plasma testing after prolonged CA/CPR suggests consumptive coagulopathy, although TEG indicates a persistent hypercoagulable state. ART-123 given before no-flow or just after CPR demonstrates antithrombotic effects, although the specific modes of action depending on the timing of administration.
Abstract 14195: Impact of Leukocyte Filtration and Leukocyte Modulation on Recovery of Heart Function After Prolonged Cardiac Arrest Treated With ECPR in a Porcine Model
Authors: Jensyn VanZalen, Takahiro Nakashima, Annie Phillips, Joseph Hill, Alyssa Enciso, Olivia Pak, Stephen Harvey, Keenan Longan, Robert Bartlett, Alvaro Rojas-Pena, Robert W Neumar
Journal: Circulation (2021)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival of patients with prolonged cardiac arrest (CA) that is refractory to standard CPR and ACLS. It has been proposed that ECPR accentuates inflammation after CA, potentially limiting its effectiveness. The benefits of leukocyte filters or leukocyte-modulating devices in conjunction with ECPR have not been studied. Hypothesis: When paired with ECPR, inflammation-modulating devices targeting leukocytes may improve recovery of cardiac function after prolonged cardiac arrest. Methods: In a randomized study, 24 swine (40±5kg) underwent 8min of untreated ventricular fibrillation CA followed by CPR with mechanical chest compressions and impedance threshold device for 30 min (total arrest time = 38min), immediately followed by 8h of ECPR with heparin anticoagulation and temperature maintained at 33°C. Group 1 (n=8) had standard ECPR system (control), Group 2 (n=8) had a leukocyte filter device (LF) added to the ECPR circuit, an and Group 3 (n=8) had a leukocyte modulation device (LMOD) added to the ECPR circuit. Recovery of cardiac function was measured using a cardiac resuscitablity score (CRS) and left ventricular ejection fraction (LVEF) via transthoracic echocardiography. Data was collected at baseline (prior CA) and after 8h of ECPR. Data analysis: single-factor ANOVA test (p&lt;0.05 significance). Results: There were no statically significant differences between the groups in CRS (Control = 3.3 ± 2.4, LF = 4.0 ± 2.8, LMOD = 2.1 ± 2.6; p=0.37) or LVEF (Control = 59% ± 27%, LF = 49% ± 29% LMOD = 34% ± 38%: p=0.34) at 8 hours after ECPR initiation (Table 1). Discussion: In this swine model of prolonged cardiac arrest treated with ECPR, addition of a leukocyte filter or leukocyte modulation device to the ECPR circuit did not improve recovery of cardiac function during the first 8 hours after initiating ECPR.
The study of tissue IgG4 in the mucous membrane of the colon in patients with inflammatory bowel disease
Authors: Yu.M. Stepanov, T.S. Tarasova, M.V. Stoikevych, Yu.A. Gaydar, N.S. Fedorova
Journal: GASTROENTEROLOGY (2021)

Background. Inflammatory bowel disease (IBD) is a global problem today, with a growing prevalence in the world. It significantly increases the economic burden on the health care system. Recently, many studies indicate the important role of immunoglobulin G4 (IgG4) in the formation of chronic inflammation in IBD and the possibility of using it as a biomarker of the inflammatory process. The purpose was to improve the diagnosis of chronic inflammatory bowel diseases by studying the status of IgG4-positive plasma cells in the mucous membrane of the colon in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Materials and methods. We have examined 34 patients with IBD, 25 with UC and 9 with CD, of them 20 women and 14 men, with an average age of (38.8 ± 3.0) and (38.2 ± 3.7) years, respectively. Patients were divided into groups depending on the nosology and severity of the disease. All patients underwent endoscopic examination of the colon to establish or clarify the diagnosis, and biopsy specimens were taken for histological and immunohistochemical examination. Results. In 13 (38.3%) of 34 examined patients, a positive result for the presence of tissue IgG4 (≥ 10 cells in the field of view) was found. Among patients with UC, 48% have a positive result of immunohistochemical examination of tissue IgG4, in people with CD, this figure is 11.1%. This gives us reason to say that in UC, elevation of tissue IgG4 levels occurs 4.4 times more often. Positive tissue IgG4 in patients with moderate UC was found 1.1 times more often than in severe UC. Among patients with mildly active disease, tissue IgG4 was not detected. Conclusions. In UC, IgG4-positive cells in the mucous layer of the colon are more common than in CD, which makes it possible to use this indicator for the differential diagnosis of ulcerative colitis and Crohn’s disease. Positive tissue IgG4 is more common in moderate form than in severe one.
Re: Jana S. Hopstaken, Joyce G.R. Bomers, Michiel J.P. Sedelaar, Massimo Valerio, Jurgen J. Fütterer, Maroeska M. Rovers. An Updated Systematic Review on Focal Therapy in Localized Prostate Cancer: What Has Changed over the Past 5 Years? Eur Urol. In press. https://doi.org/10.1016/j.eururo.2021.08.005
Authors: Anthony T. Nguyen, Mitchell Kamrava
Journal: European Urology (2021)
The germinal centre B cell response to SARS-CoV-2
Authors: Brian J. Laidlaw, Ali H. Ellebedy
Journal: Nature reviews. Immunology (2021)

The germinal centre (GC) response is critical for the generation of affinity-matured plasma cells and memory B cells capable of mediating long-term protective immunity. Understanding whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination elicits a GC response has profound implications for the capacity of responding B cells to contribute to protection against infection. However, direct assessment of the GC response in humans remains a major challenge. Here we summarize emerging evidence for the importance of the GC response in the establishment of durable and broad immunity against SARS-CoV-2 and discuss new approaches to modulate the GC response to better protect against newly emerging SARS-CoV-2 variants. We also discuss new findings showing that the GC B cell response persists in the draining lymph nodes for at least 6 months in some individuals following vaccination with SARS-CoV-2 mRNA-based vaccines. In this Review, Brian Laidlaw and Ali Ellebedy outline our current understanding of the germinal centre response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its importance for establishing protective immunity against the virus. They also consider the germinal centre responses seen following vaccination and how germinal centre responses may be modulated to induce broad protection against new variants of SARS-CoV-2.
64P Neoadjuvant toripalimab plus chemotherapy in patients with potentially resectable non-small cell lung cancer: A prospective, single-arm, phase II trial (Renaissance Study)
Authors: S. Yan, J. Chen, J. Wang, C. Lv, J. Bi, X. Yang, S. Li, Y. Wang, X. Li, Y. Yang, N. Wu
Journal: Annals of Oncology (2021)
Pipeline in Jeopardy—Challenges in Developing Patient-Oriented Interventions Researchers in Psychiatry and Opportunities for Action
Authors: Reilly R. Kayser, Melissa Arbuckle, H. Blair Simpson
Journal: JAMA Psychiatry (2021)

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 Psychiatry 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 2022 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 Psychiatry journal
Preemptive Noninvasive Ventilation to Facilitate Weaning from Mechanical Ventilation in Obese Patients at High Risk of Reintubation
Authors: Domenico Luca Grieco, Samir Jaber
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

come from teaching and research institutions in France or abroad, or from public or private research centers.L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Integrating Diversity, Equity, and Inclusion Approaches Into Treatment of Commercial Tobacco Use for Optimal Cancer Care Delivery
Authors: _ _
Journal: Journal of the National Comprehensive Cancer Network (2021)

Tobacco-related cancer incidence and mortality and commercial tobacco use have decreased steadily in recent decades, but improvements have not been equitably experienced across population subgroups. A complex interaction across socioecological domains of individual, interpersonal, community/organization, and societal/policy factors influence disparities in tobacco use, treatment, and related health outcomes. NCI’s Cancer Center Cessation Initiative (C3I) provides an ideal platform to examine and intervene on multilevel influences across the cancer control continuum to reduce any disproportionate tobacco-related burden and eliminate tobacco-related disparities. The C3I Diversity, Equity, and Inclusion (DEI) Working Group encourages cancer centers to develop, evaluate, and adopt evidence-based practices regarding DEI for prevention and treatment of commercial tobacco use across the cancer control continuum. This paper highlights how 3 C3I sites intervene to address socioecological influences on tobacco use among racially, ethnically, socioeconomically, and geographically diverse patient subgroups. It then outlines ways in which DEI considerations could be integrated into research with patients with cancer who use tobacco and practices related to standards of cancer care. Incorporating DEI considerations in the pursuit of optimal tobacco treatment could facilitate elimination of inequities in population-level cancer outcomes, spanning the full continuum of cancer care from prevention to survivorship.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2021)

While the importance of poly(ADP-ribosyl)ation (PARylation) by nuclear PARPs is clear, less is understood about mono(ADP-ribosyl)ation (MARylation).Challa and colleagues investigated how MARylation of ribosomal proteins by the ADP-ribosyl transferase PARP-16 is supported by the highly upregulated cytosolic NAD þ synthase NMNAT-2 in ovarian cancer.Sitespecific MARylation inhibited polysome assembly and translation of select mRNAs, enhancing cancer cell growth by maintaining subcellular protein homeostasis.After observing a surprising increase in translation following NMNAT-2 knockdown, the authors identified PARP-16 as the mono(ADP-ribosyl) transferase required for NMNAT-2-regulated ribosomal protein MARylation.Depletion of NMNAT-2 and PARP-16 resulted in protein aggregation and proteotoxicity in ovarian cancer cells, with alternative MARylation and mRNA loading of polysomes.The authors concluded that maintaining proteostasis is critical for cancer, which often relies on increased ribosome biogenesis and translation for growth.Expert Commentary: Cancers restrain protein translation to balance increased proliferation and proteotoxicity.NMNAT-2 and PARP-16 maintain this homeostasis in ovarian cancer in a pathway potentially applicable to other cancers.(Image courtesy of
What Is Gout?
Authors: Kevin Yip, Jessica Berman
Journal: JAMA (2021)

What Is Gout?Gout is a form of arthritis caused by the buildup of uric acid crystals in the body.Gout can cause acute inflammation of 1 or more joints (gout flare) and in severe cases can lead to permanent joint damage (chronic gouty arthritis).Uric acid crystals can also form hard lumpy deposits in the skin called tophi. How Common Is Gout?Gout affects approximately 9.2 million people in the US (about 3.9% of the adult population).It is more common in men and older people.
Identification of a small, depressed type of colorectal invasive cancer by an artificial intelligence-assisted detection system
Authors: Shin-ei Kudo, Masashi Misawa, Yuichi Mori, Yurie Kawabata, Yasuharu Maeda, Hideyuki Miyachi, Kensaku Mori
Journal: Endoscopy (2021)

A 64-year-old man underwent surveillance colonoscopy with a computer-aided detection (CADe) system (EndoBRAIN-EYE; Cybernet Systems, Tokyo, Japan) [1]. The system identified a 5-mm slightly reddish lesion in the sigmoid colon. Spraying with indigo carmine enabled identification of a clearly depressed area on the lesion ([Fig. 1], [Video 1]). The lesion showed type VI pit pattern, indicating high grade dysplasia or slightly invasive submucosal cancer [2]. Endoscopic mucosal resection was performed. Pathological examination showed a well-differentiated adenocarcinoma with slight invasion of the submucosal layer ([Fig. 2], [Fig. 3], [Fig. 4]).
Therapeutic Exon Skipping Through a CRISPR-Guided Cytidine Deaminase Rescues Dystrophic Cardiomyopathy in Vivo
Authors: Jia Li, Kaiying Wang, Yuchen Zhang, Tuan Qi, Juanjuan Yuan, Lei Zhang, Han Qiu, Jinxi Wang, Huang-Tian Yang, Yi Dai, Yan Song, Xing Chang
Journal: Circulation (2021)

Loss of dystrophin protein causes Duchenne muscular dystrophy (DMD), characterized by progressive degeneration of cardiac and skeletal muscles, and mortality in adolescence or young adulthood. Although cardiac failure has risen as the leading cause of mortality in patients with DMD, effective therapeutic interventions remain underdeveloped, in part, because of the lack of a suitable preclinical model.We analyzed a novel murine model of DMD created by introducing a 4-bp deletion into exon 4, one of the exons encoding the actin-binding domain 1 of dystrophin (referred to as DmdE4* mice). Echocardiography, microcomputed tomography, muscle force measurement, and histological analysis were performed to determine cardiac and skeletal muscle defects in these mice. Using this model, we examined the feasibility of using a cytidine base editor to install exon skipping and rescue dystrophic cardiomyopathy in vivo. AAV9-based CRISPR/Cas9-AID (eTAM) together with AAV9-sgRNA was injected into neonatal DmdE4* mice, which were analyzed 2 or 12 months after treatment to evaluate the extent of exon skipping, dystrophin restoration, and phenotypic improvements of cardiac and skeletal muscles.DmdE4* mice recapitulated many aspects of human DMD, including shortened life span (by ≈50%), progressive cardiomyopathy, kyphosis, profound loss of muscle strength, and myocyte degeneration. A single-dose administration of AAV9-eTAM instituted >50% targeted exon skipping in the Dmd transcripts and restored up to 90% dystrophin in the heart. As a result, early ventricular remodeling was prevented and cardiac and skeletal muscle functions were improved, leading to an increased life span of the DmdE4* mice. Despite gradual decline of AAV vector and base editor expression, dystrophin restoration and pathophysiological rescue of muscular dystrophy were long lasted for at least 1 year.Our study demonstrates the feasibility and efficacy to institute exon skipping through an enhanced TAM (eTAM) for therapeutic application(s).
An Updated Definition and Severity Classification of Chronic Obstructive Pulmonary Disease Exacerbations: The Rome Proposal
Authors: Bartolome R. Celli, Leonardo M. Fabbri, Shawn D. Aaron, Alvar Agusti, Robert Brook, Gerard J. Criner, Frits M. E. Franssen, Marc Humbert, John R. Hurst, Denis O’Donnell, Leonardo Pantoni, Alberto Papi, Roberto Rodriguez-Roisin, Sanjay Sethi, Antoni Torres, Claus F. Vogelmeier, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
<i>JAMA</i> and the US Preventive Services Task Force
Authors: Phil B. Fontanarosa, Robert M. Golub
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Global Percentage of Asymptomatic SARS-CoV-2 Infections Among the Tested Population and Individuals With Confirmed COVID-19 Diagnosis
Authors: Qiuyue Ma, Jue Liu, Qiao Liu, Liangyu Kang, Runqing Liu, Wenzhan Jing, Yu Wu, Min Liu
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Asymptomatic infections are potential sources of transmission for COVID-19. <h3>Objective</h3> To evaluate the percentage of asymptomatic infections among individuals undergoing testing (tested population) and those with confirmed COVID-19 (confirmed population). <h3>Data Sources</h3> PubMed, EMBASE, and ScienceDirect were searched on February 4, 2021. <h3>Study Selection</h3> Cross-sectional studies, cohort studies, case series studies, and case series on transmission reporting the number of asymptomatic infections among the tested and confirmed COVID-19 populations that were published in Chinese or English were included. <h3>Data Extraction and Synthesis</h3> This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Random-effects models were used to estimate the pooled percentage and its 95% CI. Three researchers performed the data extraction independently. <h3>Main Outcomes and Measures</h3> The percentage of asymptomatic infections among the tested and confirmed populations. <h3>Results</h3> Ninety-five unique eligible studies were included, covering 29 776 306 individuals undergoing testing. The pooled percentage of asymptomatic infections among the tested population was 0.25% (95% CI, 0.23%-0.27%), which was higher in nursing home residents or staff (4.52% [95% CI, 4.15%-4.89%]), air or cruise travelers (2.02% [95% CI, 1.66%-2.38%]), and pregnant women (2.34% [95% CI, 1.89%-2.78%]). The pooled percentage of asymptomatic infections among the confirmed population was 40.50% (95% CI, 33.50%-47.50%), which was higher in pregnant women (54.11% [95% CI, 39.16%-69.05%]), air or cruise travelers (52.91% [95% CI, 36.08%-69.73%]), and nursing home residents or staff (47.53% [95% CI, 36.36%-58.70%]). <h3>Conclusions and Relevance</h3> In this meta-analysis of the percentage of asymptomatic SARS-CoV-2 infections among populations tested for and with confirmed COVID-19, the pooled percentage of asymptomatic infections was 0.25% among the tested population and 40.50% among the confirmed population. The high percentage of asymptomatic infections highlights the potential transmission risk of asymptomatic infections in communities.
The approximate number system represents magnitude <i>and</i> precision
Authors: Charles R. Gallistel
Journal: Behavioral and Brain Sciences (2021)

Abstract Numbers are symbols manipulated in accord with the axioms of arithmetic. They sometimes represent discrete and continuous quantities (e.g., numerosities, durations, rates, distances, directions, and probabilities), but they are often simply names. Brains, including insect brains, represent the rational numbers with a fixed-point data type, consisting of a significand and an exponent, thereby conveying both magnitude and precision.
Correction: In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint blockade response to elicit systemic antitumor immunity against intraocular melanoma and its metastasis
Journal: Journal for ImmunoTherapy of Cancer (2021)

Correction: In situ immunogenic clearance induced by a combination of photodynamic therapy and rho-kinase inhibition sensitizes immune checkpoint