tbuckley/cabot-search huggingface dataset:
Assessment of Emotional Outcomes of Intraoperative Death on Surgical Team Members
Authors: Tara N. Cohen, Andrew S. Wang, Edward G. Seferian, Harry C. Sax, Bruce L. Gewertz
Journal: JAMA Surgery (2021)

This cohort study surveys surgeons, anesthesiologists, residents, nurses, and technicians at a single institution regarding their experiences of intraoperative death, particularly emotional outcomes.
Prothrombotic immune thrombocytopenia after COVID-19 vaccination
Authors: Andreas Tiede, Ulrich J. Sachs, Andreas Czwalinna, Sonja Werwitzke, Rolf Bikker, Joachim K. Krauss, Frank Donnerstag, Karin Weißenborn, Günter Höglinger, Benjamin Maasoumy, Heiner Wedemeyer, Arnold Ganser
Journal: Blood (2021)
Assessing the Association of Mitochondrial Function and Inflammasome Activation in Murine Macrophages Exposed to Select Mitotoxic Tri-Organotin Compounds
Authors: Gabrielle M. Childers, Caroline A. Perry, Barbara Blachut, Negin Martin, Carl D. Bortner, Stella Sieber, Jian-Liang Li, Michael B. Fessler, G. Jean Harry
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Mitochondrial function is implicated as a target of environmental toxicants and found in disease or injury models, contributing to acute and chronic inflammation.One mechanism by which mitochondrial damage can propagate inflammation is via activation of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing receptor (NLRP)3 inflammasome, a protein complex that processes mature interleukin ðILÞ-1b.IL-1b plays an important role in the innate immune response and dysregulation is associated with autoinflammatory disorders.OBJECTIVE: The objective was to evaluate whether mitochondrial toxicants recruit inflammasome activation and IL-1b processing.METHOD: Murine macrophages (RAW 264.7) exposed to tri-organotins (triethyltin bromide (TETBr), trimethyltin hydroxide (TMTOH), triphenyltin hydroxide (TPTOH), bis(tributyltin)oxide) [Bis(TBT)Ox] were examined for pro-inflammatory cytokine induction.TMTOH and TETBr were examined in RAW 264.7 and bone marrow-derived macrophages for mitochondrial bioenergetics, reactive oxygen species (ROS) production, and inflammasome activation via visualization of aggregate formation, caspase-1 flow cytometry, IL-1b enzyme-linked immunosorbent assay and Western blots, and microRNA (miRNA) and mRNA arrays.RESULTS: TETBr and TMTOH induced inflammasome aggregate formation and IL-1b release in lipopolysaccharide (LPS)-primed macrophages.Mitochondrial bioenergetics and mitochondrial ROS were suppressed.Il1a and Il1b induction with LPS or LPS+ATP challenge was diminished.Differential miRNA and mRNA profiles were observed.Lower miR-151-3p targeted cyclic adenosine monophosphate (cAMP)-mediated and AMPactivated protein kinase signaling pathways; higher miR-6909-5p, miR-7044-5p, and miR-7686-5p targeted Wnt beta-catenin signaling, retinoic acid receptor activation, apoptosis, signal transducer and activator of transcription 3, IL-22, IL-12, and IL-10 signaling.Functional enrichment analysis identified apoptosis and cell survival canonical pathways.CONCLUSION: Select mitotoxic tri-organotins disrupted murine macrophage transcriptional response to LPS, yet triggered inflammasome activation.The differential response pattern suggested unique functional changes in the inflammatory response that may translate to suppressed host defense or prolong inflammation.We posit a framework to examine immune cell effects of environmental mitotoxic compounds for adverse health outcomes.
Demographic, Clinical, and Mortality Trends of Law Enforcement–Related Trauma
Authors: Alexandra T. Bourdillon, Parsa P. Salehi, Jonathan Y. Lee, Benjamin Steren, Kevin Y. Pei, Yan Ho Lee
Journal: JAMA Surgery (2021)

This cross-sectional study examines demographic, clinical, and mortality trends of law enforcement–related traumatic injuries using 2014 to 2016 data from the Trauma Quality Improvement Program.
Minimal Intensity Fludarabine/Cyclophosphamide Versus Myeloablative Thiotepa/Cyclophosphamide Followed By Allogeneic Hematopoetic Stem Cell Transplantation (HSCT) for the Treatment of Acute Myeloid Leukemia (AML)— a Retrospective Single Institution Experience
Authors: Nabin Khanal, Brian E Johnson, H. Scott Boswell, Heiko Konig, Susan M Perkins, Robert P. Nelson
Journal: Blood (2017)
ABLATION VS ANTIARRHYTHMIC DRUGS AS FIRST-LINE TREATMENT OF PAROXYSMAL ATRIAL FIBRILLATION: A META-ANALYSIS OF RANDOMIZED TRIALS
Authors: Babikir Kheiri, Timothy Simpson, Ryle Przybylowicz, Miranda Merrill, Hani Alhamoud, Mohammed Osman, Khidir Dalouk, Eric Stecker, Charles Henrikson, Babak Nazer
Journal: Journal of the American College of Cardiology (2021)
Targeting DDX3X Triggers Antitumor Immunity via a dsRNA-Mediated Tumor-Intrinsic Type I Interferon Response
Authors: Hyeongjwa Choi, Juntae Kwon, Min Soon Cho, Yifan Sun, Xiaofeng Zheng, Jing Wang, Kerrie B. Bouker, John L. Casey, Michael B. Atkins, Jeffrey Toretsky, Cecil Han
Journal: Cancer Research (2021)

Induction of nucleic acid sensing-mediated type I interferon (IFN) has emerged as a novel approach to activate the immune system against cancer. Here we show that the depletion of DEAD-box RNA helicase 3X (DDX3X) triggers a tumor-intrinsic type I IFN response in breast cancer cells. Depletion or inhibition of DDX3X activity led to aberrant cytoplasmic accumulation of cellular endogenous double-stranded RNAs (dsRNA), which triggered type I IFN production through the melanoma differentiation-associated gene 5 (MDA5)-mediated dsRNA-sensing pathway. Furthermore, DDX3X interacted with dsRNA-editing ADAR1 and dual depletion of DDX3X and ADAR1 synergistically activated the cytosolic dsRNA pathway in breast cancer cells. Loss of DDX3X in mouse mammary tumors enhanced antitumor activity by increasing the tumor-intrinsic type I IFN response, antigen presentation, and tumor infiltration of cytotoxic T and dendritic cells. These findings may lead to the development of a novel therapeutic approach for breast cancer by targeting DDX3X in combination with immune-checkpoint blockade. SIGNIFICANCE: This study elucidates the novel role of DDX3X in regulating endogenous cellular dsRNA homeostasis and type I IFN signaling in breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/13/3607/F1.large.jpg.
Efficacy and Safety of Using Dual Versus Monotherapy Antiplatelet Agents in Secondary Stroke Prevention: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials
Authors: Gabriela Trifan, Philip B. Gorelick, Fernando D. Testai
Journal: Circulation (2021)

Dual antiplatelet treatment (DAPT) with aspirin plus clopidogrel for a limited time is recommended after minor noncardioembolic stroke.We performed a meta-analysis of all major studies that compared the efficacy and safety of DAPT versus monotherapy for the secondary prevention of recurrent stroke or transient ischemic attack. The primary outcomes were stroke and the composite of stroke, transient ischemic attack, acute coronary syndrome, and death from any cause. The safety outcome was major hemorrhage. Relative risk (RR) and 95% CIs were calculated. Heterogeneity was assessed by I2 and Cochrane Q statistics.The analysis included 27 358 patients, the quality of evidence was moderate to low, and the heterogeneity for all the comparisons was low (I2≤25%). Compared with monotherapy, DAPT reduced the risk of recurrent stroke (RR, 0.71 [95% CI, 0.63-0.81]) and composite outcome (RR, 0.76 [95% CI, 0.69-0.83]) but increased the risk of major bleeding (RR, 2.17 [95% CI, 1.45-3.25]). In the subgroup analysis, ≤30 days of DAPT increased the risk of hemorrhage relative to monotherapy (RR, 1.94 [95% CI, 1.08-3.52]). In the sensitivity analysis, the risk for hemorrhage with ≤30 days of DAPT after excluding the combination of aspirin plus ticagrelor was comparable to monotherapy (RR, 1.42 [95% CI, 0.77-2.60]). However, the risk for stroke recurrence and composite outcomes in the subgroup and sensitivity analyses remain decreased compared with monotherapy.DAPT decreases the risk of recurrent stroke and composite events compared with monotherapy. DAPT increases the risk of major hemorrhage, except if the treatment is limited to 30 days and does not include the combination of aspirin plus ticagrelor.
PTU-056 Improving re-bleed plans in patients with suspected significant upper gastrointestinal bleeding (ugib)
Authors: F Ti, MY Tan, CH Cheong, MW James
Journal: Gut (2017)

Introduction  The 2015 NCEPOD report1 found high rebleeding and mortality rates in patients with significant UGIB and recommended clearly documented rebleed plans. We audited the adequacy of rebleed plans at Nottingham University Hospitals, where 800 suspected UGIB patients are admitted annually.  Method  Patients who underwent emergency endoscopy for suspected acute UGIB between June - August 2015 were identified. We analysed patient demographics, endoscopy (OGD) findings, re-bleed plans and clinical outcomes. Focused recommendations and education were delivered to all endoscopy unit staff. Re-audit was performed during June - July 2016 and outcomes compared.  Results  130 patients: 81 (62.6%) men, median (range) age 61 (14-92); 49 (37.4%) women, median (range) age 73 (34-96) years underwent urgent OGD following suspected acute UGIB between June -August 2015. 42 (32.3%) had endoscopic evidence of active UGIB (21 (16%) variceal haemorrhage (VH), and 21 (16%) non-variceal haemorrhage (NVH)) and 88 (67.7%) had no evidence of bleeding. Only 23.1% (n=30) who underwent urgent OGD had a re-bleed plan but was higher in those with (20/42 (47.6%); 11.9% re-bled, 5% mortality) rather than without (10/88 (11.4%); 5.7% re-bled; 0% mortality) endoscopic signs of bleeding.  During the 4 week re-audit period after staff engagement and education, 42 patients (66.7% men, median age 60.5; 33.3% female, median age 77 years) underwent OGD for suspected UGIB. 21.4% had endoscopic evidence of active UGIB (7.1% VH; 14.3% NVH) and 78.6% had no evidence of bleeding. Rebleed plans improved overall from 23.1% to 46.3% and were higher in those with ((77.8%); 11.1% re-bled; 0% mortality) rather than without ((37.5%); 3.1% re-bled; 0% mortality) endoscopic signs of bleeding.  Most frequent re-bleed plans were repeat OGD (34.7%), CT angiogram/interventional radiology (34.7%), conservative management (16.3%) or lower GI endoscopy (6.1%). Surgery was not recommended in any initial rebleed plan.  Conclusion  Most patients with suspected acute UGIB did not have endoscopic evidence of active bleeding, but still had rebleed rates of between 3%–11%. Clear documentation of rebleed plans initially was poor, but was better in those with endoscopic signs of active bleeding. Following focused education, rebleed plans improved substantially overall from 23.1% to 46.3%, particularly in those with active bleeding from 47.6% to 77.8%, who had a higher risk of rebleeding and in-hospital mortality.  Reference  . McPherson SJ, et al. Time to get Control; NCEPOD report 2015.   Disclosure of Interest  None Declared
Comparative effectiveness of two adalimumab biosimilars in 1318 real-world patients with inflammatory rheumatic disease mandated to switch from originator adalimumab: nationwide observational study emulating a randomised clinical trial
Authors: Hafsah Nabi, Stylianos Georgiadis, Anne Gitte Loft, Oliver Hendricks, Marlene Andersen, Stavros Chrysidis, Ada Colic, Kamilla Danebod, Mohamad Redha Hussein, Maren Høgberget Kalisz, Salome Kristensen, Niels Lomborg, Natalia Manilo, Heidi Lausten Munk, Jens Kristian Pedersen, Johnny Lillelund Raun, Frank Mehnert, Niels Steen Krogh, Merete Lund Hetland, Bente Glintborg
Journal: Annals of the Rheumatic Diseases (2021)

In 2018, a nationwide mandatory switch from originator to biosimilar adalimumab was conducted in Denmark. The available biosimilar was GP2017 (Hyrimoz) in Eastern regions and SB5 (Imraldi) in Western regions. We aimed to assess the comparative effectiveness of GP2017 versus SB5 in patients with rheumatoid arthritis (RA)/psoriatic arthritis (PsA)/axial spondyloarthritis (AxSpA).Observational cohort study based on the DANBIO registry with geographical cluster pseudo-randomisation, analysed by emulating a randomised clinical trial. Main outcome was adjusted 1-year treatment retention (Cox regression). Furthermore, 6 months' remission rates (logistic regression), reasons for withdrawal and back-switching to originator were investigated (overall and stratified by indication).Overall, of 1570 eligible patients, 1318 switched and were included (467 RA/321 PsA/530 AxSpA); 623 (47%) switched to GP2017, 695 (53%) to SB5. Baseline characteristics of the two clusters were largely similar, but some differences in registration practice were observed. The combined 1-year retention rate for the two biosimilars was 89.5%. Compared with SB5, estimated risk of withdrawal for GP2017 was lower (HR 0.60; 95% CI 0.42 to 0.86) and 6 months' remission rate was higher (OR 1.72; 95% CI 1.25 to 2.37). Stratified analyses gave similar results (statistically significant for RA). During 1 year, 8.5% and 12.9% withdrew GP2017 and SB5, respectively (primarily lack of effect and adverse events), of whom 48 patients (3.6%) back-switched.This head-to-head comparison of GP2017 versus SB5 following a mandatory switch from the originator indicated differences in effectiveness in routine care. This may reflect a true difference, but other explanations, for example, differences in excipients, differences between clusters and residual confounding cannot be ruled out.
ELAMIPRETIDE IMPROVES FUNCTIONAL ASSESSMENTS WHEN COMPARED TO THE NATURAL HISTORY PROGRESSION OF CARDIOMYOPATHY-RELATED DISEASE SYMPTOMATOLOGY IN PATIENTS WITH BARTH SYNDROME: A TAZPOWER ANALYSIS
Authors: W. Reid Thompson, Ryan Manuel, Anthony Abbruscato, Jim Carr, Brittany Hornby, Hilary Vernon
Journal: Journal of the American College of Cardiology (2021)
An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice
Authors: Takeshi Kimura, Michaela Bosakova, Yosuke Nonaka, Eva Hruba, Kie Yasuda, Satoshi Futakawa, Takuo Kubota, Bohumil Fafilek, Tomas Gregor, Sara P. Abraham, Regina Gomolkova, Silvie Belaskova, Martin Pesl, Fabiana Csukasi, Ivan Duran, Masatoshi Fujiwara, Michaela Kavkova, Tomas Zikmund, Josef Kaiser, Marcela Buchtova, Deborah Krakow, Yoshikazu Nakamura, Keiichi Ozono, Pavel Krejci
Journal: Science Translational Medicine (2021)

We report reversal of the FGFR3-related skeletal dysplasia by RNA aptamer designed to neutralize FGFR3 ligand FGF2.
A kinome screen reveals that Nemo-like kinase is a key suppressor of hepatic gluconeogenesis
Authors: Yan-Xiao Ji, Yutao Wang, Peng-Long Li, Lin Cai, Xiao-Ming Wang, Lan Bai, Zhen Liu, Han Tian, Song Tian, Peng Zhang, Xiao-Jing Zhang, Xu Cheng, Yufeng Yuan, Zhi-Gang She, Yufeng Hu, Hongliang Li
Journal: Cell Metabolism (2021)
Melanocortin 4 receptor signals at the neuronal primary cilium to control food intake and body weight
Authors: Yi Wang, Adelaide Bernard, Fanny Comblain, Xinyu Yue, Christophe Paillart, Sumei Zhang, Jeremy F. Reiter, Christian Vaisse
Journal: Journal of Clinical Investigation (2021)

The melanocortin 4 receptor (MC4R) plays a critical role in the long-term regulation of energy homeostasis, and mutations in the MC4R are the most common cause of monogenic obesity. However, the precise molecular and cellular mechanisms underlying the maintenance of energy balance within MC4R-expressing neurons are unknown. We recently reported that the MC4R localizes to the primary cilium, a cellular organelle that allows for partitioning of incoming cellular signals, raising the question of whether the MC4R functions in this organelle. Here, using mouse genetic approaches, we found that cilia were required specifically on MC4R-expressing neurons for the control of energy homeostasis. Moreover, these cilia were critical for pharmacological activators of the MC4R to exert an anorexigenic effect. The MC4R is expressed in multiple brain regions. Using targeted deletion of primary cilia, we found that cilia in the paraventricular nucleus of the hypothalamus (PVN) were essential to restrict food intake. MC4R activation increased adenylyl cyclase (AC) activity. As with the removal of cilia, inhibition of AC activity in the cilia of MC4R-expressing neurons of the PVN caused hyperphagia and obesity. Thus, the MC4R signaled via PVN neuron cilia to control food intake and body weight. We propose that defects in ciliary localization of the MC4R cause obesity in human inherited obesity syndromes and ciliopathies.
SUCCESSFUL TREATMENT OF COVID-RELATED STEMI WITH ANTI-THROMBOTIC MEDICAL MANAGEMENT
Authors: Pranav Venkataraman, Michael Armstrong, Levi May, Faisal Dadi, Raj Patel, Ahmed Alabbady, Jacek Slowikowski, Ali Hama Amin, Mohd Mirza
Journal: Journal of the American College of Cardiology (2021)
ALENDRONATE ACCELERATES CALCIFICATION AND BONE FORMATION IN CHOLECALCIFEROL INDUCED IN VIVO RABBIT AORTIC STENOSIS MODEL
Authors: Sercan Okutucu, Cengiz Sabanoglu, Arzu Saglam Ayhan, Erol Tulumen, Hakan Aksoy, Ali Oto
Journal: Journal of the American College of Cardiology (2021)
経皮感作は皮膚常在性調節性T細胞を介した皮膚樹状細胞移動のin situ阻害により制限される【JST・京大機械翻訳】
Authors: Hanakawa Sho, Kitoh Akihiko, Shibuya Rintaro, Dainichi Teruki, Nomura Takashi, Honda Tetsuya, Egawa Gyohei, Otsuka Atsushi, Nakajima Saeko, Fujita Mitsugu, Kabashima Kenji
Journal: Journal of Allergy and Clinical Immunology (2019)
CHEMOREFLEX AND BAROREFLEX DYSFUNCTION IN CHRONIC HEART FAILURE: CLINICAL CORRELATES AND PROGNOSTIC SIGNIFICANCE
Authors: Francesco Gentile, Francesco Buoncristiani, Daniele Caratozzolo, Chiara Borrelli, Paolo Sciarrone, Claudio Passino, Michele Emdin, Alberto Giannoni
Journal: Journal of the American College of Cardiology (2021)
Mycotic aneurysm of the infrarenal abdominal aorta infected by Mycoplasma hyorhinis diagnosed with direct 16S ribosomal DNA sequencing
Authors: Stephan P. Keijmel, Saskia Kuipers, Michel F.P. van der Jagt, Willem J.G. Melchers, Ilse J.E. Kouijzer, Jaap ten Oever
Journal: Clinical Microbiology and Infection (2021)
Mental health after paediatric concussion: a systematic review and meta-analysis
Authors: Alice Gornall, Michael Takagi, Thilanka Morawakage, Xiaomin Liu, Vicki Anderson
Journal: British Journal of Sports Medicine (2021)

This systematic review and meta-analysis sought to rigorously examine mental health outcomes following paediatric concussion. To date, heterogeneous findings and methodologies have limited clinicians' and researchers' ability to meaningfully synthesise existing literature. In this context, there is a need to clarify mental health outcomes in a homogeneous sample, controlling for key methodological differences and applying a consistent definition of concussion across studies.Systematic review and meta-analysis.We searched Medline, Embase, PsycINFO, CINAHL, SportDiscus, Scopus and PubMed.Peer-reviewed studies published between 1980 and June 2020 that prospectively examined mental health outcomes after paediatric concussion, defined as per the Berlin Consensus Statement on Concussion in Sport.Sixty-nine articles characterising 60 unique samples met inclusion criteria, representing 89 114 children with concussion. Forty articles (33 studies) contributed to a random effects meta-analysis of internalising (withdrawal, anxiety, depression, post-traumatic stress), externalising (conduct problems, aggression, attention, hyperactivity) and total mental health difficulties across three time points post-injury (acute, persisting and chronic). Overall, children with concussion (n=6819) experienced significantly higher levels of internalising (g=0.41-0.46), externalising (g=0.25-0.46) and overall mental health difficulties compared with controls (g=0.18-0.49; n=56 271), with effects decreasing over time.Our review highlights that mental health is central to concussion recovery. Assessment, prevention and intervention of mental health status should be integrated into standard follow-up procedures. Further research is needed to clarify the mechanisms underlying observed relationships between mental health, post-concussion symptoms and other psychosocial factors. Results suggest that concussion may both precipitate and exacerbate mental health difficulties, thus impacting delayed recovery and psychosocial outcomes.
Dramatic Ventricular Shunt Complications in Pulmonary and Critical Care Medicine
Authors: Woo Young Kim, IrfanAli Kugasia, Gregory Pearson, Oleg Epelbaum
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Dramatic Ventricular Shunt Complications in Pulmonary and Critical Care Medicine." American Journal of Respiratory and Critical Care Medicine, 204(9), pp. e94–e96
A first in human trial of an oral histone deacetylase inhibitor, MS-275, in advanced solid tumor and lymphoma patients.
Authors: Q. Ryan, D. Headlee, Y. Elsayed, D. Figg, A. Sparreboom, S. Zhai, J. Trepel, A. Murgo, J. Zwiebel, E. Sausville
Journal: Cancer Research (2004)

2452  We have conducted a first in human Phase I trial using MS-275, an oral histone deacetylase inhibitor, in advanced solid tumors and lymphoma patients. The trial initially used a daily x 28, repeated every 6 weeks, dosing schedule with an accelerated titration design, beginning at 2 mg/m2 (1/10th rat maximal tolerated dose [MTD]). However, in humans the MTD was immediately exceeded at the 1st dose level with grade 3 AST, hypophosphatemia, hypoalbuminemia, pleural effusion and epigastric pain. Preliminary PK analysis suggested that the t1/2 of MS-275 in humans is substantially longer than preclinical species predicted to account for this finding. A once q14 day schedule was then implemented, starting at 2 mg/m2 with 2 mg/m2 increments. Twenty-seven patients have been enrolled on the q14 day schedule. The first course severe adverse events observed were CTC grade 3 nausea, fatigue, anorexia, and vomiting. Frequent grade 1-2 toxicities include fatigue, nausea, hypoalbuminemia, headache, thrombocytopenia, anorexia, neutropenia, and dyspepsia. The MTD was observed at 10 mg/m2 and the DLTs were nausea, anorexia and fatigue. The detailed pharmacokinetics study is underway and will be presented. Furthermore, by immunofluorescent analysis, increased histone H3 acetylation in peripheral blood mononuclear cells is apparent at all dose levels. Based on these data, a new oral schedule, weekly x 4, repeated every six weeks is presently being evaluated.
PREVALENCE OF PULMONARY HYPERTENSION IN HOSPITALIZED HEART FAILURE PATIENTS WITH AND WITHOUT AMYLOIDOSIS
Authors: Ramtej Atluri, Sujitha Velagapudi, Mukunthan Murthi, Genaro Velazquez, Hafeez Shaka, Karol Quelal, Andrea Torres
Journal: Journal of the American College of Cardiology (2021)
Abstract 16099: Electrocardiographic Response to Acute Coronary Ischemia Predicts Sudden Death
Authors: Aapo Aro, Audrey Uy-Evanado, Carmen Rusinaru, Kyndaron Reinier, Jonathan Jui, Sumeet S Chugh
Journal: Circulation (2017)

Background: Coronary ischemia is relatively common, but will trigger sudden cardiac arrest (SCA) in only a subgroup of patients. We hypothesized that electrical substrate vulnerable to acute corona...