tbuckley/cabot-search huggingface dataset:
Alternative assays to <scp>dRVVT</scp> and <scp>aPTT</scp> for lupus anticoagulant detection
Authors: Gary W. Moore
Journal: American Journal of Hematology (2020)

Lupus anticoagulants (LA) are heterogeneous antibodies and no single assay will detect every LA. Consequently, testing is commonly undertaken with both dilute Russell's viper venom time (dRVVT) and LA-responsive activated partial thromboplastin time (aPTT) to maximize detection rates. Although a huge body of evidence attests to the diagnostic utility of these assays, they have limitations that can render them unreliable in certain circumstances. Other assays are available for detecting LA but unfamiliarity, variable availability and technical concerns expressed in guidelines contribute to less usage than dRVVT and aPTT. However, assays such as Taipan snake venom time and Textarin time are insensitive to anticoagulants that compromise dRVVT and aPTT, and assays such as dilute prothrombin time can detect LA unreactive in dRVVT and aPTT. The pros and cons of alternative assays to dRVVT and APTT for LA detection are discussed.
Paralytic Agents for Intubation in the Out-of-Hospital Setting—Reply
Authors: Bertrand Guihard, Xavier Combes
Journal: JAMA (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 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
Covid-19: We need to be open about rationing ventilators
Authors: Caroline Mawer
Journal: BMJ (2020)

Inflammation causes hyperalgesia, an enhanced sensitivity to noxious stimuli. Transient receptor potential vanilloid 1 (TRPV1), a thermo-TRP ion channel activated by painful levels of heat, is an important contributor because hyperalgesia is reduced when TRPV1 is either genetically deleted or pharmacologically blocked. Inflammatory mediators such as prostaglandin-E2 or bradykinin cause hyperalgesia by activating cellular kinases that phosphorylate TRPV1, a process that has recently been shown to rely on a scaffolding protein, AKAP79, to target the kinases to TRPV1. Here we use Förster resonance energy transfer, immunoprecipitation, and TRPV1 membrane trafficking experiments to identify a key region on AKAP79, between amino acids 326–336, which is responsible for its interaction with TRPV1. A peptide identical to this domain inhibited sensitization of TRPV1 <i>in vitro</i>, and when covalently linked to a TAT peptide to promote uptake across the cell membrane the peptide inhibited <i>in vivo</i> inflammatory hyperalgesia in mice. Critically, it did so without affecting pain thresholds in the absence of inflammation. These results suggest that antagonizing the TRPV1–AKAP79 interaction will be a useful strategy for inhibiting inflammatory hyperalgesia.
Boosting delivery of rare disease therapies: the IRDiRC Orphan Drug Development Guidebook
Authors: Anneliene Hechtelt Jonker, Virginie Hivert, Michela Gabaldo, Liliana Batista, Daniel O’Connor, Annemieke Aartsma-Rus, Simon Day, Ken Sakushima, Diego Ardigo
Journal: Nature Reviews Drug Discovery (2020)
Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease
Authors: Robert Zeiser, Nikolas von Bubnoff, Jason Butler, Mohamad Mohty, Dietger Niederwieser, Reuven Or, Jeff Szer, Eva M. Wagner, Tsila Zuckerman, Bruyère Mahuzier, Judith Xu, Celine Wilke, Kunal K. Gandhi, Gérard Socié
Journal: New England Journal of Medicine (2020)

Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD.
Effects of Continuous Glucose Monitoring on Metrics of Glycemic Control in Diabetes: A Systematic Review With Meta-analysis of Randomized Controlled Trials
Authors: Maria Ida Maiorino, Simona Signoriello, Antonietta Maio, Paolo Chiodini, Giuseppe Bellastella, Lorenzo Scappaticcio, Miriam Longo, Dario Giugliano, Katherine Esposito
Journal: Diabetes Care (2020)

BACKGROUND Continuous glucose monitoring (CGM) provides important information to aid in achieving glycemic targets in people with diabetes. PURPOSE We performed a meta-analysis of randomized controlled trials (RCTs) comparing CGM with usual care for parameters of glycemic control in both type 1 and type 2 diabetes. DATA SOURCES Many electronic databases were searched for articles published from inception until 30 June 2019. STUDY SELECTION We selected RCTs that assessed both changes in HbA1c and time in target range (TIR), together with time below range (TBR), time above range (TAR), and glucose variability expressed as coefficient of variation (CV). DATA EXTRACTION Data were extracted from each trial by two investigators. DATA SYNTHESIS All results were analyzed by a random effects model to calculate the weighted mean difference (WMD) with the 95% CI. We identified 15 RCTs, lasting 12–36 weeks and involving 2,461 patients. Compared with the usual care (overall data), CGM was associated with modest reduction in HbA1c (WMD −0.17%, 95% CI −0.29 to −0.06, I2 = 96.2%), increase in TIR (WMD 70.74 min, 95% CI 46.73–94.76, I2 = 66.3%), and lower TAR, TBR, and CV, with heterogeneity between studies. The increase in TIR was significant and robust independently of diabetes type, method of insulin delivery, and reason for CGM use. In preplanned subgroup analyses, real-time CGM led to the higher improvement in mean HbA1c (WMD −0.23%, 95% CI −0.36 to −0.10, P &amp;lt; 0.001), TIR (WMD 83.49 min, 95% CI 52.68–114.30, P &amp;lt; 0.001), and TAR, whereas both intermittently scanned CGM and sensor-augmented pump were associated with the greater decline in TBR. LIMITATIONS Heterogeneity was high for most of the study outcomes; all studies were sponsored by industry, had short duration, and used an open-label design. CONCLUSIONS CGM improves glycemic control by expanding TIR and decreasing TBR, TAR, and glucose variability in both type 1 and type 2 diabetes.
Novel airway smooth muscle–mast cell interactions and a role for the TRPV4-ATP axis in non-atopic asthma
Authors: Sara J. Bonvini, Mark A. Birrell, Eric Dubuis, John J. Adcock, Michael A. Wortley, Pauline Flajolet, Peter Bradding, Maria G. Belvisi
Journal: European Respiratory Journal (2020)

Mast cell–airway smooth muscle (ASM) interactions play a major role in the immunoglobulin (Ig)E- dependent bronchoconstriction seen in asthma but less is known about IgE-independent mechanisms of mast cell activation. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) activation causes contraction of human ASM via the release of cysteinyl leukotrienes (cysLTs) but the mechanism is unknown. The objective of the present study was to investigate a role for IgE-independent, mast cell–ASM interaction in TRPV4-induced bronchospasm. Bronchoconstriction was measured in anaesthetised guinea pigs and contraction of human and guinea-pig airway tissue assessed using isometric tension measurements. Increases in intracellular [Ca 2+ ] were imaged using the Ca 2+ -sensitive dye FURA2, and time-lapse ptychography was utilised as a surrogate for contraction of ASM cells. The TRPV4 agonist GSK1016790A caused contraction in vivo in the guinea pig, and in human and guinea-pig tracheal tissue, which was inhibited by the TRPV4 antagonist GSK2193874. GSK1016790A increased [Ca 2+ ] i and released ATP in human ASM cells without causing contraction. TRPV4 and ATP evoked contraction in isolated tracheal tissue but co-culture experiments indicated a requirement for human lung mast cells. Expression profiling and pharmacological studies demonstrated that mast cell activation was dependent upon ATP activating the P2X4 receptor. Trypsin was shown to evoke contraction of tracheal tissue via activation of PAR-2-TRPV4-ATP-cysLT axis indicating the potential disease relevance of this signalling pathway. TRPV4 activation increases [Ca 2+ ] i and releases ATP from ASM cells triggering P2X4-dependent release of cysLTs from mast cells resulting in ASM contraction. This study delineates a novel mast cell–ASM interaction and TRPV4 as a driver of IgE-independent mast cell-dependent bronchospasm.
Axial spondyloarthritis: a new disease entity, not necessarily early ankylosing spondylitis [Viewpoint]
Authors: Philip Robinson, Paul Wordsworth, John Reveille, Matthew Brown
Journal: Annals of the Rheumatic Diseases (2013)

New classification criteria for axial spondyloarthritis have been developed with the goal of increasing sensitivity of criteria for early inflammatory spondyloarthritis. However these criteria substantially increase heterogeneity of the resulting disease group, reducing their value in both research and clinical settings. Further research to establish criteria based on better knowledge of the natural history of non-radiographic axial spondyloarthritis, its aetiopathogenesis and response to treatment is required. In the meantime the modified New York criteria for ankylosing spondylitis remain a very useful classification criteria set, defining a relatively homogenous group of cases for clinical use and research studies.
Lower Ischemic Heart Disease Diagnostic Costs With Treadmill Stress CMR Versus SPECT
Authors: Subha V. Raman, Rory Hachamovitch, Debbie Scandling, Wojciech Mazur, Raymond Y. Kwong, Timothy C. Wong, Erik B. Schelbert, Sean Moore, Vien Truong, Orlando P. Simonetti
Journal: JACC. Cardiovascular imaging (2020)
An in vivo genome-wide CRISPR screen identifies the RNA-binding protein Staufen2 as a key regulator of myeloid leukemia
Authors: Jeevisha Bajaj, Michael Hamilton, Yutaka Shima, Kendall Chambers, Kyle Spinler, Eric L. Van Nostrand, Brian A. Yee, Steven M. Blue, Michael Chen, David Rizzeri, Charles Chuah, Vivian G. Oehler, H. Elizabeth Broome, Roman Sasik, James Scott-Browne, Anjana Rao, Gene W. Yeo, Tannishtha Reya
Journal: Nature Cancer (2020)
Brucellosis in patients with pyrexia of unknown origin in Assam, India: a retrospective record review
Authors: Takujungla Jamir, Sahabuddin Ahmed Laskar, Vaishali Sarma, Nripendra Nath Deka
Journal: The Lancet Global Health (2020)

BackgroundGlobally, around 500 000 human brucellosis cases are reported every year. In India, the burden of human brucellosis is likely underestimated because of limited laboratory capacity. In this study, we aimed to estimate brucellosis burden in patients with pyrexia of unknown origin (PUO) attending Amsing Jorabat Sub-centre in Kamrup Metro, Assam, India—an area with 10% prevalence of animal brucellosis.MethodsWe retrospectively reviewed records of PUO patients attending Amsing Jorabat Sub-centre between Jan 1 and Oct 31, 2014. We defined a case as Brucella-positive if a Rose Bengal plate test or serum agglutination test, or both, were positive along with IgM or IgG positivity. We reviewed records of routine animal surveillance by Assam Agriculture University to see if cases had Brucella-positive animals in their farms. We used EpiInfo 7.1 to analyse data.FindingsOf the 46 PUO patients included in the study, 25 (54%) were Brucella-positive. Median age of brucellosis patients was 33 years (range 18–67 years). Among the 25 cases, 88% were men and 80% were dairy farmers. All 25 case-patients owned dairy farms or worked as farm attendants. Most common presenting symptoms were arthralgia (n=17 [68%]), fever (12 [48%]), and night sweats (12 [48%]). Patients became ill mostly during March (7 [28%]) and July (6 [24%]). Most Brucella-positive patients (17 [68%]) were from Shillongia village. All case-patients were engaged in milking and more than half (19 [76%]) had handled abortus during birthing on the farm.InterpretationMore than half of PUO cases were brucellosis cases in dairy farm workers who had brucellosis-positive animals on their farms. We recommend multisector coordination involving health and veterinary departments to improve surveillance and control of brucellosis.FundingNone.
Pathological Anti-β2-Glycoprotein I Antibodies Disrupt the Anticoagulant Activity of Annexin A5: A Possible Explanation for the Lupus Anticoagulant Paradox.
Authors: Bas de Laat, Xiao-Xuan Wu, Menno van Lummel, Ronald H.W.M. Derksen, Philip G. de Groot, Jacob H. Rand
Journal: Blood (2005)
Haploinsufficiency and Deficiency of a 7q Gene Titan (Samd9L) Predispose Leukemia Development in Cooperation with Deregulated Expression of a Transcription Factor, Evi1, or a Histone Demethylase, Fbxl10
Authors: Akiko Nagamachi, Hiroya Asou, Hirotaka Matsui, Yuko Ozaki, Daisuke Aki, Kazuko Miyazaki, Norimasa Yamasaki, Masaki Miyazaki, Linda Wolff, Richard Koller, Hideaki Oda, Toshiya Inaba, Hiroaki Honda
Journal: Blood (2008)
Widespread and tissue-specific expression of endogenous retroelements in human somatic tissues
Authors: Jean-David Larouche, Assya Trofimov, Leslie Hesnard, Gregory Ehx, Qingchuan Zhao, Krystel Vincent, Chantal Durette, Patrick Gendron, Jean-Philippe Laverdure, Éric Bonneil, Caroline Côté, Sébastien Lemieux, Pierre Thibault, Claude Perreault
Journal: Genome Medicine (2020)

Endogenous retroelements (EREs) constitute about 42% of the human genome and have been implicated in common human diseases such as autoimmunity and cancer. The dominant paradigm holds that EREs are expressed in embryonic stem cells (ESCs) and germline cells but are repressed in differentiated somatic cells. Despite evidence that some EREs can be expressed at the RNA and protein levels in specific contexts, a system-level evaluation of their expression in human tissues is lacking.Using RNA sequencing data, we analyzed ERE expression in 32 human tissues and cell types, including medullary thymic epithelial cells (mTECs). A tissue specificity index was computed to identify tissue-restricted ERE families. We also analyzed the transcriptome of mTECs in wild-type and autoimmune regulator (AIRE)-deficient mice. Finally, we developed a proteogenomic workflow combining RNA sequencing and mass spectrometry (MS) in order to evaluate whether EREs might be translated and generate MHC I-associated peptides (MAP) in B-lymphoblastoid cell lines (B-LCL) from 16 individuals.We report that all human tissues express EREs, but the breadth and magnitude of ERE expression are very heterogeneous from one tissue to another. ERE expression was particularly high in two MHC I-deficient tissues (ESCs and testis) and one MHC I-expressing tissue, mTECs. In mutant mice, we report that the exceptional expression of EREs in mTECs was AIRE-independent. MS analyses identified 103 non-redundant ERE-derived MAPs (ereMAPs) in B-LCLs. These ereMAPs preferentially derived from sense translation of intronic EREs. Notably, detailed analyses of their amino acid composition revealed that ERE-derived MAPs presented homology to viral MAPs.This study shows that ERE expression in somatic tissues is more pervasive and heterogeneous than anticipated. The high and diversified expression of EREs in mTECs and their ability to generate MAPs suggest that EREs may play an important role in the establishment of self-tolerance. The viral-like properties of ERE-derived MAPs suggest that those not expressed in mTECs can be highly immunogenic.
Internet-Based Cognitive Behavioral Therapy to Reduce Suicidal Ideation
Authors: Rebekka Büscher, Michelle Torok, Yannik Terhorst, Lasse Sander
Journal: JAMA Network Open (2020)

Suicidal ideation is a widespread phenomenon. However, many individuals at risk for suicide do not seek treatment, which might be addressed by providing low-threshold, internet-based self-help interventions.To investigate whether internet-based self-help interventions directly targeting suicidal ideation or behavior are associated with reductions in suicidal ideation.A systematic search of PsycINFO, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and the Centre for Research Excellence of Suicide Prevention (CRESP) databases for trials from inception to April 6, 2019, was performed, supplemented by reference searches. Search strings consisted of various search terms related to the concepts of internet, suicide, and randomized clinical trials.Two independent researchers reviewed titles, abstracts, and full texts. Randomized clinical trials evaluating the effectiveness of internet-based self-help interventions to reduce suicidal ideation were included. Interventions were eligible if they were based on psychotherapeutic elements. Trials had to report a quantitative measure of a suicide-specific outcome. Mobile-based and gatekeeper interventions were excluded; no further restrictions were placed on participant characteristics or date of publication.This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Risk of bias was evaluated using the Cochrane Risk of Bias Tool. Standardized mean differences were calculated using a random-effects model.Suicidal ideation was the a priori primary outcome.Six unique eligible trials (1567 unique participants; 1046 [66.8%] female; pooled mean [SD] age, 36.2 [12.5] years) were included in the systematic review and meta-analysis. All identified interventions were internet-based cognitive behavioral therapy (iCBT). Participants assigned to the iCBT condition experienced a significantly reduced suicidal ideation compared with controls following intervention in all 6 trials (standardized mean difference, -0.29; 95% CI, -0.40 to -0.19; P < .001). Heterogeneity was low (I2 = 0%). The effect appeared to be maintained at follow-up in 4 trials (standardized mean difference, -0.18; 95% CI, -0.34 to -0.02; P = .03; I2 = 36%). Studies did not report sufficient data on completed suicides and suicide attempts to assess potential associations.These results show that iCBT interventions are associated with significant reductions in suicidal ideation compared with control conditions. Considering their high scalability, iCBT interventions have the potential to reduce suicide mortality. Future research should assess the effect of these digital health interventions on suicidal behavior and identify moderators and mediators to advance understanding of the mechanisms of effectiveness of these interventions.
Abstract 15069: Stabilization of Camkii-Phosphorylated Ryr2 by Dantrolene Prevents the Development of Age-Related Cardiomyopathy Caused by CamkiiδC Overexpression
Authors: Yoko S Shimizu, Shinichi Okuda, Yoko Okamoto, Shigehiko Nishimura, Takayoshi Kato, Tetsuro Oda, Shigeki Kobayashi, Takeshi Yamamoto, Masafumi Yano
Journal: Circulation (2017)

Backgrounds: Calcium/calmodulin-dependent protein kinase II (CaMKII) has been reported to be one of the important factors for the alteration of calcium handling in heart failure, presumably mediate...
Planned omalizumab discontinuation in CSU management as a sustainable strategy: A 2‐year real‐life study
Authors: Danilo Di Bona, Eustachio Nettis, Elena Minenna, Antonella Lovecchio, Donato Paolino, Maria Cristina Nizi, Marcello Albanesi, Erminia Ridolo, Maria Filomena Caiaffa, Luigi Macchia
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Erratum: “The Role of Humidity in Associations of High Temperature with Mortality: A Multicountry, Multicity Study”
Authors: Ben Armstrong, Francesco Sera, Ana Maria Vicedo-Cabrera, Rosana Abrutzky, Daniel Oudin Åström, Michelle L. Bell, Bing-Yu Chen, Micheline de Sousa Zanotti Stagliorio Coelho, Patricia Matus Correa, Tran Ngoc Dang, Magali Hurtado Diaz, Do Van Dung, Bertil Forsberg, Patrick Goodman, Yue-Liang Leon Guo, Yuming Guo, Masahiro Hashizume, Yasushi Honda, Ene Indermitte, Carmen Íñiguez, Haidong Kan, Ho Kim, Jan Kyselý, Eric Lavigne, Paola Michelozzi, Hans Orru, Nicolás Valdés Ortega, Mathilde Pascal, Martina S. Ragettli, Paulo Hilario Nascimento Saldiva, Joel Schwartz, Matteo Scortichini, Xerxes Seposo, Aurelio Tobias, Shilu Tong, Aleš Urban, César De la Cruz Valencia, Antonella Zanobetti, Ariana Zeka, Antonio Gasparrini
Journal: Environmental Health Perspectives (2019)
Correction to: A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
Authors: Danuta R. Gawel, Jordi Serra-Musach, Sandra Lilja, Jesper Aagesen, Alex Arenas, Bengt Asking, Malin Bengnér, Janne Björkander, Sophie Biggs, Jan Ernerudh, Henrik Hjortswang, Jan-Erik Karlsson, Mattias Köpsen, Eun Jung Lee, Antonio Lentini, Xinxiu Li, Mattias Magnusson, David Martínez-Enguita, Andreas Matussek, Colm E. Nestor, Samuel Schäfer, Oliver Seifert, Ceylan Sonmez, Henrik Stjernman, Andreas Tjärnberg, Simon Wu, Karin Åkesson, Alex K. Shalek, Margaretha Stenmarker, Huan Zhang, Mika Gustafsson, Mikael Benson
Journal: Genome Medicine (2020)

An amendment to this paper has been published and can be accessed via the original article.
Out-of-Hospital Cardiac Arrest during the Covid-19 Outbreak in Italy
Authors: Enrico Baldi, Giuseppe M. Sechi, Claudio Mare, Fabrizio Canevari, Antonella Brancaglione, Roberto Primi, Catherine Klersy, Alessandra Palo, Enrico Contri, Vincenza Ronchi, Giorgio Beretta, Francesca Reali, Pierpaolo Parogni, Fabio Facchin, Davide Bua, Ugo Rizzi, Daniele Bussi, Simone Ruggeri, Luigi Oltrona Visconti, Simone Savastano
Journal: New England Journal of Medicine (2020)

Out-of-Hospital Cardiac Arrest and Covid-19 From February 21 through April 1, 2019, a total of 229 cases of out-of-hospital cardiac arrest were reported in four provinces of Lombardy, Italy. During...