tbuckley/cabot-search huggingface dataset:
Baclofen and sleep apnoea syndrome: analysis of VigiBase, the WHO pharmacovigilance database
Authors: Bruno Revol, Ingrid Jullian-Desayes, Sébastien Bailly, Michel Mallaret, Renaud Tamisier, Marie-Sara Agier, Frédéric Lador, Marie Joyeux-Faure, Jean-Louis Pépin
Journal: European Respiratory Journal (2018)

Baclofen is a centrally acting gamma aminobutyric acid (GABA)-B agonist, widely used for chronic spasticity in neurological disorders, available in oral and intrathecal formulations. Depending on the severity of spasticity and tolerance, standard treatment includes daily oral administration of 40–80 mg [1]. The main adverse effects reported with baclofen are sedation, sleepiness, weakness, dizziness and psychological disturbances [2]. According to the depressant effects of GABA on the central nervous system, baclofen might also induce or aggravate sleep-disordered breathing by depressing central ventilatory drive and/or increasing upper airway obstruction. A single oral low dose of baclofen did not significantly impair the apnoea–hypopnoea index (AHI) in a population with moderate obstructive sleep apnoea [3], but bolus intrathecal administration of the drug increased central sleep apnoea (CSA) in patients with severe spasticity [4]. Baclofen is associated with sleep apnoea syndrome especially the high oral doses prescribed for alcohol addiction <http://ow.ly/J5H730h4znW> The authors would like to thank the UMC that provided and gave permission to use the data analysed in the present study. Results and conclusions are those of the authors and not necessarily those of the National Centers, UMC or WHO. We thank Alison Foote (Grenoble Alps University Hospital, France) for critically editing the manuscript.
Abstract 18360: ACTN2 Mutations Are Associated With Cardiomyopathy and Cardiomyocyte Hypertrophy
Authors: Han Zhu, Euan Ashley, Matthew Wheeler
Journal: Circulation (2016)

Introduction: Alpha actinins belong to the spectrin gene superfamily, a diverse group of cytoskeletal proteins. In cardiac and skeletal muscle cells, they act as actin- and titin-binding proteins l...
Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization
Authors: Fei Zhao, Christine Xiao, Kathy S. Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W. Locasale, Brent A. Hanks
Journal: Immunity (2018)
Review: In suspected influenza, some rapid tests have high sensitivity and high specificity for detecting infection
Authors: Thomas Fekete
Journal: Annals of Internal Medicine (2018)

Source Citation Merckx J, Wali R, Schiller I, et al. Diagnostic accuracy of novel and traditional rapid tests for influenza infection compared with reverse transcriptase polymerase chain reaction: a systematic review and meta-analysis. Ann Intern Med. 2017;167:394-409. 28869986
Common Genetic Variants in Trypsin Regulating Genes Are Associated with AsparAginase-Associated Pancreatitis in Children with Acute Lymphoblastic Leukemia: A Ponte Di Legno Toxicity Working Group Study
Authors: Benjamin Ole Wolthers, Thomas Leth Frandsen, Andishe Attarbaschi, Shlomit Barzilai, Antonella Colombini, Gabriele Escherich, Marie Grosjean, Ramneek Gupta, Der-Cherng Liang, Anja Moricke, Chirag J Patel, Kirsten K Rasmussen, Sujith Samarasinghe, Inge M. Van Der Sluis, Martin Stanulla, Morten Tulstrup, Ester Zapotocka, Kjeld Schmiegelow
Journal: Blood (2017)
Sonic Hedgehog Is a Remotely Produced Cue that Controls Axon Guidance Trans-axonally at a Midline Choice Point
Authors: Jimmy Peng, Pierre J. Fabre, Tiphaine Dolique, Shannon M. Swikert, Laëtitia Kermasson, Tomomi Shimogori, Frédéric Charron
Journal: Neuron (2018)
Zinc transporter Slc39a8 is essential for cardiac ventricular compaction
Authors: Wen Lin, Deqiang Li, Lan Cheng, Li Li, Feiyan Liu, Nicholas J. Hand, Jonathan A. Epstein, Daniel J. Rader
Journal: Journal of Clinical Investigation (2018)

Isolated left ventricular noncompaction (LVNC) results from excessive trabeculation and impaired myocardial compaction during heart development. The extracellular matrix (ECM) that separates endocardium from myocardium plays a critical but poorly understood role in ventricular trabeculation and compaction. In an attempt to characterize solute carrier family 39 member 8-null (Slc39a8-null) mice, we discovered that homozygous null embryos do not survive embryogenesis and exhibit a cardiac phenotype similar to human LVNC. Slc39a8 encodes a divalent metal cation importer that has been implicated in ECM degradation through the zinc/metal regulatory transcription factor 1 (Zn/MTF1) axis, which promotes the expression of ECM-degrading enzymes, including Adamts metalloproteinases. Here, we have shown that Slc39a8 is expressed by endothelial cells in the developing mouse heart, where it serves to maintain cellular Zn levels. Furthermore, Slc39a8-null hearts exhibited marked ECM accumulation and reduction of several Adamts metalloproteinases. Consistent with the in vivo observations, knockdown of SLC39A8 in HUVECs decreased ADAMTS1 transcription by decreasing cellular Zn uptake and, as a result, MTF1 transcriptional activity. Our study thus identifies a gene underlying ventricular trabeculation and compaction development, and a pathway regulating ECM during myocardial morphogenesis.
Expanding the Scope of Research Ethics Consultation Services in Safeguarding Research Integrity: Moving Beyond the Ethics of Human Subjects Research
Authors: Zubin Master, Brian C. Martinson, David B. Resnik
Journal: The American Journal of Bioethics (2018)

The article by Porter and colleagues (2018) illustrates the value of research ethics consultants (RECs) to researchers, administrators, and academic institutions, but focuses primarily on their rol...
Nut Oral Immunotherapy (NOIT) for Allergy to One Nut Desensitizes to the Cross Reactive Nut
Authors: Angela R. Hague, Richard L. Wasserman, Robert W. Sugerman, Qurat Ul Ain Kamili, Dena M. Pence, Joanna G. Rolen
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 13403: Vagal Nerve Stimulation Mitigates Aberrant Gut Flora Observed in Guinea Pigs With Pressure Overload
Authors: Regenia P Campbell, Michelle Duffourc, Robert V Schoborg, Eric Beaumont
Journal: Circulation (2015)

Background: Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. The vagus nerve, which innervates the heart and abdominal organs, carries information bi-directionally along the gut/brain axis. We hypothesized that vagal nerve stimulation (VNS) could alter gut microbial flora and correct aberrations observed in fecal samples from heart failure animals. Methods and Results: A stimulating device was implanted on either the left or right vagus prior to creation of pressure overload (PO) by aortic constriction. Animals then received continuous, cycling stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end systolic and diastolic volumes, stroke volume, and cardiac output were significantly impaired in PO animals compared to baseline. VNS mitigated these effects. Animals that did not improve with VNS (15%) were categorized as non-responders. The bacterial DNA 16s ribosomal RNA gene was amplified from fecal DNA and amplicons sequenced for identification of bacterial genera present. Thirty-seven genera were identified as representing at least 0.1% of the total microbial population. Of these, the presence of 17 was disrupted by induction of PO and attenuated by VNS (six with either left or right VNS, five with right VNS only, and six with left VNS only). Metatranscriptomics analysis was then used to predict functional pathways that may be affected by the changes in diversity indicated by sequencing. Genera that express genes associated with ATP-binding cassette (ABC) transport and amino sugar/nitrogen metabolism were significantly changed by PO and VNS therapy. PO-induced changes were mitigated by left cervical vagus stimulation and exacerbated in samples from animals that did not respond to treatment. Conclusion: These data suggest that VNS may improve heart function, at least in part, by reversing pathogenic changes in gut flora that result from blood pressure overload.
Connections Between Metabolism and Epigenetics in Programming Cellular Differentiation
Authors: Danielle A. Chisolm, Amy S. Weinmann
Journal: Annual Review of Immunology (2018)

Researchers are intensifying efforts to understand the mechanisms by which changes in metabolic states influence differentiation programs. An emerging objective is to define how fluctuations in metabolites influence the epigenetic states that contribute to differentiation programs. This is because metabolites such as S-adenosylmethionine, acetyl-CoA, α-ketoglutarate, 2-hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists for the activities of epigenetic-modifying complexes and for epigenetic modifications. We discuss this topic from the perspective of specialized CD4+ T cells as well as effector and memory T cell differentiation programs. We also highlight findings from embryonic stem cells that give mechanistic insight into how nutrients processed through pathways such as glycolysis, glutaminolysis, and one-carbon metabolism regulate metabolite levels to influence epigenetic events and discuss similar mechanistic principles in T cells. Finally, we highlight how dysregulated environments, such as the tumor microenvironment, might alter programming events.
Handovers During Anesthesia Care
Authors: James P. Bagian, Douglas E. Paull
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Phase I/II trial of vorinostat combined with temozolomide and radiation therapy for newly diagnosed glioblastoma: results of Alliance N0874/ABTC 02
Authors: Evanthia Galanis, S Keith Anderson, C Ryan Miller, Jann N Sarkaria, Kurt Jaeckle, Jan C Buckner, Keith L Ligon, Karla V Ballman, Dennis F Moore, Michael Nebozhyn, Andrey Loboda, David Schiff, Manmeet Singh Ahluwalia, Eudocia Q Lee, Elizabeth R Gerstner, Glenn J Lesser, Michael Prados, Stuart A Grossman, Jane Cerhan, Caterina Giannini, Patrick Y Wen
Journal: Neuro-Oncology (2017)

Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown radiosensitizing properties in preclinical studies. This open-label, single-arm trial evaluated the maximum tolerated dose (MTD; phase I) and efficacy (phase II) of vorinostat combined with standard chemoradiation in newly diagnosed glioblastoma. Patients received oral vorinostat (300 or 400 mg/day) on days 1–5 weekly during temozolomide chemoradiation. Following a 4- to 6-week rest, patients received up to 12 cycles of standard adjuvant temozolomide and vorinostat (400 mg/day) on days 1–7 and 15–21 of each 28-day cycle. Association between vorinostat response signatures and progression-free survival (PFS) and overall survival (OS) was assessed based on RNA sequencing of baseline tumor tissue. Phase I and phase II enrolled 15 and 107 patients, respectively. The combination therapy MTD was vorinostat 300 mg/day and temozolomide 75 mg/m2/day. Dose-limiting toxicities were grade 4 neutropenia and thrombocytopenia and grade 3 aspartate aminotransferase elevation, hyperglycemia, fatigue, and wound dehiscence. The primary efficacy endpoint in the phase II cohort, OS rate at 15 months, was 55.1% (median OS 16.1 mo), and consequently, the study did not meet its efficacy objective. Most common treatment-related grade 3/4 toxicities in the phase II component were lymphopenia (32.7%), thrombocytopenia (28.0%), and neutropenia (21.5%). RNA expression profiling of baseline tumors (N = 76) demonstrated that vorinostat resistance (sig-79) and sensitivity (sig-139) signatures had a reverse and positive association with OS/PFS, respectively. Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials.
<scp>IL</scp>‐37 inhibits <scp>IL</scp>‐4/<scp>IL</scp>‐13‐induced <scp>CCL</scp>11 production and lung eosinophilia in murine allergic asthma
Authors: J. Lv, Y. Xiong, W. Li, X. Cui, X. Cheng, Q. Leng, R. He
Journal: Allergy (2018)

Abstract Background IL ‐37 is emerging as an anti‐inflammatory cytokine, particularly in innate inflammation. However, the role of IL ‐37 in Th2‐mediated allergic lung inflammation remains uncertain. We sought to determine the role and the underlying mechanisms of IL ‐37 in the development of house dust mites ( HDM )‐induced murine asthma model. Methods We examined the effect of IL ‐37 administration during the sensitization or challenge phase on Th2‐mediated allergic asthma induced by inhaled HDM . Cellular source of CCL 11 and distribution of IL ‐37 receptors, IL ‐18Rα and IL ‐1R8, were determined in HDM ‐exposed lungs. Finally, we examined the effect of IL ‐37 on CCL 11 production and STAT 6 activation in different primary lung structural cell types upon IL ‐4/ IL ‐13 stimulation. Results IL ‐37 had no effect on HDM sensitization, but when administrated during the challenge phase, significantly attenuated pulmonary eosinophilia, CCL 11 production, and airway hyper‐reactivity ( AHR ). Interestingly, IL ‐37 treatment had no significant effects on lung infiltrating T cells and Th2 cytokine production. Intranasal co‐administration of CCL 11 reversed the inhibiting effect of IL ‐37 on HDM ‐induced pulmonary eosinophilia and AHR . Furthermore, we demonstrated that CCL 11 was primarily expressed by fibroblasts and airway smooth muscle cells ( AMSC ), while IL ‐37 receptors by tracheobronchial epithelial cells ( TEC ). In vitro study showed that IL ‐37 inhibited IL ‐4/ IL ‐13‐induced STAT 6 activation and CCL 11 production by fibroblasts and AMSC , which was dependent on its direct action on TEC . Moreover, cell contact was required for the inhibitory effect of IL ‐37‐treated TEC . Conclusions IL ‐37 attenuates HDM ‐induced asthma, possibly by inhibiting IL ‐4/ IL ‐13‐induced CCL 11 production by fibroblasts and AMSC via its direct act on TEC .
Cellular Membrane Trafficking Machineries Used by the Hepatitis Viruses
Authors: Jun Inoue, Masashi Ninomiya, Tooru Shimosegawa, Mark A. McNiven
Journal: Hepatology (2018)

While the life cycles of hepatitis viruses (A, B, C, D, and E) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses “hijack” the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus are well known as leading causes of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating hepatitis C virus patients have recently been made, patients with HBV continue to require lifelong treatment, which makes a thorough understanding of the HBV life cycle essential. Importantly, these viruses have been observed to “hijack” the secretory and endocytic membrane trafficking machineries of the hepatocyte. These can include the canonical clathrin‐mediated endocytic process that internalizes virus through cell surface receptors. While these receptors are encoded by the host genome for normal hepatocellular functions, they also exhibit virus‐specific recognition. Further, functions provided by the multivesicular body, which include endosomal sorting complexes required for transport, are now known to envelope a variety of different hepatitis viruses. In this review, we summarize the recent findings regarding the cellular membrane trafficking machineries used by HBV in the context of other hepatitis viruses. (H epatology 2018; 00:000‐000).
Characteristics and Outcomes of Patients with Double-Protein Expression in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): Analysis of SWOG Study S1001 (NCT01359592)
Authors: Deborah M. Stephens, Hongli Li, Daniel Persky, Steven I. Park, Nancy L. Bartlett, Lode J. Swinnen, Carla Casulo, Jerome D. Winegarden, Louis S. Constine, Thomas J. Fitzgerald, John P. Leonard, Brad S Kahl, Michael L. Leblanc, Joo Y. Song, Richard I. Fisher, Lisa M. Rimsza, Sonali M. Smith, Jonathan W. Friedberg
Journal: Blood (2017)
Abstract 16543: Reducing Insulin-like Growth Factor-1 Receptor Expression Improves Vascular Repair and Regeneration in Whole Body Insulin Resistance
Authors: Andrew M Walker, Nadira Yuldasheva, Anshu Sengupta, Ben Mercer, Noman Ali, Peysh A Patel, V Kate Gatenby, Jessica Smith, Natalie J Haywood, Helen Imrie, Stacey L Galloway, Romana S Mughal, Anna Skromna, Natallia Makava, Stephen B Wheatcroft, Mark T Kearney, Richard M Cubbon
Journal: Circulation (2016)

Introduction: Insulin resistance is an independent risk factor for cardiovascular disease. We have previously shown that the insulin-like growth factor-1 receptor (IGF-1R) is a negative regulator o...
Functionalized Nanoparticles Efficiently Enhancing the Targeted Delivery, Tumor Penetration, and Anticancer Activity of 7‐Ethyl‐10‐Hydroxycamptothecin
Authors: Xun Liu, Jingxing Si, Qianzhi Zhang, Qian Huang, Danxia Gu, Hao Yang, Xu Chen, Youqing Shen, Meihua Sui
Journal: Advanced Healthcare Materials (2018)

Abstract The enhanced permeability and retention (EPR) effect of tumors is much more complex than initially defined, and it alone is not sufficient for targeted delivery of nanosized agents. Meanwhile, poor tumor penetration is another major challenge for the treatment of solid tumors using nanoparticles. Development of delivery systems for SN38, the active metabolite of CPT‐11 in human and a very potent anticancer molecule, has become an attractive research area. PEG x ‐p(HEMASN38) y (x and y are viable), a prodrug synthesized by using polyethylene glycol (PEG) as initiator and SN38 as monomer through atom transfer radical polymeration (ATRP) method, is previously reported. Using PEG 2.4K ‐p(HEMASN38) 3K as a model prodrug, herein an active‐targeted strategy decorated with cys‐arg‐gly‐asp‐lys (CRGDK), a peptide specifically binds to neuropilin‐1 overexpressed by tumor vessels and tumor cells, is successfully established to further improve the delivery and efficacy of SN38. CRGDK‐functionalized PEG 2.4K ‐p(HEMASN38) 3K (C‐SN38) nanoparticles and nonfunctionalized control (B‐SN38) are prepared with two distinct sizes, 30 and 100 nm. Their physiochemical and biological characteristics are investigated in vitro and in vivo with multiple tumor models. It is demonstrated for the first time that CRGDK functionalization can be a promising strategy for efficient delivery of SN38, and C‐SN38 is a potent drug candidate for the treatment of neuropilin‐1 overexpressing tumors.
Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives
Authors: Eva Schrezenmeier, David Jayne, Thomas Dörner
Journal: Journal of the American Society of Nephrology (2018)

The unique contributions of memory B cells and plasma cells in kidney diseases remain unclear. In this review, we evaluate the clinical experience with treatments directed at B cells, such as rituximab, and at plasma cells, such as proteasome inhibition, to shed light on the role of these two B lineage compartments in glomerular diseases. Specifically, analysis of these targeted interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody-mediated transplant rejection permits insight into the pathogenetic effect of these cells. Notwithstanding the limitations of preclinical models and clinical studies (heterogeneous populations, among others), the data suggest that memory B and plasma cells represent two engines of autoimmunity, with variable involvement in these diseases. Whereas memory B cells and plasma cells appear to be key in ANCA-associated vasculitis and antibody-mediated transplant rejection, respectively, SLE seems likely to be driven by both autoimmune compartments. These conclusions have implications for the future development of targeted therapeutics in immune-mediated renal disease.
Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials
Authors: Mona Bafadhel, Stefan Peterson, Miguel A De Blas, Peter M Calverley, Stephen I Rennard, Kai Richter, Malin Fagerås
Journal: The Lancet Respiratory Medicine (2018)
Individual endoscopic management of anastomotic insufficiency after esophagectomy for esophageal squamous cell carcinoma and creation of a neostomach
Authors: Edris Wedi, Philipp Schüler, Steffen Kunsch, B. Ghadimi, Ali Seif Amir Hosseini, Volker Ellenrieder, Carlo Jung
Journal: Endoscopy (2018)

A 57-year-old patient with a T3, cN0, G2, M0 esophageal squamous cell cancer received neoadjuvant radiochemotherapy according to the CROSS trial. After successful esophagectomy and consecutive gastroesophageal anastomosis, the patient recovered appropriately. Unfortunately, the patient developed circular anastomotic insufficiency with two cavities at Day 7 ([Fig. 1]). One of the cavities arose from the circular insufficiency (2 × 2 cm), and the other was formed by a stapler insufficiency of the stomach (3 × 2 cm). The final tumor stage was histologically proven to be ypT0, N0, cM0, L0, V0, R0.