tbuckley/cabot-search huggingface dataset:
Urgency to End Newborn Deaths
Authors: M.J. Friedrich
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 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
A man with chest pain and a broad QRS complex tachycardia
Authors: Ever D Grech, Bastiaan Zwart
Journal: BMJ (2018)

A 50 year old man with “heavy” chest pain was referred urgently from a local district hospital to the cardiothoracic centre because a broad QRS complex tachycardia had been noticed on electrocardiogram (ECG). The chest pain was intermittent and had started two hours before presentation. He was a cigarette smoker and his medical history included asthma and a myocardial infarction eight years earlier, for which no invasive treatment was carried out. In the past year he had experienced frequent episodes of chest pain in the early morning, but did not report exertional angina. On examination, the patient was tachycardic with a heart rate of 160 beats/min but with a normal blood pressure of 125/75 mm Hg. Physical examination was otherwise unremarkable. ECGs were recorded after referral. Figure 1 shows an ECG recorded while the patient had chest pain, and figure 2 when he was free of pain.



Fig 1 
ECG recorded while the patient was experiencing chest pain





Fig 2 
ECG recorded six minutes after the first ECG, when the patient was free of pain





### 1. What do the ECGs show?

#### Short answer

The first ECG looks suspicious for broad QRS …
Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome
Authors: Leslie B. Gordon, Heather Shappell, Joe Massaro, Ralph B. D’Agostino, Joan Brazier, Susan E. Campbell, Monica E. Kleinman, Mark W. Kieran
Journal: JAMA (2018)

<h3>Importance</h3> Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare fatal premature aging disease. There is no approved treatment. <h3>Objective</h3> To evaluate the association of monotherapy using the protein farnesyltransferase inhibitor lonafarnib with mortality rate in children with HGPS. <h3>Design, Setting, and Participants</h3> Cohort study comparing contemporaneous (birth date ≥1991) untreated patients with HGPS matched with treated patients by age, sex, and continent of residency using conditional Cox proportional hazards regression. Treatment cohorts included patients from 2 single-group, single-site clinical trials (ProLon1 [n = 27; completed] and ProLon2 [n = 36; ongoing]). Untreated patients originated from a separate natural history study (n = 103). The cutoff date for patient follow-up was January 1, 2018. <h3>Exposure</h3> Treated patients received oral lonafarnib (150 mg/m<sup>2</sup>) twice daily. Untreated patients received no clinical trial medications. <h3>Main Outcomes and Measures</h3> The primary outcome was mortality. The primary analysis compared treated patients from the first lonafarnib trial with matched untreated patients. A secondary analysis compared the combined cohorts from both lonafarnib trials with matched untreated patients. <h3>Results</h3> Among untreated and treated patients (n = 258) from 6 continents, 123 (47.7%) were female; 141 (54.7%) had a known genotype, of which 125 (88.7%) were classic (c.1824C&gt;T in<i>LMNA</i>). When identified (n = 73), the primary cause of death was heart failure (79.4%). The median treatment duration was 2.2 years. Median age at start of follow-up was 8.4 (interquartile range [IQR], 4.8-9.5) years in the first trial cohort and 6.5 (IQR, 3.7-9.0) years in the combined cohort. There was 1 death (3.7%) among 27 patients in the first trial group and there were 9 deaths (33.3%) among 27 patients in the matched untreated group. Treatment was associated with a lower mortality rate (hazard ratio, 0.12; 95% CI, 0.01-0.93;<i>P</i> = .04). In the combined cohort, there were 4 deaths (6.3%) among 63 patients in the treated group and 17 deaths (27.0%) among 63 patients in the matched untreated group (hazard ratio, 0.23; 95% CI, 0.06-0.90;<i>P</i> = .04). <h3>Conclusions and Relevance</h3> Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up. Study interpretation is limited by its observational design.
Dual MAPK/CDK Targeting in Melanoma: New Approaches, New Challenges
Authors: Ryan J. Sullivan
Journal: Cancer Discovery (2018)

Abstract Summary: Dual MAPK and CDK4/6 targeting is an emerging strategy in melanoma, but toxicity and acquired resistance are limitations. In this issue, two groups (Teh and colleagues and Romano and colleagues) show that therapeutic resistance mechanisms converge on the PI3K pathway, and inhibition of this pathway's mediators can overcome this resistance. Cancer Discov; 8(5); 532–3. ©2018 AACR. See related article by Romano et al., p. 556. See related article by Teh et al., p. 568.
Investigating the relationship between rare genetic variants and advanced fibrosis in pediatric nonalcoholic fatty liver disease
Authors: J. Wattacheril, S. Kleinstein, P.R. Shea, J. Lavine, M. Subramanian, R. Myers, J. Lefkowitch, C. Behling, S. Xanthakos, D. Goldstein
Journal: Journal of Hepatology (2018)
Even modest alcohol use is associated with greater steatosis on magnetic resonance imaging in patients with NAFLD – a pilot study
Authors: V. Ajmera, M. Le, C. Caussy, P. Nguyen, C. Hernandez, R. Bettencourt, C. Behling, M. Valasek, C. Faulkner, E. Rizo, L. Richards, C. Sirlin, R. Loomba
Journal: Journal of Hepatology (2018)
Investigation of trimethoprim/sulfamethoxazole resistance in an emerging sequence type 5 methicillin-resistant Staphylococcus aureus clone reveals discrepant resistance reporting
Authors: T.M. Harris, A.C. Bowen, D.C. Holt, D.S. Sarovich, K. Stevens, B.J. Currie, B.P. Howden, J.R. Carapetis, P.M. Giffard, S.Y.C. Tong
Journal: Clinical Microbiology and Infection (2018)
Abstract 11869: Identification of Human Lysophosphatidylcholine Acyltransferase 3 as a Novel Target Gene Regulated by Peroxisome Proliferator-activated Receptor Delta in Hepatic Cells and in Liver Tissue
Authors: Amar B Singh, Jingwen Liu
Journal: Circulation (2016)

Peroxisome proliferator-activated receptor delta (PPARD) is a transcription factor regulating many important genes involved in lipid and glucose metabolism. Hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) plays critical functions in TG secretion and ER stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Previous studies identified liver X receptor as the transcription factor controlling LPCAT3 expression in liver tissue. Here we showed for the first time that the hepatic LPCAT3 gene is transcriptionally regulated by PPARD in vitro and in vivo . Treatments of HepG2, Huh-7, and Hepa 1-6 cells with PPARD specific agonists (L-165041 and GW0742) increased LPCAT3 mRNA levels 2-3 fold of control. Adenovirus-mediated knockdown of PPARD in HepG2 cells reduced the basal level of LPCAT3 mRNA by approximately 40% compared to control and further attenuated the induction of PPARD agonist on LPCAT3 gene expression. To demonstrate the direct regulation of PPARD on LPCAT3 gene transcription, we analyzed human LPCAT3 promoter sequence and identified two putative PPAR responsive elements (PPRE-1, -171; PPRE-2, -727) within 1 kb of the proximal LPCAT3 promoter. LPCAT3 promoter assays demonstrated strong inductions of the reporter activity by PPARD agonists. Mutational analysis of the human LPCAT3 promoter revealed that the PPRE-1 is involved in conferring responsiveness to PPARD agonist mediated transcriptional activity. Direct binding of PPARD to PPRE-1 sequence was demonstrated by chromatin immunoprecipitation and gel retardation assays. Finally, we provided in vivo evidence showing that activation of PPARD by L-165041 in mice increased LPCAT3 mRNA abundance in the liver. Altogether, these new findings identify LPCAT3 as a direct PPARD target gene and suggest a novel function of PPARD in regulation of phospholipid metabolism through LPCAT3.
Responsiveness of controlled attenuation parameter (CAP) and its correlation with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) in a multi-center clinical trial of subjects with nonalcoholic steatohepatitis (NASH)
Authors: M. Noureddin, Z. Kayali, S. Harrison, P. Ruane, N. Gitlin, E. Lawitz, M. Bennett, R. Vuppalanchi, B. Freilich, E. Harting, B. Mccolgan, R. Myers, M. Middleton, C. Sirlin, M. Charlton, M. Lai, P. Mantry, R. Loomba
Journal: Journal of Hepatology (2018)
Effect of nalfurafine hydrochloride for refractory pruritus in patients with primary biliary cholangitis: a multicenter, post-marketing, single-arm, prospective study
Authors: M. Yagi, A. Tanaka, T. Namisaki, M. Abe, A. Takahashi, A. Honda, Y. Matsuzaki, H. Ohira, H. Yoshiji, H. Takikawa
Journal: Journal of Hepatology (2018)
Image Gallery: Brimonidine gel for facial erythema in Netherton syndrome
Authors: A. Filoni, M. Vestita, G. Giudice, D. Bonamonte
Journal: British Journal of Dermatology (2018)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 39‐year‐old female patient with Netherton syndrome complained of troublesome, persistent facial erythema. A thin layer of 0·33% brimonidine gel1 2 was applied to the left side of the face, and sparingly to the eyelid, and an almost complete resolution was observed after 30 min. The effect persisted for 6–7 h. No local or systemic adverse events were noted, except for moderate skin dryness. To date, the patient has used brimonidine five times with consistent response and no rebound. To our knowledge, this is the first report of the off‐label use of brimonidine to treat a genetic disease, with a rapid‐onset effect, sustained duration and good tolerability.
A Role of Renal Replacement Therapy for Acute Liver Failure
Authors: Keiichi Fujiwara, Shin Yasui, Osamu Yokosuka, Shigeto Oda, Naoya Kato
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. We read with interest the article by Cardoso et al.,1 who reported that continuous renal replacement therapy for acute liver failure (ALF) was associated with a reduction in serum ammonia level and improved 21‐day transplant‐free survival in a large, multicenter study. First of all, we applaud their efforts for the diagnosis and treatment of ALF and continuous contributions targeting whole fields of ALF as the U.S. ALF Study Group, different from the Japanese one. We realize how difficult these studies are to perform in infrequent and life‐threatening diseases like ALF. We also believe an artificial liver support system sustaining patients in good condition, including restoration of consciousness until recovery of the native liver or performance of liver transplantation, is essential for the improvement of the poor prognosis of ALF, although it does not induce liver regeneration. In European countries, the molecular adsorbent recirculating system has been shown to remove protein‐bound substances and decrease plasma concentrations of bilirubin, ammonia, and creatinine in patients with ALF. But a question is raised about the feasibility of removing substances responsible for hepatic encephalopathy through removal of albumin‐binding toxic ones alone. To the contrary, in Japan, a combination of plasma exchange (PE) and hemodiafiltration (HDF) has been performed. Hemodialysis removes low‐molecular‐weight substances, including amnonia, and hemofiltration removes middle‐molecular‐weight substances, including proinflammatory cytokines, efficiently. Therefore, we concluded that it is desirable to apply HDF for the treatment of patients with ALF. As described in the Discussion, there is still a controversy over the methodology of renal replacement therapy for ALF. However, it is a fact that more than 90% of patients recover consciousness by high‐flow dialysate HDF in combination with PE in leading Japanese liver units.2 Especially, online HDF reduces the cost and simplifies procedures for the management of encephalopathy.4 Therefore, we have not performed intracranial pressure monitor placement, which is reported to be one of major bleeding sites, for more than 20 years.
Dicer in Macrophages Prevents Atherosclerosis by Promoting Mitochondrial Oxidative Metabolism
Authors: Yuanyuan Wei, Judit Corbalán-Campos, Rashmi Gurung, Lucia Natarelli, Mengyu Zhu, Nicole Exner, Florian Erhard, Franziska Greulich, Claudia Geißler, N. Henriette Uhlenhaut, Ralf Zimmer, Andreas Schober
Journal: Circulation (2018)

Alternative macrophage activation, which relies on mitochondrial oxidative metabolism, plays a central role in the resolution of inflammation and prevents atherosclerosis. Moreover, macrophages handle large amounts of cholesterol and triglycerides derived from the engulfed modified lipoproteins during atherosclerosis. Although several microRNAs regulate macrophage polarization, the role of the microRNA-generating enzyme Dicer in macrophage activation during atherosclerosis is unknown.To evaluate the role of Dicer in atherosclerosis, Apoe-/- mice with or without macrophage-specific Dicer deletion were fed a high-fat diet for 12 weeks. Anti-argonaute 2 RNA immunoprecipitation chip and RNA deep sequencing combined with microRNA functional screening were performed in the Dicer wild-type and knockout bone marrow-derived macrophages to identify the individual microRNAs and the mRNA targets mediating the phenotypic effects of Dicer. The role of the identified individual microRNA and its target in atherosclerosis was determined by tail vein injection of the target site blockers in atherosclerotic Apoe-/- mice.We show that Dicer deletion in macrophages accelerated atherosclerosis in mice, along with enhanced inflammatory response and increased lipid accumulation in lesional macrophages. In vitro, alternative activation was limited whereas lipid-filled foam cell formation was exacerbated in Dicer-deficient macrophages as a result of impaired mitochondrial fatty acid oxidative metabolism. Rescue of microRNA (miR)-10a, let-7b, and miR-195a expression restored the oxidative metabolism in alternatively activated Dicer-deficient macrophages. Suppression of ligand-dependent nuclear receptor corepressor by miR-10a promoted fatty acid oxidation, which mediated the lipolytic and anti-inflammatory effect of Dicer. miR-10a expression was negatively correlated to the progression of atherosclerosis in humans. Blocking the interaction between ligand-dependent nuclear receptor corepressor and miR-10a by target site blockers aggravated atherosclerosis development in mice.Dicer plays an atheroprotective role by coordinately regulating the inflammatory response and lipid metabolism in macrophages through enhancing fatty acid-fueled mitochondrial respiration, suggesting that promoting Dicer/miR-10a-dependent metabolic reprogramming in macrophages has potential therapeutic implications to prevent atherosclerosis.
Do schoolbags cause back pain in children and adolescents? A systematic review
Authors: Tiê Parma Yamato, Chris G Maher, Adrian C Traeger, Christopher M Wiliams, Steve J Kamper
Journal: British Journal of Sports Medicine (2018)

To investigate whether characteristics of schoolbag use are risk factors for back pain in children and adolescents.Electronic searches of MEDLINE, EMBASE and CINAHL databases up to April 2016.Prospective cohort studies, cross-sectional and randomised controlled trials conducted with children or adolescents. The primary outcome was an episode of back pain and the secondary outcomes were an episode of care seeking and school absence due to back pain. We weighted evidence from longitudinal studies above that from cross-sectional. The risk of bias of the longitudinal studies was assessed by a modified version of the Quality in Prognosis Studies tool.We included 69 studies (n=72 627), of which five were prospective longitudinal and 64 cross-sectional or retrospective. We found evidence from five prospective studies that schoolbag characteristics such as weight, design and carriage method do not increase the risk of developing back pain in children and adolescents. The included studies were at moderate to high risk of bias. Evidence from cross-sectional studies aligned with that from longitudinal studies (ie, there was no consistent pattern of association between schoolbag use or type and back pain). We were unable to pool results due to different variables and inconsistent results.There is no convincing evidence that aspects of schoolbag use increase the risk of back pain in children and adolescents.
CD4 Helper and CD8 Cytotoxic T Cell Differentiation
Authors: Ichiro Taniuchi
Journal: Annual Review of Immunology (2018)

A fundamental question in developmental immunology is how bipotential thymocyte precursors generate both CD4+ helper and CD8+ cytotoxic T cell lineages. The MHC specificity of αβ T cell receptors (TCRs) on precursors is closely correlated with cell fate-determining processes, prompting studies to characterize how variations in TCR signaling are linked with genetic programs establishing lineage-specific gene expression signatures, such as exclusive CD4 or CD8 expression. The key transcription factors ThPOK and Runx3 have been identified as mediating development of helper and cytotoxic T cell lineages, respectively. Together with increasing knowledge of epigenetic regulators, these findings have advanced our understanding of the transcription factor network regulating the CD4/CD8 dichotomy. It has also become apparent that CD4+ T cells retain developmental plasticity, allowing them to acquire cytotoxic activity in the periphery. Despite such advances, further studies are necessary to identify the molecular links between TCR signaling and the nuclear machinery regulating expression of ThPOK and Runx3.
Understanding the tumor immune microenvironment (TIME) for effective therapy
Authors: Mikhail Binnewies, Edward W. Roberts, Kelly Kersten, Vincent Chan, Douglas F. Fearon, Miriam Merad, Lisa M. Coussens, Dmitry I. Gabrilovich, Suzanne Ostrand-Rosenberg, Catherine C. Hedrick, Robert H. Vonderheide, Mikael J. Pittet, Rakesh K. Jain, Weiping Zou, T. Kevin Howcroft, Elisa C. Woodhouse, Robert A. Weinberg, Matthew F. Krummel
Journal: Nature Medicine (2018)
Optimizing Transparency to Empower Patients
Authors: William B. Borden
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
RIG-I and Other RNA Sensors in Antiviral Immunity
Authors: Kwan T. Chow, Michael Gale, Yueh-Ming Loo
Journal: Annual Review of Immunology (2018)

Pattern recognition receptors (PRRs) survey intra- and extracellular spaces for pathogen-associated molecular patterns (PAMPs) within microbial products of infection. Recognition and binding to cognate PAMP ligand by specific PRRs initiates signaling cascades that culminate in a coordinated intracellular innate immune response designed to control infection. In particular, our immune system has evolved specialized PRRs to discriminate viral nucleic acid from host. These are critical sensors of viral RNA to trigger innate immunity in the vertebrate host. Different families of PRRs of virus infection have been defined and reveal a diversity of PAMP specificity for wide viral pathogen coverage to recognize and extinguish virus infection. In this review, we discuss recent insights in pathogen recognition by the RIG-I-like receptors, related RNA helicases, Toll-like receptors, and other RNA sensor PRRs, to present emerging themes in innate immune signaling during virus infection.
An innovative therapeutic approach for malignant mesothelioma treatment based on the use of Gd/boron multimodal probes for MRI guided BNCT
Authors: Diego Alberti, Annamaria Deagostino, Antonio Toppino, Nicoletta Protti, Silva Bortolussi, Saverio Altieri, Silvio Aime, Simonetta Geninatti Crich
Journal: Journal of Controlled Release (2018)