tbuckley/cabot-search huggingface dataset:
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Authors: Myung Ji Goh, Seonwoo Kim, Sook Young Woo, Dong Hyun Sinn
Journal: Hepatology (2019)

Potential conflict of interest: Nothing to report. We would like to express our gratitude to Huang et al. for their insightful comments on our study. We fully acknowledge that several residual confounding factors may exist, including antidiabetic medications, coffee intake, and type of antiviral therapy, as Huang et al. have suggested. In this cohort, there were 1,045 patients with diabetes using different types of antidiabetic medications, resulting in different degrees of glycemic control during the follow‐up period. We agree that antidiabetic medication may have had an effect on hepatocellular carcinoma (HCC) risk; however, given the complexity between several types of antidiabetic medications and glycemic control and considering the relatively small diabetic population in our cohort, we think this issue needs further clarification in another study. Notably, in a recent cohort study from Taiwan, metformin, an antidiabetic medication, was not associated with HCC risk in chronic hepatitis B patients, while statin was associated with HCC risk.1 Information on coffee intake was missing in our cohort. Whether the specific type of antiviral therapy (e.g., tenofovir over entecavir) determines the effect on prevention of HCC is controversial,2 and the antiviral therapy used in this study consisted of lamivudine, adefovir, telbivudine, clevudine, entecavir, and tenofovir. Hence, our results call for well‐designed prospective studies and cannot exclude the possibility of a noncausal relationship between statin use and decreased HCC risk. Regarding noninvasive tests, liver stiffness measurement was not available for most of the patients at the index visit. When aspartate aminotransferase‐to‐platelet ratio index (APRI) and Fibrosis‐4 (FIB‐4) score were used, statin use was associated with a reduced risk of HCC, whether cirrhosis was defined by APRI (hazard ratio, 0.39; 95% confidence interval, 0.20‐0.76) or FIB‐4 (hazard ratio, 0.43, 95% confidence interval, 0.21‐0.84). Lastly, we fully agree that statin use may have an effect on the progression of fibrosis or cirrhosis.3 Studies using a composite endpoint, including HCC, cirrhosis, and death from liver disease, will clearly provide further insight on the potential role of statins in patients with chronic hepatitis B.
Association of Adult Weight Gain With Major Health Outcomes Among Middle-aged Chinese Persons With Low Body Weight in Early Adulthood
Authors: Guochong Jia, Xiao-Ou Shu, Ying Liu, Hong-Lan Li, Hui Cai, Jing Gao, Yu-Tang Gao, Wanqing Wen, Yong-Bing Xiang, Wei Zheng
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The association of weight gain from early to middle adulthood with disease risk has not been adequately studied. <h3>Objective</h3> To investigate the association of adult weight gain with major health outcomes in a Chinese population with low body weight in early adulthood. <h3>Design, Setting, and Participants</h3> This population-based cohort study assessed data from 48 377 women and 35 989 men aged 40 to 59 years at recruitment in 2 prospective cohort studies in China. The Shanghai Women’s Health Study recruited 74 941 women, aged 40 to 70 years, from January 1, 1996, to December 31, 2000, and the Shanghai Men’s Health Study recruited 61 482 men, aged 40 to 74 years, from January 1, 2002, to December 31, 2006. This analysis was conducted from September 1, 2017, to April 30, 2018. <h3>Exposures</h3> Weight gain from 20 years of age to 40 to 59 years of age. <h3>Main Outcomes and Measures</h3> Mortality and incidence of cancers and other chronic diseases. <h3>Results</h3> This analysis included 48 377 women (mean [SD] age, 47.8 [5.3] years) and 35 989 men (mean [SD] age, 49.6 [5.1] years). Per 5-kg weight gain from early to middle adulthood was associated with an approximately 10% (hazard ratio [HR], 1.09; 95% CI, 1.04-1.14 for men; HR, 1.14; 95% CI, 1.11-1.19 for women) elevated all-cause mortality and a greater than 20% (HR, 1.26; 95% CI, 1.16-1.38 for men; HR, 1.23; 95% CI, 1.14-1.33 for women) cardiovascular disease–related mortality in later life among individuals who reached a body mass index (BMI) of 23 or higher at middle adulthood. Body mass index at middle adulthood also modified the association of weight gain with risk of obesity-related cancers, with weight gain of 20 kg or more associated with increased risks both for men (HR, 1.34; 95% CI, 1.07-1.67) and for women (HR 1.45; 95% CI, 1.24-1.68). No similar associations were found for individuals with a BMI of 18.5 to 22.9. Regardless of BMI, weight gain was associated with elevated risks of type 2 diabetes, hypertension, fatty liver disease, stroke, gout, and gallstones, particularly for type 2 diabetes (HR, 7.87; 95% CI, 6.91-8.97 for women; HR, 4.95; 95% CI, 4.23-5.79 for men) and fatty liver disease (HR, 3.68; 95% CI, 3.42-3.95 for women; HR, 2.83, 95% CI, 2.56-3.13 for men) in individuals with weight gain of 20 kg or more compared with those with a healthy weight. <h3>Conclusions and Relevance</h3> This study found that weight gain from early to middle adulthood was associated with disease incidence and mortality in later life. The BMI at middle adulthood modified the association of weight gain with mortality and cancer incidence but not risk of other major chronic diseases.
Improve Management of acute heart failure with ProcAlCiTonin in EUrope: results of the randomized clinical trial IMPACT EU Biomarkers in Cardiology (BIC) 18
Authors: Martin Möckel, Rudolf A. de Boer, Anna Christine Slagman, Stephan von Haehling, Morten Schou, Jörn Ole Vollert, Jan C. Wiemer, Stefan Ebmeyer, F. Javier Martín‐Sánchez, Alan S. Maisel, Evangelos Giannitsis
Journal: European Journal of Heart Failure (2019)

Aim To determine whether initiation of antibiotic therapy (ABX) by procalcitonin (PCT) within 8 h of admission in patients presenting to the emergency department with symptoms and signs of acute heart failure (AHF) and elevated natriuretic peptides would improve clinical outcomes. Methods and results The study was a randomized multicentre clinical trial conducted at 16 sites in Europe. Patients were randomized to either a PCT‐guided strategy or standard care. Patients with PCT‐guided strategy ( n = 370) had ABX initiated if PCT was &gt; 0.2 μg/L. Patients with standard care ( n = 372) had AHF care in accordance with published guidelines without PCT. The primary endpoint was 90‐day all‐cause mortality. Pre‐specified secondary endpoints included 30‐day all‐cause mortality and readmission and rate of pneumonia. The Data Safety and Review Committee recommended stopping the study for futility when 762 of the planned 792 patients had been enrolled. A total of 742 patients could be analysed. Patients were elderly (median age: 77 years), 38% were women, and had typical signs and symptoms of AHF. All‐cause mortality at 90 days was 10.3% in the PCT‐guided group vs. 8.2% in standard care ( P = 0.316). Thirty‐day readmission was significantly higher in the PCT‐guided group vs. standard care but the difference vanished until day 90. The rate of pneumonia was overall low (7.5%) and not different between groups. Conclusions In patients with AHF, a strategy of PCT‐guided initiation of ABX was not more effective than a standard care strategy in improving clinical outcomes.
Freezing of Gait and Its Levodopa Paradox
Authors: Jorik Nonnekes, Matthieu Bereau, Bastiaan R. Bloem
Journal: JAMA Neurology (2019)

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 Neurology 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 Neurology journal
Hair eruption initiates and commensal skin microbiota aggravate adverse events of anti-EGFR therapy
Authors: Jörg Klufa, Thomas Bauer, Buck Hanson, Craig Herbold, Philipp Starkl, Beate Lichtenberger, Dagmar Srutkova, Daniel Schulz, Igor Vujic, Thomas Mohr, Klemens Rappersberger, Bernd Bodenmiller, Hana Kozakova, Sylvia Knapp, Alexander Loy, Maria Sibilia
Journal: Science Translational Medicine (2019)

Epidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and therapy adherence. The lack of mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity and prevent the invasion of commensal microbiota and inflammatory skin disease. EGFR-deficient epidermis is permissive for microbiota outgrowth and displays an atopic-like TH2-dominated signature. The opening of the follicular ostia during hair eruption allows invasion of commensal microbiota into the hair follicle, initiating an additional TH1 and TH17 response culminating in chronic folliculitis. Restoration of epidermal ERK signaling via prophylactic FGF7 treatment or transgenic SOS expression rescues the barrier defect in the absence of EGFR, highlighting a therapeutic anchor point. These data reveal that commensal skin microbiota provoke atopic-like inflammatory skin diseases by invading into the follicular opening of erupting hair.
Painful and Pruritic Blisters on the Lower Lip
Authors: Mitsuhito Ota
Journal: JAMA (2019)

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
Toscana, West Nile, Usutu and tick-borne encephalitis viruses: external quality assessment for molecular detection of emerging neurotropic viruses in Europe, 2017
Authors: Chantal Reusken, Cecile Baronti, Ramona Mögling, Anna Papa, Katrin Leitmeyer, Remi N Charrel
Journal: Eurosurveillance (2019)

BackgroundNeurotropic arboviruses are increasingly recognised as causative agents of neurological disease in Europe but underdiagnosis is still suspected. Capability for accurate diagnosis is a prerequisite for adequate clinical and public health response.AimTo improve diagnostic capability in EVD-LabNet laboratories, we organised an external quality assessment (EQA) focusing on molecular detection of Toscana (TOSV), Usutu (USUV), West Nile (WNV) and tick-borne encephalitis viruses (TBEV).MethodsSixty-nine laboratories were invited. The EQA panel included two WNV RNA-positive samples (lineages 1 and 2), two TOSV RNA-positive samples (lineages A and B), one TBEV RNA-positive sample (Western subtype), one USUV RNA-positive sample and four negative samples. The EQA focused on overall capability rather than sensitivity of the used techniques. Only detection of one, clinically relevant, concentration per virus species and lineage was assessed.ResultsThe final EQA analysis included 51 laboratories from 35 countries; 44 of these laboratories were from 28 of 31 countries in the European Union/European Economic Area (EU/EEA). USUV diagnostic capability was lowest (28 laboratories in 18 countries), WNV detection capacity was highest (48 laboratories in 32 countries). Twenty-five laboratories were able to test the whole EQA panel, of which only 11 provided completely correct results. The highest scores were observed for WNV and TOSV (92%), followed by TBEV (86%) and USUV (75%).ConclusionWe observed wide variety in extraction methods and RT-PCR tests, showing a profound absence of standardisation across European laboratories. Overall, the results were not satisfactory; capacity and capability need to be improved in 40 laboratories.
Abstract 17304: Brief Exposures to Air Pollutants Dysregulates <i>PCK1</i> Expression, Carbohydrate and Lipid Metabolism in <i>ApoE</i> Knockout Mice
Authors: Rajat Gupta, Gajalakshmi Ramanathan, Yuki Zhao, Fen Yin, Jerry Ricks, Michael E Rosenfeld, Xia Yang, Jesus A Araujo
Journal: Circulation (2018)

Introduction: Previous animal studies have shown that long exposures to particulate matter (PM) and diesel exhaust particles (DEP) promote atherosclerosis. Air pollutants are also reported to cause nonalcoholic steatohepatitis (NASH), liver fibrosis and insulin resistance in animals exposed to PM&lt;2.5 μm. We hypothesized that even brief exposures to air pollutants may alter metabolic pathways that could be responsible for vascular and liver diseases. Methods: ApoE null mice were briefly exposed to diesel exhaust (DE) or filtered air (FA) to assess liver content of lipids, lipid and carbohydrate metabolism. Illumina microarrays and metabolomic analysis were performed in liver tissue. Transcriptomic data was analyzed using the Illumina Beadstudio software. Gluconeogenesis and glycogenolysis were evaluated in HepG2 cells after treatment with diesel exhaust particles (DEP). Gene expression was determined by qPCR. Results: DE exposures led to a significant increase in both liver triglyceride (Mean ± SEM, FA: 0.16 ± 0.01 vs DE: 0.22 ± 0.02 mg/mg protein, n=7, p=0.02) and cholesterol (FA: 15.53 ± 1.53 vs DE: 23.26 ± 2.16 μg/mg protein, n=5, p=0.02) content in ApoE null mice. Microarray analysis depicted a dysregulation of 477 genes, and metabolomic analysis identified 70 metabolites significantly upregulated in the DE group while 48 metabolites were downregulated. Interestingly, metabolites in the citric acid cycle demonstrated significant changes after DE exposure likely due to mitochondrial dysfunction. Key driver analysis revealed Pck1 as a key driver gene. In-vitro experiments in HepG2 cells treated with DEP exhibited a significant upregulation in PCK1 mRNA expression (DEP: 7.31 ± 0.2 vs control: 1.07 ± 0.07, n=3, p&lt;0.01). Although treatment with DEP substantially depleted glycogen content as seen by periodic acid-schiff stain in cells, it significantly enhanced gluconeogenesis (DEP: 23.3 ± 1.2 vs control: 5.5 ± 0.6 μg/ml/mg protein, n=5, p&lt;0.001), effects that were inhibited in the presence of a metabolic inhibitor of PCK1: 3-Mercaptopicolinic acid (3-MPA) (DEP: 23.28 ± 1.18 vs DEP + 3-MPA: 16.04 ± 1.16 μg/ml/mg protein, n=5, p=0.002) indicating that DEP-induced glucose production was due to increased gluconeogenesis. Conclusion: Exposure to diesel exhaust leads to multiple alterations in carbohydrate and lipid metabolism including increased glycogenolysis, gluconeogenesis and PCK1 upregulation.
The Psychopharmacology of Obsessive-Compulsive Disorder: A Preclinical Roadmap
Authors: Henry Szechtman, Brian H. Harvey, Erik Z. Woody, Kurt Leroy Hoffman
Journal: Pharmacological Reviews (2019)

This review evaluates current knowledge about obsessive-compulsive disorder (OCD), with the goal of providing a roadmap for future directions in research on the psychopharmacology of the disorder. It first addresses issues in the description and diagnosis of OCD, including the structure, measurement, and appropriate description of the disorder and issues of differential diagnosis. Current pharmacotherapies for OCD are then reviewed, including monotherapy with serotonin reuptake inhibitors and augmentation with antipsychotic medication and with psychologic treatment. Neuromodulatory therapies for OCD are also described, including psychosurgery, deep brain stimulation, and noninvasive brain stimulation. Psychotherapies for OCD are then reviewed, focusing on behavior therapy, including exposure and response prevention and cognitive therapy, and the efficacy of these interventions is discussed, touching on issues such as the timing of sessions, the adjunctive role of pharmacotherapy, and the underlying mechanisms. Next, current research on the neurobiology of OCD is examined, including work probing the role of various neurotransmitters and other endogenous processes and etiology as clues to the neurobiological fault that may underlie OCD. A new perspective on preclinical research is advanced, using the Research Domain Criteria to propose an adaptationist viewpoint that regards OCD as the dysfunction of a normal motivational system. A systems-design approach introduces the security motivation system (SMS) theory of OCD as a framework for research. Finally, a new perspective on psychopharmacological research for OCD is advanced, exploring three approaches: boosting infrastructure facilities of the brain, facilitating psychotherapeutic relearning, and targeting specific pathways of the SMS network to fix deficient SMS shut-down processes. <h3>Significance Statement</h3> A significant proportion of patients with obsessive-compulsive disorder (OCD) do not achieve remission with current treatments, indicating the need for innovations in psychopharmacology for the disorder. OCD may be conceptualized as the dysfunction of a normal, special motivation system that evolved to manage the prospect of potential danger. This perspective, together with a wide-ranging review of the literature, suggests novel directions for psychopharmacological research, including boosting support systems of the brain, facilitating relearning that occurs in psychotherapy, and targeting specific pathways in the brain that provide deficient stopping processes in OCD.
Retrospective and Prospective Study of Childhood Autoimmune Hemolytic Anemia. a Preliminary Report from the Red Cell Working Group of the Paediatric Hemato-Oncology Italian Associations (AIEOP)
Authors: Saverio Ladogana, Raffaella Colombatti, Silverio Perrotta, Angela Maggio, Matteo Maruzzi, Andrea Ciliberti, Piera Samperi, Maddalena Casale, Paola Giordano, Giovanni Carlo Del Vecchio, Teresa Perillo, Gianluca Boscarol, Lucia Dora Notarangelo, Tommaso Casini, Maurizio Miano, Silvia Fasoli, Corti Paola, Angela Guarina, Francesco Arcioni, Antonella Sau, Fiorina Giona, Giuseppe Palumbo, Paola Saracco, Angela Petrone, Federico Verzegnassi, Chiara Piccolo, Simone Cesaro, Giovanna Russo
Journal: Blood (2019)
TRITEX: chromosome-scale sequence assembly of Triticeae genomes with open-source tools
Authors: Cécile Monat, Sudharsan Padmarasu, Thomas Lux, Thomas Wicker, Heidrun Gundlach, Axel Himmelbach, Jennifer Ens, Chengdao Li, Gary J. Muehlbauer, Alan H. Schulman, Robbie Waugh, Ilka Braumann, Curtis Pozniak, Uwe Scholz, Klaus F. X. Mayer, Manuel Spannagl, Nils Stein, Martin Mascher
Journal: Genome biology (2019)

Chromosome-scale genome sequence assemblies underpin pan-genomic studies. Recent genome assembly efforts in the large-genome Triticeae crops wheat and barley have relied on the commercial closed-source assembly algorithm DeNovoMagic. We present TRITEX, an open-source computational workflow that combines paired-end, mate-pair, 10X Genomics linked-read with chromosome conformation capture sequencing data to construct sequence scaffolds with megabase-scale contiguity ordered into chromosomal pseudomolecules. We evaluate the performance of TRITEX on publicly available sequence data of tetraploid wild emmer and hexaploid bread wheat, and construct an improved annotated reference genome sequence assembly of the barley cultivar Morex as a community resource.
Outcome in Children With Standard-Risk B-Cell Acute Lymphoblastic Leukemia: Results of Children’s Oncology Group Trial AALL0331
Authors: Kelly W. Maloney, Meenakshi Devidas, Cindy Wang, Leonard A. Mattano, Alison M. Friedmann, Patrick Buckley, Michael J. Borowitz, Andrew J. Carroll, Julie M. Gastier-Foster, Nyla A. Heerema, Nina Kadan-Lottick, Mignon L. Loh, Yousif H. Matloub, David T. Marshall, Linda C. Stork, Elizabeth A. Raetz, Brent Wood, Stephen P. Hunger, William L. Carroll, Naomi J. Winick
Journal: Journal of Clinical Oncology (2019)

Children's Oncology Group (COG) AALL0331 tested whether intensified postinduction therapy that improves survival in children with high-risk B-cell acute lymphoblastic leukemia (ALL) would also improve outcomes for those with standard-risk (SR) ALL.AALL0331 enrolled 5,377 patients between 2005 and 2010. All patients received a 3-drug induction with dexamethasone, vincristine, and pegaspargase (PEG) and were then classified as SR low, SR average, or SR high. Patients with SR-average disease were randomly assigned to receive either standard 4-week consolidation (SC) or 8-week intensified augmented Berlin-Frankfurt-Münster (BFM) consolidation (IC). Those with SR-high disease were nonrandomly assigned to the full COG-augmented BFM regimen, including 2 interim maintenance and delayed intensification phases.The 6-year event-free survival (EFS) rate for all patients enrolled in AALL0331 was 88.96% ± 0.46%, and overall survival (OS) was 95.54% ± 0.31%. For patients with SR-average disease, the 6-year continuous complete remission (CCR) and OS rates for SC versus IC were 87.8% ± 1.3% versus 89.1% ± 1.2% (P = .52) and 95.8% ± 0.8% versus 95.2% ± 0.8% (P = 1.0), respectively. Those with SR-average disease with end-induction minimal residual disease (MRD) of 0.01% to < 0.1% had an inferior outcome compared with those with lower MRD and no improvement with IC (6-year CCR: SC, 77.5% ± 4.8%; IC, 77.1% ± 4.8%; P = .71). At 6 years, the CCR and OS rates among 635 nonrandomly treated patients with SR-high disease were 85.55% ± 1.49% and 92.97% ± 1.08%, respectively.The 6-year OS rate for > 5,000 children with SR ALL enrolled in AALL0331 exceeded 95%. The addition of IC to treatment for patients with SR-average disease did not improve CCR or OS, even in patients with higher MRD, in whom it might have been predicted to provide more value. The EFS and OS rates are excellent for this group of patients with SR ALL, with particularly good outcomes for those with SR-high disease.