tbuckley/cabot-search huggingface dataset:
Is live high<i>–</i>train low altitude training relevant for elite athletes? Flawed analysis from inaccurate data
Authors: Gregoire P Millet, Robert F Chapman, Olivier Girard, Franck Brocherie
Journal: British Journal of Sports Medicine (2017)

Since 2012, Lundby and Robach1–3 have consistently stated that ‘altitude training does not convincingly increase exercise performance and should not be recommended to elite (endurance) athletes’ .2 This research group suggests3 that altitude training and particularly ‘live high–train low (LHTL) may only increase total haemoglobin mass (Hbmass) [and possibly maximal oxygen consumption (VO2max)] in athletes with an initial low Hbmass value’ . This statement comes from the analysis of nine selected studies4–12 on the relationship between group mean pre-LHTL value of Hbmass and increase in Hbmass after LHTL.3 The inverse correlation (r=−0.86; P<0.01) between initial Hbmass value and percentage increase in Hbmass would suggest that athletes starting an intervention with high relative Hbmass levels have smaller chances to further increase their relative Hbmass following altitude training. The rationale behind was that those athletes had already maximised their Hbmass level by training at sea level.3

We have concerns that this statement does not seem to be supported by several other studies,13–21 done by well-respected research groups, using what are widely considered to be best-practice techniques and protocols. These studies with outcomes conflicting with works of Lundby and Robach1–3 include those with shorter time course13 14 or lower hypoxic exposures15 16 to moderate altitude (2500–3000 m), which showed Hbmass increases ranging between 2.1% and 3.7%. In fact, Lundby and Robach’s own work has shown a +5% Hbmass improvement after 17 days of altitude training in five male cross-country skiing Olympic medallists with already high initial value of 13.5 g/kg.1

However, the most problematic issue of this flawed analysis3 is that conclusions appear to rely on Hbmass measures that may be inaccurate. Indeed, three4 8 11 out of nine studies used for …
State Laws Regarding Indoor Public Use, Retail Sales, and Prices of Electronic Cigarettes — U.S. States, Guam, Puerto Rico, and U.S. Virgin Islands, September 30, 2017
Authors: Kristy Marynak, Brandon Kenemer, Brian A. King, Michael A. Tynan, Allison MacNeil, Elizabeth Reimels
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Electronic cigarettes (e-cigarettes) are the most frequently used tobacco product among U.S. youths, and past 30-day e-cigarette use is more prevalent among high school students than among adults (1,2). E-cigarettes typically deliver nicotine, and the U.S. Surgeon General has concluded that nicotine exposure during adolescence can cause addiction and can harm the developing adolescent brain (2). Through authority granted by the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration (FDA) prohibits e-cigarette sales to minors, free samples, and vending machine sales, except in adult-only facilities (3). States, localities, territories, and tribes maintain broad authority to adopt additional or more stringent requirements regarding tobacco product use, sales, marketing, and other topics (2,4). To understand the current e-cigarette policy landscape in the United States, CDC assessed state and territorial laws that 1) prohibit e-cigarette use and conventional tobacco smoking indoors in restaurants, bars, and worksites; 2) require a retail license to sell e-cigarettes; 3) prohibit e-cigarette self-service displays (e.g., requirement that products be kept behind the counter or in a locked box); 4) establish 21 years as the minimum age of purchase for all tobacco products, including e-cigarettes (tobacco-21); and 5) apply an excise tax to e-cigarettes. As of September 30, 2017, eight states, the District of Columbia (DC), and Puerto Rico prohibited indoor e-cigarette use and smoking in indoor areas of restaurants, bars, and worksites; 16 states, DC, and the U.S. Virgin Islands required a retail license to sell e-cigarettes; 26 states prohibited e-cigarette self-service displays; five states, DC, and Guam had tobacco-21 laws; and eight states, DC, Puerto Rico, and the U.S. Virgin Islands taxed e-cigarettes. Sixteen states had none of the assessed laws. A comprehensive approach that combines state-level strategies to reduce youths' initiation of e-cigarettes and population exposure to e-cigarette aerosol, coupled with federal regulation, could help reduce health risks posed by e-cigarettes among youths (2,5).
Cost Sharing Does Not Lead to an Overall Increase of Involuntary Commitments in the Netherlands—Reply
Authors: Bastian Ravesteijn, Aartjan Beekman, Richard Janssen
Journal: JAMA Psychiatry (2017)

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 Psychiatry 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 Psychiatry journal
Folate-targeted liposomal nitrooxy-doxorubicin: An effective tool against P-glycoprotein-positive and folate receptor-positive tumors
Authors: Elena Gazzano, Barbara Rolando, Konstantin Chegaev, Iris C. Salaroglio, Joanna Kopecka, Isabella Pedrini, Simona Saponara, Matteo Sorge, Ilaria Buondonno, Barbara Stella, Alessandro Marengo, Massimo Valoti, Mara Brancaccio, Roberta Fruttero, Alberto Gasco, Silvia Arpicco, Chiara Riganti
Journal: Journal of Controlled Release (2017)
Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial
Authors: Manish R Patel, John Ellerton, Jeffrey R Infante, Manish Agrawal, Michael Gordon, Raid Aljumaily, Carolyn D Britten, Luc Dirix, Keun-Wook Lee, Mathew Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold B Gelb, Junyuan Xiong, Galit Rosen, James L Gulley, Andrea B Apolo
Journal: The Lancet Oncology (2017)
Elevated polygenic burden for autism is associated with differential DNA methylation at birth
Authors: Eilis Hannon, Diana Schendel, Christine Ladd-Acosta, Jakob Grove, Christine Søholm Hansen, Shan V. Andrews, David Michael Hougaard, Michaeline Bresnahan, Ole Mors, Mads Vilhelm Hollegaard, Marie Bækvad-Hansen, Mady Hornig, Preben Bo Mortensen, Anders D. Børglum, Thomas Werge, Marianne Giørtz Pedersen, Merete Nordentoft, Joseph Buxbaum, M. Daniele Fallin, Jonas Bybjerg-Grauholm, Abraham Reichenberg, Jonathan Mill
Journal: Genome Medicine (2018)

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder characterized by deficits in social communication and restricted, repetitive behaviors, interests, or activities. The etiology of ASD involves both inherited and environmental risk factors, with epigenetic processes hypothesized as one mechanism by which both genetic and non-genetic variation influence gene regulation and pathogenesis. The aim of this study was to identify DNA methylation biomarkers of ASD detectable at birth. We quantified neonatal methylomic variation in 1263 infants—of whom ~ 50% went on to subsequently develop ASD—using DNA isolated from archived blood spots taken shortly after birth. We used matched genotype data from the same individuals to examine the molecular consequences of ASD-associated genetic risk variants, identifying methylomic variation associated with elevated polygenic burden for ASD. In addition, we performed DNA methylation quantitative trait loci (mQTL) mapping to prioritize target genes from ASD GWAS findings. We identified robust epigenetic signatures of gestational age and prenatal tobacco exposure, confirming the utility of DNA methylation data generated from neonatal blood spots. Although we did not identify specific loci showing robust differences in neonatal DNA methylation associated with later ASD, there was a significant association between increased polygenic burden for autism and methylomic variation at specific loci. Each unit of elevated ASD polygenic risk score was associated with a mean increase in DNA methylation of − 0.14% at two CpG sites located proximal to a robust GWAS signal for ASD on chromosome 8. This study is the largest analysis of DNA methylation in ASD undertaken and the first to integrate genetic and epigenetic variation at birth. We demonstrate the utility of using a polygenic risk score to identify molecular variation associated with disease, and of using mQTL to refine the functional and regulatory variation associated with ASD risk variants.
H3B-8800-G0001-101: A first in human phase I study of a splicing modulator in patients with advanced myeloid malignancies.
Authors: David P. Steensma, Michael B. Maris, Jay Yang, William Bruce Donnellan, Andrew M Brunner, Malgorzata McMasters, Peter Greenberg, Rami S. Komrokji, Virginia M. Klimek, John M. Goldberg, Nathalie Rioux, Amy Kim, Pavan Kumar, Alyssa J. Marino, Silvia Buonamici, Peter Smith, Tarek Sahmoud, Markus Warmuth, Uwe Platzbecker
Journal: Journal of Clinical Oncology (2017)

TPS7075 Background: Dysregulated mRNA splicing is important in tumorigenesis and in resistance to cancer therapy. Somatic heterozygous mutations in core spliceosome genes (e.g. SF3B1, SRSF2, U2AF1) have been reported at high frequencies in patients with myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). These mutations confer a change of function resulting in aberrant mRNA splicing that, in preclinical models, results in defects in hematopoietic cell development and myelodysplasia. Recurrent mutations in the spliceosome of patients with malignancies suggests importance in disease pathogenesis. Cells bearing splicing mutations depend on wild-type spliceosome function, suggesting the spliceosome as a therapeutic target. In vitro data indicate preferential induction of apoptosis (measured by caspase 3/7 activation) in SF3B1-mutant cells following treatment with the SF3B1 modulator H3B-8800. H3B-8800 inhibits growth in human AML cell lines, including those with mutations in U2AF1, SRSF2 or SF3B1. Oral administration of H3B-8800 modulates splicing and induces antitumor activity in xenograft leukemia models expressing mutant core spliceosome components. Methods: This study explores the safety of H3B-8800 in patients with myeloid cancers. Dose escalation (Cohort A) follows a 3+3 design with a starting dose of 1 mg daily for 5 consecutive days every 14 days in a 28 day cycle. Cohort A is open to patients with MDS, AML or CMML, irrespective of spliceosome mutations. In parallel to dose escalation, up to 6 patients with mutations of interest may be enrolled at doses determined to be safe in Cohort A (Cohort B). After determining the recommended phase 2 dose, 4 expansion cohorts will enroll patients with: (1) International Prognostic Scoring System (IPSS) low/int-1 risk MDS with SF3B1 mutations, (2) IPSS low/intermediate risk-1 MDS with mutations in SRSF2, U2AF1, or ZRSR2, (3) high/intermediate risk-2 MDS or AML, and (4) CMML; 3 and 4 having mutations in SF3B1, SRSF2, U2AF1, or ZRSR2. The first cohort enrolled 3 patients and the trial is currently enrolling patients at the second dose level. Clinical trial information: NCT02841540.
Surto de parotidite na Suecia, Fevereiro-Abril 2004
Authors: B Sartorius, P Penttinen, J Nilsson, K Johansen, K Jönsson, M Arneborn, M Löfdahl, J Giesecke
Journal: Eurosurveillance (2005)

Entre o 24 de fevereiro e o 26 de abril de 2004, 42 casos suspeitos de parotidite foram notificados na regiao de Vastra Gotaland na Suecia. Um estudo descriptivo dos casos foi realizado. Um questionario por telefone foi administrado e a eficacia vacinal por meio do metodo administrativo foi calculada. Dos 42 casos suspeitos, 31 (74%) foram questionados por telefone. Oito sobre 42 das amostras de soro eram positivas ou indeterminadas para a IgM de parotidite por ELISA. O genoma do virus foi identificado em 50% (21/42) das amostras de saliva.. Dessas 21 amostras, 11 foram seleccionadas para a sequenciacao e o virus da parotidite foi confirmado em todas. Os casos provinham principalmente de duas pequenas cidades. Dos 19 casos que tiveram uma inflamacao bilateral, 18 estavam associados a uma pequena cidade. A idade mediana dos casos interrogados era de 43 anos (5-88). Dos seis casos que necessitaram ser hospitalisados, cinco tinham mais de 30 anos. A incidencia era mais alta no grupo etario de 35 a 44 anos. A eficacia vacinal foi estimada a 65% para uma dose e 91% para duas. Este estudo descriptivo mostra o numero crescente de casos de parotidite com coberturas vacinais tambem em aumento. A eficacia vacinal foi particularmente elevada com duas doses de vacina. Visto os bem documentados fracasos da vacina primaria uma boa cobertura para duas doses tem que ser assegurada. Grandes precaucoes devem ser tomadas para evitar a formacao de agregados de pessoas adultas susceptiveis, devido ao risco acrescido de complicacoes nessas faixas etarias.
Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia
Authors: Francisco José Bermúdez-Jiménez, Víctor Carriel, Andreas Brodehl, Miguel Alaminos, Antonio Campos, Ilona Schirmer, Hendrik Milting, Beatriz Álvarez Abril, Miguel Álvarez, Silvia López-Fernández, Diego García-Giustiniani, Lorenzo Monserrat, Luis Tercedor, Juan Jiménez-Jáimez
Journal: Circulation (2017)

Desmin (DES) mutations cause severe skeletal and cardiac muscle disease with heterogeneous phenotypes. Recently, DES mutations were described in patients with inherited arrhythmogenic right ventricular cardiomyopathy/dysplasia, although their cellular and molecular pathomechanisms are not precisely known. Our aim is to describe clinically and functionally the novel DES-p.Glu401Asp mutation as a cause of inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia.We identified the novel DES mutation p.Glu401Asp in a large Spanish family with inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia and a high incidence of adverse cardiac events. A full clinical evaluation was performed on all mutation carriers and noncarriers to establish clinical and genetic cosegregation. In addition, desmin, and intercalar disc-related proteins expression were histologically analyzed in explanted cardiac tissue affected by the DES mutation. Furthermore, mesenchymal stem cells were isolated and cultured from 2 family members with the DES mutation (1 with mild and 1 with severe symptomatology) and a member without the mutation (control) and differentiated ex vivo to cardiomyocytes. Then, important genes related to cardiac differentiation and function were analyzed by real-time quantitative polymerase chain reaction. Finally, the p.Glu401Asp mutated DES gene was transfected into cell lines and analyzed by confocal microscopy.Of the 66 family members screened for the DES-p.Glu401Asp mutation, 23 of them were positive, 6 were obligate carriers, and 2 were likely carriers. One hundred percent of genotype-positive patients presented data consistent with inherited arrhythmogenic cardiomyopathy/dysplasia phenotype with variable disease severity expression, high-incidence of sudden cardiac death, and absence of skeletal myopathy or conduction system disorders. Immunohistochemistry was compatible with inherited arrhythmogenic cardiomyopathy/dysplasia, and the functional study showed an abnormal growth pattern and cellular adhesion, reduced desmin RNA expression, and some other membrane proteins, as well, and desmin aggregates in transfected cells expressing the mutant desmin.The DES-p.Glu401Asp mutation causes predominant inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia with a high incidence of adverse clinical events in the absence of skeletal myopathy or conduction system disorders. The pathogenic mechanism probably corresponds to an alteration in desmin dimer and oligomer assembly and its connection with membrane proteins within the intercalated disc.
Abstract 66: c-Fos: A new player in promotion of cancer stem-like cell properties in head and neck squamous cell carcinoma
Authors: Ratna B. Ray
Journal: Clinical Cancer Research (2017)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. We have shown that c-Fos was highly up-regulated in the HNSCC sphere forming cells. However, upregulation of c-Fos for the biology of HNSCC-CSCs remains unknown. In this study, we investigated the role of c-Fos in renewal of stemness of HNSCC and tumor growth. We demonstrated that c-Fos overexpression enhanced the epithelial-mesenchymal transition (EMT) state and expression of CSC markers (Nanog, c-Myc, Sox2 and Notch1). Ectopic expression of c-Fos in HNSCC cells also display increased number of sphere formation. We further observed that overexpression of c-Fos increased the expression of pERK and cyclin D1 in HNSCC cells. Knockdown of c-Fos in Cal27 cells impaired sphere formation. Next we examine the effect of c-Fos expression in vivo. For this, we established stable HNSCC cell line (MDA1386Tu cells) where c-Fos gene is ectopically expressed. Our results demonstrated that exogenous expression of c-Fos in non-tumorigenic MDA1386Tu cells makes these cells tumorigenic in nude mice. Further, subcutaneous transplantation of c-Fos overexpressing Cal27 cells (tumorigenic) into immunocompromised mice enhanced tumor growth as compared to parental cells. Taken together, our results strongly demonstrated a novel role of c-Fos as a regulator of EMT and cancer stem cell reprogramming in HNSCC cells. Collectively, our results offer that c-Fos may be a new target for developing therapeutic strategies against HNSCC. Citation Format: Ratna B. Ray. c-Fos: A new player in promotion of cancer stem-like cell properties in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 66.
Abstract 15130: Diagnostic Performance of Hybrid Cardiac Imaging Methods for Assessment of Significant Coronary Artery Disease Compared With Stand-Alone Coronary Computed Tomography Angiography: A Meta-Analysis
Authors: Asim Rizvi, Donghee Han, Ibrahim Danad, Bríain Ó Hartaigh, Ji Hyun Lee, Jackie Szymonifka, Paul Knaapen, Fay Y Lin, James K Min
Journal: Circulation (2016)

Introduction:  The usefulness of coronary CT angiography (CCTA) for detecting significant CAD remains suboptimal at present. Myocardial perfusion imaging (MPI) encompasses positron emission tomography, single photon-emission CT, and cardiac magnetic resonance imaging, which permit for the identification of myocardial perfusion defects to detect CAD. A hybrid approach comprising MPI and CCTA may improve diagnostic performance for detecting significant CAD.   Hypothesis:  In a meta-analysis, we aimed to assess the diagnostic performance of hybrid imaging techniques compared with CCTA alone for assessment of significant CAD.   Methods:  PubMed and Web of Knowledge were searched for relevant publications between January 1, 2000 and December 31, 2015. Studies performing hybrid imaging and CCTA for diagnosis of significant CAD (a diameter reduction of >50% or >70% by invasive coronary angiography) were included. In total, 13 articles comprising 1,029 patients and 2,339 vessels were identified, and a meta-analysis was performed to estimate pooled sensitivity, specificity, and summary receiver operating characteristic (SROC) curves.   Results:  On a per-patient basis, the pooled sensitivity of hybrid imaging was higher than CCTA [91% (95% CI: 88-93%) vs. 89% (95% CI: 86-92%)]. Similarly, specificity was higher for hybrid imaging versus CCTA [92% (95% CI: 89-94% vs. 64% (95% CI: 60-69%)]. On a per-vessel basis, sensitivity for hybrid imaging against CCTA was comparable [85% (95% CI: 82-88%) vs. 87% (95% CI: 84-90%)]. Notably, hybrid imaging yielded a specificity of 95% (95% CI: 94-96%) versus 84% (95% CI: 82-85%) for CCTA. SROC curves displayed improved discrimination for hybrid imaging beyond CCTA alone, on a per-patient (e.g., AUC = 0.97 vs. 0.92) and per-vessel (e.g., AUC = 0.97 vs. 0.93) basis, respectively.   Conclusions:  Hybrid cardiac imaging demonstrated improved diagnostic performance for identifying significant CAD compared with stand-alone CCTA.
Use of Concomitant Androgen Deprivation Therapy in Patients Treated with Early Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy: Long-term Results from a Large, Multi-institutional Series
Authors: Giorgio Gandaglia, Nicola Fossati, R. Jeffrey Karnes, Stephen A. Boorjian, Michele Colicchia, Alberto Bossi, Thomas Seisen, Cesare Cozzarini, Nadia Di Muzio, Barbara Noris Chiorda, Emanuele Zaffuto, Thomas Wiegel, Shahrokh F. Shariat, Gregor Goldner, Steven Joniau, Antonino Battaglia, Karin Haustermans, Gert De Meerleer, Valérie Fonteyne, Piet Ost, Hendrick Van Poppel, Francesco Montorsi, Alberto Briganti
Journal: European Urology (2017)