tbuckley/cabot-search huggingface dataset:
Association of Cannabis Legalization and Decriminalization With Arrest Rates of Youths
Authors: Rosanna Smart, Mark A. R. Kleiman
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
The Many Nuanced Evolutionary Consequences of Duplicated Genes
Authors: Ashley I Teufel, Mackenzie M Johnson, Jon M Laurent, Aashiq H Kachroo, Edward M Marcotte, Claus O Wilke
Journal: Molecular Biology and Evolution (2018)

Abstract Gene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub or neofunctionalization, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a nonduplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate’s interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them.
Abstract 19357: The Prevalence and Significance of Aortic Root Dilation in Highly Trained Athletes: `Relevance to the Bethesda Consensus Panel Guidelines'
Authors: Catherine Sedgwick, Sabiha Gati, Michael Papadakis, Matt Reed, Abbas Zaidi, Nabeel Sheikh, Andrew Cox, Saqib Ghani, Anne Child, Sanjay Sharma
Journal: Circulation (2012)

Introduction: Studies in highly trained athletes reveal increased aortic root dimensions compared with controls. It is unclear whether aortic root dilation represents ‘athlete’s heart’ or a potential aortopathy. The Bethesda recommendations suggest that athletes with an aortic root dimension of ≥40mm should only participate in low-intensity competitive sport. This study sought to investigate the prevalence and clinical significance of aortic root dilation in nationally ranked British athletes. Methods: Between 2004-2012, 1160 athletes (63% male; age 20.7±6.0 years; range 14-35 years; BSA 2.01±0.34m 2 ) participating in 31 sporting disciplines, underwent echocardiography as part of a pre-participation screening evaluation. Aortic root dimensions, measured at the sinus of Valsalva level, were analysed according to ESC guidelines. Results were compared to 415 healthy controls (57% male; age 22.1±6.4 years; range 14-35 years) of similar size (BSA 1.98±0.36m 2 ) and 50 patients with Marfan syndrome (54% male; age range 18-68 years). Individuals with a bicuspid valve had been excluded. Results: Athletes and controls exhibited similar mean aortic root dimensions (27.9±4.1mm, range: 16-43mm, vs. 27.9±4.3mm, range: 17-38mm; p=1.000). Marfan patients had greater mean aortic root dimensions compared with athletes (39.1±5.1mm; range 26-48 mm vs. 27.9±4.1mm). The aortic root was ≥40 mm in 6 male athletes (0.8%) and 1 female athlete (0.2%), compared with none in the controls. In contrast, 22 males (81%) and 6 females (26%) with Marfan syndrome showed an aortic root ≥40mm (p&lt;0.0001). Conclusion: Unlike other cardiac dimensions, athletes generally exhibit similar mean aortic root dimensions to controls. In absolute terms, few British athletes reveal an aortic root dimension ≥40mm. This cross sectional study provides support for the guidelines set by the expert Bethesda consensus panel.
King's Brief Interstitial Lung Disease questionnaire: responsiveness and minimum clinically important difference
Authors: Claire M. Nolan, Surinder S. Birring, Matthew Maddocks, Toby M. Maher, Suhani Patel, Ruth E. Barker, Sarah E. Jones, Jessica A. Walsh, Stephanie C. Wynne, Peter M. George, William D-C. Man
Journal: European Respiratory Journal (2019)

Health status is increasingly used in clinical practice to quantify symptom burden and as a clinical trial end-point in patients with interstitial lung disease (ILD). The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a brief, validated 15-item, disease-specific, health-related quality of life questionnaire that is increasingly used in clinical trials, but little data exist regarding the minimum clinically important difference (MCID). Using pulmonary rehabilitation as a model, we aimed to determine the responsiveness of KBILD and provide estimates of the MCID. KBILD scores, Chronic Respiratory Questionnaire (CRQ) scores, Medical Research Council (MRC) Dyspnoea score and incremental shuttle walk test (ISWT) distance were measured in 209 patients with ILD (105 with idiopathic pulmonary fibrosis (IPF)) before and after an outpatient pulmonary rehabilitation programme. Changes with intervention and Cohen's effect size were calculated. Anchor-based (linear regression and receiver operating characteristic plots) or distribution-based approaches (0.5 sd and standard error of measurement) were used to estimate the MCID of KBILD domain and total scores. KBILD, CRQ, MRC Dyspnoea and ISWT improved with intervention, and the effect sizes of KBILD domain and total scores ranged from 0.28 to 0.38. Using anchor-based estimates, the MCID estimates for KBILD-Psychological, KBILD-Breathlessness and activities, and KBILD-Total were 5.4, 4.4 and 3.9 points, respectively. Using distribution-based methods, the MCID estimate for KBILD-Chest symptoms was 9.8 points. The MCID estimates for KBILD in IPF patients were similar. In patients with ILD and IPF, KBILD is responsive to intervention with an estimated MCID of 3.9 points for the total score.
Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Cherinne Arundel, Phillip H. Lam, Gauravpal S. Gill, Samir Patel, Gurusher Panjrath, Charles Faselis, Michel White, Charity J. Morgan, Richard M. Allman, Wilbert S. Aronow, Steven N. Singh, Gregg C. Fonarow, Ali Ahmed
Journal: Journal of the American College of Cardiology (2019)
Elucidation of Codon Usage Signatures across the Domains of Life
Authors: Eva Maria Novoa, Irwin Jungreis, Olivier Jaillon, Manolis Kellis
Journal: Molecular Biology and Evolution (2019)

Because of the degeneracy of the genetic code, multiple codons are translated into the same amino acid. Despite being "synonymous," these codons are not equally used. Selective pressures are thought to drive the choice among synonymous codons within a genome, while GC content, which is typically attributed to mutational drift, is the major determinant of variation across species. Here, we find that in addition to GC content, interspecies codon usage signatures can also be detected. More specifically, we show that a single amino acid, arginine, is the major contributor to codon usage bias differences across domains of life. We then exploit this finding and show that domain-specific codon bias signatures can be used to classify a given sequence into its corresponding domain of life with high accuracy. We then wondered whether the inclusion of codon usage codon autocorrelation patterns, which reflects the nonrandom distribution of codon occurrences throughout a transcript, might improve the classification performance of our algorithm. However, we find that autocorrelation patterns are not domain-specific, and surprisingly, are unrelated to tRNA reusage, in contrast to previous reports. Instead, our results suggest that codon autocorrelation patterns are a by-product of codon optimality throughout a sequence, where highly expressed genes display autocorrelated "optimal" codons, whereas lowly expressed genes display autocorrelated "nonoptimal" codons.
A Fast Likelihood Method to Reconstruct and Visualize Ancestral Scenarios
Authors: Sohta A Ishikawa, Anna Zhukova, Wataru Iwasaki, Olivier Gascuel
Journal: Molecular Biology and Evolution (2019)

The reconstruction of ancestral scenarios is widely used to study the evolution of characters along phylogenetic trees. One commonly uses the marginal posterior probabilities of the character states, or the joint reconstruction of the most likely scenario. However, marginal reconstructions provide users with state probabilities, which are difficult to interpret and visualize, whereas joint reconstructions select a unique state for every tree node and thus do not reflect the uncertainty of inferences. We propose a simple and fast approach, which is in between these two extremes. We use decision-theory concepts (namely, the Brier score) to associate each node in the tree to a set of likely states. A unique state is predicted in tree regions with low uncertainty, whereas several states are predicted in uncertain regions, typically around the tree root. To visualize the results, we cluster the neighboring nodes associated with the same states and use graph visualization tools. The method is implemented in the PastML program and web server. The results on simulated data demonstrate the accuracy and robustness of the approach. PastML was applied to the phylogeography of Dengue serotype 2 (DENV2), and the evolution of drug resistances in a large HIV data set. These analyses took a few minutes and provided convincing results. PastML retrieved the main transmission routes of human DENV2 and showed the uncertainty of the human-sylvatic DENV2 geographic origin. With HIV, the results show that resistance mutations mostly emerge independently under treatment pressure, but resistance clusters are found, corresponding to transmissions among untreated patients.
Dihydromyricetin and Salvianolic acid B inhibit alpha-synuclein aggregation and enhance chaperone-mediated autophagy
Authors: Jia-Zhen Wu, Mustafa Ardah, Caroline Haikal, Alexander Svanbergsson, Meike Diepenbroek, Nishant N. Vaikath, Wen Li, Zhan-You Wang, Tiago F. Outeiro, Omar M. El-Agnaf, Jia-Yi Li
Journal: Translational Neurodegeneration (2019)

Progressive accumulation of α-synuclein is a key step in the pathological development of Parkinson's disease. Impaired protein degradation and increased levels of α-synuclein may trigger a pathological aggregation in vitro and in vivo. The chaperone-mediated autophagy (CMA) pathway is involved in the intracellular degradation processes of α-synuclein. Dysfunction of the CMA pathway impairs α-synuclein degradation and causes cytotoxicity. In the present study, we investigated the effects on the CMA pathway and α-synuclein aggregation using bioactive ingredients (Dihydromyricetin (DHM) and Salvianolic acid B (Sal B)) extracted from natural medicinal plants. In both cell-free and cellular models of α-synuclein aggregation, after administration of DHM and Sal B, we observed significant inhibition of α-synuclein accumulation and aggregation. Cells were co-transfected with a C-terminal modified α-synuclein (SynT) and synphilin-1, and then treated with DHM (10 μM) and Sal B (50 μM) 16 hours after transfection; levels of α-synuclein aggregation decreased significantly (68% for DHM and 75% for Sal B). Concomitantly, we detected increased levels of LAMP-1 (a marker of lysosomal homeostasis) and LAMP-2A (a key marker of CMA). Immunofluorescence analyses showed increased colocalization between LAMP-1 and LAMP-2A with α-synuclein inclusions after treatment with DHM and Sal B. We also found increased levels of LAMP-1 and LAMP-2A both in vitro and in vivo, along with decreased levels of α-synuclein. Moreover, DHM and Sal B treatments exhibited anti-inflammatory activities, preventing astroglia- and microglia-mediated neuroinflammation in BAC-α-syn-GFP transgenic mice. Our data indicate that DHM and Sal B are effective in modulating α-synuclein accumulation and aggregate formation and augmenting activation of CMA, holding potential for the treatment of Parkinson's disease.
Abstract 2385: Assessment of the Genetic Component of Hypertension
Authors: Mitsutoshi Oguri, Kimihiko Kato, Kazuhiro Yajima, Takeshi Hibino, Kiyoshi Yokoi, Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Sahoko Ichihara, Norifumi Metoki, Hidemi Yoshida, Kei Satoh, Yoshinori Nozawa, Yoshiji Yamada
Journal: Circulation (2006)

Aims Although genetic epidemiological studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remai...
Measuring Circulating Complement Activation Products in Myeloperoxidase– and Proteinase 3–Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Eveline Y. Wu, Elizabeth A. McInnis, Sonia Boyer‐Suavet, Carmen E. Mendoza, Lydia T. Aybar, Kristin B. Kennedy, Caroline J. Poulton, Candace D. Henderson, Yichun Hu, Susan L. Hogan, Peiqi Hu, Hong Xiao, Patrick H. Nachman, J. Charles Jennette, Ronald J. Falk, Donna O. Bunch
Journal: Arthritis & Rheumatology (2019)

There is accumulating evidence that complement activation is important in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) pathogenesis. This study was undertaken to investigate complement activation in AAV with myeloperoxidase (MPO) positivity and AAV with proteinase 3 (PR3) positivity after determining optimal methods for measuring activated complement factors in circulation.Participants included 98 patients with AAV (45 MPO-ANCA positive, 53 PR3-ANCA positive) and 35 healthy controls. Plasma was obtained from blood collected using EDTA tubes, with or without 100 μg/ml Futhan. Levels of Bb, C3a, C5a, soluble C5b-9 (sC5b-9), properdin, and C4d were measured by enzyme-linked immunosorbent assay. Group comparisons were made using Wilcoxon's 2-sample test. Paired data were analyzed using a matched pairs signed rank test.Compared to healthy controls, certain complement analyte levels were high in patients with active AAV with MPO positivity, including C3a (P < 0.0001), C5a (P = 0.0004), and sC5b-9 (P = 0.0007). During remission, levels of Bb (P = 0.001), C3a (P < 0.0001), and sC5b-9 (P = 0.003) were higher. Compared to healthy controls, C3a (P < 0.0001), C5a (P = 0.002), sC5b-9 (P = 0.0001), and C4d (P = 0.005) levels were higher in patients with active AAV with PR3 positivity; levels of C3a (P < 0.0001) and C4d (P = 0.007) were also higher duriing remission. There were no significant differences in any complement analyte for either ANCA serotype between patients with active disease and those with disease in remission. Among patients with paired samples, sC5-9 levels were significantly lower during disease remission compared to active disease. C5a was significantly lower among patients with disease in long-term remission who were not receiving therapy. For Bb, C5a, and sC5b-9, median levels and individual values were considerably higher in control and patient samples processed without Futhan compared to those processed with Futhan.Complement activation occurs in both MPO-positive AAV and PR3-positive AAV. The complement activation profile differs according to disease activity and possibly ANCA serotype. Futhan reduces in vitro complement activation and provides a more accurate measurement.
Bis-diketopyrrolopyrrole conjugated polymer nanoparticles as photothermic nanoagonist for specific and synergistic glioblastoma therapy
Authors: Shengliang Li, Qingyuan Deng, Xiao Li, Yongwei Huang, Xiaozhen Li, Fang Liu, Huijuan Wang, Weixia Qing, Zhonghua Liu, Chun-Sing Lee
Journal: Biomaterials (2019)
Barbara Krystyna Turk
Authors: Eva Kalmus
Journal: BMJ (2019)

Barbara Krystyna Turk (nee Zawisza) was born in Battersea, London, and grew up in south London. She left Coombe County School at 16 with 2 O levels, not believing she had a particularly academic future. She worked at St Ebbw’s Hospital and Kennedy Immunology Institute as a laboratory technician and progressed through qualifications at night school at Ewell County Technical College to degree equivalent in immunology

Despite failing to get a grade B in her chemistry A level, Barbara was accepted to study medicine at Charing Cross and Westminster Medical School. She qualified in 1985, having passed the “essential” university examinations. She proved that academic performance alone was no predictor of a successful career in medicine. …
The State of Software for Evolutionary Biology
Authors: Diego Darriba, Tomáš Flouri, Alexandros Stamatakis
Journal: Molecular Biology and Evolution (2018)

With Next Generation Sequencing data being routinely used, evolutionary biology is transforming into a computational science. Thus, researchers have to rely on a growing number of increasingly complex software. All widely used core tools in the field have grown considerably, in terms of the number of features as well as lines of code and consequently, also with respect to software complexity. A topic that has received little attention is the software engineering quality of widely used core analysis tools. Software developers appear to rarely assess the quality of their code, and this can have potential negative consequences for end-users. To this end, we assessed the code quality of 16 highly cited and compute-intensive tools mainly written in C/C++ (e.g., MrBayes, MAFFT, SweepFinder, etc.) and JAVA (BEAST) from the broader area of evolutionary biology that are being routinely used in current data analysis pipelines. Because, the software engineering quality of the tools we analyzed is rather unsatisfying, we provide a list of best practices for improving the quality of existing tools and list techniques that can be deployed for developing reliable, high quality scientific software from scratch. Finally, we also discuss journal as well as science policy and, more importantly, funding issues that need to be addressed for improving software engineering quality as well as ensuring support for developing new and maintaining existing software. Our intention is to raise the awareness of the community regarding software engineering quality issues and to emphasize the substantial lack of funding for scientific software development.
Mortality attributable to seasonal influenza in Greece, 2013 to 2017: variation by type/subtype and age, and a possible harvesting effect
Authors: Theodore Lytras, Katerina Pantavou, Elisavet Mouratidou, Sotirios Tsiodras
Journal: Eurosurveillance (2019)

IntroductionEstimating the contribution of influenza to excess mortality in the population presents substantial methodological challenges.AimIn a modelling study we combined environmental, epidemiological and laboratory surveillance data to estimate influenza-attributable mortality in Greece, over four seasons (2013/14 to 2016/17), specifically addressing the lag dimension and the confounding effect of temperature.MethodsAssociations of influenza type/subtype-specific incidence proxies and of daily mean temperature with mortality were estimated with a distributed-lag nonlinear model with 30 days of maximum lag, separately by age group (all ages, 15-64 and ≥ 65 years old). Total and weekly deaths attributable to influenza and cold temperatures were calculated.ResultsOverall influenza-attributable mortality was 23.6 deaths per 100,000 population per year (95% confidence interval (CI): 17.8 to 29.2), and varied greatly between seasons, by influenza type/subtype and by age group, with the vast majority occurring in persons aged ≥ 65 years. Most deaths were attributable to A(H3N2), followed by influenza B. During periods of A(H1N1)pdm09 circulation, weekly attributable mortality to this subtype among people ≥ 65 years old increased rapidly at first, but then fell to zero and even negative, suggesting a mortality displacement (harvesting) effect. Mortality attributable to cold temperatures was much higher than that attributable to influenza.ConclusionsStudies of influenza-attributable mortality need to consider distributed-lag effects, stratify by age group and adjust both for circulating influenza virus types/subtypes and daily mean temperatures, in order to produce reliable estimates. Our approach addresses these issues, is readily applicable in the context of influenza surveillance, and can be useful for other countries.
Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in motoneurons
Authors: Yuan Yuan, Shirley Xie, Jennifer C. Darnell, Andrew J. Darnell, Yuhki Saito, Hemali Phatnani, Elisabeth A. Murphy, Chaolin Zhang, Tom Maniatis, Robert B. Darnell
Journal: Genome biology (2018)

Alternative RNA processing plays an essential role in shaping cell identity and connectivity in the central nervous system. This is believed to involve differential regulation of RNA processing in various cell types. However, in vivo study of cell type-specific post-transcriptional regulation has been a challenge. Here, we describe a sensitive and stringent method combining genetics and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory interactions between NOVA and RNA in the mouse spinal cord motoneurons. We developed a means of undertaking motoneuron-specific CLIP to explore motoneuron-specific protein–RNA interactions relative to studies of the whole spinal cord in mouse. This allowed us to pinpoint differential RNA regulation specific to motoneurons, revealing a major role for NOVA in regulating cytoskeleton interactions in motoneurons. In particular, NOVA specifically promotes the palmitoylated isoform of the cytoskeleton protein Septin 8 in motoneurons, which enhances dendritic arborization. Our study demonstrates that cell type-specific RNA regulation is important for fine tuning motoneuron physiology and highlights the value of defining RNA processing regulation at single cell type resolution.