bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating Reductions in Ethnic Inequalities in Child Adiposity from Hypothetical Diet, Screen Time, and Sports Participation Interventions
Authors: Lara Macarena , Labrecque Jeremy A. , van Lenthe Frank J. , Voortman Trudy 
Published: July 2020

Background:
Childhood obesity is a global epidemic, and its prevalence differs by ethnicity. The objective of this study was to estimate the change in ethnic inequalities in child adiposity at age 10 resulting from interventions on diet at age 8 and screen time and sports participation at age 9.

Methods:
We conducted a population-based cohort study, the Generation R Study, from 9,749 births in Rotterdam (2002–2006), of which 9,506 children remained in the analysis. We measured ethnicity, diet, screen time, and sports participation through questionnaires; we measured weight, body mass index (BMI), fat mass index, and fat-free mass index directly. We used sequential G-estimation to estimate the reduction in inequality that would result from the interventions.

Results:
We observed that sociodemographic characteristics, diet, screen time, sports participation, and all adiposity measurements were more favorable in children from Western versus non-Western ethnic backgrounds: weight = −1.2 kg (95% confidence interval [CI] = −1.7, −0.8), BMI = −1.0 kg/m2 (CI = −1.2, −0.9), and fat mass index = −0.8 kg/m2 (CI = −0.9, −0.7). We estimated that extreme intervention (maximum diet score of 10, no screen time, and >4 hours/week of sports) reduced ethnic inequalities by 21% (CI = 8%, 35%) for weight, 9% (CI = 4%, 14%) for BMI, and 9% (CI = 6%, 13%) for fat mass index. A diet score ≥5 points, screen time ≤2 hours/day, and sports participation >2 hours/week reduced ethnic inequalities by 17% (CI = 6%, 28%) for weight, 7% (CI = 3%, 11%) for BMI, and 7% (CI = 4%, 10%) for fat mass index.

Conclusions:
Our results are consistent with the hypothesis that interventions integrating diet, screen time, and sports participation have a moderate impact on reducing ethnic inequalities in child adiposity.
Magnesium Sulfate Administration in Moderate Coronary Artery Disease Patients Improves Atherosclerotic Risk Factors: A Double-Blind Clinical Trial Study
Authors: Farshidi Hossein , Sobhani Ali R. , Eslami Mahdiye , Azarkish Fariba , Eftekhar Ebrahim , Keshavarz Mansoor , Soltani Nepton 
Published: July 2020

Abstract:
Magnesium (Mg) deficiency is known to promote vascular and cardiac dysfunctions such as atherosclerosis. This study investigated the effect of oral MgSO4 therapy to improve lipid profile and serum oxidized LDL level and its receptor (LOX1) in moderate coronary atherosclerotic patients. In this randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease were selected according to angiography findings. Participants were divided into 2 groups including Mg-treated (n = 32) and placebo (n = 32) The patients received either placebo or MgSO4 supplement capsule, containing 300 mg MgSO4 for 6 months on a daily basis. Lipid profile, HbA1c, 2h postprandial (2hpp) blood glucose, fasting blood sugar, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), oxidized low-density lipoprotein, and lectin-like ox-LDL receptor 1 (LOX1) concentrations were measured at baseline and every 3 months. HbA1c, serum LOX1, and oxidized low-density lipoprotein concentrations were significantly lower in the Mg-treated group than the placebo group 3 months after MgSO4 administration. 2hpp, serum low-density lipoprotein cholesterol, SGPT, SGOT levels, and HbA1c levels significantly improved in the Mg-treated group compared with the placebo-received group. Overall, the results of this study showed that magnesium treatment improved some of the major risk factors of atherosclerosis. According to the results of liver function tests (SGOT and SGPT), magnesium therapy seems to be safe in patients with moderate atherosclerotic plaque. Therefore, it is suggested that magnesium to be used along with other atherosclerosis control drugs.
Effects of phytoestrogen supplementation on intermediate cardiovascular disease risk factors among postmenopausal women: a meta-analysis of randomized controlled trials
Authors: Wolters Maike , Dejanovic Gordana M. , Asllanaj Eralda , Günther Kathrin , Pohlabeln Hermann , Bramer Wichor M. , Ahrens Jenny , Nagrani Rajini , Pigeot Iris , Franco Oscar H. , Ahrens Wolfgang , Muka Taulant , Glisic Marija 
Published: July 2020

Abstract

Importance:
Phytoestrogens are becoming popular constituents of human diets and are increasingly used by postmenopausal women.

Objective:
Our study aims to determine the effects of phytoestrogen supplementation on intermediate cardiovascular disease (CVD) risk factors in postmenopausal women.

Evidence review:
Five electronic databases (Medline, EMBASE, Web of Science, Cochrane CENTRAL, Google Scholar) were systematically searched to identify eligible studies, that is, randomized controlled trials (RCTs) that assessed the association of phytoestrogen supplementation with CVD risk factors (serum lipids, homocysteine, fibrinogen, markers of inflammation, oxidative stress and endothelial function, carotid intima-media thickness [CIMT]) in postmenopausal women. Data were extracted by two independent reviewers using a predefined data collection form.

Findings:
In total, 56 RCTs were identified, including 4,039 individual postmenopausal women. There was substantial heterogeneity in quality across studies. Twenty-six (46%) RCTs showed poor quality and there was an indication of publication bias presence for some of the biomarkers. Results are reported in pooled mean difference (95% CI) of changes. Use of phytoestrogens was associated with a decrease in serum total cholesterol (−0.27 mmol/L [−0.41 to −0.13]), low-density lipoprotein (−0.25 mmol/L [−0.37 to −0.13]), triglycerides (−0.20 mmol/L [−0.28 to −0.11]), and apolipoprotein B (−0.13 g/L [−0.23 to −0.03]) and with an increase in serum apolipoprotein A-1 (0.04 g/L [0.02-0.07]. Also, phytoestrogen supplementation was associated with a decrease in serum intercellular adhesion molecule 1 (−18.86 ng/mL [−30.06 to −7.65]) and E-selectin (−2.32 ng/mL [−4.05 to −0.59]). There was no association observed between phytoestrogen supplementation and inflammatory markers, fibrinogen, homocysteine, or other endothelial function markers. In contrast, use of phytoestrogens was associated with an increase in CIMT (9.34 μm [95% CI, 0.39-18.29]). Effect estimates of phytoestrogen supplementation on oxidative stress could not be pooled.

Conclusions and Relevance:
Phytoestrogen supplementation seems to modestly improve the CVD risk profile of postmenopausal women by influencing blood lipids and parameters of endothelial function. In women with an increased risk of atherosclerosis, although modest, a harmful effect on CIMT progression may be present. Because of limited quality and the heterogeneous nature of the current evidence, additional rigorous studies are needed to explore the role of phytoestrogens in menopausal cardiovascular health.

Video Summary
: http://links.lww.com/MENO/A593.
Adolescent suicide: what can pediatricians do?
Authors: Breslin Kirsten , Balaban Julie , Shubkin Catherine D. 
Published: July 2020

Purpose of review
Suicide is a major public health concern and the second leading cause of death for adolescents. Faced with an already-high prevalence and increasing rates over the past decade, pediatricians feel inadequately prepared to manage a suicidal patient. This article will review the changing rates of suicide, discuss recent literature on risk factors, identify methods to screen for suicidal thoughts and suggest an approach to counseling a suicidal patient. Finally, there will be a brief discussion on safety planning and public health measures to help reduce suicide rates.

Recent findings
Rates of attempted suicide and death by suicide have been increasing for more than a decade. Risk assessment of potential suicidality remains very challenging, as the risk factors are multifactorial. However, some common risk factors persist including sexual minority identification and family or personal history of mental health issues. Although keeping these and other risk factors in mind, regular screening of adolescents for depression and self-harm is important. Finally, the best safety plans and treatment methods appear to be team-based.

Summary
It remains the responsibility of pediatricians to stay aware of risk factors, regularly screen adolescents and prioritize collaborative safety planning for suicidal patients.
A Latent Class Analysis of Manic and Psychotic Symptoms
Authors: Pignon Baptiste , Peyre Hugo , Noblins Emmanuel , Rolland Benjamin , Thomas Pierre , Vaiva Guillaume , Roelandt Jean-Luc , Benradia Imane , Amad Ali , Geoffroy Pierre A. 
Published: July 2020

Abstract
Bipolar spectrum disorders encompass heterogeneous clinical manifestations and comorbidities. A latent class analysis (LCA) was performed in 1846 subjects who experienced an episode of abnormally elevated or irritable mood to identify homogeneous groups of subjects, based on the distribution of 11 manic and 7 psychotic symptoms. LCA identified five classes: 1) two classes with irritability and with low and high level of psychosis (respectively “irritable,” 29.1% of the sample, and “irritable-psychotic,” 16.2%); 2) a class with expansive mood and hyperactivity (“expansive-hyperactive,” 12.7%); and 3) two classes with manic symptoms and high and low level of psychosis (“manic-psychotic,” 15.0%, and “manic,” 27.2%). “Irritable” displayed lower rates of depressive episode, panic, and substance use disorders. Manic-psychotic displayed higher rates of depressive episode, panic, generalized anxiety, and substance use disorders. Use of mental health treatment more frequent in manic-psychotic and manic classes. Five classes of bipolar spectrum disorders were characterized by different sociodemographic and clinical patterns.
Development of an Interdisciplinary Healthcare Team for Pressure Injury Management
Authors: Al-Mansour Leena Ali , Dudley-Brown Sharon , Al-Shaikhi Abdullah 
Published: July 2020

PURPOSE:
The purpose of this quality improvement project was to create an interdisciplinary healthcare team for the management of patients with stage 3, stage 4, and unstageable pressure injuries (PIs), improve the communication among the interdisciplinary healthcare team, test the educational level of the nursing staff regarding PI management, and conduct quarterly PI prevalence surveys to decrease the rate of the hospital-acquired pressure injuries (HAPIs).

PARTICIPANTS AND SETTING:
Patients with stage 3, stage 4, and unstageable PIs in medical adult inpatient units of a private tertiary hospital located in the eastern province of Saudi Arabia were included in the study.

APPROACH:
During the project period (February 21, 2017, to May 23, 2017), a healthcare team was formed consisting of a hospitalist, a plastic surgeon, a case manager, a dietitian, a physiotherapist, and wound and home health nurses. The team communication and staff adherence to the care plan were measured through an audit tool. Nurses' educational level was measured by pre- and posttest assessments. In addition, a quarterly PI survey day was conducted twice to monitor the occurrence of HAPIs and to reevaluate nursing staff knowledge of management of HAPIs.

OUTCOMES:
Results showed improvement in communication within the interdisciplinary team regarding care of patients with HAPIs, with 100% staff adherence to the plan of care. In addition, unit-based educational sessions conducted to measure staff knowledge showed a statistically significant increase (P < .000). Although small, the HAPI rate decreased from 5.9% to 5% during this short 3-month study.
A shortcut in forward genetics: concurrent discovery of mutant phenotype and causal mutation in Arabidopsis M2 families via MAD-mapping
Authors: Holmes Danalyn R. , Mobitzer Robert , Wunderlich Markus , Sun Hequan , Kasmi Farid El , Schneeberger Korbinian , Lahaye Thomas 
Published: July 2020

ABSTRACTForward genetics is a powerful tool to establish phenotype-genotype correlations in virtually all areas of plant biology and has been particularly successful in the model plant Arabidopsis. This approach typically starts with a phenotype in an M2 mutant, followed by identifying a causal DNA change in F2 populations resulting from a cross between the mutant and a wildtype individual. Ultimately, two additional generations are needed to pinpoint causal DNA changes upon mutant identification. We postulated that genome-wide allele frequency distributions within the mutants of M2 families facilitate discrimination of causal versus non-causal mutations, essentially eliminating the need for F2 populations. In a proof-of-principle experiment, we aimed to identify signalling components employed by the executor-type resistance (R) protein, Bs4C, from pepper (Capsicum pubescens). In a native setting,Bs4Cis transcriptionally activated by and mediates recognition of the transcription activator-like effector AvrBs4 from the bacterial pathogenXanthomonas. Arabidopsis containing an estradiol-inducibleBs4Ctransgene was used in a conditionally lethal screen to identify second-site suppressor mutations. Whole genome sequencing was used forM2 mutantallele-frequencydistribution (MAD) mapping in three independent M2 families. MAD-mapping uncovered that all three families harboured mutations inXRN4, a novel component of executor R protein pathways. Our work demonstrates that causal mutations observed in forward genetic screens can be identified immediately in M2 families instead of derived F2 families. Notably, the timesaving concept of MAD mapping should be applicable to most crop species and will advance the appeal of forward genetics beyond applications in fundamental research.SIGNIFICANCEForward genetics has uncovered numerous genes that govern plant immune reactions. This procedure relies on mutant plants with modified immune reactions followed by identification of causal DNA changes in derived F2 progeny. We developed a novel forward genetics concept where causal DNA changes are identified in the initial M2 mutants, making time consuming establishment of F2 populations obsolete. To confirm the feasibility of the concept, we mutagenized transgenic Arabidopsis seeds containing the cell death executing resistance geneBs4Cfrom pepper. Whole-genome sequencing of identified mutant families that lack aBs4C-dependent cell death revealed theXRN4gene as a novel component ofBs4C-dependent cell death. This confirms our hypothesis that causal mutations can be identified directly within phenotypically selected mutant families.
KDM5 inhibition offers a novel therapeutic strategy for the treatment ofKMT2Dmutant lymphomas
Authors: Heward James A , Konali Lola , D’Avola Annalisa , Close Karina , Yeomans Alison , Philpott Martin , Dunford James , Rahim Tahrima , Al Seraihi Ahad F , Wang Jun , Korfi Koorosh , Araf Shamzah , Iqbal Sameena , Bewicke-Copley Findlay , Kumar Emil , Barisic Darko , Calaminici Maria , Clear Andrew , Gribben John , Johnson Peter , Neve Richard , Okosun Jessica , Oppermann Udo , Melnick Ari , Packham Graham , Fitzgibbon Jude 
Published: July 2020

AbstractLoss-of-function mutations inKMT2Dare a striking feature of the germinal centre (GC) lymphomas, resulting in decreased H3K4 methylation and altered gene expression. We hypothesised that inhibition of the KDM5 family, which demethylates H3K4me3/me2, would re-establish H3K4 methylation and restore the expression of genes repressed upon loss ofKMT2D. KDM5-inhibition increased H3K4me3 levels and caused an anti-proliferative responsein vitro, which was markedly greater in both endogenous and CRISPR-editedKMT2Dmutant DLBCL cell lines, whilst tumour growth was inhibited inKMT2Dmutant xenograftsin vivo. KDM5-inhibition reactivated both KMT2D-dependent and -independent genes, resulting in diminished B-cell receptor signalling and altered expression of BCL2 family members, including BCL2 itself, allowing it to synergise with agents targeting these pathways. KDM5-inhibition may offer an effective therapeutic strategy for amelioratingKMT2Dloss-of-function mutations in GC-lymphomas.Statement of significanceWe detail a novel way of reverting the effects of loss-of-function mutations in the histone methyltransferaseKMT2Dby inhibiting the KDM5 demethylase family, increasing levels of H3K4me3 and restoring expression of KMT2D regulated genes.
Single-Cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning theC. elegansEmbryo
Authors: Ma Xuehua , Zhao Zhiguang , Xiao Long , Xu Weina , Wang Yangyang , Zhang Yanping , Wu Gang , Du Zhuo 
Published: July 2020

SUMMARYA high-resolution protein atlas is essential for understanding the molecular basis of biological processes. Using protein-fusion reporters and imaging-based single-cell analyses, we present a protein expression atlas ofC. elegansembryogenesis encompassing 266 transcription factors (TFs) in nearly all (90%) lineage-resolved cells. Single-cell analysis reveals a combinatorial code and cascade that elucidate the regulatory hierarchy between a large number of lineage-, tissue-, and time-specific TFs in spatiotemporal fate patterning. Guided by expression, we identify essential functions of CEH-43/DLX, a lineage-specific TF, and ELT-1/GATA3, a well-known skin fate specifier, in neuronal specification; and M03D4.4 as a pan-muscle TF in converging muscle differentiation in the body wall and pharynx. Finally, systems-level analysis of TF regulatory state uncovers lineage- and time-specific kinetics of fate progression and widespread detours of the trajectories of cell differentiation. Collectively, our work reveals a single-cell molecular atlas and general principles underlying the spatiotemporal patterning of a metazoan embryo.
Drastic shift in flowering phenology, an instant reproductive isolation mechanism, explains the population structure ofImperata cylindricain Japan
Authors: Nomura Yasuyuki , Shimono Yoshiko , Mizuno Nobuyuki , Miyoshi Ikuya , Iwakami Satoshi , Sato Kazuhiro , Tominaga Tohru 
Published: July 2020

AbstractReproductive isolation plays an important role in population differentiation and speciation, thus enhancing biodiversity in wild plants. Hybridisation sometimes involves rapid reproductive isolation between parents and their hybrids through the novel traits of hybrids derived from a new combination of genomes. Here, we report how a hybrids’ new phenotype contributes to rapid reproductive isolation between two ecotypes ofImperata cylindrica. The two ecotypes differ in their flowering phenology and habitats. An analysis with genetic markers revealed that hybrid populations consisted of only F1individuals. Both parental ecotypes flowered in spring, but F1s flowered in fall. This drastic shift in flowering phenology prevented backcrossing parental ecotypes to F1. F1s flowered in fall and dispersed seeds in winter. The germination percentage of seeds set on F1was extremely low in their habitats, and seedlings did not survive due to the low temperatures in winter, resulting in the absence of a F2generation. In conclusion, flowering phenology mismatch promotes reproductive isolation between parents and F1, resulting in a hybrid population consisting of only F1s.
EPySeg: a coding-free solution for automated segmentation of epithelia using deep learning
Authors: Aigouy Benoit , Prud’Homme Benjamin 
Published: July 2020

AbstractEpithelia are dynamic tissues that self-remodel during their development. At morphogenesis, the tissue-scale organization of epithelia is obtained through a sum of individual contributions of the cells constituting the tissue. Therefore, understanding any morphogenetic event first requires a thorough segmentation of its constituent cells. This task, however, usually implies extensive manual correction, even with semi-automated tools. Here we present EPySeg, an open source, coding-free software that uses deep learning to segment epithelial tissues automatically and very efficiently. EPySeg, which comes with a straightforward graphical user interface, can be used as a python package on a local computer, or on the cloud via Google Colab for users not equipped with deep-learning compatible hardware. By alleviating human input in image segmentation, EPySeg accelerates and improves the characterization of epithelial tissues for all developmental biologists.
Evidence accumulation under uncertainty – a neural marker of emerging choice and urgency
Authors: Parés-Pujolràs Elisabeth , Travers Eoin , Ahmetoglu Yoana , Haggard Patrick 
Published: July 2020

AbstractTo interact meaningfully with its environment, an agent must integrate external information with its own internal states. However, information about the environment is often noisy. In our task participants had to monitor a stream of discrete visual stimuli over time and decide whether or not to act, on the basis of either strong or weak evidence. We found that the classic P3 event-related potential evoked by sequential evidence items item of evidence tracked decision-making processes and encoded participants’ choice, both when evidence was strong and when it was weak. We also found that the readiness potential, a classic marker of self-paced actions, was observed preceding all actions - even when those were strongly driven by external evidence. Computational modelling showed that both neural dynamics and behavioural results can be explained by a combination of (a) competition between mutually inhibiting accumulators for the two categorical choice outcomes, and (b) a context-dependent urgency signal.
Phenotypic analysis of an MLL-AF4 gene regulatory network reveals indirect CASP9 repression as a mode of inducing apoptosis resistance
Authors: Harman Joe R. , Thorne Ross , Jamilly Max , Tapia Marta , Crump Nicholas T. , Rice Siobhan , Beveridge Ryan , Morrissey Edward , de Bruijn Marella F.T.R , Roberts Irene , Roy Anindita , Fulga Tudor A. , Milne Thomas A. 
Published: July 2020

ABSTRACTRegulatory interactions mediated by transcription factors (TFs) make up complex networks that control cellular behavior. Fully understanding these gene regulatory networks (GRNs) offers greater insight into the consequences of disease-causing perturbations than studying single TF binding events in isolation. Chromosomal translocations of theMixed Lineage Leukemia gene(MLL) produce MLL fusion proteins such as MLL-AF4, causing poor prognosis acute lymphoblastic leukemias (ALLs). MLL-AF4 is thought to drive leukemogenesis by directly binding to genes and inducing aberrant overexpression of key gene targets, including anti-apoptotic factors such as BCL-2. However, this model minimizes the potential for circuit generated regulatory outputs, including gene repression. To better understand the MLL-AF4 driven regulatory landscape, we integrated ChIP-seq, patient RNA-seq and CRISPR essentiality screens to generate a model GRN. This GRN identified several key transcription factors, including RUNX1, that regulate target genes using feed-forward loop and cascade motifs. We used CRISPR screening in the presence of the BCL-2 inhibitor venetoclax to identify functional impacts on apoptosis. This identified an MLL-AF4:RUNX1 cascade that repressesCASP9,perturbation of which disrupts venetoclax induced apoptosis. This illustrates how our GRN can be used to better understand potential mechanisms of drug resistance acquisition.Graphical abstract captionA network model of the MLL-AF4 regulatory landscape identifies feed-forward loop and cascade motifs. Functional screening using CRISPR and venetoclax identified an MLL-AF4:RUNX1:CASP9repressive cascade that impairs drug-induced cell death.