bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of a Triple‐chamber Bag Parenteral Nutrition in Children Ages up to 24 Months
Authors: Arnell Henrik , Valla Frederic V. , Malfilâtre Geneviève , Pladys Patrick , Senterre Thibault , Pontes‐Arruda Alessandro 
Published: September 2019

ABSTRACTObjectives:Hypermagnesemia has been reported in preterm neonates treated with commercial pediatric triple‐chamber bag (3CB) parenteral nutrition (PN). This postmarketing study was requested by the European Medicines Agency to assess the safety of a 3CB PN product in full‐term neonates and children up to 24 months of age.Methods:This prospective, multicenter, observational study enrolled hospitalized, full‐term, newborn infants and children up to 24 months of age receiving >70% of nutrition as PN and requiring ≥50% of nutrition as PN for ≥5 days. All patients received 3CB PN during the study for ⩽15 days. The primary outcome was serum magnesium, summarized by age group (0–1, >1–12, and >12–24 months). Secondary outcomes were nutritional intake and adverse events (AEs), including clinically significant abnormal laboratory results and vital signs.Results:A total of 102 eligible patients were included. Median (interquartile range) parenteral magnesium intake was 0.23 (0.18–0.30) mmol · kg−1 · day−1. Mean serum magnesium showed no consistent changes during treatment in any age group. One moderate and 3 mild AEs of hypermagnesemia were reported in 4 patients (3.9%), all ages 0 to 1 month. Other AEs in >2 patients were hypertriglyceridemia (6.9%), laryngitis (3.9%), hyperkalemia, hypokalemia, hyponatremia, hypophosphatemia, and neonatal hypotension (each 2.9%). Other serum electrolytes were stable, and revealed no safety concerns.Conclusions:Mean serum magnesium levels were not affected by 3CB PN in full‐term neonates and children up to 24 months of age. The risk of hypermagnesemia AEs was low when providing median parenteral magnesium of 0.2 to 0.3 mmol · kg−1 · day−1 in this population.
Necrotic Loxoscelism of the Scalp
Authors: Horta Ricardo , Barreiro Diogo 
Published: September 2019

Abstract
A 15 month old boy was referred to our department after he and his mother moved to our country. He had been bitten by a brown recluse spider (Loxosceles reclusa) at the age of 7 months, in Brazil. Initially, he presented to the emergency department of his local hospital with rash in the scalp, near the bite. After a few days, he developed systemic disease with multiorgan failure and was admitted on intensive care unit, where he has been treated for 2 months. During this hospital stay he developed skin necrosis of the scalp, right preauricular, mandibular, and neck regions. He also developed right foot ischemia, which resulted in amputation. At the discharge time, he was under topical treatment with silver sulfadiazine, which was maintained until our observation, 8 months after being bitten. The child was successfully treated, and is now stable and awaiting lower limb prosthetic replacement.
Loxoscelism (bites by spiders of the genus Loxosceles) is the only proven arachnological cause of dermonecrosis. The brown recluse spider, Loxosceles reclusa, is the best known and can cause necrotic dermatologic injury throw an enzyme, sphingomyelinase D, that has been shown to be cytotoxic to endothelial and red blood cells. Although the majority of persons bitten by a brown recluse spider probably will not seek medical attention, some patients may develop systemic loxoscelism, especially children.
Myelomeningocele: Medical Considerations and Stomatologic Aspects in the Dental Treatment
Authors: Amaral Cristhiane Olívia Ferreira do , Nardeli Caroline Soares , Saito Isabela Caroline , Valério Juliana Suguimoto , Filho Marcelo Sávio Paiva Amaral , Straioto Fabiana Gouveia 
Published: September 2019

Abstract
The aim was to analyze systemic and oral aspects of patients with myelomeningocele (MMC), relevant for their dental treatment. Dental treatment of these individuals requires the dentist's extensive knowledge and careful information to determine the dental treatment plan. Thirty participants aged 3 to 16 years were divided into 2 groups: study group (15 MMC individuals) and control group (15 healthy subjects). All patients were evaluated for: systemic conditions, use of medications, sequela of the underlying pathology, oral hygiene, diseases, convulsion, cerebrospinal fluid (CSF), allergy, behavior, learning, and mouth physical examination to assess the oral conditions. The study group presented: higher percentage using drugs (P < 0.05), 40% had convulsions (P < 0.05), 86.67% using CSF shunt, 53.33% presented latex allergies (P < 0.05), 53.33% were classified as anxious and with cognitive deficit (P < 0.05), showed more gingivitis (P < 0.05). The MMC individuals, in the majority, have shown cognitive impairment and anxious behavior, use of controlled drugs, convulsion, CSF shunt use, and latex allergy. The presence of periodontal tissue damage was higher in patients with MMC.
Evaluation of Reproducible and Transparent Research Practices in Sports Medicine Research: A Cross-sectional study
Authors: Evans Sheridan , Fladie Ian A. , Anderson J. Michael , Tritz Daniel , Vassar Matt 
Published: September 2019

AbstractBackgroundIn recent years, urgency has been placed on the “reproducibility crisis” facing biomedical research. Despite efforts toward improvement, certain elements needed to reproduce a study are often lacking from publications. The current state of reproducibility within the sports medicine research community remains unknown.PurposeOur study sought to evaluate the presence of eight indicators of reproducibility and transparency to determine the current state of research reporting in sports medicine research.Study DesignCross-sectional reviewMethodsUsing the National Library of Medicine catalog, we identified 41 MEDLINE-indexed, English language sports medicine journals. From the 41 journals, we randomly sampled 300 publications that were recorded on PubMed as being published between January 1, 2014, and December 31, 2018. Two investigators extracted data in duplicate and blinded fashion.ResultsOf the 300 publications sampled, 280 were accessible and were screened for empirical data. Studies that lack empirical data were excluded from our analysis. Of the remaining 195 with empirical data, 10 (5.13%) publications provided data availability statements, 1 (0.51%) provided a protocol, 0 (0.0%) provided an analysis script, and 9 (4.62%) were pre registered.ConclusionReproducibility and transparency indicators are lacking in sports medicine publications. The majority of publications lack the necessary resources for reproducibility such as material, data, analysis scripts, or protocol availability. While the current state of reproducibility cannot be fixed overnight, we feel combined efforts of data sharing, open access, and verifying disclosure statements can help to improve overall reporting.
Induction of hierarchy and time through one-dimensional probability space with certain topologies
Authors: Adachi Shun 
Published: September 2019

AbstractIn a previous study, the authors utilized a single dimensional operationalization of species density that at least partially demonstrated dynamic system behavior. For completeness, a theory needs to be developed related to homology/cohomology, induction of the time dimension, and system hierarchies. The topological nature of the system is carefully examined and for testing purposes, species density data for a wild Dictyostelia community data are used in conjunction with data derived from liquid-chromatography mass spectrometry of proteins. Utilizing a Clifford algebra, a congruent zeta function, and a Weierstraß ℘ function in conjunction with a type VI Painlevé equation, we confirmed the induction of hierarchy and time through one-dimensional probability space with certain topologies. This process also served to provide information concerning interactions in the model. The previously developed “small s” metric can characterize dynamical system hierarchy and interactions, using only abundance data along time development.
Acute cerebellar knockdown ofSgcereproduces salient features of Myoclonus-dystonia (DYT11) in mice
Authors: Washburn Samantha G. , Fremont Rachel , Moreno M. Camila , Angueyra Chantal , Khodakhah Kamran 
Published: September 2019

AbstractMyoclonus dystonia (DYT11) is a movement disorder caused by loss-of-function mutations inSGCEand characterized by involuntary jerking and dystonia that frequently improve after drinking alcohol. Existing transgenic mouse models of DYT11 exhibit only mild motor symptoms, possibly due to rodent-specific developmental compensation mechanisms, which have limited the study of neural mechanisms underlying DYT11. To circumvent potential compensation, we used short hairpin RNA (shRNA) to acutely knock down Sgcein the adult mouse and found that this approach produced dystonia and repetitive, myoclonic-like movements in mice that improved after administration of ethanol. Acute knockdown ofSgcein the cerebellum, but not the basal ganglia, produced motor symptoms, likely due to aberrant cerebellar activity. The acute knockdown model described here reproduces the salient features of DYT11 and provides a platform to study the mechanisms underlying symptoms of the disorder, and to explore potential therapeutic options.
Genetic drug target validation using Mendelian randomization
Authors: Schmidt A F , Finan C , Gordillo-Marañón M , Asselbergs F W , Freitag D F , Patel R S , Tyl B , Chopade S , Faraway R , Zwierzyna M , Hingorani A D 
Published: September 2019

AbstractMendelian randomisation analysis has emerged as an important tool to elucidate the causal relevance of a range of environmental and biological risk factors for human disease. However, inference on cause is undermined if the genetic variants used to instrument a risk factor of interest also associate with other traits that open alternative pathways to the disease (horizontal pleiotropy). We show how the ‘no horizontal pleiotropy assumption’ in MR analysis is strengthened when proteins are the risk factors of interest. Proteins are the proximal effectors of biological processes encoded in the genome, and are becoming assayable on an-omics scale. Moreover, proteins are the targets of most medicines, so Mendelian randomization (MR) studies of drug targets are becoming a fundamental tool in drug development. To enable such studies we introduce a formal mathematical framework that contrasts MR analysis of proteins with that of risk factors located more distally in the causal chain from gene to disease. Finally, we illustrate key model decisions and introduce an analytical framework for maximizing power and elucidating the robustness of drug target MR analyses.
The Object Space Task reveals a dissociation between semantic-like and episodic-like memory in a mouse model of Kleefstra Syndrome
Authors: Schut Evelien H.S. , Alonso Alejandra , Smits Steven , Khamassi Mehdi , Samanta Anumita , Negwer Moritz , Kasri Nael Nadif , Lobato Irene Navarro , Genzel Lisa 
Published: September 2019

AbstractKleefstra syndrome is a disorder caused by a mutation in theEHMT1gene characterized in humans by general developmental delay, mild to severe intellectual disability and autism. Here, we characterized semantic- and episodic-like memory in theEhmt1+/-mouse model using the Object Space Task. We combined conventional behavioral analysis with automated analysis by deep-learning networks, a session-based computational learning model and a trial-based classifier.Ehmt1+/-mice showed more anxiety-like features and generally explored objects less, but the difference decreased over time. Interestingly, when analyzing memory-specific exploration,Ehmt1+/-show increased expression of semantic-like memory, but a deficit in episodic-like memory. A similar dissociation of semantic and episodic memory performance has been previously reported in humans with autism. Using our automatic classifier to differentiate between genotypes, we found that semantic-like memory features are better suited for classification than general exploration differences. Thus, detailed behavioral classification with the Object Space Task produced a more detailed behavioral phenotype of theEhmt1+/-mouse model.One Sentence SummaryEhmt1+/-mice show decreased exploration and episodic-like memory but increased semantic-like memory In the Object Space Task. (143 of 150)
Genetic underpinnings of sociability in the UK Biobank
Authors: Bralten J , Klemann CJHM , Mota NR , De Witte W , Arango C , Fabbri C , Kas MJ , van der Wee N , Penninx BWJH , Serretti A , Franke B , Poelmans G 
Published: September 2019

ABSTRACTDifficulties with sociability include a tendency to avoid social contacts and activities, and to prefer being alone rather than being with others. While sociability is a continuously distributed trait in the population, decreased sociability represent a common early manifestation of multiple neuropsychiatric disorders such as Schizophrenia (SCZ), Bipolar Disorder (BP), Major Depressive Disorder (MDD), Autism Spectrum Disorders (ASDs), and Alzheimer’s disease (AD). We aimed to investigate the genetic underpinnings of sociability as a continuous trait in the general population. In this respect, we performed a genome-wide association study (GWAS) using a sociability score based on 4 social functioning-related self-report questions in the UK Biobank sample (n=342,461) to test the effect of individual genetic variants. This was followed by LD score analyses to investigate the genetic correlation with psychiatric disorders (SCZ, BP, MDD, ASDs) and a neurological disorder (AD) as well as related phenotypes (Loneliness and Social Anxiety). The phenotypic data indeed showed that the sociability score was decreased in individuals with ASD, (probable) MDD, BP and SCZ, but not in individuals with AD. Our GWAS showed 604 genome-wide significant SNPs, coming from 18 independent loci (SNP-based h2=0.06). Genetic correlation analyses showed significant correlations with SCZ (rg=0.15, p=9.8e-23), MDD (rg=0.68, p=6.6e-248) and ASDs (rg=0.27, p=4.5e-28), but no correlation with BP (rg=0.01, p=0.45) or AD (rg=0.04, p=0.55). Our sociability trait was also genetically correlated with Loneliness (rg=0.45, p=2.4e-8) and Social Anxiety (rg=0.48, p=0.002). Our study shows that there is a significant genetic component to variation in population levels of sociability, which is relevant to some psychiatric disorders (SCZ, MDD, ASDs), but not to BP and AD.
Network propagation of rare mutations in Alzheimer’s disease reveals tissue-specific hub genes and communities
Authors: Scelsi Marzia A. , Napolioni Valerio , Greicius Michael D. , Altmann Andre ,   for the Alzheimer’s Disease Neuroimaging Initiative (ADNI),   the Alzheimer’s Disease Sequencing Project (ADSP)
Published: September 2019

ABSTRACTBackgroundState-of-the-art rare variant association testing methods aggregate the contribution of rare variants in biologically relevant genomic regions to boost statistical power. However, testing single genes separately does not consider the complex interaction landscape of genes, nor the downstream effects of non-synonymous variants on protein structure and function. Here we present the NETwork Propagation-based Assessment of Genetic Events (NETPAGE), an integrative approach aimed at investigating the biological pathways through which rare variation results in complex disease phenotypes.ResultsWe applied NETPAGE to sporadic, late-onset Alzheimer’s disease (AD), using whole-genome sequencing from the AD Neuroimaging Initiative (ADNI) cohort, as well as whole-exome sequencing from the AD Sequencing Project (ADSP). NETPAGE is based on network propagation, a framework that models information flow on a graph and simulates the percolation of genetic variation through gene networks. The result of network propagation is a set of smoothed gene scores used to predict disease status through sparse regression. The application of NETPAGE to AD enabled the identification of a set of connected genes whose smoothed mutation profile acted as a robust predictor of case-control status, based on gene interactions in the hippocampus. Additionally, smoothed scores significantly correlated with risk of conversion to AD in Mild Cognitive Impairment (MCI) subjects. Lastly, we showed tissue-specific transcriptional dysregulation of the core genes in two independent RNA-seq datasets, as well as significant enrichments in terms and gene sets with known connections to AD.ConclusionsThe presented framework enables enhanced genetic association testing for a wide range of traits, diseases, and sample sizes.
Pangenome Analysis of Enterobacteria Reveals Richness of Secondary Metabolite Gene Clusters and their Associated Gene Sets
Authors: Mohite Omkar S. , Lloyd Colton J. , Monk Jonathan M. , Weber Tilmann , Palsson Bernhard O. 
Published: September 2019

AbstractThe growing number of sequenced genomes enables the study of secondary metabolite biosynthetic gene clusters (BGC) in phyla beyond well-studied soil bacteria. We mined 2627 enterobacterial genomes to detect 8604 BGCs, including nonribosomal peptide synthetases, siderophores, polyketide-nonribosomal peptide hybrids, and 60 other BGC types, with an average of around 3.3 BGCs per genome. These BGCs represented 212 distinct BGC families, of which only 20 have associated products in the MIBiG standard database with functions such as siderophores, antibiotics, and genotoxins. Pangenome analysis identified genes associated with a specific BGC encoding for colon cancer-related colibactin. In one example, we associated genes involved in the type VI secretion system with the presence of a colibactin BGC inEscherichia. This richness of BGCs in enterobacteria opens up the possibility to discover novel secondary metabolites, their physiological roles and provides a guide to identify and understand PKS associated gene sets.
Adipokines set neural tone by regulating synapse number
Authors: Brent Ava E. , Rajan Akhila 
Published: September 2019

SummaryEnergy sensing neural circuits decide to expend or conserve resources by integrating tonic steady-state energy store information with phasic signals for hunger and food intake. Tonic signals, in the form of adipose tissue-derived adipokines, set the baseline level of energy-sensing neuron activity, providing context for interpretation of phasic messages. However, the mechanism by which tonic adipokine information establishes baseline neuronal function is unclear. Here we show that Upd2, a Drosophila Leptin ortholog, regulates actin-based synapse reorganization by reducing inhibitory synaptic contacts, thereby providing a permissive neural tone for insulin release under conditions of nutrient surplus. Unexpectedly, Insulin acts on the same upstream inhibitory neurons to conversely increase synapse number, hence re-instating negative tone. Our results suggest that two surplus-sensing hormonal systems, Leptin/Upd2 and Insulin, converge on a neuronal circuit with opposing outcomes that establish tonic, energy-store-dependent neuron activity.HighlightsThe adipokine Upd2 regulates number of inhibitory synaptic contacts on Insulin neurons.Upd2 activates an actin-regulating complex of Arouser, Basigin, and Gelsolin in target neurons.Arouser, Basigin, and Gelsolin reduce the extent of inhibitory contact on Insulin neurons.Insulin resets negative tone by increasing the number of synaptic contacts made by its own upstream inhibitory neurons.
PARPi synthetic lethality derives from replication-associated single-stranded DNA gaps
Authors: Cong Ke , Kousholt Arne Nedergaard , Peng Min , Panzarino Nicholas J. , Lee Wei Ting Chelsea , Nayak Sumeet , Krais John , Calvo Jennifer , Bere Matt , Rothenberg Eli , Johnson Neil , Jonkers Jos , Cantor Sharon B. 
Published: September 2019

AbstractBRCA1 or BRCA2 (BRCA)-deficient tumor cells have defects in DNA double strand break repair by homologous recombination (HR) and fork protection (FP) that are thought to underlie the sensitivity to poly(ADP-ribose) polymerase inhibitor (PARPi). Given the recent finding that PARPi accelerates DNA replication, it was proposed that high speed DNA replication leads to DNA double strand breaks (DSBs). Here, we tested the alternative hypothesis that PARPi sensitivity in BRCA deficient cells results from combined replication dysfunction that causes a lethal accumulation of replication-associated single-stranded DNA (ssDNA) gaps. In support of a gap toxicity threshold, PARPi-induced ssDNA gaps accumulate more excessively in BRCA deficient cells and are suppressed inde novoand genetic models of PARPi resistance while defects in HR or FP often lack this correlation. We also uncouple replication speed from lethality. The clear link between PARPi sensitivity and ssDNA gaps provides a new paradigm for understanding synthetic lethal interactions.
Replication gaps are a cancer vulnerability counteracted by translesion synthesis
Authors: Nayak Sumeet , Calvo Jennifer A. , Cong Ke , Berthiaume Emily , Jackson Jessica , Dash Radha Charon , Vindigni Alessandro , Hadden Kyle M. , Cantor Sharon B. 
Published: September 2019

SUMMARYThe replication stress response which serves as an anti-cancer barrier is activated not only by DNA damage and replication obstacles, but also oncogenes, mystifying how cancer evolves. Here, we identify that oncogene expression, similar to cancer therapies, induces single stranded DNA (ssDNA) gaps that reduce cell fitness, unless suppressed by translesion synthesis (TLS). DNA fiber analysis and electron microscopy reveal that TLS restricts replication fork slowing, reversal, and fork degradation without inducing replication fork gaps. Evidence that TLS gap suppression is fundamental to cancer, a small molecule inhibitor targeting the TLS factor, REV1, not only disrupts DNA replication and cancer cell fitness, but also synergizes with gap-inducing therapies. This work illuminates that gap suppression during replication is critical for cancer cell fitness and therefore a targetable vulnerability.