bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal abstinence syndrome: an update
Authors: Sanlorenzo Lauren A. , Stark Ann R. , Patrick Stephen W. 
Published: January 2018

Purpose of review
The current review provides an update focused on the evolving epidemiology of neonatal abstinence syndrome (NAS), factors influencing disease expression, advances in clinical assessment of withdrawal, novel approaches to NAS treatment, and the emerging role of quality improvement in assessment and management of NAS.

Recent findings
The rise in the incidence of NAS disproportionately occurred in rural and suburban areas. Polysubstance exposure and genetic polymorphisms have been shown to modify NAS expression and severity. New bedside assessments using a limited number of factors to identify infants with NAS result in fewer infants receiving pharmacotherapy. In addition, buprenorphine may be a promising therapeutic alternative to morphine to treat NAS. Lastly, local, state, and national quality improvement initiatives have emerged as an effective mechanism to advance the care of infants with NAS.

Summary
NAS remains a critical public health issue associated with significant medical, economic, and personal burdens. Emerging data on associated risk factors, assessment of and treatment for NAS provide clinicians and hospitals with new knowledge and an urgency to promote standardization of care for infants with NAS.
Editorial (Spring) Board? Gender Composition in High-impact General Surgery Journals Over 20 Years
Authors: Harris Chelsea A. , Banerjee Tanima , Cramer Monica , Manz Shannon , Ward Sarah T. , Dimick Justin , Telem Dana A. 
Published: January 2018

Objective:
To quantify gender composition of 10 high-impact general surgery journals, delineate how board composition has changed over time, and evaluate qualification metrics by gender.

Background:
Underrepresentation of women on editorial boards may contribute to the gender-based achievement gap in surgery.

Methods:
We performed a cross-sectional analysis of the editorial board gender composition among 10 high-impact general surgery journals in 1997, 2007, and 2017. Univariate and multivariate regression analyses were used to assess differences in editors’ H-indices, academic rank, and number of advanced degrees. Differences in editor turnover and multiple board positions were evaluated for each time interval.

Results:
Over 20 years, the proportion of women on editorial boards increased from 5% to 19%. After controlling for time since board certification, no differences between men and women's number of advanced degrees, H-indices, or academic rank remained significant. Women and men were equally likely to hold multiple board positions (1997 P = 0.74; 2007 P = 0.42; 2017 P = 0.69), but men's editorial board tenure was longer across each time interval (1997–2007 P = 0.003; 2007–2017 P < 0.001; 1997–2017 P = 0.01).

Conclusions:
Women surgeons have a small but growing presence on surgical editorial boards, and gender-based qualification differences are likely attributable to practice length. Men's longer tenure on editorial boards may drive some of the observed disparity by limiting new appointment opportunities. Strategies such as imposing term limits or instituting merit-based performance reviews may help editorial boards capture the field's changing demographics.
Adipocytokines in Steatotic Liver Surgery/Transplantation
Authors: Jiménez-Castro Mónica B. , Casillas-Ramírez Araní , Negrete-Sánchez Elsa , Avalos-de León Cindy G. , Gracia-Sancho Jordi , Peralta Carmen 
Published: January 2018

AbstractBecause of the shortage of liver grafts available for transplantation, the restrictions on graft quality have been relaxed, and marginal grafts, such as steatotic livers, are now accepted. However, this policy change has not solved the problem, because steatotic liver grafts tolerate ischemia-reperfusion (I/R) injury poorly. Adipocytokines differentially modulate steatosis, inflammation, and fibrosis and are broadly present in hepatic resections and transplants. The potential use of adipocytokines as biomarkers of the severity of steatosis and liver damage to aid the identification of high-risk steatotic liver donors and to evaluate hepatic injury in the postoperative period are discussed. The hope of finding new therapeutic strategies aimed specifically at protecting steatotic livers undergoing surgery is a strong impetus for identifying the mechanisms responsible for hepatic failure after major surgical intervention. Hence, the most recently described roles of adipocytokines in steatotic livers subject to I/R injury are discussed, the conflicting results in the literature are summarized, and reasons are offered as to why strategic pharmacologic control of adipocytokines has yet to yield clinical benefits. After this, the next steps needed to transfer basic knowledge about adipocytokines into clinical practice to protect marginal livers subject to I/R injury are presented. Recent strategies based on adipocytokine regulation, which have shown efficacy in various pathologies, and hold promise for hepatic resection and transplantation are also outlined.
The evolution, distribution and diversity and of endogenous circoviral elements
Authors: Dennis Tristan P.W , de Souza William Marciel , Marsile-Medun Soledad , Singer Joshua B. , Wilson Sam J. , Gifford Robert J. 
Published: January 2018

AbstractCircoviruses (family Circoviridae) are small, non-enveloped viruses that have short, single-stranded DNA genomes. Circovirus sequences are frequently recovered in metagenomic investigations, indicating that these viruses are widespread, yet they remain relatively poorly understood. Endogenous circoviral elements (CVe) are DNA sequences derived from circoviruses that occur in vertebrate genomes. CVe can provide unique, retrospective information about the biology and evolution of circoviruses. In this study, we screened 362 vertebrate genome assemblies in silico to generate a catalog of CVe loci. We identified a total of 179 CVe sequences, most of which have not been reported previously. We show that these CVe loci reflect at least 19 distinct germline integration events. We determine the structure of CVe loci, identifying some that show evidence of potential functionalization. We also identify orthologous copies of CVe in snakes, fish, birds, and mammals, allowing us to add new calibrations to the timeline of circovirus evolution. Finally, we observed that some ancient CVe group robustly with contemporary circoviruses in phylogenies, with all sequences within these groups being derived from the same host class or order, implying a hitherto underappreciated stability in circovirus-host relationships. The openly available dataset constructed in this investigation provides new insights into circovirus evolution, and can be used to facilitate further studies of circoviruses and CVe.AbbreviationsCVeendogenous circoviral elementORFopen reading frameCapCapsidRepReplicasessDNAsingle-stranded DNA
Analysis of functional connectivity and oscillatory power using DICS: from raw MEG data to group-level statistics in Python
Authors: Vliet Marijn van , Liljeström Mia , Aro Susanna , Salmelin Riitta , Kujala Jan 
Published: January 2018

AbstractCommunication between brain regions is thought to be facilitated by the synchronization of oscillatory activity. Hence, large-scale functional networks within the brain may be estimated by measuring synchronicity between regions. Neurophysiological recordings, such as magnetoencephalography (MEG) and electroencephalography (EEG), provide a direct measure of oscillatory neural activity with millisecond temporal resolution. In this paper, we describe a full data analysis pipeline for functional connectivity analysis based on dynamic imaging of coherent sources (DICS) of MEG data. DICS is a beamforming technique in the frequency-domain that enables the study of the cortical sources of oscillatory activity and synchronization between brain regions. All the analysis steps, starting from the raw MEG data up to publication-ready group-level statistics and visualization, are discussed in depth, including methodological considerations, rules of thumb and tradeoffs. We start by computing cross-spectral density (CSD) matrices using a wavelet approach in several frequency bands (alpha, theta, beta, gamma). We then provide a way to create comparable source spaces across subjects and discuss the cortical mapping of spectral power. For connectivity analysis, we present a canonical computation of coherence that facilitates a stable estimation of all-to-all connectivity. Finally, we use group-level statistics to limit the network to cortical regions for which significant differences between experimental conditions are detected and produce vertex-and parcel-level visualizations of the different brain networks. Code examples using the MNE-Python package are provided at each step, guiding the reader through a complete analysis of the freely available openfMRI ds000117 “familiar vs. unfamiliar vs. scrambled faces” dataset. The goal is to educate both novice and experienced data analysts with the “tricks of the trade” necessary to successfully perform this type of analysis on their own data.
Non-linear transfer characteristics of stimulation and recording hardware account for spurious low-frequency artifacts during amplitude modulated transcranial alternating current stimulation (AM-tACS)
Authors: Kasten Florian H. , Negahbani Ehsan , Fröhlich Flavio , Herrmann Christoph S. 
Published: January 2018

AbstractAmplitude modulated transcranial alternating current stimulation (AM-tACS) has been recently proposed as a possible solution to overcome the pronounced stimulation artifact encountered when recording brain activity during tACS. In theory, AM-tACS does not entail power at its modulating frequency, thus avoiding the problem of spectral overlap between brain signal of interest and stimulation artifact. However, the current study demonstrates how weak non-linear transfer characteristics inherent in stimulation and recording hardware can reintroduce spurious artifacts at the modulation frequency. The input-output transfer functions (TFs) of different stimulation setups were measured. The setups included basic recordings of signal-generator and stimulator outputs as well as M/EEG phantom measurements. 6th-degree polynomial regression models were fitted to model the input-output TFs of each setup. The resulting TF models were applied to digitally generated AM-tACS signals to predict the location of spurious artifacts in the spectrum. All four setups measured for the study exhibited low-frequency artifacts at the modulation frequency and its harmonics when recording AM-tACS. Fitted TF models showed non-linear contributions significantly different from zero (all p < .05) and successfully predicted the frequency of artifacts observed in AM-signal recordings. Results suggest that even weak non-linearities of stimulation and recording hardware can lead to spurious artifacts at the modulation frequency and its harmonics. Thus, findings emphasize the need for more linear stimulation devices for AM-tACS and careful analysis procedures, which take into account these low-frequency artifacts to avoid confusion with effects of AM-tACS on the brain.
Methyl-CpG binding domain 2 (Mbd2) is an Epigenetic Regulator of Autism-Risk Genes and Cognition
Authors: Lax Elad , DoCarmo Sonia , Enuka Yehoshua , Sapozhnikov Daniel M. , Welikovitch Lindsay A. , Mahmood Niaz , Rabbani Shafaat A. , Wang Liqing , Britt Jonathan P. , Hancock Wayne W. , Yarden Yosef , Szyf Moshe 
Published: January 2018

AbstractThe Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown.Here we show that Mbd2-deficiency in mice (Mbd2−/−) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2−/− mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brains of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Hippocampal Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2−/− mice.These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD individuals.
Variation in Genome-wide NF-kappaB RELA Binding Sites upon Microbial Stimuli and Identification of a Virus Response Profile
Authors: Borghini Lisa , Lu Jinhua , Hibberd Martin , Davila Sonia 
Published: January 2018

AbstractNF-kB transcription factors are master regulators of the innate immune response. Activated downstream of pathogen recognition receptors, they regulate the expression of genes to help fighting infections as well as recruiting the adaptive immune system. NF-kB responds to a wide variety of signals, but the processes by which stimulus-specificity is attained remain unclear. Here, we characterized the response of one NF-kB member, RELA, to four stimuli mimicking infection in human nasopharyngeal epithelial cells. Comparing genome-wide RELA binding, we observed stimulus-specific sites, although most sites overlapped across stimuli. Specifically, the response to Poly I:C – mimicking viral dsRNA and signalling through TLR3 – induced a distinct RELA profile, binding in the vicinity of antiviral genes and correlating with corresponding gene expression. This group of binding sites was also enriched in Interferon Regulatory Factor (IRF) motifs and showed overlapping with IRFs binding sites. A novel NF-kB target, OASL was further validated and showed TLR3-specific activation. This work showed that some RELA DNA binding sites varied in activation response following different stimulations and that interaction with more specialized factors could help achieve this stimulus-specific activity. Our data provide a genomic view of regulated host response to different pathogen stimuli.
Homology Directed Repair by Cas9:Donor Co-localization in Mammalian Cells
Authors: Roche Philip J.R. , Gytz Heidi , Hussain Faiz , Cameron Christopher J.F. , Paquette Denis , Blanchette Mathieu , Dostie Josée , Nagar Bhushan , Akavia Uri David 
Published: January 2018

AbstractHomology directed repair (HDR) induced by site specific DNA double strand breaks (DSB) with CRISPR/Cas9 is a precision gene editing approach that occurs at low frequency in comparison to indel forming non homologous end joining (NHEJ). In order to obtain high HDR percentages in mammalian cells, we engineered Cas9 protein fused to a high-affinity monoavidin domain to deliver biotinylated donor DNA to a DSB site. In addition, we used the cationic polymer, polyethylenimine, to deliver Cas9 RNP-donor DNA complex into the cell. Combining these strategies improved HDR percentages of up to 90% in three tested loci (CXCR4, EMX1, and TLR) in standard HEK293 cells. Our approach offers a cost effective, simple and broadly applicable gene editing method, thereby expanding the CRISPR/Cas9 genome editing toolbox.SummaryPrecision gene editing occurs at a low percentage in mammalian cells using Cas9. Colocalization of donor with Cas9MAV and PEI delivery raises HDR occurrence.
Whole Genome Sequencing and Rare Variant Analysis in Essential Tremor Families
Authors: Odgerel Zagaa , Hernandez Nora , Park Jemin , Ottman Ruth , Louis Elan D. , Clark Lorraine N. 
Published: January 2018

ABSTRACTEssential tremor (ET) is one of the most common movement disorders. The etiology of ET remains largely unexplained. Whole genome sequencing (WGS) is likely to be of value in understanding a large proportion of ET with Mendelian and complex disease inheritance patterns. In ET families with Mendelian inheritance patterns, WGS may lead to gene identification where WES analysis failed to identify the causative variant due to incomplete coverage of the entire coding region of the genome. Alternatively, in ET families with complex disease inheritance patterns with gene x gene and gene x environment interactions enrichment of functional rare coding and non-coding variants may explain the heritability of ET. We performed WGS in eight ET families (n=40 individuals) enrolled in the Family Study of Essential Tremor. The analysis included filtering WGS data based on allele frequency in population databases, rare variant classification and association testing using the Mixed-Model Kernel Based Adaptive Cluster (MM-KBAC) test and prioritization of candidate genes identified within families using phenolyzer. WGS analysis identified candidate genes for ET in 5/8 (62.5%) of the families analyzed. WES analysis in a subset of these families in our previously published study failed to identify candidate genes. In one family, we identified a deleterious and damaging variant (c.1367G>A, p.(Arg456Gln)) in the candidate gene,CACNA1G, which encodes the pore forming subunit of T-type Ca(2+) channels, CaV3.1, and is expressed in various motor pathways and has been previously implicated in neuronal autorhythmicity and ET. Other candidate genes identified includeSLIT3(family D), which encodes an axon guidance molecule and in three families, phenolyzer prioritized genes that are associated with hereditary neuropathies (family A,KARS, family B,KIF5Aand family F,NTRK1). This work has identified candidate genes and pathways for ET that can now be prioritized for functional studies.
Microbiota-independent antiviral protection conferred by aminoglycoside antibiotics
Authors: Gopinath Smita , Kim Myoungjoo V. , Rakib Tasfia , Wong Patrick W. , van Zandt Michael , Barry Natasha A. , Kaisho Tsuneyasu , Goodman Andrew L. , Iwasaki Akiko 
Published: January 2018

AbstractAntibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. We have identified a novel antiviral effect of commonly used aminoglycoside antibiotics. We show that mucosal application of aminoglycosides increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota as aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by TLR3, and required TIR-domain-containing adapter-inducing interferon-β (TRIF), signaling adaptor, and interferon regulatory factors 3 (IRF3) and IRF7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express TLR3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistancein vivo.
miR-10b Deficiency Affords Atherosclerosis Resistance
Authors: Nakahara Masako , Kobayashi Norihiko , Oka Masako , Nakano Kenta , Okamura Tadashi , Yuo Akira , Saeki Kumiko 
Published: January 2018

AbstractHuman vascular endothelial cells (ECs) are categorized into two groups; pro-stenotic (Type-I) and anti-stenotic (Type-II) ECs, and one of the master genes for a stress-induced “Type-II-to-Type-I” degeneration is Regulator of G-protein signaling 5 (RGS5). Here we show that miR-10b is a crucial downstream mediator in RGS5-dependent degeneration. We also demonstrated the miR-10bhigh Type-I EC exosome has a trans effect which suppresses anti-proliferative abilities of Type-II ECs. Moreover, we found miR-10b-deficient mice showed a resistance to experimental atherosclerosis, where high-fat-high-cholesterol-diet-fed mice were subjected to partial carotid ligation. Furthermore, we determined the key target of miR-10b was Latent transforming growth factor-β binding protein 1 (LTBP1), which is a regulator of TGF-β signaling. Compatible with a commonly accepted view that TGF-β creates the major growth-inhibitory signal against vascular smooth muscle cells, TGF-β inhibitor treatments abolished anti-proliferative functions of Type-II ECs. Therefore, RGS5/miR-10b/LTBP1/TGF-β axis plays a leading role in quality control of ECs.
Antagonistic regulation with a unique setpoint, integral and double integral action
Authors: Thorsen Kristian , Ruoff Peter , Drengstig Tormod 
Published: January 2018

AbstractSeveral biochemical species are in organisms controlled in a pairwise manner i.e., two different species (e.g., hormone, enzyme, transporter protein) work to control the concentration of a third chemical species. Such pairs are often antagonistic, meaning that one of the controller species acts to increase whereas the other controller species acts to decrease the amount of the controlled species. How antagonistic systems interact to achieve regulation and to avoid competing against each other is not fully understood. An issue is how two antagonistic hormones can agree upon one common setpoint. We present here a new type of antagonistic regulatory system that has a single unique setpoint inherently defined by the system. The regulatory system controls the concentration of a chemical species with both integral and double integral action, achieving tight control. We show by the use of an analytical stability analysis, using the principle of vanishing perturbations, that the setpoint is asymptotically stable. Finally the prospect of treating the presented system as a part of a larger family of antagonistic regulatory systems with unique setpoints, integral and double integral action is discussed.