bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Survey of Prescribers' Attitudes, Knowledge, Comfort, and Fear of Consequences Related to an Opioid Overdose Education and Naloxone Distribution Program
Authors: Peckham Alyssa M. , Niculete Maria E. , Steinberg Howard , Boggs Douglas L. 
Published: October 2017

Context:
The alarming increase in opioid-related fatalities has placed the United States in the midst of an opioid epidemic. In an effort to reduce opioid-related fatalities, each Veterans Affairs (VA) hospital is responsible for development of an OEND (Overdose Education and Naloxone Distribution) program to enhance naloxone distribution.

Objective:
To assess attitudes, knowledge, comfort level, and fear of consequences at the prescriber level related to the OEND program at VA Connecticut Healthcare System (VACHS).

Design:
Anonymous surveys were administered to VACHS prescribers to assess attitude, knowledge, comfort level, and fear of consequences using a 5-point Likert scale.

Setting:
VACHS.

Participants:
VACHS prescribers (primary care physicians/internists, psychiatrists, physician assistants/advanced practice registered nurses, pharmacists) in primary care/medicine, mental health, and substance use disorder (SUD).

Methods:
Differences across 4 domains were analyzed using analysis of variance testing, and pairwise post hoc analysis was conducted using Tukey's HSD for all significant findings. Regression modeling was conducted to evaluate correlations between each group and survey responses.

Main Outcome:
Identify differences and potential barriers to program implementation across professions and practice specialty.

Results:
While primary care/medicine, mental health, and SUD prescribers had positive attitudes toward dispensing naloxone, SUD clinicians reported being more comfortable, more knowledgeable, and less fearful of consequences. In general, psychiatrists reported to be more knowledgeable and comfortable prescribing naloxone. In addition, prescribers who received naloxone training reported themselves to be more comfortable, more knowledgeable, and less fearful of the consequences of dispensing naloxone.

Conclusions:
Results indicate that barriers to OEND implementation continue to exist, and not all clinicians or practice specialties at VACHS are comfortable with dispensing naloxone. A targeted approach to training health care clinicians may lead to increased acceptance of naloxone dispensing. Additional research is needed to elicit the best method of improved acceptance of naloxone to expand naloxone access.
Revisiting the Skin Lines on the Forehead and Glabellar Area
Authors: Hwang Kun 
Published: October 2017

Abstract
This paper attempted to revisit the skin lines in forehead and glabellar area.
Using PubMed, Scopus, and Google, papers describing skin tension lines of face were searched. Papers with illustrations or pictures of the facial lines were selected and reviewed. The studies of the skin lines in the forehead and glabellar area were analyzed.
Langer used the term “cleavage of the cutis, anatomical lines.” Over the forehead, he found a border zone of horizontal folds that were interrupted many times by the ascending folds coming from the flabella area. Cox used the terms “cleavage lines of the skin” and “lines of increased tension.” In the glabellar area, cleavage lines were vertical and extended to the forehead. Rubin used the term “skin line.” In the midline area over the nose, the skin wrinkled vertically. Kraissl used the term “normal wrinkle line.” Above the nose, “curving vertical lines” were observed. Straith et al used the terms “normal tension line,” and “Langer line.” In the glabellar area, the horizontal lines from the upper eyelids became “curved vertically” until meeting the supra-brow horizontal line. Borges used the term “relaxed skin tension line.” At the medial end of the eyebrow, his relaxed skin tension line ran obliquely upward and medially, to meet the contralateral line. Namikawa et al used the term “cleavage lines of the skin.” It ran mediosuperiorly to inferolaterally, bordering the linea mediana anterior in glabellar area.
Following the consensus of most authors, a curved vertical line following the glabellar frown is recommended for incisions for flaps or grafts.
Community Lighting for Older Adults
Authors: Nastasi Julie Ann , Baumann Brynn , Glanton Shannon , Gordan Stephanie , Gower Natalie , Kennedy Caitlin , Mertz Layne , Russo Deanna , Williams Courtney 
Published: October 2017

Objective:
To develop an understanding of community lighting and its impact on older adults.

Subjects and Methods:
This mixed-methods study addressed lighting in 94 facilities in a 3×3 block area. Lux, the amount of light on a surface area, was measured in key areas within facilities.

Results and Conclusions:
The amount of light and glare varied within and across facilities. Because of variability of lighting and glare, it is recommended to train older adults in techniques to increase lighting and decrease glare in the community.
Accessible Fall Prevention Interventions for Older Adults With Low Vision
Authors: Blaylock Sarah E. , Vogtle Laura K. , Warren Mary 
Published: October 2017

Objectives:
To assess fall prevention services and provide information on tailoring interventions for older adults with low vision.

Methods:
A phenomenological qualitative design was conducted using semistructured interviews of visually impaired older adults. Interviews were audio recorded and transcribed verbatim for analysis.

Results:
Despite frequent falls, participants received limited fall interventions. Participants described key elements of an accessible intervention including visually accessible handouts tailored for visually impaired persons, multiple delivery methods, and an accessible location.

Conclusions:
Participants affirmed a lack of fall prevention services and provided insight into how to design educational interventions for older adults with vision impairment.
Recent advances in the management of symptomatic vertebral artery stenosis
Authors: Drazyk Anna M. , Markus Hugh S. 
Published: October 2017

Purpose of review
Vertebrobasilar stenosis accounts for 20% of posterior circulation strokes and is associated with high risk of early stroke recurrence. We review data from randomized controlled trials examining whether stenting may reduce this risk, including the recently published Vertebral Artery Ischaemia Stenting Trial (VIST).

Recent findings
VIST and VAST (Vertebral Artery Stenting Trial), having recruited both intracranial and extracranial vertebral stenosis and showed a low rate of perioperative stroke for extracranial (0 and 2%, respectively), but a higher rate for intracranial stenosis (15 and 22%, respectively). In VIST, the primary endpoint of stroke occurred in five patients in the stent group vs. 12 in the medical group (hazard ratio 0.40; 95% confidence interval 0.14–1.13, P = 0.08), although when days from last symptoms were adjusted for, the hazard ratio was 0.34 (95% confidence interval 0.12–0.98; P = 0.046). SAMMPRIS (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis) recruited only intracranial vertebral stenosis and showed a better outcome with intensive medical therapy than stenting.

Summary
Stenting of extracranial stenosis can be performed with a low operative risk. VIST suggests it may reduce longer term stroke risk, but this needs confirming in larger trials. For intracranial stenosis, due to a higher operative risk, current evidence favours medical treatment. SAMMPRIS have emphasized the need for intensive medical therapy whether or not stenting is performed.
The Drosophila small conductance potassium channel (SK) negatively regulates nociception
Authors: Walcott Kia , Mauthner Stephanie , Tsubouchi Asako , Robertson Jessica , Tracey W. Daniel 
Published: October 2017

SummaryInhibition of nociceptor activity is important for the prevention of spontaneous pain and hyperalgesia. To identify the critical K+channels that regulate nociceptor excitability we performed a forward genetic screen using aDrosophilalarval nociception paradigm. Knockdown of three K+channel loci, thesmall conductance calcium-activated potassium channel(SK),seizureandtiwaz, resulted in marked hypersensitive nociception behaviors. In more detailed studies ofSK, we found that hypersensitive phenotypes could be recapitulated with a genetically null allele. Importantly, the null mutant phenotype could be rescued with tissue specific expression of anSKcDNA in nociceptors. Optical recordings from nociceptive neurons showed a significant increase in mechanically activated Ca2+signals inSKmutant nociceptors. SK showed expression in peripheral neurons. Interestingly SK proteins localized to axons of these neurons but were not detected in dendrites. Our findings suggest a major role for SK channels in the regulation of nociceptor excitation and they are inconsistent with the hypothesis that the important site of action is within dendrites.Highlights–Specific potassium channels regulate nociceptor excitability.–SK channels have a critical function in nociception.–SK channels specifically localize to sensory axons–SK channels are not detectable in sensory dendrites.
Osteo-Oto-Hepato-Enteric Syndrome (O2HE) is caused by loss of function mutations inUNC45A
Authors: Esteve Clothilde , Francescatto Ludmila , Tan Perciliz L. , Bourchany Aurélie , De Leusse Cécile , Marinier Evelyne , Blanchard Arnaud , Bourgeois Patrice , Brochier-Armanet Céline , Bruel Ange-Line , Delarue Arnauld , Duffourd Yannis , Ecochard-Dugelay Emmanuelle , Hery Géraldine , Huet Frédéric , Gauchez Philippe , Gonzales Emmanuel , Guettier-Bouttier Catherine , Komuta Mina , Lacoste Caroline , Maudinas Raphaelle , Mazodier Karin , Rimet Yves , Rivière Jean-Baptiste , Roquelaure Bertrand , Sigaudy Sabine , Stephenne Xavier , Thauvin-Robinet Christel , Thevenon Julien , Sarles Jacques , Levy Nicolas , Badens Catherine , Goulet Olivier , Hugot Jean-Pierre , Katsanis Nicholas , Faivre Laurence , Fabre Alexandre 
Published: October 2017

AbstractDespite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. Whole exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A), as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss of function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.
High-affinity low-capacity and low-affinity high-capacity N-acetyl-2-aminofluorene (AAF) macromolecular binding sites are revealed during the growth cycle of adult rat hepatocytes in primary culture
Authors: Koch K.S. , Moran T. , Shier W.T. , Leffert H.L. 
Published: October 2017

ABSTRACTLong-term cultures of primary adult rat hepatocytes were used to study the effects of N-acetyl-2-aminofluorene (AAF) on hepatocyte proliferation during the growth cycle; on the initiation of hepatocyte DNA synthesis in quiescent cultures; and, on hepatocyte DNA replication following the initiation of DNA synthesis. Scatchard analyses were used to identify the pharmacologic properties of radiolabeled AAF metabolite binding to hepatocyte macromolecules. Two classes of growth cycle-dependent AAF metabolite binding sites – a high-affinity low-capacity site (designated Site I) and a low-affinity high-capacity site (designated Site II) – associated with two spatially distinct classes of macromolecular targets, were revealed. Based upon radiolabeled AAF metabolite binding to purified hepatocyte genomic DNA or to DNA, RNA, proteins and lipids from isolated nuclei, Site IDAY 4targets (KD[APPARENT]≈ 2-4 x 10−6M and BMAX[APPARENT]≈ 6 pmols/106cells/24 h) were consistent with genomic DNA; and with AAF metabolized by a nuclear cytochrome P450. Based upon radiolabeled AAF binding to total cellular lysates, Site IIDAY 4targets (KD[APPARENT]≈ 1.5 x 10−3M and BMAX[APPARENT]≈ 350 pmols/106cells/24 h) were consistent with cytoplasmic proteins; and with AAF metabolized by cytoplasmic cytochrome P450s. DNA synthesis was not inhibited by concentrations of AAF that saturated DNA binding in the neighborhood of the Site I KD. Instead, hepatocyte DNA synthesis inhibition required higher concentrations of AAF approaching the Site II KD. These observations raise the possibility that carcinogenic DNA adducts derived from AAF metabolites form below concentrations of AAF that inhibit replicative and repair DNA synthesis.
Gene expression in patient-derived neural progenitors implicates WNT5A signaling in the etiology of schizophrenia
Authors: Evgrafov Oleg V , Armoskus Chris , Wrobel Bozena B , Spitsyna Valeria N , Souaiaia Tade , Herstein Jennifer S. , Walker Christopher P , Nguyen Joseph D , Camarena Adrian , Weitz Jonathan R , Kim Jae Mun ‘Hugo’ , Duarte Edder Lopez , Wang Kai , Simpson George M , Sobell Janet L , Medeiros Helena , Pato Michele T , Pato Carlos N , Knowles James A 
Published: October 2017

AbstractBACKGROUNDGWAS of schizophrenia demonstrated that variations in the non-coding regions are responsible for most of common variation heritability of the disease. It is hypothesized that these risk variants alter gene expression. Thus, studying alterations in gene expression in schizophrenia may provide a direct approach to understanding the etiology of the disease. In this study we useCulturedNeural progenitor cells derived fromOlfactoryNeuroepithelium (CNON) as a genetically unaltered cellular model to elucidate the neurodevelopmental aspects of schizophrenia.METHODSWe performed a gene expression study using RNA-Seq of CNON from 111 controls and 144 individuals with schizophrenia. Differentially expressed (DEX) genes were identified with DESeq2, using covariates to correct for sex, age, library batches and one surrogate variable component.RESULTS80 genes were DEX (FDR<10%), showing enrichment in cell migration, cell adhesion, developmental process, synapse assembly, cell proliferation and related gene ontology categories. Cadherin and Wnt signaling pathways were positive in overrepresentation test, and, in addition, many genes are specifically involved in Wnt5A signaling. The DEX genes were significantly, enriched in the genes overlapping SNPs with genome-wide significant association from the PGC GWAS of schizophrenia (PGC SCZ2). We also found substantial overlap with genes associated with other psychiatric disorders or brain development, enrichment in the same GO categories as genes with mutationsde novoin schizophrenia, and studies of iPSC-derived neural progenitor cells.CONCLUSIONSCNON cells are a good model of the neurodevelopmental aspects of schizophrenia and can be used to elucidate the etiology of the disorder.
Draft genomes of the fungal pathogen Phellinus noxius in Hong Kong
Authors: Tsang Karen Sze Wing , Lam Regent Yau Ching , Kwan Hoi Shan 
Published: October 2017

AbstractThe fungal pathogen Phellinus noxius is the underlying cause of brown root rot, a disease with causing tree mortality globally, causing extensive damage in urban areas and crop plants. This disease currently has no cure, and despite the global epidemic, little is known about the pathogenesis and virulence of this pathogen.Using Ion Torrent PGM, Illumina MiSeq and PacBio RSII sequencing platforms with various genome assembly methods, we produced the draft genome sequences of four P. noxius strains isolated from infected trees in Hong Kong to further understand the pathogen and identify the mechanisms behind the aggressive nature and virulence of this fungus. The resulting genomes ranged from 30.8Mb to 31.8Mb in size, and of the four sequences, the YTM97 strain was chosen to produce a high-quality Hong Kong strain genome sequence, resulting in a 31Mb final assembly with 457 scaffolds, an N50 length of 275,889 bp and 96.2% genome completeness. RNA-seq of YTM97 using Illumina HiSeq400 was performed for improved gene prediction. AUGUSTUS and Genemark-ES prediction programs predicted 9,887 protein-coding genes which were annotated using GO and Pfam databases. The encoded carbohydrate active enzymes revealed large numbers of lignolytic enzymes present, comparable to those of other white-rot plant pathogens. In addition, P. noxius also possessed larger numbers of cellulose, xylan and hemicellulose degrading enzymes than other plant pathogens. Searches for virulence genes was also performed using PHI-Base and DFVF databases revealing a host of virulence-related genes and effectors. The combination of non-specific host range, unique carbohydrate active enzyme profile and large amount of putative virulence genes could explain the reasons behind the aggressive nature and increased virulence of this plant pathogen.The draft genome sequences presented here will provide references for strains found in Hong Kong. Together with emerging research, this information could be used for genetic diversity and epidemiology research on a global scale as well as expediting our efforts towards discovering the mechanisms of pathogenicity of this devastating pathogen.
Identification of Cell States Using Super-Enhancer RNA
Authors: Tu Yueh-Hua , Juan Hsueh-Fen , Huang Hsuan-Cheng 
Published: October 2017

AbstractA new class of regulatory elements called super-enhancers, comprised of multiple neighboring enhancers, have recently been reported to be the key transcriptional drivers of cellular, developmental, and disease states. Here, we propose to define super-enhancer RNA as highly expressed enhancer RNAs that are transcribed from a cluster of localized genomic regions. Using the cap analysis of gene expression sequencing data from FANTOM5, we systematically explored the enhancer and messenger RNA landscapes in hundreds of different cell types in response to various environments. Applying non-negative matrix factorization (NMF) to super-enhancer RNA profiles, we found that different cell types were well classified. In addition, through the NMF of individual time-course profiles from a single cell-type, super-enhancer RNAs were clustered into several states with progressive patterns. We further investigated the enriched biological functions of the proximal genes involved in each pattern, and found that they were associated with the corresponding developmental process. The proposed super-enhancer RNAs can act as a good alternative, without the complicated measurement of histone modifications, for identifying important regulatory elements of cell type specification and identifying dynamic cell states.
Transcriptional regulation by NR5A2 couples cell differentiation and inflammation in the pancreas
Authors: Cobo Isidoro , Martinelli Paola , Flández Marta , Bakiri Latifa , Zhang Mingfeng , Carrillo-de-Santa-Pau Enrique , Jia Jinping , Thommesen Liv , Bruland Torunn , del Pozo Natalia , Olson Sara , Smith Jill , Bamlet William R. , Petersen Gloria M , Malats Núria , Amundadottir Laufey T , Wagner Erwin F. , Real Francisco X 
Published: October 2017

AbstractTissue-specific differentiation and inflammatory programmes are thought to independently contribute to disease. The orphan nuclear receptor NR5A2 is a key regulator of pancreas differentiation and SNPs in or near the human gene are associated with risk of pancreatic cancer. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration, and cooperates with mutant KRas in tumor progression. Through global transcriptomic analysis, we uncover a basal pre-inflammatory state in the pancreas of Nr5a2 heterozygous mice that is reminiscent of pancreatitis-induced inflammation and is conserved in histologically normal human pancreata with reduced NR5A2 mRNA expression. In Nr5a2+/− mice, Nr5a2 undergoes a dramatic transcriptional switch relocating from tissue-specific to inflammatory loci thereby promoting AP-1-dependent gene transcription. Importantly, deletion of c-Jun in the pancreas of these mice rescues the pre-inflammatory phenotype and the defective regenerative response to damage. These findings provide compelling evidence that the same transcriptional networks supporting homeostasis in normal tissue can be subverted to foster inflammation upon genetic or environmental constraints.
Energy demand and the context-dependent effects of genetic interactions
Authors: Hoekstra Luke A. , Julick Cole R. , Mika Katelyn M. , Montooth Kristi L. 
Published: October 2017

ABSTRACTGenetic effects are often context dependent, with the same genotype differentially affecting phenotypes across environments, life stages, and sexes. We used an environmental manipulation designed to increase energy demand during development to investigate energy demand as a general physiological explanation for context-dependent effects of mutations, particularly for those mutations that affect metabolism. We found that increasing the photoperiod during which Drosophila larvae are active during development phenocopies a temperature-dependent developmental delay in a mitochondrial-nuclear genotype with disrupted metabolism. This result indicates that the context-dependent fitness effects of this genotype are not specific to the effects of temperature and may generally result from variation in energy demand. The effects of this genotype also differ across life stages and between the sexes. The mitochondrial-nuclear genetic interaction disrupts metabolic rate in growing larvae, but not in adults, and compromises female, but not male, reproductive fitness. These patterns are consistent with a model where context-dependent genotype-phenotype relationships may generally arise from differences in energy demand experienced by individuals across environments, life stages, and sexes.IMPACT SUMMARYGenetic effects on traits are often context dependent, such that a genotype that improves fitness under one context may have no effect or even a deleterious effect in another context. The external environment is a common context that affects the degree to which a genotype determines a phenotype, but the internal environment of an organism (e.g., its genetic background, sex or life stage) also provides an important context that may modify the phenotypic expression of a genotype. Here we combine new data on the phenotypic effects of a well-characterized genetic interaction between the mitochondrial and nuclear genomes of the fruit fly Drosophila with prior observations to support a model of energy demand as a general explanation for context-dependent genetic effects, particularly for mutations that affect metabolism. We show that the magnitude of fitness effects of this genetic interaction correlates positively with the degree of energy demand among developmental treatments that accelerate growth rate, across developmental stages that differ in the cost of growth, and between sexes with potentially different costs of reproduction. These internal and external contexts create variable demands on energy metabolism that will impact the efficacy of natural selection acting on metabolic mutations in populations.