bluuebunny/crossref_metadata_2025_split huggingface dataset:
EnhancerAtlas 2.0: an updated resource with enhancer annotation in 586 tissue/cell types across nine species
Authors: Gao Tianshun , Qian Jiang 
Published: October 2019

AbstractEnhancers are distal cis-regulatory elements that activate the transcription of their target genes. They regulate a wide range of important biological functions and processes, including embryogenesis, development, and homeostasis. As more and more large-scale technologies were developed for enhancer identification, a comprehensive database is highly desirable for enhancer annotation based on various genome-wide profiling datasets across different species. Here, we present an updated database EnhancerAtlas 2.0 (http://www.enhanceratlas.org/indexv2.php), covering 586 tissue/cell types that include a large number of normal tissues, cancer cell lines, and cells at different development stages across nine species. Overall, the database contains 13 494 603 enhancers, which were obtained from 16 055 datasets using 12 high-throughput experiment methods (e.g. H3K4me1/H3K27ac, DNase-seq/ATAC-seq, P300, POLR2A, CAGE, ChIA-PET, GRO-seq, STARR-seq and MPRA). The updated version is a huge expansion of the first version, which only contains the enhancers in human cells. In addition, we predicted enhancer–target gene relationships in human, mouse and fly. Finally, the users can search enhancers and enhancer–target gene relationships through five user-friendly, interactive modules. We believe the new annotation of enhancers in EnhancerAtlas 2.0 will facilitate users to perform useful functional analysis of enhancers in various genomes.
American Indian/Alaska Native Smokers’ Utilization of a Statewide Tobacco Quitline: Engagement and Quitting Behaviors From 2008 to 2018
Authors: Lienemann Brianna A , Cummins Sharon E , Tedeschi Gary J , Wong Shiushing , Zhu Shu-Hong 
Published: October 2019

AbstractIntroductionThe objective of this study was to examine access, engagement, and quitting behaviors of American Indian/Alaska Native (AIAN) callers to the California Smokers’ Helpline. Telephone counseling is the primary function of the quitline. The overarching theoretical framework for California’s quitline is social cognitive theory, although it also utilizes motivational interviewing and cognitive-behavioral strategies.Aims and MethodsAIAN (n = 16 089) and White (n = 173 425) California quitline callers from 2009 to 2018 were compared on their characteristics, engagement, and quitting behaviors. Quitline callers responded to a telephone survey at intake. A random selection was called for evaluation 7 months later (White n = 8194, AIAN n = 764). Data from the 2009 to 2017 California Health Interview Survey (CHIS) were used as a reference point for AIANs (AIAN n = 1373).ResultsThe quitline and CHIS had similar proportions of AIANs (4.6% vs. 4.3%, respectively). AIAN smokers were more likely than White smokers to report physical (53.6% vs. 44.9%) and mental (65.7% vs. 57.8%) health conditions at intake. AIANs were more likely to participate in counseling than White callers (67.1% vs. 65.7%). Among those who received counseling, AIANs had greater odds than White smokers of making a quit attempt (adjusted odds ratio = 1.39 [1.06, 1.81]) and similar odds of quitting for 180 days (adjusted odds ratio = 0.95 [0.69, 1.31]).ConclusionsRates of access, engagement, and quitting suggest that individualized quitline counseling was as effective with AIANs as it was with White smokers. Increasing efforts to refer AIANs to existing state quitlines can help more smokers quit.ImplicationsThis study showed that AIAN smokers were well represented among California quitline callers, even without a targeted campaign. It also found that AIAN smokers engaged in quitline services and were as able to quit as their White counterparts were, even after adjusting for other baseline characteristics. One implication is that public health programs can promote quitlines using broad-based campaigns knowing that they will still motivate AIAN smokers to seek help. Another implication is that a standard, individualized counseling protocol delivered by culturally competent quitline staff can effectively help AIAN smokers to quit.
Upper limb motor improvement in chronic stroke after combining botulinum toxin A injection and multi-joints robot-assisted therapy: a case report
Authors: Martino Cinnera Alex , Pucello Alessandra , Lupo Alessandro , Gimigliano Francesca , Mammucari Elisa , Cicero Dario Lo , Iosa Marco , Paolucci Stefano , Morone Giovanni 
Published: October 2019

Abstract
Spasticity is one of the major complications after stroke. Botulinum toxin type A (BoNT-A) injection is commonly used to manage focal spasticity. However, it is uncertain whether BoNT-A can improve activities of daily living function of paretic arm. The recovery of functions of the affected arm is also the aim of robotic upper limb (UL) therapy. The motorized exoskeleton assists the patient in a large 3D work environment by promoting movement for the UL (shoulder, elbow, wrist, hand). The combination of the BoNT-A injection and the robotic therapy might enhance functional recovery after stroke. We reported the case of a chronic stroke patient in which the injection of BoNT-A was combined with multi-joint exoskeleton training. The patient showed improvement in the motor control of the UL, supporting the feasibility of this approach.
Antiretroviral-responsive confluent and reticulated papillomatosis: a case report of an unusual association
Authors: Ballout Rami A , Helou Gilbert , Maatouk Ismael 
Published: October 2019

Abstract
This is the case of a 29-year-old male newly diagnosed with advanced HIV (CD4 < 35cells/mm3), presenting to us with hyperpigmented and scaly non-pruritic macules over his chest and upper abdomen of several weeks duration. Woodlamp examination was negative, but a skin biopsy suggested confluent and reticulated papillomatosis (CRP). Given his lack of any of the condition’s identifiable triggers and the unusually rapid resolution of his lesions shortly after antiretroviral therapy initiation, an immunodeficiency-related etiology for his CRP was entertained. Autoimmune disorders and atopic conditions have been well reported previously as possible triggers of CRP. However, in this report, we raise immunodeficiency as a possible trigger of CRP as well, such that immune dysregulation overall (autoimmunity or immunodeficiency) can contribute to CRP ontogenesis. To our best knowledge, this is the first report to date suggesting a possible association between CRP, a rare dermatological condition, and acquired immunodeficiency syndrome.
Nonalcoholic fatty liver disease as a risk factor for Clostridium difficile-associated diarrhea
Authors: Nseir W B , Hussein S H H , Farah R , Mahamid M N , Khatib H H , Mograbi J M , Peretz A , Amara A E 
Published: October 2019

Abstract

Aims
Clostridium difficile is the most common cause of infectious nosocomial diarrhea among adults in developed countries. Nonalcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease and it is associated with bacterial infections. Our goal was to assess whether NAFLD considered a risk factor for C. difficile-associated diarrhea (CDAD).

Methods
We conducted a retrospective study of patients admitted with CDAD at Baruch Padeh Medical Center, Poria, Israel during a period of four years. Data on demographic characteristics, clinical signs, underlying conditions, presence of fatty liver based on computed tomography/ultrasonography imaging and several risk factors for CDI were collected. The control group included patients with diarrhea who were negative for CDT and had been hospitalized during the same period. The controls were matched for age (±5 years) and gender.

Results
Totally, 115/164 patients with CDAD met the inclusion criteria. The control group was consisted of 115 hospitalized patients with non-CDAD. The mean age of all the participants (230) was 69.57 ± 18 years. NAFLD was found in 76/115 (66%) patients with CDAD vs. 35/115 (30.4%) in the control group, P &lt; 0.001. Moreover, we found significant associations between CDAD group and metabolic syndrome, prior use of antibiotic in the last 3 months, NAFLD and high serum levels of C-reactive protein. Multivariate analysis showed that NAFLD, odds ratio 1.51, 95% confidence interval 1.2–1.95, P = 0.05 was significantly associated with CDAD.

Conclusions
This retrospective study showed that NAFLD is a risk factor for CDAD. Moreover, metabolic syndrome and high serum levels of C-reactive protein were significantly associated with the risk of CDAD.
Normal versus extraordinary societal impact: how to understand, evaluate, and improve research activities in their relations to society?
Authors: Sivertsen Gunnar , Meijer Ingeborg 
Published: October 2019

Abstract
Societal impact of research does not occur primarily as unexpected extraordinary incidents of particularly useful breakthroughs in science. It is more often a result of normal everyday interactions between organizations that need to create, exchange, and make use of new knowledge to further their goals. We use the distinctions between normal and extraordinary societal impact and between organizational- and individual-level activities and responsibilities to discuss how science–society relations can better be understood, evaluated, and improved by focusing on the organizations that typically interact in a specific domain of research.
OPTIMIZATION OF RADIATION DOSE IN CT IMAGING: ESTABLISHING THE INSTITUTIONAL DIAGNOSTIC REFERENCE LEVELS AND PATIENT DOSE AUDITING
Authors: Razali Mohd Amir Syahmi Mat , Ahmad Muhamad Zabidi , Shuaib Ibrahim Lutfi , Osman Noor Diyana 
Published: October 2019

Abstract
The aim of this study was to propose local diagnostic reference levels (LDRLs) for the most common computed tomography (CT) examinations (including contrast and non-contrast scan phase) performed at Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia (USM), Malaysia. A retrospective CT dose survey of 1488 subjects from January 2015 until December 2018 was performed at AMDI USM, Malaysia. The proposed DRLs were established at 50th and 75th percentile of dose distribution for all dose metrics (CT dose index [CTDI]; CTDIvol, CTDIw and dose–length product). The proposed LDRLs were compared with national DRLs and other established DRLs. The 10 most common CT examinations at AMDI were thorax–abdomen–pelvis (TAP) CT (46%), followed by pelvis CT (17%), abdomen–pelvis CT (10%), brain/head CT (9%) and other CT protocols. The local DRLs were established using the third quartile values of dose distribution and were categorized based on CT region protocols. Most of the proposed DRLs were exceeded the national DRLs (63%) and other international DRLs (67%). From the dose auditing, almost half of the recent dose data (for year 2018) exceeded the proposed local DRLs and the unusual dose were observed in TAP, brain/head and pelvis CT examinations. The unusual higher dose could be due to higher mAs settings, higher number of scan phase for contrast study and higher pitch factor. The local DRLs should be established for dose optimization and reduction of the occurrence of excessive radiation exposure to the patients. The establishment of the Ads and LDRLs should also consider all the factors that affect the variation in DRLs such as CT technology, scanning protocols and population characteristics. The local dose distribution should always be revised for improvement of the current local practice.
Normalizing the Abnormal: Do Antipsychotic Drugs Push the Cortex Into an Unsustainable Metabolic Envelope?
Authors: Turkheimer Federico E , Selvaggi Pierluigi , Mehta Mitul A , Veronese Mattia , Zelaya Fernando , Dazzan Paola , Vernon Anthony C 
Published: October 2019

AbstractThe use of antipsychotic medication to manage psychosis, principally in those with a diagnosis of schizophrenia or bipolar disorder, is well established. Antipsychotics are effective in normalizing positive symptoms of psychosis in the short term (delusions, hallucinations and disordered thought). Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood. In this article, we propose a novel model of the long-term effects of antipsychotic administration focusing on the changes in brain metabolic homeostasis induced by the medication. We propose here that the brain metabolic normalization, that occurs in parallel to the normalization of psychotic symptoms following antipsychotic treatment, may not ultimately be sustainable by the cerebral tissue of some patients; these patients may be characterized by already reduced oxidative metabolic capacity and this may push the brain into an unsustainable metabolic envelope resulting in tissue remodeling. To support this perspective, we will review the existing data on the brain metabolic trajectories of patients with a diagnosis of schizophrenia as indexed using available neuroimaging tools before and after use of medication. We will also consider data from pre-clinical studies to provide mechanistic support for our model.
Why Do We Do What We Do? The Values of the Social History of Medicine
Authors: McKay Richard A 
Published: October 2019

Abstract
At the Society for the Social History of Medicine (SSHM)’s biennial conference in Liverpool in July 2018, members gathered to discuss a short working paper developed by the Society’s executive committee to articulate the values underpinning the SSHM’s mission. The occasion marked the first public discussion of this document, in development since 2015, which was intended to encourage disciplinary self-awareness and engagement, to give a sense of the breadth and importance of work carried out in our field and to spark broader discussion. To further these aims as the Society celebrates its fiftieth anniversary, the working paper appears here, accompanied by a foreword from the Society’s Policy Development Officer and the lightly revised invited responses shared that day by five members at different career stages.
Model-Based Species Delimitation: Are Coalescent Species Reproductively Isolated?
Authors: Campillo Luke C , Barley Anthony J , Thomson Robert C 
Published: October 2019

AbstractA large and growing fraction of systematists define species as independently evolving lineages that may be recognized by analyzing the population genetic history of alleles sampled from individuals belonging to those species. This has motivated the development of increasingly sophisticated statistical models rooted in the multispecies coalescent process. Specifically, these models allow for simultaneous estimation of the number of species present in a sample of individuals and the phylogenetic history of those species using only DNA sequence data from independent loci. These methods hold extraordinary promise for increasing the efficiency of species discovery but require extensive validation to ensure that they are accurate and precise. Whether the species identified by these methods correspond to the species that would be recognized by alternative species recognition criteria (such as measurements of reproductive isolation) is currently an open question and a subject of vigorous debate. Here, we perform an empirical test of these methods by making use of a classic model system in the history of speciation research, flies of the genus Drosophila. Specifically, we use the uniquely comprehensive data on reproductive isolation that is available for this system, along with DNA sequence data, to ask whether Drosophila species inferred under the multispecies coalescent model correspond to those recognized by many decades of speciation research. We found that coalescent based and reproductive isolation-based methods of inferring species boundaries are concordant for 77% of the species pairs. We explore and discuss potential explanations for these discrepancies. We also found that the amount of prezygotic isolation between two species is a strong predictor of the posterior probability of species boundaries based on DNA sequence data, regardless of whether the species pairs are sympatrically or allopatrically distributed. [BPP; Drosophila speciation; genetic distance; multispecies coalescent.]
Fluorescent Reporter Zebrafish Line for Estrogenic Compound Screening Generated Using a CRISPR/Cas9-Mediated Knock-in System
Authors: Abdelmoneim Ahmed , Clark Cedric L , Mukai Motoko 
Published: October 2019

AbstractAn increasing number of compounds in our diet and environment are being identified as estrogenic, causing serious and detrimental effects on human, animal, and ecosystem health. Time- and cost-effective biological tools to detect and screen these compounds with potential high-throughput capabilities are in ever-growing demand. We generated a knock-in zebrafish transgenic line with enhanced green fluorescent protein (EGFP) driven by the regulatory region upstream of vitellogenin 1 (vtg1), a well-studied biomarker for estrogenic exposure, using CRISPR/Cas9 technology. Exposure to 17β-estradiol (E2: 0–625 nM) starting at 4-h post-fertilization in dechorionated embryos resulted in the significant induction of hepatic EGFP with ≥5 nM E2 as early as 3-days post-fertilization. Concentration- and time-dependent increase in the percentage of hepatic EGFP-positive larvae and extent of fluorescence expression, categorized into 3 expression levels, were observed with E2 exposure. A strong correlation between the levels of EGFP mRNA, vtg1 mRNA, and EGFP fluorescence levels were detected. Image analysis of the area and intensity of hepatic EGFP fluorescence resulted in high-fidelity quantitative measures that could be used in automated screening applications. In addition, exposure to bisphenol A (0–30 μM) resulted in quantitative responses showing promise for the use of this transgenic line to assess estrogenic activity of endocrine-disrupting chemicals. These results demonstrate that this novel knock-in zebrafish reporter allows for distinct screening of in vivo estrogenic effects, endpoints of which can be used for laboratory testing of samples for estimation of possible human and environmental risks.
Proximal Tubular Vacuolization and Hypersensitivity to Drug-Induced Nephrotoxicity in Male Mice With Decreased Expression of the NADPH-Cytochrome P450 Reductase
Authors: Ding Liang , Li Lei , Liu Senyan , Bao Xiaochen , Dickman Kathleen G , Sell Stewart S , Mei Changlin , Zhang Qing-Yu , Gu Jun , Ding Xinxin 
Published: October 2019

AbstractThe effect of variations in the expression of cytochrome P450 reductase (CPR or POR) is determined in mice with decreased POR expression to identify potential vulnerabilities in people with low POR expression. There is an age-dependent appearance of increasing vacuolization in the proximal tubules of the renal cortex in 4- to 9-month-old male (but not female) Cpr-low (CL) mice. These mice have low POR expression in all cells of the body and upregulation of lysosome-associated membrane protein 1 expression in the renal cortex. Vacuolization is also seen in extrahepatic CL and extrarenal CL male mice, but not in mice with tissue-specific Por deletion in liver, intestinal epithelium, or kidney. The occurrence of vacuolization is accompanied by increases in serum blood-urea-nitrogen levels. Male CL mice are hypersensitive to cisplatin- and gentamicin-induced renal toxicity at 3 months of age, before proximal tubular (PT) vacuoles are detectable. At doses that do not cause renal toxicity in wild-type mice, both drugs cause substantial increases in serum blood-urea-nitrogen levels and PT vacuolization in male but not female CL mice. The hypersensitivity to drug-induced renal toxicity is accompanied by increases in circulating drug levels. These novel findings demonstrate deficiency of renal function in mice with globally reduced POR expression and suggest that low POR expression may be a risk factor for drug-induced nephrotoxicity in humans.
Associations between outdoor temperature and bright sunlight with metabolites in two population-based European cohorts
Authors: Eveleens Maarse Boukje C , Loh Nellie Y. , Karpe Fredrik , Rosendaal Frits R , van Heemst Diana , Mook-Kanamori Dennis O , van Dijk Ko Willems , Rensen Patrick CN , Kooijman Sander , Christodoulides Constantinos , Noordam Raymond 
Published: October 2019

AbstractContext: Outdoor temperature and bright sunlight may directly and/or indirectly modulate systemic metabolism.Objective: We assessed the associations between outdoor temperature and bright sunlight duration with metabolomics.Design: meta-analysis of two cross-sectional studies.Setting: Two population-based European cohort studies.Patients or other participants: Non-diabetic individuals from the Oxford BioBank (OBB; N=6,368; mean age 47.0 years, males 44%) and the Netherlands Epidemiology of Obesity (NEO; N=5,916; mean age 55.6 years, males 43%) studies.Intervention(s): Data on mean outdoor bright sunlight and temperature collected from local weather stations in the week prior to blood sampling.Main Outcome Measure(s): Serum levels of 148 metabolites measured using NMR spectroscopy, including 14 lipoprotein subclasses.Statistical analyses: Multivariable linear regression analyses adjusted for age, sex, body mass index, season and either outdoor temperature or bright sunlight. Summary statistics from the OBB and NEO cohorts were combined using fixed-effect meta-analyses.Results: A higher mean outdoor temperature was associated with increased concentrations of lipoprotein (sub)particles and certain amino acids such as phenylalanine and leucine. In contrast, longer mean hours of bright sunlight were specifically associated with lower concentrations of very low density lipoprotein (sub)particles. The direction of effects was consistent between the OBB and NEO, although effect sizes were generally larger in the OBB.Conclusions: Increased bright sunlight duration is associated with an improved metabolic profile whilst higher outdoor temperature may adversely impact cardiometabolic health.
A single-sample circadian biomarker that performs across populations and platforms
Authors: Wu Gang , Ruben Marc D. , Francey Lauren J. , Smith David F. , Sherrill Joseph D. , Oblong John E. , Mills Kevin J. , Hogenesch John B. 
Published: October 2019

ABSTRACTBackgroundFor circadian medicine to influence health, such as when to take a drug or undergo a procedure, a practical way to measure body time is needed. Recent machine learning algorithms show that gene expression data from blood and skin can provide reliable estimates of body time. However, for clinical viability, a biomarker must be easily measured and generalizable to a broad population. It is not clear that any circadian biomarker yet satisfies these criteria.ResultsWe analyzed 24 h molecular rhythms in human dermis and epidermis at three distinct body sites, leveraging both longitudinal and population data. Circadian clock function was strongest in the epidermis, regardless of body site. We identified a 12-gene biomarker set that reported circadian phase to within 3 hours from a single sample of epidermis—the skin’s most superficial layer. This set performed well across body sites, ages, sexes, and detection platforms.ConclusionsThis research shows that the clock in epidermis is more robust than dermis regardless of body site. To encourage ongoing validation of this biomarker in diverse populations, diseases, and experimental designs, we developed SkinPhaser—a user-friendly app to test biomarker performance in datasets (https://github.com/gangwug/SkinPhaser).