bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation marks inter-nucleosome linker regions throughout the human genome
Authors: Berman Benjamin P. , Liu Yaping , Kelly Theresa K. 
Published: January 2018

Background: Nucleosome organization and DNA methylation are two mechanisms that are important for proper control of mammalian transcription, as well as epigenetic dysregulation associated with cancer. Whole-genome DNA methylation sequencing studies have found that methylation levels in the human genome show periodicities of approximately 190 bp, suggesting a genome-wide relationship between the two marks. A recent report (Chodavarapu et al., 2010) attributed this to higher methylation levels of DNA within nucleosomes. Here, we analyzed a number of published datasets and found a more compelling alternative explanation, namely that methylation levels are highest in linker regions between nucleosomes.
Results: Reanalyzing the data from (Chodavarapu et al., 2010), we found that nucleosome-associated methylation could be strongly confounded by known sequence-related biases of the next-generation sequencing technologies. By accounting for these biases and using an unrelated nucleosome profiling technology, NOMe-seq, we found that genome-wide methylation was actually highest within linker regions occurring between nucleosomes in multi-nucleosome arrays. This effect was consistent among several methylation datasets generated independently using two unrelated methylation assays. Linker-associated methylation was most prominent within long Partially Methylated Domains (PMDs) and the positioned nucleosomes that flank CTCF binding sites. CTCF adjacent nucleosomes retained the correct positioning in regions completely devoid of CpG dinucleotides, suggesting that DNA methylation is not required for proper nucleosomes positioning.
Conclusions: The biological mechanisms responsible for DNA methylation patterns outside of gene promoters remain poorly understood. We identified a significant genome-wide relationship between nucleosome organization and DNA methylation, which can be used to more accurately analyze and understand the epigenetic changes that accompany cancer and other diseases.
Levodopa-stimulated dopamine release in Tourette syndrome
Authors: Black Kevin J , Piccirillo Marilyn L. , Koller Jonathan M. , Hseih Tiffany , Wang Lei , Mintun Mark A. 
Published: January 2018

RATIONALE: Several lines of evidence suggest that dopamine (DA)-influenced neuronal pathways may malfunction in Tourette Syndrome (TS). Some PET studies support the hypothesis of presynaptic abnormalities in levodopa uptake, dopamine synthesis, or dopamine release.
OBJECTIVE: Directly test the presynaptic hypothesis using a new approach.
METHODS: We used positron emission tomography (PET) and [11C]raclopride (RAC*) to measure synaptic dopamine release before and during levodopa and placebo infusions (with carbidopa) in 5neuroleptic-naïve adults with TS and 5 matched control subjects. The primary analysis examined RAC* binding potential (BPND) in predefined volumes of interest (VOIs). A secondary analysis compared BPND voxel by voxel over the entire brain.
RESULTS: (1) Baseline RAC* BPND did not differ significantly between groups, though nucleus accumbens BPND was higher in TS (16%, p=0.051). (2) DA release declined from before to during infusions (p=0.014), including with placebo. (3) This decline was smaller in TS (p=0.080). (4) Levodopa’s effect on BPND differed significantly in right midbrain (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects, and in parahippocampal gyrus (p=0.02, corrected).
DISCUSSION: Our finding that a before/after RAC* design is confounded by time and/or expectation effects may have implications for other RAC* PET studies. The smaller decrease of BPND with time in TS may be attributable to impaired habituation to the scan environment. Levodopa’s opposite effect on RAC* binding in TS dopaminergic midbrain but may signify an abnormal response to dopaminergic stimulation in TS.
HIV-positive parents disclosure-related preparation activities in Kenya
Authors: Gachanja Grace , Burkholder Gary J , Ferraro Aimee 
Published: January 2018

Background. HIV disclosure from parent to child is a complex and challenging issue that needs to be approached carefully. Little is known about how parents prepare for and perform disclosure to children in resource-poor nations and what resources are needed. This study was conducted to describe the lived experiences of HIV-positive parents and their children during the disclosure process in Kenya.
Methods. This qualitative phenomenological study's data was collected using in-depth semi-structured interviews with 34 participants consisting of HIV-positive parents, HIV-positive and negative children, and healthcare professionals. The Van Kaam method was used to analyze the data.
Results. Parents take years to prepare for disclosure, proceeding when they perceive themselves capable and ready; and their children are receptive to the news. Preparation activities include thinking about and making disclosure plans, reading information, teaching children about the disease without disclosure while improving the parent-child relationship, praying regularly and attending religious activities, seeking counseling, and attending support group meetings.
Conclusion. Parents perform a number of activities to get themselves and their children ready for disclosure. These activities are crucial in the timely delivery of disclosure. Understanding the importance of these activities helps healthcare professionals assist parents to deliver disclosure faster after diagnosis of illness.
Natural selection increases mutational robustness in complex diseases: Mendelian evidence from early versus late onset common diseases
Authors: Baysal Bora E 
Published: January 2018

Background. Natural selection operates on genetically influenced phenotypic variations that confer differential survival or reproductive advantages. Common diseases are frequently associated with increased mortality and disability and complex heritable factors play an important role in their pathogenesis. Hence, common diseases should trigger the process of natural selection with subsequent population genetic response. However, empirical impact of natural selection on genetics of complex diseases is poorly understood. In this paper, I hypothesize that negative selection of diseased individuals leads to systemic genetic differences between common diseases that primarily occur before or during the reproductive years (early onset) and those that occur after the reproductive years (late onset).
Methods. To test this hypothesis, a comprehensive literature survey of highly penetrant (80% or more) nonpleiotropic, nonsyndromic susceptibility genes (hereafter defined as Mendelian phenocopies) was completed for early versus late onset common diseases, organized using the World Health Organization (WHO) ICD-10 classification scheme. An average age at sporadic disease onset of 30 years was selected for dividing early versus late onset common diseases.
Results. Mendelian phenocopies were identified for 16 primarily late onset common diseases from 9 distinct WHO diagnostic categories. Late onset common diseases with Mendelian phenocopies include papillary renal carcinoma, obesity, Alzheimer disease, Parkinson disease, frontotemporal dementia, amyotrophic lateral sclerosis, primary open angle glaucoma, age-related hearing loss, coronary artery disease, stroke, pancreatitis, thrombotic thrombocytopenic purpura, systemic lupus erythematosus, inclusion body myositis, Paget's disease of bone and focal segmental glomerulosclerosis (steroid resistant). In contrast, no Mendelian phenocopy was found for any primarily early onset common disease (p<5.8x10-4). Thus, highly predictive rare variants are present for a subset of late onset common diseases, but not for early onset common diseases.
Discussion. These findings suggest that genetic architecture of early onset common diseases is more robust against the phenotypic expression of highly penetrant predisposing mutations than is the case for late onset common diseases. The primary candidate for increased genetic robustness in early onset common diseases is proposed to be natural selection.
Temporal variability is a personalized feature of the human microbiome
Authors: Flores Gilberto E , Caporaso J Gregory , Henley Jessica B , Rideout Jai Ram , Domogala Daniel , Chase John , Leff Jonathan W , Vázquez-Baeza Yoshiki , Gonzalez Antonio , Knight Rob , Dunn Robert R , Fierer Noah 
Published: January 2018

Background: It is now apparent that the complex microbial communities found on and in the human body (the human microbiome) vary across individuals. What has largely been missing from previous studies is an understanding of how these communities vary over time within individuals. To the extent to which it has been considered, it is often assumed that temporal variability is negligible for healthy adults. Here we address this gap in understanding by profiling the forehead, gut (fecal), palm, and tongue microbial communities in 85 adults, weekly over three months.
Results: We found that skin (forehead and palm) varied most in the number of taxa present, whereas gut and tongue communities varied more in the relative abundances of taxa. Within each body habitat, there was a wide range of temporal variability across the study population, with some individuals consistently harboring more variable communities than others. The best predictor of these differences in variability across individuals was microbial diversity; individuals with more diverse gut or tongue communities were less variable than individuals with less diverse communities.
Conclusions: This expanded sampling allowed us to observe consistently high levels of temporal variability in both diversity and community structure in all body habitats studied. These findings suggest that temporal dynamics may need to be considered when attempting to link changes in microbiome structure to changes in health status.Furthermore, our findings show that, not only is the composition of an individual’s microbiome highly personalized, but their degree of temporal variability is also a personalized feature.
Action and cognition in task oriented coping: Factor structure and internal consistency of the CISS-21 with an Indian sample
Authors: Golpelwar Mayank 
Published: January 2018

Objective : Although the Coping Instrument for Stressful Situations – 21 item scale (CISS-21) offers excellent psychometric stability in samples from various countries, data about its validity and reliability among Indian samples is not easily accessible. The current study presents these data from a sample consisting of urban Indians working in the global service sector.
Method : Two hundred and seventy four professionals working in highly paying service sector jobs in India completed the CISS-21. The data was analyzed using principal factor analysis and reliability analysis.
Results : Instead of the three-factor structure consisting of emotion-oriented, avoidance-oriented, and task-oriented coping strategies, a four-factor structure emerged. This resulting structure indicates that the current Indian sample perceived the task-oriented coping strategy as comprising of two distinct sub-factors: One involving cognitive-appraisal based mechanisms and another where a direct action-based approach is preferred.
Conclusion : among the Indian sample involved in the current study, CISS-21 appears to be a reliable and valid scale, albeit with a four instead of three factor structure. Naïve dialecticism and Biculturalism are presented and discussed as possible reasons for this unique factor structure.
Prolactin and fMRI response to SKF38393 in the baboon
Authors: Miller Brad D. , Marks Lauren A. , Koller Jonathan , Newman Blake J. , Bretthorst G. Larry , Black Kevin J 
Published: January 2018

Background: This study’s goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select promising agonists and to guide design details for the single-dose studies needed to generate dose-response curves.
Methods: We studied 6 male baboons (Papio anubis) under low-dose isoflurane anesthesia after i.m. ketamine. Time course studies charted the changes in plasma prolactin levels over time after anesthesia alone or after an intravenous (i.v.) dose of the dopamine D1-like agonists SKF82958 and SKF38393 or the D2-like agonist pramipexole. In the single-dose dopamine agonist studies, one dose of SKF38393 (ranging from 0.0928 – 9.28 mg/kg, N=5 animals) or pramipexole (0.00928 – 0.2 mg/kg, N=1) was given i.v. during a 40-minute blood oxygen level dependent (BOLD) fMRI session, to determine BOLD and plasma prolactin responses to different drug concentrations. BOLD response was quantified as the area under the time-signal curve for the first 15 minutes after the start of the drug infusion, compared to the linearly predicted signal from the baseline data before drug. The ED50(estimated dose that produces 50% of the maximal possible response to drug) for SKF38393 was calculated for the serum prolactin response and for phMRI responses in hypothalamus, pituitary, striatum and midbrain.
Results: Prolactin rose 2.4- to 12-fold with anesthesia alone, peaking around 50-90 minutes after ketamine administration and gradually tapering off but still remaining higher than baseline on isoflurane 3-5 hours after ketamine. Baseline prolactin level increased with age. SKF82958 0.1mg/kg i.v. produced no noticeable change in plasma prolactin concentration. SKF38393 produced a substantial increase in prolactin release that peaked at around 20-30 minutes and declined to pre-drug levels in about an hour. Pramipexole quickly reduced prolactin levels below baseline, reaching a nadir 2-3 hours after infusion. SKF38393 produced clear, dose-responsive BOLD signal changes, and across the four regions, ED50 was estimated at 1.6-7.7mg/kg.
Conclusions: In the baboon, the dopamine D1receptor agonist SKF38393 produces clear plasma prolactin and phMRI dose-response curves. Variability in age and a modest sample size limit the precision of the conclusions.
High prevalence of asymptomatic carrier state with 2009 pandemic influenza virus in a remote rural South Indian community in the year 2012
Authors: Kumar Anita A , Palamaner Subash Shantha Ghanshyam , Sethi Mansha , Khanna Rohit C 
Published: January 2018

Introduction:
There is scarcity of global data with regards to rates of asymptomatic carrier state due to 2009 pandemic H1N1 influenza virus. It will be interesting to study asymptomatic carrier state in the year 2012 when the global pandemic has been controlled. In this study we have attempted to evaluate the rates of asymptomatic carrier state due to this virus in a remote rural community from South India.
Methods:
380 consecutive, asymptomatic, community living adults without history of respiratory illness in the last 30 days were studied. Demographic and clinical profile was noted. Throat swab was obtained and tested by RT-PCR (reverse transcriptase polymerase chain reaction) for swine influenza A (HINI) as per CDC (Centers for Disease Control) protocol. Participants who were positive in this test were followed weekly by clinical evaluation for a period of 4 weeks to look for onset of respiratory symptoms.
Results:
Mean age was 42.58 yrs. Males formed 48.3% of the cohort. Mean body mass index was 23.62 kg/m2. 16.3% and 10.5% were diagnosed to have diabetes mellitus and hypertension respectively. None of the study participants had received seasonal influenza vaccine or pandemic H1N1 influenza vaccine. RT-PCR identified asymptomatic infection in 41 participants (10.8%). In uni-variate and multi-variate logistic regression analysis there were no significant associations between having asymptomatic carrier state, diabetes diagnosis, gender, age, BMI, hemoglobin A1C%. On follow-up none of the 41 positive participants developed respiratory symptoms.
Conclusion:
High prevalence of asymptomatic carrier state after 2009 H1N1 influenza virus pandemic was found in our study in the year 2012. The significance of asymptomatic infection remains unclear.
Causal relationship between occupational dysfunction and depression in healthcare workers: A study using structural equation model
Authors: Teraoka Mutsumi , Kyougoku Makoto 
Published: January 2018

Purpose: The purpose of this study is to identify the impacts of occupational dysfunction on depression in healthcare workers (nurses, physical therapists, and occupational therapists) in hospitals.
Methods: Healthcare workers responded to a questionnaire based on the Classification and Assessment of Occupational Dysfunction (CAOD) and Center for Epidemiologic Studies Depression Scale (CES-D). CAOD and CES-D were examined using the following methods: descriptive statistics, exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and a causal sequence model.
Results: CFA of CAOD had 16 items and 5 factors (CFI=0.958, TLI=0.946, RMSEA＝0.092). CFA of CES-D had 20 items and 4 factors (CFI=0.950, TLI=0.942, RMSEA=0.060). The results suggest that occupational dysfunction had positive causal effects on depression (CFI=0.926, TLI=0.920, RMSEA=0.059).
Conclusion: This model refers to the relationship between depression and occupational dysfunction. Therefore, assessment and intervention on classification of occupational dysfunction for healthcare workers would be beneficial in the prevention of depression.
Effects of mapping algorithms on gene selection for RNA-Seq analysis: pulmonary response to acute neonatal hyperoxia
Authors: Chu Chin-Yi , Bhattacharya Soumyaroop , Zhou Zhongyang , Yee Min , Lopez Ashley , Lunger Valerie A , Buczynski Bradley , Oreilly Michael , Mariani Thomas 
Published: January 2018

Background: A major goal of RNA-Seq data analysis is to reconstruct the full set of gene transcripts expressed in a biological sample in order to quantify their expression levels. The process typically involves multiple steps including mapping short sequence reads to a reference genome, and estimating expression levels based on these mappings. Multiple algorithms and approaches for each processing step exist, and the impact of different methods on estimation of gene expression is not entirely clear.
Methods: We evaluated the impact of three common mapping algorithms on differential expression analysis in an RNA-Seq dataset describing the lung response to acute neonatal hyperoxia. RNA-Seq data generated using the Illumina platform were mapped and aligned using CASAVA, TopHat, and SHRiMP against the mouse genome. Significance Analysis of Microarrays and Cuffdiff were used to identify differentially expressed genes between hyperoxia-challenged and age matched control mice.
Results: 1403 genes were detected as differentially expressed by least one mapping and gene selection method. A majority of genes (>65%) were identified by all three mapping methods, regardless of the gene selection approach. Expression patterns for 52 genes were examined by quantitative polymerase chain reaction (qPCR). Importantly, we found different validation rates for genes selected by each method; 72% for CASAVA, 69% for TopHat and 63% for SHRiMP. Surprisingly, the validation rate for genes selected by all three mapping methods was no greater than the best single method.
Conclusion: The choice of mapping strategy impacts the reliability of gene selection for RNA-Seq data analysis.
A new large scale global morphological phylogeny of turtles
Authors: Rabi Márton , Sterli Juliana , Joyce Walter G 
Published: January 2018

We developed a new global turtle matrix using morphological characters to test the age of the turtle crown and to assess the origin and phylogeny of various controversial clades along the turtle stem and within Pan-Cryptodira.
We significantly increased both character and taxon sampling relative to earlier global matrices with special emphasis on Jurassic and Cretaceous stem-cryptodires. Further improvements included the complete, observation-based re-scoring of all previously sampled taxa and the reduction of subjective character assignments with the help of consensusbuilding between the members of our working group for each scoring.
We confirm the previous conclusion that the turtle crown has an extensive phylogenetic stem and that the age of the crown is approximately Middle Jurassic in age. The addition of new fossils allows reinterpreting purported Laurasian meiolaniforms as part of a paraphyletic grade of Mesozoic Laurasian basal turtles, including Solemydidae, Sichuanchelyidae, and Kallokibotion bajazidi. A paraphyletic Cryptodira with a deeply nested Pleurodira (as signaled by some recent morphological and molecular analyses) is not recovered when only stem-pleurodires are included in the analysis. This demonstrates conclusively that the false signal is caused by marked morphological convergences between crown cryptodires and pleurodires. We find little or no support for the chelydrid affinities of Platysternon megacephalum which had previously been inferred by morphological analyses, in conspicuous contrast with molecular results. Similarly, little support remains for a Trionychia-Kinosternoidea clade, which had been consistently recovered in earlier morphological studies, again in contrast with molecular phylogenies. Contrary to previous hypotheses, our analysis advocates sea turtle monophyly and argue for a diverse Cretaceous stem, including bizarre, giant forms belonging to the extinct clade Protostegidae. Derived members of Protostegidae nevertheless show remarkable similarities with dermochelyids as a result of parallel evolution.
Despite increased taxon and character sampling, we are still unable to fully replicate the molecular phylogeny of turtles. This is frustrating because the stratigraphic distribution of fossil turtles is more consistent with molecular results. The likely reason for this disparity comes from the high degree of homoplasy in turtles, notable gaps in the fossil record, and the rapid and early diversification of extant turtle lineages soon after the appearance of the turtle crown. The latter is also suggested by the overall good support at the end of the branches and low resolution at the nodes connecting their stem. Future fossil discoveries, particularly from the Jurassic of Gondwana and Southeast Asia, will likely help resolve these issues. In the meantime, we support employing the consensual molecular scaffold for global morphological analyses of turtles.