bluuebunny/crossref_metadata_2025_split huggingface dataset:
Device-assisted Enteroscopy for Obscure Gastrointestinal Bleeding in the Setting of Thienopyridine Antiplatelet Therapy
Authors: Bollinger Elizabeth E. , Spera Melissa A. , Raines Daniel L. 
Published: April 2016

Background:
Current guidelines recommend suspending thienopyridine therapy 5 to 7 days before therapeutic endoscopy to reduce the risk of bleeding-related complication. However, interruption of antiplatelet therapy may increase the risk of a cardiovascular event. The aim of this study was to evaluate the safety and diagnostic yield of device-assisted enteroscopy (DAE) with endoscopic therapy in patients receiving thienopyridine antiplatelet therapy.

Materials and Methods:
A retrospective chart review was performed for patients treated in the LSU Health Sciences Gastroenterology Clinics between the dates of October 4, 2007 and February 15, 2015. A total of 774 enteroscopy procedures were reviewed to identify patients on active thienopyridine therapy at the time of DAE.

Results:
During the study period, a total of 68 patients underwent DAE while on thienopyridine therapy. Confirmed or suspected small bowel bleeding was the most common procedural indication. A total of 143 endoscopic interventions were performed, primarily argon plasma coagulation for ablation of intestinal angioectasias. There were no significant bleeding-related complications associated with these procedures. In addition, the diagnostic yield for these procedures was high (77%) with a significant percentage of patients in the thienopyridine group found to have an active bleeding source at the time of DAE.

Conclusions:
The performance of DAE procedures with endoscopic intervention such as argon plasma coagulation may be safe in patients on thienopyridine therapy. Continuing thienopyridines may also increase the diagnostic yield of these procedures by promoting active bleeding from the culprit source.
Population-representative Incidence of Acute-On-Chronic Liver Failure
Authors: Qin Gang , Shao Jian-Guo , Zhu Yong-Chang , Xu Ai-Dong , Yao Jian-Hua , Wang Xu-Lin , Qian Yin-Kun , Wang Hua-Yu , Shen Yi , Lu Peng , Wang Lu-Jun 
Published: April 2016

Background:
Acute-on-chronic liver failure (ACLF) is a major cause of hepatic death in the world, but no population-based studies have evaluated the incidence of ACLF. This study was conducted to determine the incidence and short-term outcomes of ACLF in a region of Eastern China.

Methods:
In this prospective cross-sectional study, we collected data from public hospitals in Nantong city between January 1, 2005, and December 31, 2014. All hospitals with admission potential for ACLF patients were included. The primary outcome was ACLF defined as severe jaundice and coagulopathy with underlying chronic liver disease, according to diagnostic and laboratory criteria suggested by Chinese Society for Hepatology (CSH).

Results:
During the 10-year period, a consecutive sample of 1934 ACLF patients was included in this study. The overall ACLF incidence rate over the 10-year period was 2.53 (95% confidence interval, 2.16-2.91) per 100,000 population per year, decreasing from 3.35 in 2005 to 2.06 in 2014. Chronic hepatitis B virus (HBV) infection was the leading cause of chronic liver disease and HBV reactivation was the most common cause of acute hepatic event. The 28-day mortality for the ACLF patients had a clear decline during the study period, form 50.39% in 2005 to 35.44% in 2014.

Conclusions:
In the Eastern China population, the incidence of ACLF is decreasing and the prognosis improving. Short-term mortality was associated with the presence of cirrhosis and growing age. While ACLF remains a life-threatening disorder, our findings suggest that nationwide and long-term cohorts should be conducted for the natural history of ACLF.
Short article: Faldaprevir, deleobuvir and ribavirin in IL28B non-CC patients with HCV genotype-1a infection included in the SOUND-C3 phase 2b study
Authors: Zeuzem Stefan , Mantry Parvez , Soriano Vicente , Buynak Robert J. , Dufour Jean-François , Pockros Paul J. , Wright David , Angus Peter , Buti Maria , Stern Jerry O. , Kadus Werner , Vinisko Richard , Böcher Wulf , Mensa Federico J. 
Published: April 2016

Background
SOUND-C3 was a multicentre, open-label, phase 2b study exploring the safety and efficacy of the interferon-free combination of faldaprevir (an NS3/A4 protease inhibitor), deleobuvir (BI 207127, a non-nucleoside polymerase inhibitor) and ribavirin in treatment-naive patients with chronic hepatitis C virus (HCV) genotype-1 infection. Results in patients with HCV genotype-1b and in IL28B CC genotype patients with HCV genotype-1a have been described previously. This report describes the results in IL28B non-CC genotype patients with HCV genotype-1a.

Methods
Patients were randomized to receive faldaprevir 120 mg once daily with deleobuvir at either 800 mg twice daily (b.i.d.; N=26) or 600 mg three times daily (t.i.d.; N=25), and weight-based ribavirin for 24 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12).

Results
In each group, five patients completed 24 weeks of treatment. SVR12 rates were 19% (5/26) and 8% (2/25) in the b.i.d. and t.i.d. groups, respectively. On-treatment breakthrough [50% (13/26) and 68% (17/25) in the b.i.d. and t.i.d. groups, respectively] was the most frequent reason for not achieving SVR12. Adverse events led to premature treatment discontinuation in six (23%) patients in the b.i.d. group and in two patients (8%) in the t.i.d. group. The majority of adverse events were mild or moderate; the most frequently reported were nausea (67%), fatigue (35%) and diarrhoea (35%).

Conclusion
In this small study, the interferon-free regimen of faldaprevir, deleobuvir and ribavirin resulted in high rates of virological breakthrough and low rates of SVR12 in IL28B non-CC genotype patients infected with genotype-1a HCV (
http://www.clinicaltrials.gov
NCT01132313).
Efficacy of Cognitive Behavioral Therapy for Insomnia in Older Adults With Occult Sleep-Disordered Breathing
Authors: Fung Constance H. , Martin Jennifer L. , Josephson Karen , Fiorentino Lavinia , Dzierzewski Joseph M. , Jouldjian Stella , Tapia Juan Carlos Rodriguez , Mitchell Michael N. , Alessi Cathy 
Published: April 2016

ABSTRACT

Objectives
The aims of the study were to determine whether mild, occult sleep-disordered breathing (SDB) moderates the efficacy of cognitive behavioral therapy for insomnia (CBTI) in older adults and to explore whether CBTI reduces the number of patients eligible for positive airway pressure (PAP) therapy.

Methods
Data were analyzed for 134 adults 60 years or older with insomnia and apnea-hypopnea index (AHI) of less than 15 who were randomized to a larger study of CBTI versus a sleep education control. Sleep outcomes (sleep onset latency, total wake time, wake after sleep onset, sleep efficiency, Pittsburgh Sleep Quality Index) were compared between CBTI and control at 6 months using repeated-measures analysis of variance adjusted for baseline values. AHI of 5 or greater versus less than 5 was included as an interaction term to evaluate changes in sleep outcomes. The number of participants at baseline and 6 months with mild SDB for whom insomnia was their only other indication for PAP was also compared between CBTI and control.

Results
AHI status (AHI ≥ 5 [75.5% of participants] versus AHI < 5) did not moderate improvements in sleep associated with CBTI (all p values ≥ .12). Nine (45.0%) of 20 participants with mild SDB for whom insomnia was their only other indication for PAP therapy at baseline no longer had another indication for PAP at 6 months, with no significant difference between CBTI and control.

Conclusions
CBTI improves sleep in older veterans with insomnia and untreated mild SDB. Larger trials are needed to assess whether CBTI reduces the number of patients with mild SDB eligible for PAP.
Depression and Anxiety Screens as Predictors of 8-Year Incidence of Myocardial Infarction and Stroke in Primary Care Patients
Authors: Stewart Jesse C. , Hawkins Misty A.W. , Khambaty Tasneem , Perkins Anthony J. , Callahan Christopher M. 
Published: April 2016

ABSTRACT

Objective
Because depression and anxiety are typically studied in isolation, our purpose was to examine the relative importance of these overlapping emotional factors in predicting incident cardiovascular disease (CVD).

Methods
We examined depression and anxiety screens, and their individual items, as predictors of incident hard CVD events, myocardial infarction, and stroke for 8 years in a diverse sample of 2041 older primary care patients initially free of CVD. At baseline, participants completed self-report depression and anxiety screens. Data regarding CVD events were obtained from an electronic medical record system and the Centers for Medicare and Medicaid Services analytic files.

Results
During follow-up, 683 (33%) experienced a CVD event. Cox proportional hazards models—adjusted for demographic and CVD risk factors—revealed that a positive anxiety screen, but not a positive depression screen, was associated with an increased risk of a hard CVD event in separate models (Years 0–3: anxiety hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.21−1.96, p < .001; Years 3+: anxiety HR = 0.99, CI = 0.81−1.21), p = .93; depression HR = 1.10, CI = 0.88−1.36, p = .41), as well as when entered into the same model (Years 0–3: anxiety HR = 1.53, CI = 1.20−1.95, p < .001; Years 3+: anxiety HR = 0.99, CI = 0.80−1.21, p = .99; depression HR = 1.03, CI = 0.82−1.29, p = .82). Analyses examining individual items and secondary outcomes showed that the anxiety-CVD association was largely driven by the feeling anxious item and the myocardial infarction outcome.

Conclusions
Anxiety, especially feeling anxious, is a unique risk factor for CVD events in older adults, independent of conventional risk factors and depression. Anxiety deserves increased attention as a potential factor relevant to CVD risk stratification and a potential target of CVD primary prevention efforts.
Associations Between Depression and Obesity in Parents and Their Late-Adolescent Offspring: A Community-Based Study
Authors: Marmorstein Naomi R. , Iacono William G. 
Published: April 2016

ABSTRACT

Objective
Major depressive disorder (MDD) and obesity are associated within individuals, but little is known about the association between MDD and obesity within families. We hypothesized that parental MDD would predict increased risk for adolescent obesity and that parental obesity would predict increased risk for adolescent MDD.

Methods
Participants were drawn from the community-based Minnesota Twin Family Study (N = 7307; 17 years old: n = 3774). Parents and their 17-year-old offspring were assessed for MDD using a structured diagnostic interview, and direct assessments of height and weight were conducted (and diagnoses of obesity were derived from these measurements).

Results
Parental MDD was associated with offspring obesity (odds ratio [OR] = 1.74, 95% confidence interval [CI] = 1.24–2.46). ORs representing the risk associated with maternal and paternal MDD were similar (OR = 1.42, 95% CI = 1.02–1.92; OR = 1.40, 95% CI = 0.88–2.20, respectively). This parental effect remained significant when adjusting for parental obesity and offspring MDD (OR = 1.67, 95% CI = 1.18–2.37). Maternal obesity was associated with increased risk for MDD in offspring (OR = 1.32, 95% CI = 1.06–1.64), but paternal obesity was associated with decreased risk for MDD among offspring (OR = 0.70, 95% CI = 0.54–0.91). These effects remained significant when adjusting for parental MDD and offspring obesity (OR = 1.36, 95% CI = 1.07–1.73; OR = 0.65, CI = 0.49–0.87, respectively). There were no differences in these findings by offspring sex (p values for all tests of a sex interaction term > .374).

Conclusions
We found general support for hypothesized cross-disorder associations between MDD and obesity in parents and offspring, suggesting that a shared etiology may underlie these associations. Contrary to prediction, paternal obesity was associated with decreased risk for offspring MDD, a finding that requires further investigation.
Mortality in Women With Anorexia Nervosa: The Role of Comorbid Psychiatric Disorders
Authors: Kask Jan , Ekselius Lisa , Brandt Lena , Kollia Natasa , Ekbom Anders , Papadopoulos Fotios C. 
Published: April 2016

ABSTRACTObjectiveTo investigate mortality in anorexia nervosa (AN) with a psychiatric comorbidity.MethodsUsing Swedish registers, data for 8069 female inpatients with AN were retrospectively collected for 1973–2010. Mortality patterns were assessed using standardized mortality ratios (SMRs), Cox regression-derived hazard ratios, and incidence rate ratios. A control cohort of 76,995 women was used.ResultsPatients with AN and a psychiatric comorbidity had higher mortality rates did than those without a comorbidity. The SMRs for patients with AN and a psychiatric comorbidity were 5.4 (95% confidence interval [CI] = 4.6–6.4) and 18.1 (95% CI = 15.2–21.3) for natural and unnatural causes of death, respectively. The SMRs for patients with AN without a comorbidity were 2.8 (95% CI = 2.3–3.5) and 3.1 (95% CI = 2.2–4.1) for natural and unnatural causes of death, respectively. The adjusted hazard ratios for mortality from natural or unnatural causes were 2.0 (95% CI = 1.5–2.7) and 5.7 (95% CI = 3.9–8.2), respectively. Incidence rate ratios comparing patients with AN and controls, both with psychiatric comorbidities, suggest a negative synergistic effect of comorbid AN and psychiatric disorder on mortality, which was greater for unnatural causes of death.ConclusionsMortality in patients with AN was greater in the presence of a psychiatric comorbidity, and even more pronounced for unnatural causes of death and suicides. Substance abuse, especially alcohol use disorder, increased mortality from natural causes of death. These findings highlight the need for early detection and treatment of psychiatric comorbidity in AN, to potentially improve long-term outcomes.
Graph analysis of structural brain networks in Alzheimer’s disease
Authors: John Majnu , Ikuta Toshikazu , Ferbinteanu Janina 
Published: April 2016

ABSTRACTBackgroundChanges in brain connectivity in patients with early Alzheimer’s disease (AD) have been investigated using graph analysis. However, these studies were based on small data sets, explored a limited range of network parameters, and did not focus on more restricted sub-networks, where neurodegenerative processes may introduce more prominent alterations.MethodsIn this study, we constructed structural brain networks out of 87 regions by using data from 135 healthy elders and 100 early AD patients selected from the Open Access Series of Imaging Studies (OASIS) database. We evaluated the graph properties of these networks by investigating metrics of network efficiency, small world properties, segregation, product measures of complexity, and entropy. Because degenerative processes take place at different rates in different brain areas, analysis restricted to sub-networks may reveal changes otherwise undetected. Therefore, we first analyzed the graph properties of a network encompassing all brain areas considered together, and then repeated the analysis after dividing the brain areas into two sub-networks constructed by applying a clustering algorithm.ResultsAt the level of large scale network, the analysis did not reveal differences between AD patients and controls. In contrast, the same analysis performed on the two sub-networks revealed modifications accompanying AD. Changes in small world properties suggested that the ability to engage concomitantly in integration and segregation of information diminished with AD in the sub-network containing the areas of medial temporal lobe known to be heaviest and earliest affected. In contrast, we found that the second network showed an increase in small world propensity, a novel metric that unbiasedly quantifies small world structure. Complexity and entropy measures indicated that the intricacy of connection patterns and structural diversity decreased in both sub-networks.ConclusionsThese results show that neurodegenerative processes impact volumetric networks in a non-global fashion. Our findings provide new quantitative insights into topological principles of structural brain networks and their modifications during early stages of Alzheimer’s disease.
Evolutionary mysteries in meiosis
Authors: Lenormand Thomas , Engelstadter Jan , Johnston Susan E. , Wijnker Erik , Haag Christoph R. 
Published: April 2016

AbstractMeiosis is a key event of sexual life cycles in eukaryotes. Its mechanistic details have been uncovered in several model organisms, and most of its essential features have received various and often contradictory evolutionary interpretations. In this perspective, we present an overview of these often “weird” features. We discuss the origin of meiosis (origin of ploidy reduction and recombination, two-step meiosis), its secondary modifications (in polyploids or asexuals, inverted meiosis), its importance in punctuating life cycles (meiotic arrests, epigenetic resetting, meiotic asymmetry, meiotic fairness) and features associated with recombination (disjunction constraints, heterochiasmy, crossover interference and hotspots). We present the various evolutionary scenarios and selective pressures that have been proposed to account for these features, and we highlight that their evolutionary significance often remains largely mysterious. Resolving these mysteries will likely provide decisive steps towards understanding why sex and recombination are found in the majority of eukaryotes.
Neighborhood regulation by lncRNA promoters, transcription, and splicing
Authors: Engreitz Jesse M. , Haines Jenna E. , Munson Glen , Chen Jenny , Perez Elizabeth M. , Kane Michael , McDonel Patrick E. , Guttman Mitchell , Lander Eric S. 
Published: April 2016

AbstractMammalian genomes are pervasively transcribed to produce thousands of spliced long noncoding RNAs (lncRNAs), whose functions remain poorly understood. Because recent evidence has implicated several specific lncRNA loci in the local regulation of gene expression, we sought to determine whether such local regulation is a property of many lncRNA loci. We used genetic manipulations to dissect 12 genomic loci that produce lncRNAs and found that 5 of these loci influence the expression of a neighboring gene incis. Surprisingly, however, none of these effects required the specific lncRNA transcripts themselves and instead involved general processes associated with their production, including enhancer-like activity of gene promoters, the process of transcription, and the splicing of the transcript. Interestingly, such effects are not limited to lncRNA loci: we found similar effects on local gene expression at 4 of 6 protein-coding loci. These results demonstrate that ‘crosstalk’ among neighboring genes is a prevalent phenomenon that can involve multiple mechanisms andcisregulatory signals, including a novel role for RNA splicing. These mechanisms may explain the function and evolution of some genomic loci that produce lncRNAs.
Efficiency of genome-wide association study in open-pollinated populations
Authors: Viana José Marcelo Soriano , Mundim Gabriel Borges , Silva Fabyano Fonseca e , Garcia Antonio Augusto Franco 
Published: April 2016

ABSTRACTGenome-wide association studies (GWAS) with plant species have employed inbred lines panels. Thus, to our knowledge, no information is available on theory and efficiency of GWAS in open-pollinated populations. Our objectives are to present quantitative genetics theory for GWAS, evaluate the relative efficiency of GWAS in non-inbred and inbred populations and in an inbred lines panel, and assess factors affecting GWAS, such as linkage disequilibrium (LD), sample size, and quantitative trait locus (QTL) heritability. Fifty samples of 400 individuals from populations with LD were simulated. Individuals were genotyped for 10,000 single nucleotide polymorphisms (SNPs) and phenotyped for traits with different degrees of dominance controlled by 10 QTLs and 90 minor genes. The average SNP density was 0.1 centiMorgan and the trait heritabilities were 0.4 and 0.8. We assessed GWAS efficiency based on the power of QTL detection, number of false-positive associations, bias in the estimated QTL position, and range of the significant SNPs for the same QTL. When the LD between a QTL and one or more SNPs is restricted to markers very close to or within the QTL, GWAS in open-pollinated populations can be highly efficient, depending mainly on QTL heritability and sample size. GWAS achieved the highest power of QTL detection, the smallest number of false-positive associations, and the lowest bias in the estimated QTL position for the inbred lines panel correcting for population structure. Under low QTL heritability and reduced sample size, GWAS is ineffective for non-inbred and inbred populations and for inbred lines panel.
Characterization of a putative NsrR homologue inStreptomyces venezuelaereveals a new member of the Rrf2 superfamily
Authors: Munnoch John T. , Martinez Ma Teresa Pellicer , Svistunenko Dimitri A. , Crack Jason C. , Le Brun Nick E. , Hutchings Matthew I. 
Published: April 2016

AbstractMembers of the Rrf2 superfamily of transcription factors are widespread in bacteria but their functions are largely unexplored. The few that have been characterized in detail sense nitric oxide (NsrR), iron limitation (RirA), cysteine availability (CymR) and the iron sulfur (Fe-S) cluster status of the cell (IscR). In this study we combined ChIP- and dRNA-seq within vitrobiochemistry to characterize a putative NsrR homologue inStreptomyces venezuelae.ChIP-seq analysis revealed that rather than regulating the nitrosative stress response likeStreptomyces coelicolorNsrR, Sven6563 binds to a conserved motif at a different, much larger set of genes with a diverse range of functions, including a number of regulators, genes required for glutamine synthesis, NADH/NAD(P)H metabolism, as well as general DNA/RNA and amino acid/protein turn over. Our biochemical experiments further show that Sven6563 has a [2Fe-2S] cluster and that the switch between oxidized and reduced cluster controls its DNA binding activityin vitro.To our knowledge, both the sensing domain and the putative target genes are novel for an Rrf2 protein, suggesting Sven6563 represents a new member of the Rrf2 superfamily. Given the redox sensitivity of its Fe-S cluster we have tentatively named the protein RsrR forRedox sensitive responseRegulator.
Artefactual origin of biphasic cortical spike-LFP correlation
Authors: Okun Michael 
Published: April 2016

AbstractElectrophysiological data acquisition systems introduce various distortions into the signals they record. While such distortions were discussed previously, their effects are often not appreciated. Here I show that the biphasic shape of cortical spike-triggered LFP average (stLFP), reported in multiple studies, is likely an artefact introduced by high-pass filter of the neural data acquisition system when the actual stLFP has a single trough around the zero lag.