bluuebunny/crossref_metadata_2025_split huggingface dataset:
Own and partner pain intensity in older couples: longitudinal effects on depressive symptoms
Authors: Polenick Courtney A. , Brooks Jessica M. , Birditt Kira S. 
Published: May 2017

Abstract
Chronic pain has been linked to depression among individuals and their partners. Yet, little is known about long-term mutual influences between pain intensity and depressive symptoms within couples as they age. Using a nationally representative U.S. sample of wives and husbands aged 50 and older (mean = 64.53, SD = 7.86), this study explored the links between own and partner pain intensity and depressive symptoms across an 8-year period. A total of 963 heterosexual married couples drawn from the Health and Retirement Study completed interviews biennially from 2006 to 2014. Dyadic growth curve models examined mutual associations within couples and controlled for sociodemographic characteristics, length of marriage, and marital quality, along with self-rated health, number of chronic health conditions, and functional disability. For wives and husbands, their own greater baseline pain intensity was significantly linked to their own higher levels of depressive symptoms. Unexpectedly, wives with greater baseline pain intensity reported decreases in their depressive symptoms over time. There were also partner effects such that husbands' greater pain intensity at baseline was associated with increases in wives' depressive symptoms over time. Findings highlight the importance of considering both individual and spousal associations between pain intensity and depressive symptoms in later life. Understanding how individual and couple processes unfold may yield critical insights for the development of intervention and prevention efforts to maintain mental health among older chronic pain patients and their spouses.
Identifying Patient and Provider-specific Gaps in Care Among Patients With Hepatitis B
Authors: Kushner Tatyana , Lam Robert , Gray Daniel L. , Kaplan David E. , Serper Marina 
Published: May 2017

Goals:To examine patient, provider, and health system barriers to clinical follow-up among US veterans with chronic hepatitis B virus (HBV).Background:Studies have demonstrated deficiencies in clinical care and follow-up in HBV; however, patient, provider, and health-system barriers in non-Asian populations are understudied.Study:A retrospective cohort of 517 US veterans with chronic HBV at 3 diverse Veterans Affairs sites from 1999 to 2015. Laboratory testing and completion of clinical appointments were collected for 2 years following initial presentation.Results:Among HBV patients, 36% had drug abuse, 41% alcohol misuse, and 45% had psychiatric disorders. Patients had an average of 4.4 primary care visits within 2 years of the index hepatitis B surface antigen positive result, 38% had psychiatry visits, 21% had a psychiatric hospitalization; 26% saw gastroenterology/hepatology specialists. Within 1 year of the index hepatitis B surface antigen positive result, 75% had alanine aminotransferase testing, 14% had HBV entered into the problem list, and 8% had serologic confirmation. In multivariable analyses, cirrhosis [odds ratio (OR)=3.42; 95% confidence interval (CI), 1.84-6.36] was associated with higher odds of appropriate laboratory testing, alcohol misuse (OR=0.45; 95% CI, 0.29-0.80) was associated lower odds. Cirrhosis (OR=2.03; 95% CI, 1.11-3.72) and ≥2 primary care visits per year (OR=1.06; 95% CI, 1.01-1.11) were associated with higher odds of completing gastroenterology/hepatology consultation, whereas ≥1 psychiatric hospitalization in 2 years was associated with lower odds (OR=0.53; 95% CI, 0.34-0.82).Conclusions:In a diverse cohort of veterans with high psychiatric comorbidity and substance abuse, important patient and provider factors influence appropriate follow-up care. Future studies should evaluate the impact of provider education and care coordination strategies in HBV.
Seroprevalence of antibodies and antigens against hepatitis A–E viruses in refugees and asylum seekers in Germany in 2015
Authors: Jablonka Alexandra , Solbach Philipp , Wöbse Michael , Manns Michael P. , Schmidt Reinhold E. , Wedemeyer Heiner , Cornberg Markus , Behrens Georg M.N. , Hardtke Svenja 
Published: May 2017

Background
Migration because of miscellaneous political crises in countries in the Middle East and Africa is a global challenge for whole Europe from an economic, social, and public health view. There is an urgent need to generate comprehensive, evidence-based data to expedite further screening and vaccination strategies.

Methods
A total of 604 individuals ranging in age from 2 to 68 years who enrolled at a single reception center were tested for the prevalence of serologic markers for hepatitis virus types A, B, C, D, and E (HAV, HBV, HCV, HDV, HEV), respectively.

Results
Anti-HAV antibody prevalence was 91.2 and 70.3% in children younger than 18 years of age. The prevalence of anti-HEV antibodies was 20.1% among the individuals. 3.0% were positive for hepatitis B surface antigen, whereas 15.2% tested positive for anti-hepatitis B core antigen. None of the refugees tested positive for anti-HDV. 14.1% of refugees were vaccinated against hepatitis B and had a protective anti-hepatitis B surface level of at least 10 mIU/ml. Significant differences in vaccination status were found between the regions (Eastern Mediterranean Region with 77/482 (16.0%; 95% confidence interval=12.7–19.3%) versus African Region with 1/55 (1.8%; 95% confidence interval=0–5.0%). The prevalence of anti-HCV antibodies was 1.2% (n=7), with 0.7% HCV RNA positivity; 16.7% of hepatitis B surface antigen-positive individuals were HCV coinfected (n=3).

Conclusion
The prevalence of refugees with previous exposure to hepatitis viruses was higher than that in the general German population, but lower than in other migrant populations in Germany. The vaccination status against hepatitis B was poor.
HIV Infection Increases the Risk of Incident Psoriasis: A Nationwide Population-Based Cohort Study in Taiwan
Authors: Yen Yung-Feng , Jen I-An , Chen Marcelo , Lan Yu-Ching , Lee Chun-Yuan , Chuang Pei-Hung , Lee Yun , Arthur Chen Yi-Ming 
Published: May 2017

Background:HIV can cause an imbalance of T lymphocytes, which may contribute to the onset of psoriasis. However, the association of HIV with incident psoriasis has not been extensively studied.Objectives:The aim of this nationwide population-based cohort study was to determine the association of HIV with incident psoriasis.Methods:Since January 1, 2000, we identified adult people living with HIV/AIDS (PLWHA) from the Taiwan National Health Insurance Research Database. A control cohort without HIV infection, matched for age and sex, was selected for comparison. All patients were followed until December 31, 2012, and observed for the occurrence of psoriasis. The time-dependent Cox proportional hazards model was used to determine the association of HIV with incident psoriasis, while considering death as a competing risk event.Results:Of the 102,070 patients (20,294 PLWHA and 81,776 matched controls), 248 (0.24%) had incident psoriasis during a mean follow-up period of 5.53 years, including 81 (0.40%) PLWHA and 171 (0.21%) controls. After adjusting for age, sex, and comorbidities, HIV infection was found to be an independent risk factor for incident psoriasis (adjusted hazard ratio, 1.80; 95% confidence interval: 1.38 to 2.36).Conclusions:The population of PLWHA is living longer; clinicians need to be aware of their higher risk of psoriasis.
Active HCV Replication but Not HCV or CMV Seropositive Status Is Associated With Incident and Prevalent Type 2 Diabetes in Persons Living With HIV
Authors: De Luca Andrea , Lorenzini Patrizia , Castagna Antonella , Puoti Massimo , Gianotti Nicola , Castelli Francesco , Mastroianni Claudio , Maggiolo Franco , Antinori Andrea , Guaraldi Giovanni , Lichtner Miriam , d'Arminio Monforte Antonella ,   for the ICONA Foundation Study
Published: May 2017

Objective:
To analyze the association between chronic hepatitis C virus (HCV) and cytomegalovirus (CMV) infections with type 2 diabetes in HIV-infected patients.

Methods:
HIV-1-infected patients enrolled in ICONA, a prospective cohort study involving 42 tertiary care centers in Italy, were selected with the following characteristics: for the diabetes incidence analysis, all patients with available CMV IgG results (first available test = baseline) and without type 2 diabetes were followed until onset of type 2 diabetes, last available clinical follow-up, death or September 30, 2014, whichever occurred first; for the prevalence analysis, all ICONA patients were analyzed at their last follow-up visit. Main outcome measures were the new onset of type 2 diabetes (incidence analysis) and the prevalence of type 2 diabetes at last follow-up.

Results:
During 38,062 person-years of follow-up (PYFU) in 6505 individuals, we observed 140 cases of incident type 2 diabetes (Incidence rate 3.7, 95% CI: 3.1 to 4.3, per 1000 PYFU). In a multivariable Poisson regression model, HCV-antibody (Ab)+/HCV RNA+ patients [adjusted relative rate versus HCV-Ab negative 1.73 (95% CI: 1.08 to 2.78)] but not HCV Ab+RNA− or CMV IgG+ patients, had a higher risk of diabetes. Among 12,001 patients, 306 (2.5%) prevalent cases of type 2 diabetes were detected. HCV Ab+RNA+ status was independently associated with prevalent diabetes (adjusted Odds Ratio vs HCV Ab− 2.49; 95% CI: 1.08 to 5.74), whereas HCV-Ab+/HCV RNA− and CMV IgG+ status were not.

Conclusion:
In HIV-infected individuals, active HCV replication but not prior HCV exposure or latent CMV infection is associated with incident and prevalent type 2 diabetes.
Novel Adjunct Drugs Reverse Endothelial Glycocalyx Damage After Hemorrhagic Shock in Rats
Authors: Torres Filho Ivo P. , Torres Luciana N. , Salgado Christi , Dubick Michael A. 
Published: May 2017

ABSTRACT

Introduction:
There is interest in the small-volume therapeutic use of adjunct drugs for treating hemorrhagic shock (HS). However, critical information is only partially available on mechanisms of action of promising compounds such as adenosine-lidocaine-magnesium (ALM), beta-hydroxybutyrate plus melatonin (BHB/M), and poloxamer 188 (P-188). Therefore, we tested the hypothesis that these adjuncts would reverse HS-induced damage to microvascular endothelial glycocalyx and hemodynamics.

Methods:
After baseline, 40% of total blood volume was removed from 44 anesthetized Sprague–Dawley male rats. One hour after hemorrhage, animals were resuscitated using ALM, BHB/M, or P-188 followed by lactated Ringer's (LR, 15 mL/kg). Control animals were not treated (SHAM) or received LR alone. Sampled blood was used to quantify shed syndecan-1 in plasma; multiple systemic physiological parameters were recorded. In vivo glycocalyx thickness, microvascular permeability, and microhemodynamics were evaluated in >200 cremaster venules using intravital videomicroscopy.

Results:
Compared with baseline, resuscitation using adjuncts was associated with glycocalyx restoration of 97 ± 9% (ALM), 75 ± 8% (BHB/M), and 85 ± 5% (P-188): significantly higher than LR-only (56 ± 4%). Significantly better permeability, similar to SHAM values, was measured after ALM and P-188, and low plasma syndecan-1 levels were measured after resuscitation with all adjuncts. Microhemodynamic changes were relatively small while systemic parameters such as mean arterial pressure and lactate improved but remained below or above the baseline, respectively, as expected from this hypotensive resuscitation model.

Conclusion:
The drugs ALM, BHB/M, and P-188 provide beneficial effects as adjuncts to hypotensive resuscitation in this HS model by mechanisms involving changes at the microvascular level including the glycocalyx.
Reparameterization of PAM50 expression identifies novel breast tumor dimensions and leads to discovery of a breast cancer susceptibility locus at 12q15
Authors: Madsen Michael J , Knight Stacey , Sweeney Carol , Factor Rachel , Salama Mohamed , Rajamanickam Venkatesh , Welm Bryan E , Arunachalam Sasi , Jones Brandt , Rowe Kerry , Cessna Melissa , Thomas Alun , Kushi Lawrence H , Caan Bette J , Bernard Philip S , Camp Nicola J 
Published: May 2017

AbstractIt is well-known that breast tumors exhibit different expression patterns that can be used to assign intrinsic subtypes – the PAM50 assay, for example, categorizes tumors into: Luminal A, Luminal B, HER2-enriched and Basal-like – yet tumors are often more complex than categorization can describe. We used 911 sporadic breast tumors to reparameterize expression from the PAM50 genes to five orthogonal tumor dimensions using principal components (PC). Three dimensions captured intrinsic subtype, two dimensions were novel, and all replicated in 945 TCGA tumors. By definition dimensions are independent, an important attribute for inclusion in downstream studies exploring effects of tumor diversity. One application where tumor subtyping has failed to provide impact is susceptibility genetics. Germline genetic heterogeneity reduces power for gene-finding. The identification of heritable tumor characteristics has potential to increase homogeneity. We compared 238 breast tumors from high-risk pedigrees not attributable toBRCA1orBRCA2to 911 sporadic breast tumors. Two PC dimensions were significantly enriched in the pedigrees (intrinsic subtypes were not). We performed proof-of-concept gene-mapping in one enriched pedigree and identified a 0.5 Mb genomewide significant region at 12q15 that segregated to the 8 breast cancer cases with the most extreme PC tumors through 32 meioses (p=2.6×10−8). In conclusion, our study: suggests a new approach to describe tumor diversity; supports the hypothesis that tumor characteristics are heritable providing new avenues for germline studies; and proposes a new breast cancer locus. Reparameterization of expression patterns may similarly inform other studies attempting to model the effects of tumor heterogeneity.
Mitochondrial pseudogenes suggest repeated inter-species hybridization among direct human ancestors
Authors: Popadin Konstantin , Gunbin Konstantin , Peshkin Leonid , Annis Sofia , Fleischmann Zoe , Kraytsberg Genya , Markuzon Natalya , Ackermann Rebecca R. , Khrapko Konstantin 
Published: May 2017

AbstractThe hypothesis that the evolution of humans involved hybridization between diverged species has been actively debated in recent years. We present novel evidence in support of this hypothesis: the analysis of nuclear pseudogenes of mtDNA (“NUMTs”). NUMTs are considered “mtDNA fossils”, as they preserve sequences of ancient mtDNA and thus carry unique information about ancestral populations. Our comparison of a NUMT sequence shared by humans, chimpanzees, and gorillas with their mtDNAs implies that, around the time of divergence between humans and chimpanzees, our evolutionary history involved the interbreeding of individuals whose mtDNA had diverged as much as ~4.5 Myr prior. This large divergence suggests a distant interspecies hybridization. Additionally, analysis of two other NUMTs suggests that such events occurred repeatedly. Our findings suggest a complex pattern of speciation in primate human ancestors and provide a potential explanation for the mosaic nature of fossil morphology found at the emergence of the hominin lineage.
High-risk Autism Spectrum Disorder Utah pedigrees: a novel Shared Genomic Segments analysis
Authors: Darlington Todd M , Bilder Deborah , Morgan Jubel , Jerominski Leslie , Rajamanickam Venkatesh , Sargent Rob , Camp Nicola J , Coon Hilary H 
Published: May 2017

AbstractProgress in gene discovery for Autism Spectrum Disorder (ASD) has been rapid over the past decade, with major successes in validation of risk of predominantly rare, penetrant,de novoand inherited mutations in over 100 genes (de Rubies et al., 2015; Sanders et al., 2015). However, the majority of individuals with ASD diagnoses do not carry a rare, penetrant genetic risk factor. In fact, recent estimates suggest that most of the genetic liability of ASD is due to as yet undiscovered common, less penetrant inherited variation (Gaugler et al., 2014) which is much more difficult to detect. The study of extended, high-risk families adds significant information in our search for these common inherited risk factors. Here, we present results of a new, powerful pedigree analysis method (Shared Genomic Segments—SGS) on three large families from the Utah Autism Research Program. The method improves upon previous methods by allowing for within-family heterogeneity, and identifying exact region boundaries and subsets of cases who share for targeted follow-up analyses. Our SGS analyses identified one genome-wide significant shared segment on chromosome 17 (q21.32, p=1.47x10-8). Additional regions with suggestive evidence were identified on chromosomes 3, 4, 6, 8, 11, 13, 14, 15, and 18. Several of these segments showed evidence of sharing across families. Genes of interest in these regions includeATP8A1,DOCK3,CACNA2D2,ITGB3,AMBRA1,FOLH1,DGKZ,MTHFS,ARNT2,BTN2A2,BTN3A1,BTN3A3,BTN2A1, andBTN1A1. We are exploring multiple other lines of evidence to follow up these implicated regions and genes.
MutPred2: inferring the molecular and phenotypic impact of amino acid variants
Authors: Pejaver Vikas , Urresti Jorge , Lugo-Martinez Jose , Pagel Kymberleigh A. , Lin Guan Ning , Nam Hyun-Jun , Mort Matthew , Cooper David N. , Sebat Jonathan , Iakoucheva Lilia M. , Mooney Sean D. , Radivojac Predrag 
Published: May 2017

AbstractWe introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions, generates molecular mechanisms potentially causative of disease, and returns interpretable pathogenicity score distributions on individual genomes. While its prioritization performance is state-of-the-art, a novel and distinguishing feature of MutPred2 is the probabilistic modeling of variant impact on specific aspects of protein structure and function that can serve to guide experimental studies of phenotype-altering variants. We demonstrate the utility of MutPred2 in the identification of the structural and functional mutational signatures relevant to Mendelian disorders and the prioritization ofde novomutations associated with complex neurodevelopmental disorders. We then experimentally validate the functional impact of several variants identified in patients with such disorders. We argue that mechanism-driven studies of human inherited diseases have the potential to significantly accelerate the discovery of clinically actionable variants.Availability:http://mutpred.mutdb.org/
Epigenome-wide association study of asthma and wheeze in childhood and adolescence
Authors: Arathimos Ryan , Suderman Matthew , Sharp Gemma C , Burrows Kimberley , Granell Raquel , Tilling Kate , Gaunt Tom R , Henderson John , Ring Susan , Richmond Rebecca , Relton Caroline L 
Published: May 2017

AbstractAsthma heritability has only been partially explained by genetic variants and is known to be sensitive to environmental factors, implicating epigenetic modifications such as DNA methylation in its pathogenesis.Using data collected in the Avon Longitudinal Study of Parents and Children (ALSPAC), we assessed associations of asthma and wheeze with DNA methylation at 7.5 years and 16.5 years, at over 450,000 CpG sites in DNA from the peripheral blood of approx. 1000 participants. We used Mendelian randomization (MR), a method of causal inference that uses genetic variants as instrumental variables, to infer the direction of association between DNA methylation and asthma.We identified 302 CpGs associated with current asthma status (FDR-adjusted P-value <0.05) and 445 with current wheeze status at 7.5 years, with substantial overlap between the two. Genes annotated to the 302 associated CpGs were enriched for pathways related to movement of cellular/subcellular components, locomotion, interleukin-4 production and eosinophil migration. All associations attenuated when adjusted for eosinophil and neutrophil cell count estimates. At 16.5 years, two sites were associated with current asthma after adjustment for cell counts. The CpGs mapped to theAP2A2andIL5RAgenes, with a -2.32 [95% CI -1.47,-3.18] and -2.49 [95% CI -1.56,-3.43] change in percentage methylation in asthma cases respectively. Two-sample bi-directional MR indicated a causal effect of asthma on DNA methylation at several CpG sites at 7.5 years. However, associations did not persist after adjustment for multiple testing. There was no evidence of a causal effect of asthma on DNA methylation at either of the two CpG sites at 16.5 years.The majority of observed associations are driven by higher eosinophil cell counts in asthma cases, acting as an intermediate phenotype, with important implications for future studies of DNA methylation in atopic diseases.
A comparative study of endoderm differentiation in humans and chimpanzees
Authors: Blake Lauren E. , Thomas Samantha M. , Blischak John D. , Hsiao Chiaowen Joyce , Chavarria Claudia , Myrthil Marsha , Gilad Yoav , Pavlovic Bryan J. 
Published: May 2017

AbstractThere is substantial interest in the evolutionary forces that shaped the regulatory framework that is established in early human development. Progress in this area has been slow because it is difficult to obtain relevant biological samples. Inducible pluripotent stem cells (iPSCs) provide the ability to establish in vitro models of early human and non-human primate developmental stages. Using matched iPSC panels from humans and chimpanzees, we comparatively characterized gene regulatory changes through a four-day timecourse differentiation of iPSCs (day 0) into primary streak (day 1), endoderm progenitors (day 2), and definitive endoderm (day 3). As might be expected, we found that differentiation stage is the major driver of variation in gene expression levels, followed by species. We identified thousands of differentially expressed genes between humans and chimpanzees in each differentiation stage. Yet, when we considered gene-specific dynamic regulatory trajectories throughout the timecourse, we found that 75‥ of genes, including nearly all known endoderm developmental markers, have similar trajectories in the two species. Interestingly, we observed a marked reduction of both intra-and inter-species variation in gene expression levels in primitive streak samples compared to the iPSCs, with a recovery of regulatory variation in endoderm progenitors. The reduction of variation in gene expression levels at a specific developmental stage, paired with overall high degree of conservation of temporal gene regulation, is consistent with the dynamics of developmental canalization. Overall, we conclude that endoderm development in iPSC-based models are highly conserved and canalized between humans and our closest evolutionary relative.