bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Intimate Partner Violence and Antiretroviral Therapy Initiation Among Female Sex Workers Newly Diagnosed With HIV in Zambia: A Prospective Study
Authors: Oldenburg Catherine E. , Ortblad Katrina F. , Chanda Michael M. , Mwale Magdalene , Chongo Steven , Kanchele Catherine , Kamungoma Nyambe , Fullem Andrew , Bärnighausen Till 
Published: August 2018

Background:
Intimate partner violence (IPV) is common among female sex workers (FSW) globally. Here, we prospectively assessed the relationship between IPV and engagement in HIV care in a cohort of FSW who had been newly diagnosed with HIV.

Methods:
Data arose from the Zambian Peer Educators for HIV Self-Testing study, a randomized controlled trial of HIV self-test distribution among FSW in 3 transit towns in Zambia. Participants were self-reported to be HIV-uninfected or unaware of their status at baseline. IPV in the previous 12 months was assessed at baseline. At 4 months, participants were asked the results of their last HIV test and those who reported testing positive were asked whether they had engaged in HIV-related care and started antiretroviral therapy (ART).

Results:
Of 964 participants, 234 (24.3%) reported that they were living with HIV at 4 months. Of these 234 participants, 142 (60.7%) reported a history of IPV (past 12 months) at baseline and at 4 months, 152 (65.0%) reported that they were in HIV-related care, and 132 (56.7%) reported that they had initiated ART. Participants who reported IPV had significantly reduced odds of engagement in care (adjusted odds ratio = 0.48, 95% confidence interval: 0.26 to 0.91) and ART initiation (adjusted odds ratio = 0.40, 95% confidence interval: 0.22 to 0.72).

Conclusions:
FSW living with HIV in Zambia reported very high rates of IPV. Structural and individual interventions for violence prevention are urgently needed to better protect this population. Given the strong negative relationship between IPV and engagement in HIV-related care, such interventions could also substantially improve HIV-related health outcomes.
Angiostrongylus cantonensis in travelers: clinical manifestations, diagnosis, and treatment
Authors: Ansdell Vernon , Wattanagoon Yupaporn 
Published: August 2018

Purpose of review

Angiostrongylus cantonensis eosinophilic meningitis is a neglected, yet important emerging disease, which has been increasingly recognized in travelers. In this review, we describe the occurrence of the disease in travelers, sources of infection, clinical manifestations, diagnosis, and currently recommended treatment.

Recent findings
Various intermediate hosts and/or paratenic hosts can be the source of infection in humans. Serological tests for antibody may be negative early in the course of the disease but PCR for antigen detection in the CSF has recently been developed and may help to make the diagnosis at an earlier stage. High-dose corticosteroids (e.g. prednisolone 60 mg per day for at least 1–2 weeks) are currently the recommended treatment. Efficacy and safety of antihelminthic drugs for treatment remains controversial because of theoretical concerns that they may worsen the inflammatory response to dead and dying worms. Previous clinical trials were conducted with small numbers of participants and were underpowered. Further well designed clinical trials are urgently needed.

Summary
Awareness about increasing numbers of A. cantonensis eosinophilic meningitis in travelers is very important. Travelers should be advised about possible sources of infection. Diagnosis should be confirmed by antigen or antibody detection in blood or CSF. High-dose corticosteroids are the recommended treatment. The efficacy of various antihelminthic drugs is unproven. A large-scale, double-blind, randomized, controlled trial of antihelminthic drug involving antihelminthic drugs such as albendazole is necessary to prove the efficacy before formally advocating their use on a regular basis
The relationship between muscle mass and function in cancer cachexia: smoke and mirrors?
Authors: Ramage Michael I. , Skipworth Richard J.E. 
Published: August 2018

Purpose of reviewRandomized clinical trials of cancer cachexia interventions are based on the premise that an increase in the muscle mass of patients is associated with consequent improvements in muscle function, and ultimately, quality of life. However, recent trials that have succeeded in demonstrating increases in lean body mass have been unable to show associated increases in patient physical function. In this review, we examine the potential causes for this lack of association between muscle mass and function in cancer cachexia, paying particular attention to those factors that may be at play when using body composition analysis techniques involving cross-sectional imaging. Moreover, we propose a new population-specific model for the relationship between muscle mass and physical function in patients with cancer cachexia.Recent findingsThe ROMANA 1 and 2 trials of anamorelin (a novel ghrelin agonist) and the POWER 1 and 2 trials of enobosarm (a selective androgen receptor modulator) were able to demonstrate improvements in patient lean body mass, but not the functional co-primary endpoints of handgrip strength and stair climb power, respectively. We report similar confirmatory findings in other studies, and describe potential reasons for these observations.SummaryThe relationship between muscle mass and muscle function is complex and unlikely to be linear. Furthermore, the relationship is influenced by the techniques used to assess nutritional endpoints [e.g. computed tomography (CT)]; the nature of the chosen physical function outcome measures; and the sex and severity of the recruited cachectic patients. Such factors need to be considered when designing intervention trials for cancer cachexia with functional endpoints.
Impact of Deceased Donor Cardiac Arrest Time on Postpancreas Transplant Graft Function and Survival
Authors: Schroering Joel R. , Mangus Richard S. , Powelson John A. , Fridell Jonathan A. 
Published: August 2018

Introduction
Transplantation of pancreas allografts from donors that have experienced preprocurement cardiopulmonary arrest (PPCA) is not common, though use of PPCA grafts is routine in liver and kidney transplantation. This article reviews a large number of PPCA pancreas grafts at a single center and reports posttransplant outcomes including early graft dysfunction, length of hospital stay, rejection, and early and late graft survival.

Methods
Preprocurement cardiopulmonary arrest, arrest time, and donor and recipient pancreatic enzyme levels were collected from electronic and written medical records. The PPCA donors were stratified into 4 groups: none, less than 20 minutes, 20-39 minutes, and 40 minutes or greater. Graft survival was assessed at 7 and 90 days and at 1 year. Long-term graft survival was assessed by Cox regression analysis.

Results
The records of 606 pancreas transplants were reviewed, including 328 (54%) simultaneous pancreas and kidney transplants. Preprocurement cardiopulmonary arrest occurred in 176 donors (29%; median time, 20 minutes). Median peak donor lipase was higher in PPCA donors (40 μ/L vs 29 μ/L, P = 0.02). Posttransplant, peak recipient amylase, and lipase levels were similar (P = 0.63). Prolonged arrest time (>40 minutes) was associated with higher donor peak lipase and lower recipient peak amylase (P = 0.05 for both). Stratified by donor arrest time, there was no difference in 7-day, 90-day, or 1-year graft survival. Cox regression comparing the 4 groups demonstrated no statistical difference in 10-year survival.

Conclusions
These results support transplantation of pancreas allografts from PPCA donors. Prolonged asystole was associated with higher peak donor serum lipase but lower peak recipient serum amylase. There were no differences in allograft survival.
Development of an environmental DNA method for monitoring fish communities: ground truthing in diverse lakes with characterised fish faunas
Authors: Li Jianlong , Hatton-Ellis Tristan W. , Lawson Handley Lori-Jayne , Kimbell Helen S. , Benucci Marco , Peirson Graeme , Hänfling Bernd 
Published: August 2018

AbstractAccurate, cost-effective monitoring of fish is required to assess the quality of lakes under the European Water Framework Directive (WFD). Recent studies have shown that environmental DNA (eDNA) metabarcoding is an effective and non-invasive method, which can provide semi-quantitative information on fish communities in large lakes.This study further investigated the potential of eDNA metabarcoding as a tool for WFD status assessment by collecting and analysing water samples from eight Welsh lakes and six meres in Cheshire, England, with well described fish faunas. Water samples (N= 252) were assayed using two mitochondrial DNA regions (Cytb and 12S rRNA).eDNA sampling indicated the presence of very similar species in the lakes compared to those expected on the basis of existing and historical information. In total, 24 species were detected with a total of 111 species occurrences in the lakes studied using eDNA. Secondly, there was a significant positive correlation between expected faunas and eDNA data in terms of confidence of species occurrence (Spearman’sr= 0.74,df= 109,p<; 0.001). Thirdly, eDNA data can estimate relative abundance with the standard five-level classification scale (“DAFOR”). Lastly, four ecological fish communities were characterised using eDNA data which agrees with the pre-defined lake types according to environmental characteristics.Synthesis and applications. This study provides further evidence that eDNA metabarcoding could be a powerful and non-invasive monitoring tool for WFD purpose in a wide range of lake types, considerably outperforming other methods for community level analysis.
Investigating functional brain network integrity using a traditional and novel diagnostic system for neurodevelopmental disorders
Authors: Dajani Dina R. , Burrows Catherine A. , Odriozola Paola , Baez Adriana , Nebel Mary Beth , Mostofsky Stewart H. , Uddin Lucina Q. 
Published: August 2018

AbstractBackgroundCurrent diagnostic systems for neurodevelopmental disorders do not have clear links to underlying neurobiology, limiting their utility in identifying targeted treatments for individuals. Several factors contribute to this issue, including the use of small samples in neuroimaging research and heterogeneity within diagnostic categories. Here, we aimed to investigate differences in functional brain network integrity between traditional diagnostic categories (autism spectrum disorder [ASD], attention-deficit/hyperactivity disorder [ADHD], typically developing [TD]) and carefully consider the impact of comorbid ASD and ADHD on functional brain network integrity in a large sample. We also assess the neurobiological validity of a novel, potential alternative nosology based on behavioral measures of executive function.MethodFive-minute resting-state fMRI data were obtained from 168 children (128 boys, 40 girls) with ASD, ADHD, comorbid ASD and ADHD, and TD children. Independent component analysis and dual regression were used to compute within- and between-network functional connectivity metrics at the individual level.ResultsNo significant group differences in within- nor between-network functional connectivity were observed between traditional diagnostic categories (ASD, ADHD, TD) even when stratified by comorbidity (ASD+ADHD, ASD, ADHD, TD). Similarly, subgroups classified by executive functioning levels showed no group differences.ConclusionsUsing clinical diagnosis and behavioral measures of executive function, no group differences were observed among the categories examined. Therefore, we suggest that brain imaging metrics may more effectively define clinical subgroups than behavioral metrics, and may contribute to the establishment of a neurobiologically valid nosology for neurodevelopmental disorders.
Quantitative mass spectrometry to interrogate proteomic heterogeneity in metastatic lung adenocarcinoma and validate a novel somatic mutation CDK12-G879V
Authors: Zhang Xu , Nguyen Khoa Dang , Rudnick Paul , Roper Nitin , Kawaler Emily , Maity Tapan K. , Asasthi Shivangi , Gao Shaojian , Biswas Romi , Venugopalan Abhilash , Cultraro Constance M. , Fenyö David , Guha Udayan 
Published: August 2018

AbstractLung cancer is the leading cause of cancer death both in men and women. Tumor heterogeneity is an impediment to targeted treatment of all cancers, including lung cancer. Here, we sought to characterize changes in tumor proteome and phosphoproteome by longitudinal, prospective collection of tumor tissue of an exceptional responder lung adenocarcinoma patient who survived with metastatic lung adenocarcinoma for more than seven years with HER2-directed therapy in combination with chemotherapy. We employed “Super-SILAC” and TMT labeling strategies to quantify the proteome and phosphoproteome of a lung metastatic site and ten different metastatic progressive lymph nodes collected across a span of seven years, including five lymph nodes procured at autopsy. We identified specific signaling networks enriched in lung compared to the lymph node metastatic sites. We correlated the changes in protein abundance with changes in copy number alteration (CNA) and transcript expression. To further interrogate the mass spectrometry data, patient-specific database was built incorporating all the somatic variants identified by whole genome sequencing (WGS) of genomic DNA from the lung, one lymph node metastatic site and blood. An extensive validation pipeline was built for confirmation of variant peptides. We validated 360 spectra corresponding to 55 germline and 6 somatic variant peptides. Targeted MRM assays demonstrated expression of two novel variant somatic peptides, CDK12-G879V and FASN-R1439Q, with expression in lung and lymph node metastatic sites, respectively. CDK12 G879V mutation likely results in a nonfunctional CDK12 kinase and chemotherapy susceptibility in lung metastatic sites. Knockdown of CDK12 in lung adenocarcinoma cells results in increased chemotherapy sensitivity, explaining the complete resolution of the lung metastatic sites in this patient.
A pipeline for rapidly generating genetically engineered mouse models of pancreatic cancer using invivoCRISPRCas9 mediated somatic recombination
Authors: Ideno Noboru , Yamaguchi Hiroshi , Okumara Takashi , Huang Jonathon , Brun Mitchel J. , Ho Michelle L. , Suh Junghae , Gupta Sonal , Maitra Anirban , Ghosh Bidyut 
Published: August 2018

ABSTRACTGenetically engineered mouse models (GEMMs) that recapitulate the major genetic drivers in pancreatic ductal adenocarcinoma (PDAC) have provided unprecedented insights into the pathogenesis of this lethal neoplasm. Nonetheless, generating an autochthonous model is an expensive, time consuming and labor intensive process, particularly when tissue specific expression or deletion of compound alleles are involved. In addition, many of the current PDAC GEMMs cause embryonic, pancreas-wide activation or loss of driver alleles, neither of which reflects the cognate human disease scenario. The advent of CRISPR/Cas9 based gene editing can potentially circumvent many of the aforementioned shortcomings of conventional breeding schema, but ensuring the efficiency of gene editingin vivoremains a challenge. Here we have developed a pipeline for generating PDAC GEMMs of complex genotypes with high efficiency using a single “workhorse” mouse strain expressing Cas9 in the adult pancreas under ap48promoter. Using adeno-associated virus (AAV) mediated delivery of multiplexed guide RNAs (sgRNAs) to the adult murine pancreas ofp48-Cre; LSL-Cas9mice, we confirm our ability to express an oncogenicKrasG12Dallele through homology-directed repair (HDR), in conjunction with CRISPR-induced disruption of cooperating alleles (Trp53, Lkb1andArid1A). The resulting GEMMs demonstrate a spectrum of precursor lesions (pancreatic intraepithelial neoplasia [PanIN] or Intraductal papillary mucinous neoplasm [IPMN] with eventual progression to PDAC. Next generation sequencing of the resulting murine PDAC confirms HDR of oncogenicKrasG12Dallele at the endogenous locus, and insertion deletion (“indel”) and frameshift mutations of targeted tumor suppressor alleles. By using a single “workhorse” mouse strain and optimal AAV serotype forin vivogene editing with combination of driver alleles, we have created a facile autochthonous platform for interrogation of the PDAC genome.
Analysis of Polygenic Score Usage and Performance in Diverse Human Populations
Authors: Duncan LE , Shen H , Gelaye B , Ressler KJ , Feldman MW , Peterson RE , Domingue BW 
Published: August 2018

AbstractStudies examining relationships between genotypic and phenotypic variation have historically been carried out on people of European ancestry. Efforts are underway to address this limitation, but until they succeed, the legacy of a Euro-centric bias will continue to hinder research, including the use of polygenic scores, which are individual-level metrics of genetic risk. Ongoing debate surrounds the generalizability of polygenic scores based on genome-wide association studies (GWAS) conducted in European ancestry samples, to non-European ancestry samples. We analyzed the first decade of polygenic scoring studies (2008-2017, inclusive), and found that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants. Only 3.8% of studies were carried out on samples of African, Hispanic, or Indigenous peoples. We find that effect sizes for European ancestry-derived polygenic scores are only 36% as large in African ancestry samples, as in European ancestry samples (t=−10.056, df=22, p=5.5×10−10). Analyzing global populations, we show that relationships between height polygenic scores and height are highly dependent on methodological choices in polygenic score construction, highlighting the need for caution in interpreting population level differences in distributions of polygenic scores, as currently calculated. These findings bolster the rationale for large-scale GWAS in diverse human populations and highlight the need for better handling of linkage disequilibrium and variant frequencies when applying scores to non-European samples.
Nascent chromatin occupancy profiling reveals locus and factor specific chromatin maturation dynamics behind the DNA replication fork
Authors: Gutiérrez Mónica P. , MacAlpine Heather K. , MacAlpine David M. 
Published: August 2018

AbstractProper regulation and maintenance of the epigenome is necessary to preserve genome function. However, in every cell division, the epigenetic state is disassembled and then re-assembled in the wake of the DNA replication fork. Chromatin restoration on nascent DNA is a complex and regulated process that includes nucleosome assembly and remodeling, deposition of histone variants, and the re-establishment of transcription factor binding. To study the genome-wide dynamics of chromatin restoration behind the DNA replication fork, we developed Nascent Chromatin Occupancy Profiles (NCOPs) to comprehensively profile nascent and mature chromatin at nucleotide resolution. While nascent chromatin is inherently less organized than mature chromatin, we identified locus specific differences in the kinetics of chromatin maturation that were predicted by the epigenetic landscape, including the histone variant H2A.Z which marked loci with rapid maturation kinetics. The chromatin maturation at origins of DNA replication was dependent on whether the origin underwent initiation or was passively replicated from distal-originating replication forks suggesting distinct chromatin assembly mechanisms between activated and disassembled pre-replicative complexes. Finally, we identified sites that were only occupied transiently by DNA-binding factors following passage of the replication fork which may provide a mechanism for perturbations of the DNA replication program to shape the regulatory landscape of the genome.
Viral Infection Skews Immunoglobulin Light Chain Repertoire Diversity
Authors: Schwartz John C. , Murtaugh Michael P. 
Published: August 2018

AbstractAntibody responses are fundamentally important to effector and memory mechanisms of disease resistance. Antibody repertoire diversity and its response to natural infection is poorly understood, yet is a prerequisite for molecular and structural elucidation of functionally protective immunity to viral infections. Using a swine model of mammalian viral infection, we observed marked changes following infection with the major porcine pathogen, porcine reproductive and respiratory syndrome virus (PRRSV). Deep sequencing of >516,000 light chain VJ mRNA genes showed that, similar to humans, swine utilize both lambda and kappa loci equivalently. However, V and J gene usage were highly restricted; ≥99% of lambda light chains were IGLV3 and IGLV8 family members joined to IGLJ2 or IGLJ3, and 100% of kappa locus transcripts were IGKV1 or IGKV2 with only IGKJ2. Complementarity-determining region (CDR) variation was limited. Nevertheless, total diversity richness estimates were 2.3 × 105 for lambda and 1.5 × 105 for kappa, due in part to extensive germline variation in framework regions and allelic variation. Infection by PRRSV reduced total richness due to expression of several highly abundant clonal populations. Antibody light chain repertoires differed substantially among individuals, thus illustrating extensive potential variation in immune response in outbred populations. These findings demonstrate that individual variation in light chain repertoires may be an important component of variable antibody responses to infection and vaccination, and that swine are a relevant model of human antibody diversification in which the immune response capacity is critical to understanding individual variation in immune protection against disease.Conflict of interest statementThe authors declare no conflicts of interest.Highlightsλ and κ light chain diversity is equivalent to heavy chain diversityHigh diversity is present despite limited gene segment usagePRRSV infection increases abundance of dominant λ and κ VJ clonesHigh levels of variation are present among animals
Short Term Evolutionary Dynamics ofEscherichia Coliin Different Carbon Environments
Authors: Choudhury Debika , Saini Supreet 
Published: August 2018

AbstractStarting from a parentalE. coliK-12 MG1655 strain, we evolve cells in five different carbon environments-glucose, arabinose, xylose, rhamnose, and a mixture of these four sugars (in a predefined ratio) for approximately 2,000 generations. At the end of the adaptation period, we quantify and compare growth dynamics of the strains in a variety of environments. The evolved strains show no specialized adaptation towards growth in the carbon medium in which they were evolved. Rather, in all environments, the evolved strains exhibited a reduced lag phase and an increased growth rate. Sequencing results reveal that these dynamical properties are not introduced via mutations in the precise loci associated with utilization of the sugar in which the bacterium was evolved in. These phenotypic changes are rather likely introduced via mutationselsewhere onthe genome. Sugar systems are known to exhibit hierarchy in utilization. Evolution in a defined environment, in our experimental framework, does not alter this hierarchy.