bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of Treatment-experienced HIV-infected African Children and Adolescents Initiating Darunavir and/or Etravirine-based Antiretroviral Treatment
Authors: Corrigan Bethany , Mukui Irene , Mulenga Lloyd , Mthethwa Nobuhle , Letsie Mosilinyane , Bruno Stephanie , Rakhmanina Natella 
Published: November 2017

Background:
Data are limited on the selection and sequencing of second-line and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program.

Methods:
This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV-based and/or ETR-based ART. Descriptive statistics were used.

Results:
Study enrolled 48 patients (45.8% women; median age = 15 years [interquartile range 17.7–10.3]) at 9 clinical sites in Zambia, Swaziland, Kenya and Lesotho. The majority (87.5%; n = 42) had received ≥2 prior ART regimens; most (81.2%) had received lopinavir/ritonavir-based ART before switch. All patients had detectable HIV RNA (median = 56,653 copies/mL). Forty seven patients (98.9%) had HIV genotype results: 41 (87.2%) had ≥1 nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistance mutation (RM), predominantly M184V (76.6%; n = 36); 31 (65.9%) had ≥1 non-NRTI-RM, including 27 (57.4%) with ≥1 ETR-RM; 30 (63.8%) had ≥3 protease inhibitor RM, including 20 (42.6%) with ≥1 DRV-RM. For new ART regimens, DRV and raltegravir were most frequently prescribed (83.3%; n = 40 on DRV and raltegravir, each). Eighteen patients (37.5%) were initiated on the NRTI-sparing ART.

Conclusions:
In our study, a significant proportion of treatment-experienced African children and adolescents had one or more DRV-RM and ETR-RM. For the new regimen, more than a third of pediatric patients failing second-line ART were prescribed NRTI-sparing regimens. Better understanding of the current approaches to pediatric ART sequencing in resource-limited settings is needed.
Lessons Learned From iCare: A Postexamination Text-Messaging-Based Program With Sexual Assault Patients
Authors: Hicks Danielle L. , Patterson Debra , Resko Stella 
Published: November 2017

ABSTRACT

Background:
Although beneficial, few sexual assault patients seek follow-up healthcare or counseling after a medical forensic examination. Mobile technology interventions may help patients engage in postcare, but there is a dearth of research on patients’ utilization of these interventions. The current study examines patients’ engagement with a 4-week postassault text message program (iCare), which assessed patients’ safety and well-being, if they needed assistance with accessing nonoccupational postexposure prophylaxis, or scheduling appointments for follow-up pregnancy and sexually transmitted infection testing, and their experience with the criminal justice system.

Methods:
This pilot study collected data from 40 adult patient records and texting communications between the nurse and patients. We utilized descriptive statistics to examine patient utilization of the program.

Results:
Sixty-five percent of the patients responded at least once during the program, but only two responded to every text. Nearly a quarter of the patients (22.5%) requested the texts to stop before the end of the program. A larger portion of the patients (42.5%) did not opt out but stopped replying by the third message. The program appeared to be helpful for increasing the amount of communication between the nurse and the patient, but patients rarely utilized the nurse’s offers of assistance (e.g., counseling, advocacy).

Discussion:
Text interventions appear to be effective for relaying information but may be limited for increasing postexamination service utilization for sexual assault patients. Future research should examine areas of patient needs in the weeks and months postexamination that can be addressed in text interventions.
Accuracy of First-Trimester Combined Test in Screening for Trisomies 21, 18 and 13
Authors: Santorum M. , Wright D. , Syngelaki A. , Karagioti N. , Nicolaides K. H. 
Published: November 2017

(Abstracted from Ultrasound Obstet Gynecol 2017;49:714–720)
In the last few years, major accomplishments have been made in the screening of trisomies through the development of maternal blood cell-free DNA (cfDNA) analysis. In a previous study, this group published a statistical algorithm used to calculate patient's risks for trisomies 21, 18, and 13 based on patient-specific information obtained from a combined clinical test.
Nontraumatic Convexal Subarachnoid Hemorrhage Accompanied by Sylvian Hematoma
Authors: Ninomiya Kenji , Fukasawa Maki , Kawakami Yuka , Fuke Chiaki , Miyazaki Tetsuji 
Published: November 2017

Abstract
We describe an autopsy case of nontraumatic convexal subarachnoid hemorrhage (cSAH) accompanied by sylvian hematoma. A woman in her 50s was found dead in her house. On autopsy, massive cSAH accompanied by sylvian hematoma was observed. Because of the absence of subarachnoid hemorrhage (SAH) in the basal cistern, initial suspicion was that of a traumatic SAH. After a detailed investigation, a ruptured cerebral aneurysm of the distal middle cerebral artery was found in the hematoma, and the cSAH in this case was confirmed to be endogenous. Convexal subarachnoid hemorrhages typically result from traumatic injury, whereas endogenous cSAHs are exceedingly rare. Autopsy findings of a sylvian hematoma with SAH may result from endogenous hemorrhage from ruptured aneurysm of the distal middle cerebral artery. Detailed investigation of the hematoma may help identify the culprit lesion and help arrive at the correct postmortem diagnosis.
Deaths Associated With Brotizolam Poisoning From a Single Drug Overdose
Authors: Sakai Kentaro , Saito Kazuyuki , Takada Aya , Hikiji Wakako , Kikuchi Yosuke , Fukunaga Tatsushige 
Published: November 2017

Abstract
Brotizolam is a short-acting hypnotic in the benzodiazepine family, and fatal poisonings by an overdose of brotizolam are rare. This report describes 4 cases of deaths associated with brotizolam poisoning from a single drug overdose. The ages ranged from 51 to 90 years, and the postmortem interval between death and tissue sampling was 1.5 to 2.5 days. These deaths were classified as 1 homicide and 3 suicides. The concentration of the brotizolam ranged from 0.05 to 0.21 mg/L in the blood samples. Ethanol, which could cause mild alcohol intoxication, was detected in the blood samples from 2 cases. Postmortem examinations did not find any significant pathologic conditions, except for a case of death by drowning in a bathtub due to brotizolam poisoning. These 4 cases suggest that a brotizolam overdose should not be underestimated in terms of its fatal effects, particularly when situations involve alcohol intoxication, injury subsequent to the poisoning, or underlying medical conditions including aging.
A Rare Case of Isolated Atrial Myocarditis Causing Death With no Post Mortem Computed Tomography Scan Correlation
Authors: Tse Rexson , Garland Jack , Kesha Kilak , Triggs Yvonne , Modahl Lucy , Milne David , Yap Zhi , Stables Simon 
Published: November 2017

Abstract
Acute myocarditis is a potentially fatal cardiac pathology that is thought to cause sudden death through arrhythmia and cardiac failure. Of the different subtypes, lymphocytic myocarditis is the most common form. The pathophysiology of myocarditis can be generally diffuse or focally involve the ventricles, but less frequently affects the atria. Although the clinical literature reports isolated atrial myocarditis as a cause of atrial fibrillation and enlargement, there is scant postmortem literature on the findings of this pathology. We report a fatal case of isolated lymphocytic atrial myocarditis affecting only the left atrium in a 56-year-old man, where microscopy of the left atrium confirmed a florid lymphocytic myocarditis. Retrospective postmortem computed tomography scan review did not show any abnormalities on the left atrial wall.
Inhibition of Skin Wound Contraction by Nanofibrillar Cellulose Hydrogel
Authors: Nuutila Kristo , Laukkanen Antti , Lindford Andrew , Juteau Susanna , Nuopponen Markus , Vuola Jyrki , Kankuri Esko 
Published: November 2017

Background:Although wound contraction is an essential part of healing, excessive contraction can compromise healing through induction of scarring and fibrosis. This in turn leads to development of wound contractures that limit elasticity and function. Major research efforts have focused on development of novel therapeutic approaches to gain inhibitory control over wound contraction. Despite these efforts, the need for cost-effective, clinically feasible, and effective agents to inhibit wound contraction remains.Methods:In this study, the authors investigated the effect of nanofibrillar cellulose hydrogel on wound contraction both in vitro and in vivo. Two different porcine full-thickness wounds (8-mm punch-biopsy wounds and 4 × 4-cm wounds covered with a 1:3-meshed split-thickness skin graft) were treated with or without nanofibrillar cellulose or carboxymethylcellulose (Purilon hydrogel), which was used as a reference treatment. Wound contraction was observed macroscopically, and histologic sections were taken at 14-day follow-up.Results:Nanofibrillar cellulose hydrogel inhibited 70 percent of punch-biopsy wound contraction, whereas the carboxymethylcellulose hydrogel was ineffective. Importantly, application of nanofibrillar cellulose on split-thickness skin grafts did not inhibit epithelialization of the interstices or cell migration from the graft.Conclusion:The authors’ results, although preliminary, indicate a potential for nanofibrillar cellulose hydrogel as a novel material for controlling excessive wound contraction.
Whole-transcriptome causal network inference with genomic and transcriptomic data
Authors: Wang Lingfei , Michoel Tom 
Published: November 2017

AbstractReconstruction of causal gene networks can distinguish regulators from targets and reduce false positives by integrating genetic variations. Its recent developments in speed and accuracy have enabled whole-transcriptome causal network inference on a personal computer. Here we demonstrate this technique with program Findr on 3,000 genes from the Geuvadis dataset. Subsequent analysis reveals major hub genes in the reconstructed network.
Estimating heritability without environmental bias
Authors: Young Alexander I. , Frigge Michael L. , Gudbjartsson Daniel F. , Thorleifsson Gudmar , Bjornsdottir Gyda , Sulem Patrick , Masson Gisli , Thorsteinsdottir Unnur , Stefansson Kari , Kong Augustine 
Published: November 2017

AbstractHeritability measures the proportion of trait variation that is due to genetic inheritance. Measurement of heritability is of importance to the nature-versus-nurture debate. However, existing estimates of heritability could be biased by environmental effects. Here we introduce relatedness disequilibrium regression (RDR), a novel method for estimating heritability. RDR removes environmental bias by exploiting variation in relatedness due to random segregation. We use a sample of 54,888 Icelanders with both parents genotyped to estimate the heritability of 14 traits, including height (55.4%, S.E. 4.4%) and educational attainment (17.0%, S.E. 9.4%). Our results suggest that some other estimates of heritability could be inflated by environmental effects.
On the emergence of structural complexity in RNA replicators
Authors: Oliver Carlos G. , Reinharz Vladimir , Waldispühl Jérôme 
Published: November 2017

AbstractThe RNA world hypothesis relies on the ability of ribonucleic acids to spontaneously acquire complex structures capable of supporting essential biological functions. Multiple sophisticated evolutionary models have been proposed for their emergence, but they often assume specific conditions. In this work we explore a simple and parsimonious scenario describing the emergence of complex molecular structures at the early stages of life. We show that at specific GC-content regimes, an undirected replication model is sufficient to explain the apparition of multi-branched RNA secondary structures – a structural signature of many essential ribozymes. We ran a large scale computational study to map energetically stable structures on complete mutational networks of 50-nucleotide-long RNA sequences. Our results reveal that the sequence landscape with stable structures is enriched with multi-branched structures at a length scale coinciding with the appearance of complex structures in RNA databases. A random replication mechanism preserving a 50% GC-content may suffice to explain a natural enrichment of stable complex structures in populations of functional RNAs. By contrast, an evolutionary mechanism eliciting the most stable folds at each generation appears to help reaching multi-branched structures at highest GC content.
The function of the prereplicative complex and SCF complex components during Drosophila wing development
Authors: Kohzaki Hidetsugu 
Published: November 2017

AbstractChromosomal DNA replication machinery functions in the growing cells and organs in multicellular organisms. We previously demonstrated that its knockdown in several tissues of Drosophila led to a rough eye phenotype, the loss of bristles in the eye and female sterile. In this paper, we investigated in detail the wing phenotype using RNAi flies, and observed that the knockdown not only of Mcm10 but also of some other prereplicative complex components demonstrated wing phenotypes, using Gal4-driver flies. Surprisingly, some SCF complex components, which control cell cycle progression via protein degradation, also showed the wing phenotype. These results showed that the DNA replication machinery contributes to wing development independent of growth, probably through defects in DNA replication and protein degradation at specific places and times.Summary statementWe recently outlined the prereplicative complex components, including Mcm10 and SCF complex functions, during Drosophila wing development. In this paper, we detail these findings.
Genetic risk for neurodegenerative disorders, and its overlap with cognitive ability and physical function
Authors: Hagenaars Saskia P. , Radakovic Ratko , Crockford Christopher , Fawns-Ritchie Chloe ,   International FTD-Genomics Consortium (IFGC), Harris Sarah E. , Gale Catharine R. , Deary Ian J. 
Published: November 2017

AbstractINTRODUCTIONIt is unclear whether polygenic risk for neurodegenerative disease is associated with cognitive performance and physical health.METHODSThis study tested whether polygenic scores for Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS), or frontotemporal dementia (FTD) are associated with cognitive performance and physical health. Group-based analyses were performed to compare associations with cognitive and physical function outcomes in the top and bottom 10% for the three neurodegenerative polygenic risk scores.RESULTSHigher polygenic risk scores for AD, ALS, and FTD were associated with lower cognitive performance. Higher polygenic risk scores for FTD was also associated with increased forced expiratory volume in 1s and peak expiratory flow. A significant group difference was observed on the symbol digit substitution task between individuals with high polygenic risk for FTD and high polygenic risk for ALS.DISCUSSIONOur results suggest overlap between polygenic risk for neurodegenerative disorders, cognitive function and physical health.
Independent assessment and improvement of wheat genome assemblies using Fosill jumping libraries
Authors: Lu Fu-Hao , McKenzie Neil , Kettleborough George , Heavens Darren , Clark Matthew D. , Bevan Michael W. 
Published: November 2017

AbstractBackgroundThe accurate sequencing and assembly of very large, often polyploid, genomes remain a challenging task, limiting long range sequence information and phased sequence variation for applications such as plant breeding. The 15 Gb hexaploid bread wheat genome has been particularly challenging to sequence, and several contending approaches recently generated accurate long range assemblies. Understanding errors in these assemblies is important for optimising future sequencing and assembly approaches and for comparative genomics.ResultsHere we use a Fosill 38 Kb jumping library to assess medium and longer range order of different publicly available wheat genome assemblies. Modifications to the Fosill protocol generated longer Illumina sequences and enabled comprehensive genome coverage. Analyses of two independent BAC based chromosome-scale assemblies, two independent Illumina whole genome shotgun assemblies, and a hybrid long read (PacBio) and short read (Illumina) assembly were carried out. We revealed a variety of discrepancies using Fosill mate-pair mapping and validated several of each class. In addition, Fosill mate-pairs were used to scaffold a whole genome Illumina assembly, leading to a three-fold increase in N50 values.ConclusionsOur analyses, using an independent means to validate different wheat genome assemblies, show that whole genome shotgun assemblies are significantly more accurate by all measures compared to BAC-based chromosome scale assemblies. Although current whole genome assemblies are reasonably accurate and useful, additional steps will be needed for the rapid, cost effective and complete sequencing and assembly of wheat genomes.
An epithelial-mesenchymal-amoeboid transition gene signature reveals subtypes of breast cancer progression and metastasis
Authors: Emad Amin , Ray Tania , Jensen Tor W. , Parat Meera , Natrajan Rachael , Sinha Saurabh , Ray Partha S. 
Published: November 2017

AbstractCancer cells within a tumor are known to display varying degrees of metastatic propensity but the molecular basis underlying such heterogeneity remains unclear. We analyzed genome-wide gene expression data obtained from primary tumors of lymph node-negative breast cancer patients using a novel metastasis biology-based Epithelial-Mesenchymal-Amoeboid Transition (EMAT) gene signature, and identified subtypes associated with distinct prognostic profiles. EMAT subtype status improved prognosis accuracy of clinical parameters and statistically outperformed traditional breast cancer intrinsic subtypes even after adjusting for treatment variables. Additionally, analysis of 3D spheroids from an in vitro isogenic model of breast cancer progression reveals that EMAT subtypes display progression from premalignant to malignant and pre-invasive to invasive cancer. EMAT classification is a biologically informed method to assess metastasis risk in early stage, lymph node-negative breast cancer patients.
A Bayesian approach to mediation analysis predicts 206 causal target genes in Alzheimer’s disease
Authors: Park Yongjin , Sarkar Abhishek K , He Liang , Davila-Velderrain Jose , De Jager Philip L , Kellis Manolis 
Published: November 2017

AbstractCharacterizing the intermediate phenotypes, such as gene expression, that mediate genetic effects on complex diseases is a fundamental problem in human genetics. Existing methods utilize genotypic data and summary statistics to identify putative disease genes, but cannot distinguish pleiotropy from causal mediation and are limited by overly strong assumptions about the data. To overcome these limitations, we develop Causal Multivariate Mediation within Extended Linkage disequilibrium (CaMMEL), a novel Bayesian inference framework to jointly model multiple mediated and unmediated effects relying only on summary statistics. We show in simulation that CaMMEL accurately distinguishes between mediating and pleiotropic genes unlike existing methods. We applied CaMMEL to Alzheimer’s disease (AD) and found 206 causal genes in sub-threshold loci (p < 10−4). We prioritized 21 genes which mediate at least 5% of local genetic variance, disrupting innate immune pathways in AD.
Male age is associated with extra-pair paternity, but not with extra-pair mating behaviour
Authors: Girndt Antje , Chng Charlotte Wen Ting , Burke Terry , Schroeder Julia 
Published: November 2017

AbstractExtra-pair paternity is the result of copulation between a female and a male other than her social partner. In socially monogamous birds, old males are most likely to sire extra-pair offspring. The male manipulation and female choice hypotheses predict that age-specific male mating behaviour could explain this old-over-young male advantage. These hypotheses have been difficult to test because copulations and the individuals involved are hard to observe. Here, we studied the mating behaviour and pairing contexts of captive house sparrows,Passer domesticus. Our set-up mimicked the complex social environment experienced by wild house sparrows. We found that middle-aged males, that would be considered old in natural populations, gained most extra-pair paternity. However, both female solicitation behaviour and subsequent extra-pair matings were unrelated to male age. Further, copulations were more likely when solicited by females than those initiated by males (i.e. unsolicited copulations), and unsolicited within-pair copulations were more common than unsolicited extrapair copulations. To conclude, our results did not support either hypotheses regarding age-specific male mating behaviour. Instead, female choice, independent of male age, governed copulation success, especially in an extra-pair context and post-copulatory mechanisms might determine why older males sire more extra-pair offspring.
Smg5is required for multiple nonsense-mediated mRNA decay pathways inDrosophila
Authors: Nelson Jonathan O. , Förster Dominique , Frizzell Kimberly A. , Luschnig Stefan , Metzstein Mark M. 
Published: November 2017

ABSTRACTThe nonsense-mediated mRNA decay (NMD) pathway is a cellular quality control and post-transcriptional gene regulatory mechanism and is essential for viability in most multicellular organisms. A complex of proteins has been identified to be required for NMD function to occur, however the individual contribution of each of these factors to the NMD process is not well understood. Central to the NMD process are two proteins Upf1 (SMG-2) and Upf2 (SMG-3), which are found in all eukaryotes and are absolutely required for NMD in all organisms in which it has been examined. The other known NMD factors, Smg1, Smg5, Smg6, and Smg7 are more variable in their presence in different orders of organisms, and are thought to have a more regulatory role. Here we present the first genetic analysis of the NMD factorSmg5inDrosophila. Surprisingly, we find that unlike the other analyzedSmggenes in this organism,Smg5is essential for NMD activity. We found this is due at least in part to a role for Smg5 in the activity of two separable NMD-target decay mechanisms: endonucleolytic cleavage and 5′-to-3′ exonucleolytic decay. Redundancy between these degradation pathways explains why someDrosophilaNMD genes are not required for all NMD-pathway activity. We also found that while the NMD componentSmg1has only a minimal role inDrosophilaNMD during normal conditions, it becomes essential when NMD activity is compromised by partial loss ofSmg5function. Our findings suggest that not all NMD complex components are required for NMD function at all times, but instead are utilized in a context dependent mannerin vivo.