bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjuvant ribavirin and longer direct‐acting antiviral treatment duration improve sustained virological response among hepatitis C patients at risk of treatment failure
Authors: Lu Mei , Wu Kuan‐Han , Li Jia , Moorman Anne C. , Spradling Philip R. , Teshale Eyasu H. , Boscarino Joseph A. , Daida Yihe G. , Schmidt Mark A. , Rupp Loralee B. , Zhang Talan , Trudeau Sheri , Gordon Stuart C. 
Published: June 2019

AbstractThe role of ribavirin (RBV) in the era of direct‐acting antivirals (DAA) is not clear, and DAA studies have been largely genotype‐ and regimen‐specific. Using data from the Chronic Hepatitis Cohort Study, we evaluated the role of RBV and increased DAA treatment duration among patients with chronic hepatitis C (HCV) in routine clinical care. We performed multivariable analysis of data from 4133 patients receiving any of the following: sofosbuvir (SOF); daclatasvir + SOF; grazoprevir + elbasvir; paritaprevir/ritonavir + ombitasvir; simeprevir + SOF; and SOF + ledipasvir; SOF + velpatasvir ± voxilaprevir; and glecaprevir + pibrentasvir—all with/ without RBV. Inverse probability treatment weighting was used to adjust for treatment selection bias. Sustained virological response (SVR) was defined by undetectable HCV RNA 12 weeks after end of therapy. The overall SVR rate was 95%. Mean treatment duration was 12 ± 4.5 weeks. The final model included treatment duration and diabetes, as well as the interaction of RBV with previous treatment status (treatment naïve, interferon treatment failure [TF] or previous DAA TF), cirrhosis status, and HCV genotype (GT). Each one‐month increment of treatment duration increased odds of SVR by 99% (aOR = 1.99). Diabetes, previous DAA TF, and decompensated cirrhosis significantly reduced odds of SVR. RBV significantly increased the likelihood of SVR among patients with decompensated cirrhosis (aOR = 5.05), previous DAA treatment failure (aOR = 5.43), and GT3 (aOR = 13.28). Among RBV‐free regimens, patients with GT3 were less likely to achieve SVR than those with GT1 or 2 (aOR 0.07). Diabetes, decompensated cirrhosis, and prior DAA TF independently reduced the likelihood of SVR. Longer treatment duration increased likelihood of SVR. Conclusion: RBV increased likelihood of SVR among patients with GT3, previous DAA TF, or decompensated cirrhosis.
Clinical pharmacokinetics of a dexmedetomidine–methadone combination in dogs undergoing routine anaesthesia after buccal or intramuscular administration
Authors: Di Cesare Federica , Gioeni Daniela , Ravasio Giuliano , Pellegrini Alberto , Lucatello Lorena , Bisutti Vittoria , Villa Roberto , Cagnardi Petra 
Published: June 2019

AbstractThis study aimed to define the pharmacokinetic profiles of dexmedetomidine and methadone administered simultaneously in dogs by either an oral transmucosal route or intramuscular route and to determine the bioavailability of the oral transmucosal administration relative to the intramuscular one of both drugs, so as the applicability of this administration route in dogs. Twelve client‐owned dogs, scheduled for diagnostic procedures, were treated with a combination of dexmedetomidine hydrochloride (10 μg/kg) and methadone hydrochloride (0.4 mg/kg) through an oral transmucosal route or intramuscularly. Oral transmucosal administration caused ptyalism in most subjects, and intramuscular administration caused transient peripheral vasoconstriction. The results showed reduced and delayed absorption of both dexmedetomidine and methadone when administered through an oral transmucosal route, with median (range) Cmax values of 0.82 (0.42–1.49) ng/ml and 13.22 (2.80–52.30) ng/ml, respectively. The relative bioavailability was low: 16.34% (dexmedetomidine) and 15.5% (methadone). Intramuscular administration resulted in a more efficient absorption profile, with AUC and Cmax values for both drugs approximately 10 times higher. Dexmedetomidine and methadone administered simultaneously by an oral transmucosal route using injectable formulations were not well absorbed through the oral mucosa. Nevertheless, additional studies on these drugs combination using alternative administration routes are recommended.
Total liver phosphatidylcholine content associates with non‐alcoholic steatohepatitis and glycine N‐methyltransferase expression
Authors: Männistö Ville , Kaminska Dorota , Kärjä Vesa , Tiainen Mika , de Mello Vanessa D. , Hanhineva Kati , Soininen Pasi , Ala‐Korpela Mika , Pihlajamäki Jussi 
Published: June 2019

AbstractBackground & AimsAlterations in liver phosphatidylcholine (PC) metabolism have been implicated in the pathogenesis of non‐alcoholic fatty liver disease (NAFLD). Although genetic variation in the phosphatidylethanolamine N‐methyltransferase (PEMT) enzyme synthesizing PC has been associated with disease, the functional mechanism linking PC metabolism to the pathogenesis of non‐alcoholic steatohepatitis (NASH) remains unclear.MethodsSerum PC levels and liver PC contents were measured using proton nuclear magnetic resonance (NMR) spectroscopy in 169 obese individuals [age 46.6 ± 10 (mean ± SD) years, BMI 43.3 ± 6 kg/m2, 53 men and 116 women] with histological assessment of NAFLD; 106 of these had a distinct liver phenotype. All subjects were genotyped for PEMT rs7946 and liver mRNA expression of PEMT and glycine N‐methyltransferase (GNMT) was analysed.ResultsLiver PC content was lower in those with NASH (P = 1.8 x 10−6) while serum PC levels did not differ between individuals with NASH and normal liver (P = 0.591). Interestingly, serum and liver PC did not correlate (rs = −0.047, P = 0.557). Serum PC and serum cholesterol levels correlated strongly (rs = 0.866, P = 7.1 x 10−49), while liver PC content did not correlate with serum cholesterol (rs = 0.065, P = 0.413). Neither PEMT V175M genotype nor PEMT expression explained the association between liver PC content and NASH. Instead, liver GNMT mRNA expression was decreased in those with NASH (P = 3.8 x 10−4) and correlated with liver PC content (rs = 0.265, P = 0.001).ConclusionsDecreased liver PC content in individuals with the NASH is independent of PEMT V175M genotype and could be partly linked to decreased GNMT expression.
The intermingling of benthic macroinvertebrate communities during a period of shifting range: The “East of Nantucket” Atlantic Surfclam Survey and the existence of transient multiple stable states
Authors: Powell Eric N. , Mann Roger , Kuykendall Kelsey M. , Long M. Chase , Timbs Jeremy R. 
Published: June 2019

AbstractA survey of the region eastward of Nantucket provided an opportunity to examine the cold temperate–boreal boundary along the high‐energy Great South Channel. Here described are the benthic macroinvertebrate community types encountered, with a focus on the influence of climate change on the range boundaries of the benthic biomass dominants and the potential existence of transient multiple stable states. The survey identified three primary community types. The shallowest sites were occupied by a surfclam‐dominated community, comprising an abundance of large (≥150 mm) surfclams, and a few common attached epibiota primarily attached to exposed surfclam shell. Two communities exist at intermediate depths, one dominated by submarket and small market‐size surfclams (<150 mm) and the other, created by mussel mats and their attendant epibiota, crabs, sea urchins, and other mobile epifauna. Mussels are a foundational species, establishing a hard‐bottom terrain conducive to these other denizens in soft‐bottom habitat. Cobbles were nearly ubiquitous, rocks were routinely recovered, and boulders were encountered occasionally. Slow growing attached epibionts were exceedingly rare and mobile epifauna were not obviously associated with these large sedimentary particles; nor were the surfclam or mussel communities. The frequency of barnacle scars suggests sediment scour under the high‐flow regime characteristic of the surveyed region, which voids the habitat potential of these sedimentary particles. The abundance of surfclam shell indicates that surfclams have inhabited the shoaler depths for an extended time; limited shell at deeper sites supports the inference from the absence of large animals that these sites are relatively newly colonized and represent further evidence of an offshore shift in range brought on by increasing bottom water temperatures. The dichotomous nature of the two primary community types at mid‐depths suggests that these two communities represent multiple stable states brought on by the interaction of an invading cold temperate species with the receding boreal fauna resulting in a transient intermingling of species, which, however, structure the habitat into exclusionary stable states rather than overlapping in a co‐occurrence ecotone.
Ex vivo HSC expansion challenges the paradigm of unidirectional human hematopoiesis
Authors: Papa Luena , Djedaini Mansour , Hoffman Ronald 
Published: June 2019

AbstractUnderstanding mechanisms that determine the behavior of human hematopoietic stem cells (HSCs) is essential for developing novel strategies to expand ex vivo the number of fully functional HSCs. In this review, we focus on the complex interplay between intrinsic mechanisms regulated by transcriptional and mitochondrial networks and extrinsic signals imposed by the bone marrow microenvironment, which in concert regulate the balance between HSC self‐renewal and differentiation. Such integrated signaling mechanisms that dictate the fate of HSCs in vivo must be recapitulated ex vivo to achieve successful expansion of clinically relevant HSCs. We also highlight some of the most recent ex vivo HSC expansion strategies that have currently entered clinical development. Finally, based on the evidence reviewed here and lessons learned from ex vivo HSC expansion, we raise some critical questions regarding HSC fate and the cellular plasticity of hematopoietic cells that challenge the unidirectional model of human hematopoiesis.
Analysis of the genetic architecture of maize kernel size traits by combined linkage and association mapping
Authors: Liu Min , Tan Xiaolong , Yang Yan , Liu Peng , Zhang Xiaoxiang , Zhang Yinchao , Wang Lei , Hu Yu , Ma Langlang , Li Zhaoling , Zhang Yanling , Zou Chaoying , Lin Haijian , Gao Shibin , Lee Michael , Lübberstedt Thomas , Pan Guangtang , Shen Yaou 
Published: June 2019

SummaryKernel size‐related traits are the most direct traits correlating with grain yield. The genetic basis of three kernel traits of maize, kernel length (KL), kernel width (KW) and kernel thickness (KT), was investigated in an association panel and a biparental population. A total of 21 single nucleotide polymorphisms (SNPs) were detected to be most significantly (P < 2.25 × 10−6) associated with these three traits in the association panel under four environments. Furthermore, 50 quantitative trait loci (QTL) controlling these traits were detected in seven environments in the intermated B73 × Mo17 (IBM) Syn10 doubled haploid (DH) population, of which eight were repetitively identified in at least three environments. Combining the two mapping populations revealed that 56 SNPs (P < 1 × 10−3) fell within 18 of the QTL confidence intervals. According to the top significant SNPs, stable‐effect SNPs and the co‐localized SNPs by association analysis and linkage mapping, a total of 73 candidate genes were identified, regulating seed development. Additionally, seven miRNAs were found to situate within the linkage disequilibrium (LD) regions of the co‐localized SNPs, of which zma‐miR164e was demonstrated to cleave the mRNAs of Arabidopsis CUC1, CUC2 and NAC6 in vitro. Overexpression of zma‐miR164e resulted in the down‐regulation of these genes above and the failure of seed formation in Arabidopsis pods, with the increased branch number. These findings provide insights into the mechanism of seed development and the improvement of molecular marker‐assisted selection (MAS) for high‐yield breeding in maize.
Genome‐wide quantitative trait loci reveal the genetic basis of cotton fibre quality and yield‐related traits in a Gossypium hirsutum recombinant inbred line population
Authors: Zhang Zhen , Li Junwen , Jamshed Muhammad , Shi Yuzhen , Liu Aiying , Gong Juwu , Wang Shufang , Zhang Jianhong , Sun Fuding , Jia Fei , Ge Qun , Fan Liqiang , Zhang Zhibin , Pan Jingtao , Fan Senmiao , Wang Yanling , Lu Quanwei , Liu Ruixian , Deng Xiaoying , Zou Xianyan , Jiang Xiao , Liu Ping , Li Pengtao , Iqbal Muhammad Sajid , Zhang Chuanyun , Zou Juan , Chen Hong , Tian Qin , Jia Xinhe , Wang Baoqin , Ai Nijiang , Feng Guoli , Wang Yumei , Hong Mei , Li Shilin , Lian Wenming , Wu Bo , Hua Jinping , Zhang Chaojun , Huang Jinyong , Xu Aixia , Shang Haihong , Gong Wankui , Yuan Youlu 
Published: June 2019

SummaryCotton is widely cultivated globally because it provides natural fibre for the textile industry and human use. To identify quantitative trait loci (QTLs)/genes associated with fibre quality and yield, a recombinant inbred line (RIL) population was developed in upland cotton. A consensus map covering the whole genome was constructed with three types of markers (8295 markers, 5197.17 centimorgans (cM)). Six fibre yield and quality traits were evaluated in 17 environments, and 983 QTLs were identified, 198 of which were stable and mainly distributed on chromosomes 4, 6, 7, 13, 21 and 25. Thirty‐seven QTL clusters were identified, in which 92.8% of paired traits with significant medium or high positive correlations had the same QTL additive effect directions, and all of the paired traits with significant medium or high negative correlations had opposite additive effect directions. In total, 1297 genes were discovered in the QTL clusters, 414 of which were expressed in two RNA‐Seq data sets. Many genes were discovered, 23 of which were promising candidates. Six important QTL clusters that included both fibre quality and yield traits were identified with opposite additive effect directions, and those on chromosome 13 (qClu‐chr13‐2) could increase fibre quality but reduce yield; this result was validated in a natural population using three markers. These data could provide information about the genetic basis of cotton fibre quality and yield and help cotton breeders to improve fibre quality and yield simultaneously.
A case series of demodicosis in children
Authors: Douglas Annyella , Zaenglein Andrea L. 
Published: June 2019

AbstractDemodex mites are commensal inhabitants of the pilosebaceous unit that are typically absent or at low numbers in childhood. When they are present, they can cause a primary eruption or exacerbate an underlying facial dermatosis. Here we report five cases of demodicosis occurring in childhood, the clinical presentations, and responses to treatment. Papulopustular lesions predominate, prompting the advice “pustules on noses, think demodicosis!”
Examining time‐dependent effects of water, sanitation, and hygiene (WASH) interventions using an agent‐based model
Authors: Kang Jeon‐Young , Aldstadt Jared 
Published: June 2019

AbstractThe effects of water, sanitation, and hygiene (WASH) interventions have been well acknowledged to reduce the risk from diarrheal disease‐causing pathogens. In spite of the recognized importance of WASH interventions on the reduction of diarrheal disease, there are still gaps in the understanding of the time‐varying effects of interventions. To bridge this research gap, we developed agent‐based models (ABMs) of diarrheal disease transmission in a community context. In the model, infections occur via two pathways: (i) between household members within the household environment and (ii) from the community environment outside the household. To measure the effectiveness of WASH interventions, we performed global sensitivity analysis (GSA) at the macro and micro temporal scales, varying the level of intervention coverage in the community. We simulated three intervention strategies, implemented separately in the experiments. The clean drinking water intervention, sanitation intervention, and hand washing intervention had similar success rates in the long‐term. The handwashing intervention had the largest immediate effect. This highlights that proper short‐ and long‐term intervention strategies need to be considered for disease control and the effective management of limited resources.
How do I audit intraoperative blood component utilization in cardiac surgery?
Authors: Hensley Nadia B. , Cho Brian C. , Visagie Mereze , Lester Laeben C. , Abernathy James H. , Frank Steven M. 
Published: June 2019

BACKGROUNDPatient blood management programs are tasked with auditing transfusions for appropriateness; however, cardiac surgical programs have high variability in blood utilization. After benchmarking intraoperative blood utilization as higher than expected, we devised effective methods for audits with feedback to the cardiac anesthesiologists that are described in this report.STUDY DESIGN AND METHODSRed blood cell (RBC), plasma, platelet (PLT), and cryoprecipitate transfusion data were collected from the electronic record system for 2242 patients having cardiac surgery from July 2016 until July 2018. In July 2017, we performed audits with feedback using rank‐order bar graphs displayed on the anesthesiology office door for intraoperative blood utilization. Individual providers were compared to their peers for all four major blood components, with the goal of improving practice by reducing variability.RESULTSAfter the audits with feedback, the intraoperative mean units/patient decreased for RBCs (from 1.9 to 1.2 units/patient; p = 0.0004), for plasma (from 1.8 to 1.2 units/patient; p = 0.0038), and for PLTs (from 0.7 to 0.4 units/patient; p < 0.0001), but not for cryoprecipitate (from 0.24 to 0.18 units/patient; p = 0.13). Whole hospital (from admit to discharge) utilization decreased significantly for plasma and PLTs, but the changes for RBCs and cryoprecipitate were nonsignificant.CONCLUSIONDespite challenges in abstracting data from the electronic medical record, using such data to create provider‐specific audits with feedback can be an effective tool to promote quality improvement. Future plans include audits with feedback for providers who order transfusion outside the operating room.
Protein Secretion in Spirochetes
Authors: Zückert Wolfram R. 
Published: June 2019

ABSTRACT

Spirochetes form a separate phylum of bacteria with two membranes but otherwise unusual morphologies and envelope structures. Distinctive common features of
Borrelia
,
Leptospira
, and
Treponema
include the sequestration of flagella to the periplasm and thin peptidoglycan cell walls that are more closely associated with the inner membrane. Outer membrane compositions differ significantly between the genera.
Leptospira
most closely track Gram-negative bacteria due to the incorporation of lipopolysaccharides.
Treponema
and
Borrelia
outer membranes lack lipopolysaccharide, with treponemes expressing only a few outer membrane proteins and
Borrelia
displaying a dizzying diversity of abundant surface lipoproteins instead. Phylogenetic and experimental evidence indicates that spirochetes have adapted various modules of bacterial export and secretion pathways to build and maintain their envelopes. Export and insertion pathways in the inner membrane appear conserved, while spirochetal experimentation with various envelope architectures over time has led to variations in secretion pathways in the periplasm and outer membrane. Classical type I to III secretion systems have been identified, with demonstrated roles in drug efflux and export of flagellar proteins only. Unique activities of periplasmic proteases, including a C-terminal protease, are involved in maturation of some periplasmic proteins. Proper lipoprotein sorting within the periplasm appears to be dependent on functional Lol pathways that lack the outer membrane lipoprotein insertase LolB. The abundance of surface lipoproteins in
Borrelia
and detailed protein sorting studies suggest a lipoprotein secretion pathway that either extends Lol through the outer membrane or bypasses it altogether. Proteins can be released from cells in outer membrane vesicles or, rarely, as soluble proteins.
Hostile Takeover: Hijacking of Endoplasmic Reticulum Function by T4SS and T3SS Effectors Creates a Niche for Intracellular Pathogens
Authors: Tsai April Y. , English Bevin C. , Tsolis Renée M. 
Published: June 2019

ABSTRACT
After entering a cell, intracellular pathogens must evade destruction and generate a niche for intracellular replication. A strategy shared by multiple intracellular pathogens is the deployment of type III secretion system (T3SS)- and type IV secretion system (T4SS)-injected proteins (effectors) that subvert cellular functions. A subset of these effectors targets activities of the host cell’s endoplasmic reticulum (ER). Effectors are now appreciated to interfere with the ER in multiple ways, including capture of secretory vesicles, tethering of pathogen vacuoles to the ER, and manipulation of ER-based autophagy initiation and the unfolded-protein response. These strategies enable pathogens to generate a niche with access to cellular nutrients and to evade the host cell’s defenses.
Children’s views on taking medicines and participating in clinical trials
Authors: Nordenmalm Sofia , Kimland Elin , Ligas Franca , Lehmann Birka , Claverol Joana , Nafria Begonya , Tötterman Ann Marie , Pelle Benjamin 
Published: June 2019

IntroductionLimited information is available on the views of children taking medicines and participating in clinical trials. These views may contribute to a better understanding of what can be improved on in the development of medicines from their perspective.ObjectiveTo collect children’s views on taking medicines and participating in clinical trials.Materials and methodsA question-based survey was conducted among children living in European Union countries between January and August 2015.ResultsAlmost 900 children aged 10–17 years from Finland, Germany, Sweden, Spain and Hungary responded. Almost 40% had a chronic health condition. The most commonly used pharmaceutical forms were solid or liquid medicines for oral use and injectable medicines. Bad taste and pain during administration were reported as common problems. Of 785 respondents, 17% had been taking part in a clinical trial. Most respondents would potentially agree to take part in a clinical trial because the investigational medicine might improve their own health or that of other children. Concern that the investigational medicine might be harmful was the main reason to refuse participation, if asked to. Over half of the respondents were willing to learn more about clinical trials, preferably online.ConclusionsIt is necessary to involve children in the development of age-appropriate pharmaceutical forms and in the design of clinical trials. Children and their carers should be provided with age-appropriate medical information in the most suitable channels. We have identified some common problems that children experience when taking medicines, and we conclude that children are interested in learning more and giving their opinions on clinical trials.