bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of CD4+ T cell subsets and HIV susceptibility in the inner and outer foreskin of Ugandan men
Authors: Galiwango Ronald Moses , Yegorov Sergey , Joag Vineet , Prodger Jessica , Shahabi Kamnoosh , Huibner Sanja , Muyanja Enoch , Kabuubi Brian Roy , Namuniina Annmarie , Nalutaaya Annet , Ssemaganda Aloysius , Lutwama Fredrick , Kitandwe Paul Kato , Nanvubya Annet , Mpendo Juliet , Bagaya Bernard , Kiwanuka Noah , Kaul Rupert 
Published: May 2019

AbstractProblemBiological mechanisms of foreskin HIV acquisition are poorly defined. The inner foreskin is preferentially infected in explant models, so we hypothesized that this site would be enriched for HIV‐susceptible CD4+ T cells and proinflammatory/chemoattractant cytokines.Method of studyA total of 42 HIV‐uninfected Ugandan men without genital symptoms provided foreskin tissues and swabs at the time of elective penile circumcision. The immune phenotype of foreskin‐derived CD4+ T cells and entry of a CCR5‐tropic HIV pseudovirus was characterized, and specific cytokine levels assayed by multiplexed chemiluminescent ELISA.ResultsUnexpectedly, outer foreskin CD4+ T cells more frequently expressed CCR5 (median 29.2% vs 22.9%, P = 0.01) and CD69 (median 36.5% vs 15%, P < 0.01), and on a per‐cell basis, HIV entry was higher. However, overall CD4+ T cell density was approximately twofold higher in the inner foreskin, and several highly susceptible T cell subsets were increased at this site, including Th17 cells (20.0% vs 14.1%, P = 0.0021). Specific pro‐inflammatory cytokine levels were also higher on the inner foreskin surface (IL‐17, IL‐8, RANTES and IL‐1β; all P < 0.05).ConclusionThere was marked heterogeneity in CD4+ T cell populations and immune milieu between inner and outer foreskin tissues. Despite higher per‐cell viral entry into CD4+ T cells from the outer foreskin, the higher target cell density and enriched pro‐inflammatory cytokines of the inner foreskin suggest that this may be a preferential site for HIV acquisition.
Distal locked or unlocked nailing for stable intertrochanteric fractures? A meta‐analysis
Authors: Yan Wen‐Shan , Cao Wei‐Li , Sun Ming , Ma Deng‐Yue , Zhang Peng 
Published: May 2019

BackgroundTo date, there are just several studies comparing distal locked nails with distal unlocked nails in treating intertrochanteric fractures. We report the first meta‐analysis about this issue.MethodsSystematic search was conducted for studies in PubMed, Embase and Cochrane Library. Meta‐analyses were performed regarding intra operative outcomes, complications and functional outcomes.ResultsPooled results showed insignificant difference between distal locking group and distal unlocking group in hip pain (relative risk (RR) 1.14, 95% confidence interval (CI) 0.59–2.19), distal tip fracture (RR 1.08, 95% CI 0.37–3.11), lag screw cut‐out (RR 1.60, 95% CI 0.54–4.78), delayed or nonunion (RR 1.32, 95% CI 0.25–7.06), deep vein thrombosis (RR 1.06, 95% CI 0.23–4.84), wound infection (RR 0.58, 95% CI 0.28–1.22), Harris hip score (standard mean deviation (SMD) 0.03, 95% CI −0.15 to 0.21) and walking ability. However, significant difference was detected in operation time (SMD 0.77, 95% CI 0.36–1.17), fluoroscopy exposure time (SMD 1.02, 95% CI 0.52–1.52), blood loss (SMD 0.80, 95% CI 0.62–0.99) and total incision length (SMD 1.16, 95% CI 0.86–1.47). Result of trial sequential analysis indicated conclusive evidence.ConclusionCurrent evidence indicates that the distal locked intramedullary nails should not be recommended as routine choice for stable intertrochanteric fractures.
Beta diversity of aquatic invertebrates increases along an altitudinal gradient in a Neotropical mountain
Authors: Castro Diego M. P. , Callisto Marcos , Solar Ricardo R. C. , Macedo Diego R. , Fernandes Geraldo W. 
Published: May 2019

AbstractMountains harbor rich biodiversity and high levels of endemism, particularly due to changes in environmental conditions over short spatial distances, which affects species distribution and composition. Studies on mountain ecosystems are increasingly needed, as mountains are highly threatened despite providing ecosystem services, such as water supply for half of the human population. We aimed to understand the patterns and drivers of alpha and beta diversities of aquatic invertebrates in headwater streams along an altitudinal gradient in the second largest South American mountain range, the Espinhaço mountains. Headwater streams were selected at each 100 m of elevation along an altitudinal gradient ranging from 800 to 1400 m asl, where three substrate types per stream were sampled: leaf litter, gravel, and cobbles. Environmental variables were sampled to represent local riparian canopy cover, instream physical habitat, water quality, climatic data, and land use. Generalized linear models and mixed models were used to test relationships between altitude and the richness and abundance of invertebrates and to assess the influence of environmental variables on the same metrics. Patterns of spatial variation in aquatic invertebrate assemblages along the altitudinal gradient were assessed using multiplicative beta diversity partitioning. The richness and abundance of aquatic invertebrates decreased with increasing altitude, whereas beta diversity increased with increasing altitude. Significant differences in assemblage composition and in relative abundance of invertebrates were observed for both substrates and altitude. We thus show that the high regional beta diversity in aquatic ecosystems in the studied site is due to the high turnover among areas.Abstract in Portuguese is available with online material.
Sacral nerve stimulation for bowel dysfunction following low anterior resection: a systematic review and meta‐analysis
Authors: Huang Y. , Koh C. E. 
Published: May 2019

AbstractAimLow anterior resection syndrome (LARS) can affect up to 70% of all patients with rectal cancer. In the last two decades, sacral nerve stimulation (SNS) has emerged as an effective treatment for faecal incontinence. There is some encouraging literature on the use of SNS in patients with LARS. The purpose of this review is to provide an up to date review on the utility of SNS on LARS.MethodA literature search was conducted using the MEDLINE, Embase and PubMed databases (January 1981–March 2019). Studies identified were appraised with standard selection criteria. Data points were extracted, and meta‐analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses.ResultsTen studies met the inclusion criteria and were included in this study. All studies used the Cleveland Clinic Incontinence Score (CCIS), whereas the low anterior resection syndrome score (LARS score) was used in three studies. Overall median improvement in the scoring system was 67.0% (range 35.5%–88.2%) after SNS implantation. There was a significant reduction in CCIS after SNS implantation (mean difference 11.23, 95% confidence interval 9.38–13.07, Z = 11.90, P < 0.00001). The LARS score was also significantly reduced after using SNS in patients with LARS (mean difference 17.87, 95% confidence interval 10.15–25.59, Z = 4.54, P < 0.00001).ConclusionUse of SNS may provide symptomatic benefits for patients with LARS refractory to medical therapy. However, the current level of evidence remains limited. A large multicentre study of SNS for LARS using the validated LARS score is warranted. In addition, the cost‐effectiveness of SNS for patients with LARS needs further exploration.
Loss of 5‐hydroxymethylcytosine immunohistochemical expression is a useful diagnostic aid for distinguishing hepatocellular carcinoma in cytology fine needle aspiration specimens
Authors: Zhu Xiaoqin , Dresser Karen , Chen Benjamin J. 
Published: May 2019

AbstractObjectiveDisruption of the DNA methylation pathway involving 5‐hydroxymethylcytosine (5hmC) has been implicated in hepatic tumour development. The aim of this study was to investigate the expression of 5hmC in malignant and benign hepatic mass lesions and evaluate the diagnostic utility of deficient 5hmC expression in hepatocellular carcinoma (HCC).MethodsOur study consisted of 48 fine needle aspiration (FNA) cytological cases (30 cases positive for HCC, 18 cases negative for malignancy) and 39 liver resection specimens (30 HCCs and nine hepatic adenomas [HAs]). A 5hmC immunohistochemistry score (range 0‐9) was calculated by multiplying the percentage (0 = no staining; 1 = 1%‐10%; 2 = 11%‐50%; 3 = 51%‐100%) and intensity scores (0‐3+). A score of ≤2 was considered deficient for 5hmC.ResultsIn resection specimens, 5hmC expression was deficient in 90% of HCC cases. Surrounding cirrhotic nodules and 78% of HA cases exhibited intact 5hmC expression. In FNA cytological specimens, expression of 5hmC was deficient in nearly all cases of HCC (96.7%, 29/30 cases). Admixed benign hepatocytes exhibited predominantly intact expression of 5hmC with moderate to strong nuclear staining in the majority of the benign hepatocytes. 5hmC was strongly expressed by endothelial cells, lymphocytes and neutrophils in the background. Many 5hmC‐negative HCC clusters were highlighted by characteristic endothelial wrapping with strong 5hmC expression in the endothelial cells.Conclusions5hmC can serve as an important diagnostic tool for the diagnosis of HCC by aiding in the distinction of HCC from HA or cirrhotic nodules in both liver resection and FNA specimens.
Effects of sodium‐glucose cotransporter inhibitors on cardiorenal and metabolic systems: Latest perspectives from the outcome trials
Authors: Lim Soo 
Published: May 2019

Diabetes mellitus is strongly linked to high risk of cardiovascular and renal disorders. Diabetes management requires coordinated efforts to manage multiple cardiometabolic risk factors. Diabetes mellitus is also associated with poor outcome in patients after cardiovascular events and renal complications. However, whether specific antidiabetic agents are safer and more efficacious than other drugs for preventing and treating these cardiometabolic and renal diseases is debated.To date, results are available from 12 cardiovascular outcome trials focusing mainly on major adverse cardiovascular events and renal outcomes with new antidiabetic agents (4 with dipeptidyl peptidase‐4 inhibitors, 3 with sodium–glucose cotransporter‐2 (SGLT2) inhibitors, and 5 with glucagon‐like peptide‐1 analogues). Among them, the studies of SGLT2 inhibitors showed favourable results both for cardiovascular and renal outcomes. It would be crucial to dissect the effects of SGLT2 inhibitors on cardiorenal and metabolic systems, to determine whether it is better to prescribe SGLT2 inhibitors compared with other antidiabetic medications.
Sodium‐glucose co‐transporter inhibitors as adjunctive treatment to insulin in type 1 diabetes: A review of randomized controlled trials
Authors: Boeder Schafer , Edelman Steven V. 
Published: May 2019

AbstractMany patients with type 1 diabetes (T1D) struggle to achieve glycaemic control and experience significant fluctuations in glucose concentrations, despite insulin treatment. Sodium‐glucose co‐transporter (SGLT)‐2 inhibitors and dual SGLT‐1/2 inhibitors increase glucose elimination via the kidneys and reduce hyperglycaemia via insulin‐independent mechanisms. This review examines available efficacy and safety data for these agents under investigation as adjunctive therapy for T1D. Across randomized trials of up to 52 weeks, SGLT‐2 inhibitors or SGLT‐1/2 inhibitors as an adjunct to insulin demonstrated significant reductions in glycated haemoglobin, glucose exposure, and measures of glycaemic variability, as well as increased time in the target glycaemic range, compared with placebo. Non‐glycaemic benefits included reductions in body weight and insulin doses, as well as improvements in some cardiovascular risk factors and treatment satisfaction. SGLT‐2 inhibitors and SGLT‐1/2 inhibitors were associated with similar rates of hypoglycaemia but a higher incidence of genitourinary infections, compared with placebo. Diabetic ketoacidosis occurred more often with SGLT‐2 inhibitors and SGLT‐1/2 inhibitors vs placebo, although the incidence was generally low. Risk mitigation strategies in light of clinical trial data are also discussed. Positive data from randomized controlled trials of the SGLT‐2 inhibitor dapagliflozin have led to the approval of dapagliflozin as an adjunct to insulin in adults with T1D having body mass index ≥27 kg/m2 in whom insulin does not provide adequate glycaemic control in Europe and to approval as an adjunct to insulin for adults with T1D in Japan.
Having it all overseas: Aid workers and the international division of reproductive labour
Authors: Hannaford Dinah 
Published: May 2019

AbstractThis article examines the dynamics of power and privilege at work in international development through the prism of domestic service for expat aid workers in developing countries. Drawing on ethnographic fieldwork amid aid workers and their domestic staff in Dakar, Senegal, I argue that access to affordable care work greatly enhances the lives of women who work overseas in development. The postcolonial underdevelopment and poverty that aid work addresses is paradoxically critical to the aid workers' own access to affordable care, family balance and the means to do their jobs. I put this insight into the larger scholarly conversation about domestic work and global inequality, including on the Global Care Chain.
Programmed cell death ligand‐1 (PD‐L1) expression in extrahepatic biliary tract cancers: a comparative study using 22C3, SP263 and E1L3N anti‐PD‐L1 antibodies
Authors: Ahn Soomin , Lee Yangkyu , Kim Ji‐Won , Lee Jong‐Chan , Hwang Jin‐Hyeok , Yoon Yoo‐Seok , Cho Jai Young , Han Ho‐Seong , Choi YoungRok , Kim Haeryoung 
Published: May 2019

AimsPembrolizumab has shown promising results for patients with programmed cell death ligand‐1 (PD‐L1)‐positive advanced biliary tract cancer in an ongoing clinical trial. However, data on PD‐L1 expression in bile duct cancers is limited, and the frequency of PD‐L1 positivity varies, which may be partly due to the assay used. The aim of this study was to evaluate PD‐L1 expression status in bile duct cancers by using 22C3, SP263 and E1L3N antibodies.Methods and resultsWe evaluated PD‐L1 expression in tissue microarrays of 183 extrahepatic bile duct cancers, including 89 perihilar and 94 distal bile duct cancers, by using 22C3, SP263 and E1L3N. When the 22C3 assay was used, tumoral PD‐L1 was shown to be expressed in 16.9% of cases at a 1% threshold. When the SP263 and E1L3N assays were used, tumoral PD‐L1 was shown to be expressed in 26% and 7.1% of cases, respectively. When whole tissue sections were examined, 59.6% of PD‐L1‐positive cases showed a low percentage (<10%) of positive tumour cells. Tumoral PD‐L1 positivity was associated with poor histological differentiation (P = 0.017) and the biliary epithelial phenotype (P = 0.041). High tumoral PD‐L1 expression (≥10%) was associated with worse overall survival (OS) and disease‐free survival (DFS) (OS, P = 0.012; DFS, P = 0.042).ConclusionsPD‐L1 was expressed in a small subset of patients with bile duct cancer, and the percentage of positive tumour cells was low in PD‐L1‐positive cases. The SP263 assay showed the highest PD‐L1 positivity in both tumour cells and immune cells, followed by the 22C3 and E1L3N assays. High PD‐L1 expression was associated with a poor prognosis in extrahepatic bile duct cancer patients.
Real‐world Australian data reflect very high sustained virologic response at 12 weeks with direct acting antiviral therapy for hepatitis C and suggests highly achievable even in those without an end‐of‐treatment response
Authors: Williams James , Lucarelli Nicolas , Nicoll Amanda , Lubel John 
Published: May 2019

AbstractThere are limited real‐world data on the efficacy of direct acting antiviral (DAA) therapy for hepatitis C (HCV) in Australia. In this study, the efficacy of DAA therapy for HCV was compared between cirrhotic and non‐cirrhotic cohorts. Patients without end‐of‐treatment response (EoTR) were observed to ascertain likelihood of achieving sustained virological response at 12 weeks post‐treatment (SVR12). A total of 334 patients with HCV was included. Overall SVR12 was 96.7% with minimal differences in SVR12 between the cirrhosis and non‐cirrhosis groups (95.7 and 97.3%). There were 20 patients (5.99%) that failed to achieve an EoTR of which 80.0% (n = 16) went on to achieve SVR12. These results suggest DAA therapy is effective with high rates of SVR12 even in patients that do not achieve an EoTR.
Tillering and small grain 1 dominates the tryptophan aminotransferase family required for local auxin biosynthesis in rice
Authors: Guo Tao , Chen Ke , Dong Nai‐Qian , Ye Wang‐Wei , Shan Jun‐Xiang , Lin Hong‐Xuan 
Published: May 2019

AbstractAuxin is a crucial phytohormone, controlling multiple aspects of plant growth and responses to the changing environment. However, the role of local auxin biosynthesis in specific developmental programs remains unknown in crops. This study characterized the rice tillering and small grain 1 (tsg1) mutant, which has more tillers but a smaller panicle and grain size resulting from a reduction in endogenous auxin. TSG1 encodes a tryptophan aminotransferase that is allelic to the FISH BONE (FIB) gene. The tsg1 mutant showed hypersensitivity to indole‐3‐acetic acid and the competitive inhibitor of aminotransferase, L‐kynurenine. TSG1 knockout resulted in an increased tiller number but reduction in grain number and size, and decrease in height. Meanwhile, deletion of the TSG1 homologs OsTAR1, OsTARL1, and OsTARL2 caused no obvious changes, although the phenotype of the TSG1/OsTAR1 double mutant was intensified and infertile, suggesting gene redundancy in the rice tryptophan aminotransferase family. Interestingly, TSG1 and OsTAR1, but not OsTARL1 and OsTARL2, displayed marked aminotransferase activity. Meanwhile, subcellular localization was identified as the endoplasmic reticulum, while phylogenetic analysis revealed functional divergence of TSG1 and OsTAR1 from OsTARL1 and OsTARL2. These findings suggest that TSG1 dominates the tryptophan aminotransferase family, playing a prominent role in local auxin biosynthesis in rice.
Arabidopsis ADC1 functions as an Nδ‐acetylornithine decarboxylase
Authors: Lou Yann‐Ru , Ahmed Sheaza , Yan Jian , Adio Adewale M. , Powell Hannah M. , Morris Paul F. , Jander Georg 
Published: May 2019

AbstractPolyamines are small aliphatic amines found in almost all organisms, ranging from bacteria to plants and animals. In most plants, putrescine, the metabolic precursor for longer polyamines, such as spermidine and spermine, is produced from arginine, with either agmatine or ornithine as intermediates. Here we show that Arabidopsis thaliana (Arabidopsis) arginine decarboxylase 1 (ADC1), one of the two known arginine decarboxylases in Arabidopsis, not only synthesizes agmatine from arginine, but also converts Nδ‐acetylornithine to N‐acetylputrescine. Phylogenetic analyses indicate that duplication and neofunctionalization of ADC1 and NATA1, the enzymes that synthesize Nδ‐acetylornithine in Arabidopsis, co‐occur in a small number of related species in the Brassicaceae. Unlike ADC2, which is localized in the chloroplasts, ADC1 is in the endoplasmic reticulum together with NATA1, an indication that these two enzymes have access to the same substrate pool. Together, these results are consistent with a model whereby NATA1 and ADC1 together provide a pathway for the synthesis of N‐acetylputrescine in Arabidopsis.
Photoexcited phytochrome B interacts with brassinazole resistant 1 to repress brassinosteroid signaling in Arabidopsis
Authors: Dong Huixue , Liu Jie , He Guanhua , Liu Pan , Sun Jiaqiang 
Published: May 2019

AbstractPhotoreceptor phytochrome B (phyB) mediates a variety of light responses in plants. To further elucidate the molecular mechanisms of phyB‐regulated hypocotyl elongation, we performed firefly luciferase complementation imaging (LCI) screening for phyB‐interacting transcription factors (TFs). LCI assays showed that phyB possibly interacts with brassinazoleresistant 1 (BZR1), BZR2, AUXIN RESPONSE FACTOR 6 (ARF6), and several WRKY DNA‐binding TFs in a red light‐dependent manner. Furthermore, biochemical assays demonstrated that photoexcited phyB specifically interacts with non‐phosphorylated BZR1, the physiologically active form of a master TF in brassinosteroid (BR) signaling, and this interaction can be competitively interfered by phytochrome‐interacting factor 4. Furthermore, we showed that phyB can directly interact with the DNA‐binding domain of BZR1 and affect the enrichment of BZR1 on the chromatin of target genes. Moreover, our genetic evidence and RNA‐seq analysis demonstrated that phyB negatively regulates BR signaling. Together, we revealed that photoexcited phyB directly interacts with the TF BZR1 to repress BR signaling in Arabidopsis.
Trends in hospitalizations for chronic liver disease‐related liver failure in the United States, 2005‐2014
Authors: Kim Donghee , Cholankeril George , Li Andrew A. , Kim Won , Tighe Sean P. , Hameed Bilal , Kwo Paul Y. , Harrison Stephen A. , Younossi Zobair M. , Ahmed Aijaz 
Published: May 2019

AbstractBackground & AimsCurrent estimates of the population‐based disease burden of liver failure or end‐stage liver disease (ESLD) are lacking. We investigated recent trends in hospitalizations and in‐hospital mortality among patients with ESLD in the United States (US).MethodsA retrospective analysis was performed utilizing the National Inpatient Sample from 2005 to 2014. We defined ESLD as either decompensated cirrhosis or hepatocellular carcinoma (HCC), criteria obtained from the International Classification of Diseases, Ninth Revision. Nationwide rates of hospitalization and in‐hospital mortality were analysed from 2005 to 2014.ResultsHospitalization rates for decompensated cirrhosis during this period increased from 105.3/100 000 persons to 159.9/100 000 persons. In terms of HCC, hospitalization rates increased from 13.6/100 000 to 22.1/100 000. In patients with non‐alcoholic fatty liver disease (NAFLD)‐related decompensated cirrhosis, the hospitalization rate increased from 13.4/100 000 to 32.1/100 000 with an annual incremental increase of 10.6%, a magnitude twofold higher than other aetiologies. The proportion of NAFLD among hospitalizations with ESLD steadily increased from 12.7% to 20.1% for decompensated cirrhosis while the proportion of chronic hepatitis C (HCV) and alcoholic liver disease (ALD) declined (from 29.3% to 27.6% for HCV; from 39.0% to 37.4% for ALD). Although the overall in‐hospital mortality rates for ESLD declined during the study, mortality rates for NAFLD‐related decompensated cirrhosis showed no significant change.ConclusionsAmong aetiologies of chronic liver disease, NAFLD demonstrated the fastest growing rate of hospitalizations in non‐HCC patients with ESLD in the US. Our study highlights the need for a focus on NAFLD‐related hospitalizations and its impact on resource utilization.