bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-genome sequence of the oriental lung fluke Paragonimus westermani
Authors: Oey Harald , Zakrzewski Martha , Narain Kanwar , Devi K Rekha , Agatsuma Takeshi , Nawaratna Sujeevi , Gobert Geoffrey N , Jones Malcolm K , Ragan Mark A , McManus Donald P , Krause Lutz 
Published: December 2018

Abstract

Background
Foodborne infections caused by lung flukes of the genus Paragonimus are a significant and widespread public health problem in tropical areas. Approximately 50 Paragonimus species have been reported to infect animals and humans, but Paragonimus westermani is responsible for the bulk of human disease. Despite their medical and economic importance, no genome sequence for any Paragonimus species is available.

Results
We sequenced and assembled the genome of P. westermani, which is among the largest of the known pathogen genomes with an estimated size of 1.1 Gb. A 922.8 Mb genome assembly was generated from Illumina and Pacific Biosciences (PacBio) sequence data, covering 84% of the estimated genome size. The genome has a high proportion (45%) of repeat-derived DNA, particularly of the long interspersed element and long terminal repeat subtypes, and the expansion of these elements may explain some of the large size. We predicted 12,852 protein coding genes, showing a high level of conservation with related trematode species. The majority of proteins (80%) had homologs in the human liver fluke Opisthorchis viverrini, with an average sequence identity of 64.1%. Assembly of the P. westermani mitochondrial genome from long PacBio reads resulted in a single high-quality circularized 20.6 kb contig. The contig harbored a 6.9 kb region of non-coding repetitive DNA comprised of three distinct repeat units. Our results suggest that the region is highly polymorphic in P. westermani, possibly even within single worm isolates.

Conclusions
The generated assembly represents the first Paragonimus genome sequence and will facilitate future molecular studies of this important, but neglected, parasite group.
Annotation of the Giardia proteome through structure-based homology and machine learning
Authors: Ansell Brendan R E , Pope Bernard J , Georgeson Peter , Emery-Corbin Samantha J , Jex Aaron R 
Published: December 2018

Abstract

Background
Large-scale computational prediction of protein structures represents a cost-effective alternative to empirical structure determination with particular promise for non-model organisms and neglected pathogens. Conventional sequence-based tools are insufficient to annotate the genomes of such divergent biological systems. Conversely, protein structure tolerates substantial variation in primary amino acid sequence and is thus a robust indicator of biochemical function. Structural proteomics is poised to become a standard part of pathogen genomics research; however, informatic methods are now required to assign confidence in large volumes of predicted structures.

Aims
Our aim was to predict the proteome of a neglected human pathogen, Giardia duodenalis, and stratify predicted structures into high- and lower-confidence categories using a variety of metrics in isolation and combination.

Methods
We used the I-TASSER suite to predict structural models for ~5,000 proteins encoded in G. duodenalis and identify their closest empirically-determined structural homologues in the Protein Data Bank. Models were assigned to high- or lower-confidence categories depending on the presence of matching protein family (Pfam) domains in query and reference peptides. Metrics output from the suite and derived metrics were assessed for their ability to predict the high-confidence category individually, and in combination through development of a random forest classifier.

Results
We identified 1,095 high-confidence models including 212 hypothetical proteins. Amino acid identity between query and reference peptides was the greatest individual predictor of high-confidence status; however, the random forest classifier outperformed any metric in isolation (area under the receiver operating characteristic curve = 0.976) and identified a subset of 305 high-confidence-like models, corresponding to false-positive predictions. High-confidence models exhibited greater transcriptional abundance, and the classifier generalized across species, indicating the broad utility of this approach for automatically stratifying predicted structures. Additional structure-based clustering was used to cross-check confidence predictions in an expanded family of Nek kinases. Several high-confidence-like proteins yielded substantial new insight into mechanisms of redox balance in G. duodenalis—a system central to the efficacy of limited anti-giardial drugs.

Conclusion
Structural proteomics combined with machine learning can aid genome annotation for genetically divergent organisms, including human pathogens, and stratify predicted structures to promote efficient allocation of limited resources for experimental investigation.
Circulating vitamin D concentrations and risk of breast and prostate cancer: a Mendelian randomization study
Authors: Jiang Xia , Dimou Niki L , Al-Dabhani Kawthar , Lewis Sarah J , Martin Richard M , Haycock Philip C , Gunter Marc J , Key Timothy J , Eeles Rosalind A , Muir Kenneth , Neal David , Giles Graham G , Giovannucci Edward L , Stampfer Meir , Pierce Brandon L , Schildkraut Joellen M , Warren Andersen Shaneda , Thompson Deborah , Zheng Wei , Kraft Peter , Tsilidis Konstantinos K ,   PRACTICAL, CRUK, BPC3, CAPS and PEGASUS consortia
Published: December 2018

AbstractBackgroundObservational studies have suggested an association between circulating vitamin D concentrations [25(OH)D] and risk of breast and prostate cancer, which was not supported by a recent Mendelian randomization (MR) analysis comprising 15 748 breast and 22 898 prostate-cancer cases. Demonstrating causality has proven challenging and one common limitation of MR studies is insufficient power.MethodsWe aimed to determine whether circulating concentrations of vitamin D are causally associated with the risk of breast and prostate cancer, by using summary-level data from the largest ever genome-wide association studies conducted on vitamin D (N = 73 699), breast cancer (Ncase = 122 977) and prostate cancer (Ncase = 79 148). We constructed a stronger instrument using six common genetic variants (compared with the previous four variants) and applied several two-sample MR methods.ResultsWe found no evidence to support a causal association between 25(OH)D and risk of breast cancer [OR per 25 nmol/L increase, 1.02 (95% confidence interval: 0.97–1.08), P = 0.47], oestrogen receptor (ER)+ [1.00 (0.94–1.07), P = 0.99] or ER− [1.02 (0.90–1.16), P = 0.75] subsets, prostate cancer [1.00 (0.93–1.07), P = 0.99] or the advanced subtype [1.02 (0.90–1.16), P = 0.72] using the inverse-variance-weighted method. Sensitivity analyses did not reveal any sign of directional pleiotropy.ConclusionsDespite its almost five-fold augmented sample size and substantially improved statistical power, our MR analysis does not support a causal effect of circulating 25(OH)D concentrations on breast- or prostate-cancer risk. However, we can still not exclude a modest or non-linear effect of vitamin D. Future studies may be designed to understand the effect of vitamin D in subpopulations with a profound deficiency.
Long-term outcomes of patients with stable coronary disease and chronic kidney dysfunction: 10-year follow-up of the Medicine, Angioplasty, or Surgery Study II Trial
Authors: Lima Eduardo Gomes , Charytan David M , Hueb Whady , de Azevedo Diogo Freitas Cardoso , Garzillo Cibele Larrosa , Favarato Desiderio , Linhares Filho Jaime Paula Pessoa , Martins Eduardo Bello , Batista Daniel Valente , Rezende Paulo Cury , Hueb Alexandre Ciappina , Ramires José Antonio Franchini , Kalil Filho Roberto 
Published: December 2018

Abstract

Background
Chronic kidney disease (CKD) is associated with a worse prognosis in patients with stable coronary artery disease (CAD); however, there is limited randomized data on long-term outcomes of CAD therapies in these patients. We evaluated long-term outcomes of CKD patients with CAD who underwent randomized therapy with medical treatment (MT) alone, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG).

Methods
Baseline estimated glomerular filtration rate (eGFR) was obtained in 611 patients randomized to one of three therapeutic strategies in the Medicine, Angioplasty, or Surgery Study II trial. Patients were categorized in preserved renal function and mild or moderate CKD groups depending on their eGFR (≥90, 89–60 and 59–30 mL/min/1.73 m2, respectively). The primary clinical endpoint, a composite of overall death and myocardial infarction, and its individual components were analyzed using proportional hazards regression (Clinical Trial registration information: http://www.controlled-trials.com. Registration number: ISRCTN66068876).

Results
Of 611 patients, 112 (18%) had preserved eGFR, 349 (57%) mild dysfunction and 150 (25%) moderate dysfunction. The primary endpoint occurred in 29.5, 32.4 and 44.7% (P = 0.02) for preserved eGFR, mild CKD and moderate CKD, respectively. Overall mortality incidence was 18.7, 23.8 and 39.3% for preserved eGFR, mild CKD and moderate CKD, respectively (P = 0.001). For preserved eGFR, there was no significant difference in outcomes between therapies. For mild CKD, the primary event rate was 29.4% for PCI, 29.1% for CABG and 41.1% for MT (P = 0.006) [adjusted hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.07–0.88; P = 0.03 for PCI versus MT; and adjusted HR = 0.48; 95% CI 0.31–0.76; P = 0.002 for CABG versus MT]. We also observed higher mortality rates in the MT group (28.6%) compared with PCI (24.1%) and CABG (19.0%) groups (P = 0.015) among mild CKD subjects (adjusted HR = 0.44, 95% CI 0.25–0.76; P = 0.003 for CABG versus MT; adjusted HR = 0.56, 95% CI 0.07–4.28; P = 0.58 for PCI versus MT). Results were similar with moderate CKD group but did not achieve significance.

Conclusions
Coronary interventional therapy, both PCI and CABG, is associated with lower rates of events compared with MT in mild CKD patients &gt;10 years of follow-up. More study is needed to confirm these benefits in moderate CKD.
Labour’s declining share of national income in Ireland and Denmark: the national specificities of structural change
Authors: Flaherty Eoin , Riain Seán Ó 
Published: December 2018

AbstractThe share of national income going to workers has decreased steadily across Europe since the 1980s. This apparently uniform decrease in labour’s share conceals differences amongst states however—in ‘liberal’ Ireland, this fall has been drastic, while that of ‘social democratic’ Denmark has been moderate. This article presents a parallel time series analysis of institutional and structural factors shaping labour’s share in Ireland and Denmark. Our results show that factors common to the study of variation in labour’s share operate in different ways in different countries, both in magnitude and causal mechanism. We find that stressors such as global trade, foreign investment and high-tech growth produce different effects in each location. Equally, protections such as unionization, leftist cabinets and welfare spending display contradictory effects in both locations. We conclude that ‘power resource’ models of labour share should be supplemented with comparative approaches that emphasize how institutionalized socio-political logics mediate returns to labour.
Evaluation of a Quality Improvement Intervention That Eliminated Routine Use of Opioids After Cesarean Delivery
Authors: Holland Erica , Bateman Brian T. , Cole Naida , Taggart Ashley , Robinson Laura A. , Sugrue Ronan , Xu Xinling , Robinson Julian N. 
Published: December 2018

OBJECTIVE:
To evaluate the effects of eliminating the routine use of oral opioids for postcesarean delivery analgesia on postcesarean opioid consumption.

METHODS:
At a tertiary care center, we implemented a quality improvement intervention among faculty practice patients undergoing cesarean delivery, which consisted of 1) eliminating routine ordering of oral opioids after cesarean delivery, 2) implementing guidelines for ordering a short course of opioids when deemed necessary, and 3) coupling opioid prescribing at discharge to patterns of opioid use in-hospital combined with shared decision-making. All patients, both before and after the intervention, were administered neuraxial opioids and scheduled acetaminophen and nonsteroidal antiinflammatory medications in the absence of contraindications. The primary outcome was the percentage of women who used any opioids postoperatively in-hospital. Secondary outcomes included the percentage of women discharged with a prescription for opioids, the quantity of opioids used in-hospital, pain scores, satisfaction, opioid-related side effects, and opioid prescriptions ordered in the 6 weeks after delivery. The effects of this intervention were assessed based on a chart review of patient data and a survey of patients in the 12 weeks before and 12 weeks after the intervention.

RESULTS:
We evaluated the records of 191 postcesarean delivery patients before and 181 after the intervention. Less than half of women used oral opioids in-hospital after the intervention, 82 (45%) compared with 130 (68%) before (P<.001). However, there was no change in pain scores or overall satisfaction with pain relief. Postintervention, only 40% of patients were discharged with prescriptions for opioids compared with 91% of patients before the intervention (P<.001).

CONCLUSION:
Eliminating routine ordering of oral opioids after cesarean delivery is associated with a significant decrease in opioid consumption while maintaining the same levels of pain control and patient satisfaction. Oral opioids are not needed by a large proportion of women after cesarean delivery.
Novel immunological and clinical insights in vascularized composite allotransplantation
Authors: Kollar Branislav , Pomahac Bohdan , Riella Leonardo V. 
Published: December 2018

Purpose of review
Vascularized composite allotransplantation (VCA) is a promising approach to restore the quality of life of carefully selected patients that suffered extensive injury. Although acute rejection occurs very frequently, still little is known about the specific characteristics of the VCA immune response. This review aims to highlight the current development in the field of VCA concerning the immunobiology and management of upper extremity and face transplant recipients.

Recent findings
T-cell mediated rejection is the predominant mechanism of allograft injury in VCA. As current histological classification does not differentiate types of rejection, novel evidence using NanoString has determined a molecular signature that helps identify antibody-mediated rejection in comparison to T-cell mediated rejection. Additionally, long-term follow-up of VCA patients progressively reveals various features of chronic rejection, and novel immunosuppressive approaches such as costimulation blockade found its way into immunosuppressive regimens of VCA recipients, unraveling its potential benefits as well as limitations. Finally, novel noninvasive biomarkers were recently evaluated and showed promise to differentiate the severity of acute rejection, and consequently, the intensity of treatment required.

Summary
With growing knowledge about the immunobiology in VCA, novel approaches to immunosuppressive therapy and immune monitoring will help better manage patients and improve long-term VCA outcomes.
AQP1 and AQP3 Expression are Associated With Severe Symptoms and Poor-prognosis of the Pancreatic Ductal Adenocarcinoma
Authors: Zou Wen , Yang Zhulin , Li Daiqiang , Liu Ziru , Zou Qiong , Yuan Yuan 
Published: December 2018

Background:
Approximately 80% of patients with pancreatic ductal adenocarcinoma (PDAC) have metastatic disease with poor prognosis, but clinically available biomarkers for the diagnosis, prediction of prognosis, and target therapy have not yet been identified.

Objective:
To investigate the expression of aquaporin-1 (AQP1) and AQP3 protein and their clinicopathological significances in PDACs.

Materials and Method:
AQP1 and AQP3 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues was measured by immunohistochemistry.

Results:
Western blot showed that AQP1 and AQP3 protein expression was significantly higher in PDAC tissues than that in benign pancreatic tissues (P<0.01). Immunohistochemistry showed that the percentages of positive AQP1 and AQP3 expressions were significantly higher in PDAC tumors than that in peritumoral tissues, benign, and normal pancreatic tissues (P<0.01). Benign pancreatic lesions with positive AQP1 and AQP3 expression exhibited a dysplasia or intraepithelial neoplasia. The percentage of cases with positive AQP1 and AQP3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion, and having low Tumor, Node and Metastasis (TNM) stage disease than in patients with lymph node metastasis, invasion, and high TNM stage disease (P<0.05 or <0.01). Kaplan-Meier survival analysis showed that positive AQP1 and AQP3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive AQP1 and AQP3 expression was independent poor prognosis factors in PDAC patients. The area under the curve of receiver operating characteristic curve was 0.669 for AQP1 and 0.707 for AQP3, respectively.

Conclusions:
Positive AQP1 and AQP3 expressions are associated with the tumorigenesis and progression of PDAC. Both AQP1 and AQP3 are a diagnostic marker of PDAC and a predictive marker of poor prognosis in PDAC patients.
Association Between Erectile Dysfunction and Carotid Subclinical Atherosclerosis in HIV-Infected Patients
Authors: Bernal Enrique , Torres Marcos , Alcaraz Antonia , Alcaraz Maria Jose , Rosa Vicente de la , Valero Salvador , Muñoz Angeles , Onteniente María , Vicente Tomas , Cano Alfredo 
Published: December 2018

Background:
Erectile dysfunction (ED) is frequent in HIV-infected patients, and it can be associated with atherosclerosis and cardiovascular events. So, the objective was to evaluate whether the presence of moderate–severe ED was a marker of subclinical atherosclerosis (SCA) in HIV-infected patients.

Methods:
A cross-sectional study was conducted in a cohort of HIV-infected patients. The presence of ED was assessed using the International Index of Erectile Function (IIEF-5) questionnaire. The presence of SCA was determined by calculating the mean carotid intima–media thickness with Doppler ultrasound. A logistic regression analysis was performed to check the variables associated with SCA.

Results:
One hundred thirty-nine men of 45 (10) years of age were included, of which 130 (94.9%) received antiretroviral therapy. In 30 (22%) patients, the Framingham score was higher than 10%. In 36 (25.9%) patients, ED was detected in a moderate–severe degree and in 53 (38.1%), SCA was detected. In the multivariate analysis, variables independently associated with the presence of SCA were as follows: older age [odds ratio (OR) = 1.22, confidence interval (CI) 95%: 1.1 to 1.35, P < 0.001] and moderate–severe ED (OR = 4.68, CI 95%: 1.18 to 18.5; P = 0.028). Variables associated with moderate–severe ED were as follows: age (OR = 1.107, CI 95%: 1.041 to 1.17, P < 0.001) and having antibodies for hepatitis C virus (OR = 5.12, CI 95%: 1.54 to 17.03, P < 0.001).

Conclusions:
HIV-Infected patients often have moderate–severe ED, especially the elderly and coinfected patients with hepatitis C virus. ED can be an early clinical manifestation of incipient atherosclerosis, so its presence should involve a deep control of cardiovascular risk factors and using a regimen with a better atherogenic profile.
The effect of plasma lipids and lipid lowering interventions on bone mineral density: a Mendelian randomization study
Authors: Zheng Jie , Brion Marie-Jo , Kemp John P. , Warrington Nicole M. , Borges Maria-Carolina , Hemani Gibran , Richardson Tom , Qiao Zhen , Haycock Philip , Ala-Korpela Mika , Smith George Davey , Tobias Jon H. , Evans David M. 
Published: December 2018

AbstractStatin treatment increases bone mineral density (BMD) and reduces fracture risk, but the underlying mechanism is unclear. We used Mendelian randomization (MR) to assess whether this relation is explained by a specific effect in response to statin use, or by a general effect of lipid-lowering. We utilized 400 single nucleotide polymorphisms (SNPs) robustly associated with plasma lipid levels and results from a heel BMD GWAS (derived from quantitative ultrasound) in 426,824 individuals from the UK Biobank. We performed univariate and multivariable MR analyses of low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels on BMD. To test whether the effect of statins on BMD was mediated by lowering lipid levels, MR was repeated with and without SNPs in theHMGCRregion, the gene targeted by statins. Univariate MR analyses provided evidence for a causal effect of LDL-C on BMD (β= −0.060; −0.084 to −0.036; P = 4×10-6; standard deviation change in BMD per standard deviation change in LDL-C, with 95% CI), but not HDL or triglycerides. Multivariable MR analysis suggested that the effect of LDL-C on BMD was independent of HDL-C and triglycerides, and sensitivity analyses involving MR Egger and weighted median MR approaches suggested that the LDL-C results were robust to pleiotropy. MR analyses of LDL-C restricted to SNPs in theHMGCRregion showed similar effects on BMD(β= −0.083; −0.132 to −0.034; P = 0.001) to those excluding these SNPs (β= −0.063; −0.090 to −0.036; P = 8×10-6). Bidirectional MR analyses provided some evidence for a causal effect of BMD on plasma LDL-C levels. Our results suggest that effects of statins on BMD are at least partly due to their LDL-C lowering effect. Further studies are required to examine the potential role of modifying plasma lipid levels in treating osteoporosis.