bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin E is an effective treatment for nonalcoholic steatohepatitis in HIV mono-infected patients
Authors: Sebastiani Giada , Saeed Sahar , Lebouche Bertrand , de Pokomandy Alexandra , Szabo Jason , Haraoui Louis-Patrick , Routy Jean-Pierre , Wong Philip , Deschenes Marc , Ghali Peter , Klein Marina 
Published: October 2019

Objective:
HIV-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown.

Design:
Single-centre, phase IV, open-label, single arm clinical trial.

Methods:
HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) at least 248 dB/m and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) greater than 130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks postdiscontinuation. Generalized linear mixed effects models were used to evaluate changes in alanine aminotransferase (ALT), CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pretreatment trends.

Results:
A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared with baseline, 24 weeks of vitamin E treatment improved ALT [−27 units/l; 95% confidence interval (CI) −37 to −17], CAP scores (−22 dB/m; 95% CI −42 to −1) and CK-18 (−123 units/l; 95% CI −201 to −46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up.

Conclusion:
In this first clinical trial, we showed that vitamin E is an effective and well tolerated treatment for NASH in HIV-infected patients.
Impact of Significant Coronary Artery Calcification Reported on Low-Dose Computed Tomography Lung Cancer Screening
Authors: Mendoza Dexter P. , Kako Bashar , Digumarthy Subba R. , Shepard Jo-Anne O. , Little Brent P. 
Published: October 2019

Background:
Coronary artery calcification (CAC) is a common and important incidental finding in low-dose computed tomography (LDCT) performed for lung cancer screening (LCS). The impact of these incidental findings on patient management is unclear.

Purpose:
The goals of our study were to determine the impact of reporting CAC on patient management and to determine whether standardized reporting of CAC affects the likelihood of future interventions.

Methods:
In this IRB-approved retrospective study, we queried our LCS database for reports of LDCT performed between January 2016 and September 2018. All reports with significant findings of CAC designated with the letter “S” for any Lung-RADS category were selected. The grading of CAC was extracted from the reports. Medical records were reviewed for each patient to determine demographics, clinical history, medications, and cardiac-related diagnostic and interventional procedures. The changes in management after the report of significant CAC on LDCT were documented. Statistical analysis with Student t test and Pearson χ2 test was performed.

Results:
A total of 756/3110 patients (mean age: 67±6.4 y; M=466, 61.6%: F=290, 38.4%) were reported to have significant CAC on LDCT for LCS. Of them, 236/756 patients (31.2%) had established coronary artery disease (CAD) at baseline, before the initial LDCT. A change in management was observed in 155/756 patients (20.5%). The most common changes in management included the following: alteration in medication regimen (n=114/155, 73.5%), stress testing (n=65/155, 41.9%), and referral to a cardiologist (36/155, 23.2%). Percutaneous coronary intervention (4, 2.6%) and surgery (3, 1.9%) were uncommon. Changes in management were more common in those without established CAD and in those whose CAC was semiquantitatively graded (35% vs. 25%, P=0.02).

Conclusion:
CAC is a common significant finding in LDCT for LCS. Reporting of CAC in patients with nonestablished CAD and semiquantitative assessment resulted in changes in management.
Elective Surgery for Diverticulitis and the Risk of Recurrence and Ostomy
Authors: Thornblade Lucas W. , Simianu Vlad V. , Davidson Giana H. , Flum David R. 
Published: October 2019

Objective:
To assess the comparative risk of recurrence and ostomy after elective resection or medical therapy for uncomplicated diverticulitis, incorporating outpatient episodes of recurrence.

Background:
While surgeons historically recommended colon resection for uncomplicated diverticulitis to reduce the risk of recurrence or colostomy, no prior studies have quantified this risk when considering outpatient episodes of disease. It remains to be determined whether surgery actually decreases those risks.

Methods:
Retrospective cohort study employing an adjusted time-to-event analysis to assess the relationship of medical or surgical treatment with diverticulitis recurrence and/or receipt of an ostomy. Subjects were adults with ≥1 year continuous enrollment treated for ≥2 episodes of uncomplicated diverticulitis from a nationwide commercial claims dataset (2008–2014).

Results:
Of 12,073 patients (mean age 56 ± 14 yr, 59% women), 19% underwent elective surgery and 81% were treated by medical therapy on their second treatment encounter for uncomplicated diverticulitis. At 1 year, patients treated by elective surgery had lower rates of recurrence (6%) versus those treated by medical therapy (32%) [15% vs 61% at 5 years, adjusted hazard ratio 0.17 (95% confidence interval: 0.15–0.20)]. At 1 year, the rate of ostomy after both treatments was low [surgery (inclusive of stoma related to the elective colectomy), 4.0%; medical therapy, 1.6%].

Conclusions:
Elective resection for uncomplicated diverticulitis decreases the risk of recurrence, still 6% to 15% will recur within 5 years of surgery. The risk of ostomy is not lower after elective resection, and considering colostomies related to resection, ostomy prevention should not be considered an appropriate indication for elective surgery.
A Decade of Damage Control Resuscitation
Authors: Cole Elaine , Weaver Anne , Gall Lewis , West Anita , Nevin Daniel , Tallach Rosel , O’Neill Breda , Lahiri Sumitra , Allard Shubha , Tai Nigel , Davenport Ross , Green Laura , Brohi Karim 
Published: October 2019

Objective:
The aim of this study was to identify the effects of recent innovations in trauma major hemorrhage management on outcome and transfusion practice, and to determine the contemporary timings and patterns of death.

Background:
The last 10 years have seen a research-led change in hemorrhage management to damage control resuscitation (DCR), focused on the prevention and treatment of trauma-induced coagulopathy.

Methods:
A 10-year retrospective analysis of prospectively collected data of trauma patients who activated the Major Trauma Centre's major hemorrhage protocol (MHP) and received at least 1 unit of red blood cell transfusions (RBC).

Results:
A total of 1169 trauma patients activated the MHP and received at least 1 unit of RBC, with similar injury and admission physiology characteristics over the decade. Overall mortality declined from 45% in 2008 to 27% in 2017, whereas median RBC transfusion rates dropped from 12 to 4 units (massive transfusion rates from 68% to 24%). The proportion of deaths within 24 hours halved (33%–16%), principally with a fall in mortality between 3 and 24 hours (30%–6%). Survivors are now more likely to be discharged to their own home (57%–73%). Exsanguination is still the principal cause of early deaths, and the mortality associated with massive transfusion remains high (48%). Late deaths are now split between those due to traumatic brain injury (52%) and multiple organ dysfunction (45%).

Conclusions:
There have been remarkable reductions in mortality after major trauma hemorrhage in recent years. Mortality rates continue to be high and there remain important opportunities for further improvements in these patients.
Effects of Intraoperative Fluid Balance During Liver Transplantation on Postoperative Acute Kidney Injury: An Observational Cohort Study
Authors: Carrier François Martin , Chassé Michaël , Sylvestre Marie-Pierre , Girard Martin , Legendre-Courville Lancelot , Massicotte Luc , Bilodeau Marc 
Published: October 2019

Background.
Liver transplant recipients suffer many postoperative complications. Few studies evaluated the effects of fluid management on these complications. We conducted an observational cohort study to evaluate the association between intraoperative fluid balance and postoperative acute kidney injury (AKI) and other postoperative complications.

Methods.
We included consecutive adult liver transplant recipients who had their surgery between July 2008 and December 2017. Our exposure was intraoperative fluid balance, and our primary outcome was the grade of AKI at 48 hours after surgery. Our secondary outcomes were the grade of AKI at 7 days, the need for postoperative renal replacement therapy, postoperative red blood cell transfusions, time to first extubation, time to discharge from the intensive care unit (ICU), and 1-year survival. Every analysis was adjusted for potential confounders.

Results.
We included 532 transplantations in 492 patients. We observed no effect of fluid balance on either 48-hour AKI, 7-day AKI, or on the need for postoperative renal replacement therapy after adjustments for confounders. A higher fluid balance increased the time to ICU discharge, and increased the risk of dying (hazard ratio = 1.21 [1.04,1.40]).

Conclusions.
We observed no association between intraoperative fluid balance and postoperative AKI. Fluid balance was associated with longer time to ICU discharge and lower survival. This study provides insight that might inform the design of a clinical trial on fluid management strategies in this population.
Long-term Graft Survival and Graft Function Following Pregnancy in Kidney Transplant Recipients: A Systematic Review and Meta-analysis
Authors: van Buren Marleen C. , Schellekens Anouk , Groenhof T. Katrien J. , van Reekum Franka , van de Wetering Jacqueline , Paauw Nina D. , Lely A. Titia 
Published: October 2019

Background.
The incidence of pregnancy in kidney transplantation (KT) recipients is increasing. Studies report that the incidence of graft loss (GL) during pregnancy is low, but less data are available on long-term effects of pregnancy on the graft.

Methods.
Therefore, we performed a meta-analysis and systematic review on GL and graft function, measured by serum creatinine (SCr), after pregnancy in KT recipients, stratified in years postpartum. Furthermore, we included studies of nulliparous KT recipients.

Results.
Our search yielded 38 studies on GL and 18 studies on SCr. The pooled incidence of GL was 9.4% within 2 years after pregnancy, 9.2% within 2–5 years, 22.3% within 5–10 years, and 38.5% >10 years postpartum. In addition, our data show that, in case of graft survival, SCr remains stable over the years. Only within 2 years postpartum, Δ SCr was marginally higher (0.18 mg/dL, 95%CI [0.05-0.32], P = 0.01). Furthermore, no differences in GL were observed in 10 studies comparing GL after pregnancy with nulliparous controls. Systematic review of the literature showed that mainly prepregnancy proteinuria, hypertension, and high SCr are risk factors for GL.

Conclusions.
Overall, these data show that pregnancy after KT has no effect on long-term graft survival and only a possible effect on graft function within 2 years postpartum. This might be due to publication bias. No significant differences were observed between pre- and postpartum SCr at longer follow-up intervals.
Reassessing the observational evidence for nitrogen deposition impacts in acid grassland: Spatial Bayesian linear models indicate small and ambiguous effects on species richness
Authors: Pescott O.L. , Jitlal M. 
Published: October 2019

AbstractNitrogen deposition (Ndep) is considered a significant threat to plant diversity in grassland ecosystems around the world. The evidence supporting this conclusion comes from both observational and experimental research, with “space-for-time” substitution surveys of pollutant gradients a significant portion of the former. However, estimates of regression coefficients for Ndep impacts on species richness, derived with a focus on causal inference, are hard to locate in the observational literature. Some influential observational studies have presented estimates from univariate models, overlooking the effects of omitted variable bias, and/or have used P-value-based stepwise variable selection (PSVS) to infer impacts, a strategy known to be poorly suited to the accurate estimation of regression coefficients. Broad-scale spatial autocorrelation has also generally been unaccounted for. We re-examine two UK observational datasets that have previously been used to investigate the relationship between Ndep and plant species richness in acid grasslands, a much-researched habitat in this context. One of these studies (Stevens et al. 2004, Science, 303:1876–1879) estimated a large negative impact of Ndep on richness through the use of PSVS; the other reported smaller impacts (Maskell et al. 2010, Glob. Change Biol., 16:671–679), but did not explicitly report regression coefficients or partial effects, making the actual size of the estimated Ndep impact difficult to assess. We reanalyse both datasets using a spatial Bayesian linear model estimated using integrated nested Laplace approximation (INLA). Contrary to previous results, we found similar-sized estimates of the Ndep impact on plant richness between studies, both with and without bryophytes, albeit with some disagreement over the most likely direction of this effect. Our analyses suggest that some previous estimates of Ndep impacts on richness from space-for-time substitution studies are likely to have been over-estimated, and that the evidence from observational studies could be fragile when confronted with alternative model specifications, although further work is required to investigate potentially nonlinear responses. Given the growing literature on the use of observational data to estimate the impacts of pollutants on biodiversity, we suggest that a greater focus on clearly reporting important outcomes with associated uncertainty, the use of techniques to account for spatial autocorrelation, and a clearer focus on the aims of a study, whether explanatory or predictive, are all required.
Detecting prodromal Alzheimer’s disease with MRI through deep learning
Authors: Feng Xinyang , Provenzano Frank A. , Small Scott A. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2019

ABSTRACTDeep learning applied to MRI for Alzheimer’s classification is hypothesized to improve if the deep learning model implicates disease’s pathophysiology. The challenge in testing this hypothesis is that large-scale data are required to train this type of model. Here, we overcome this challenge by using a novel data augmentation strategy and show that our MRI-based deep learning model classifies Alzheimer’s dementia with high accuracy. Moreover, a class activation map was found dominated by signal from the hippocampal formation, a site where Alzheimer’s pathophysiology begins. Next, we tested the model’s performance in prodromal Alzheimer’s when patients present with mild cognitive impairment (MCI). We retroactively dichotomized a large cohort of MCI patients who were followed for up to 10 years into those with and without prodromal Alzheimer’s at baseline and used the dementia-derived model to generate individual ‘deep learning MRI’ scores. We compared the two groups on these scores, and on other biomarkers of amyloid pathology, tau pathology, and neurodegeneration. The deep learning MRI scores outperformed nearly all other biomarkers, including—unexpectedly—biomarkers of amyloid or tau pathology, in classifying prodromal disease and in predicting clinical progression. Providing a mechanistic explanation, the deep learning MRI scores were found to be linked to regional tau pathology, through investigations using cross-sectional, longitudinal, premortem and postmortem data. Our findings validate that a disease’s known pathophysiology can improve the design and performance of deep learning models. Moreover, by showing that deep learning can extract useful biomarker information from conventional MRIs, the advantages of this model extend practically, potentially reducing patient burden, risk, and cost.
A Comparative Study of Topology-based Pathway Enrichment Analysis Methods
Authors: Ma Jing , Shojaie Ali , Michailidis George 
Published: October 2019

AbstractBackgroundPathway enrichment analysis is extensively used in the analysis of Omics data for gaining biological insights into the functional roles of pre-defined subsets of genes, proteins and metabolites. A large number of methods have been proposed in the literature for this task. The vast majority of these methods use as input expression levels of the biomolecules under study together with their membership in pathways of interest. The latest generation of pathway enrichment methods also leverages information on the topology of the underlying pathways, which as evidence from their evaluation reveals, lead to improved sensitivity and specificity. Nevertheless, a systematic empirical comparison of such methods is still lacking, making selection of the most suitable method for a specific experimental setting challenging. This comparative study of nine network-based methods for pathway enrichment analysis aims to provide a systematic evaluation of their performance based on three real data sets with different number of features (genes/metabolites) and number of samples.ResultsThe findings highlight both methodological and empirical differences across the nine methods. In particular, certain methods assess pathway enrichment due to differences both across expression levels and in the strength of the interconnectedness of the members of the pathway, while others only leverage differential expression levels. In the more challenging setting involving a metabolomics data set, the results show that methods that utilize both pieces of information (with NetGSA being a prototypical one) exhibit superior statistical power in detecting pathway enrichment.ConclusionThe analysis reveals that a number of methods perform equally well when testing large size pathways, which is the case with genomic data. On the other hand, NetGSA that takes into consideration both differential expression of the biomolecules in the pathway, as well as changes in the topology exhibits a superior performance when testing small size pathways, which is usually the case for metabolomics data.
Altered germline cyst and oocyte differentiation inTex14mutant mice reveal a new mechanism underlying female reproductive life-span
Authors: Nuzhat Nafisa , Ikami Kanako , Abbott Haley , Tanner Heather , Spradling Allan C. , Lei Lei 
Published: October 2019

AbstractIn adult mammalian females, primordial follicles that form in the fetal/neonatal ovary are the only source to sustain adult ovarian function. Our previous studies revealed that during oocyte differentiation and primordial follicle formation in mouse fetal ovaries, primary oocytes form via gaining cytoplasm and organelles from sister germ cells that are connected to them by intercellular bridges within germline cysts. To better understand the role of intercellular bridges in oocyte differentiation, we analyzed mutant females lackingtestis-expressed 14 (Tex14), a gene involved in cytokinesis and bridge formation. InTex14-/-fetal ovaries, germ cells divide to form a reduced number of cysts in which sister germ cells are still connected via syncytia or fragmented cell membranes, rather than normal intercellular bridges. Compared with wildtype cysts,Tex14-/-cysts fragment at a higher frequency and produce a greatly reduced number of primary oocytes with highly precocious cytoplasmic enrichment and enlarged volume. By contrast,Tex14+/-germline cysts are less fragmented and generate primary oocytes that are smaller than wild type. Interestingly, enlargedTex14-/-primary oocytes are much more stable than wild type oocytes and more efficiently sustain folliculogenesis, whereas undersizedTex14+/-primary oocytes turn over at an accelerated rate. Our observations directly link the nature of fetal germ cell connectivity to cytoplasmic enrichment during oocyte differentiation and to oocyte developmental potential in the adult ovary. Our results imply that the duration of adult ovarian function is strongly influenced by the number of primary oocytes acquiring highly enriched cytoplasm during oocyte differentiation in fetal ovaries, rather than just by the size of the primordial follicle pool.
Large-scale Analysis of 2,152 dataset reveals key features of B cell biology and the antibody repertoire
Authors: Yang Xiujia , Wang Minhui , Shi Dianchun , Zhang Yanfang , Zeng Huikun , Zhu Yan , Lan Chunhong , Wu Jiaqi , Deng Yang , Guo Shixin , Xu Lijun , Ma Cuiyu , Zhang Yanxia , Wu Rongrong , Ou Jinxia , Liu Chu-jun , Chang Changqing , Yang Wei , Zhang Huijie , Chen Jun , Qin Lijie , Zhou Hongwei , Bei Jin-Xin , Wei Lai , Cao Guangwen , Yu Xueqing , Zhang Zhenhai 
Published: October 2019

AbstractAntibody repertoire sequencing (Ig-seq) has been widely used in studying humoral responses, with promising results. However, the promise of Ig-seq has not yet been fully realized, and key features of the antibody repertoire remain elusive or controversial. To clarify these key features, we analyzed 2,152 high-quality heavy chain antibody repertoires, representing 582 donors and a total of 360 million clones. Our study revealed that individuals exhibit very similar gene usage patterns for germline V, D, and J genes and that 53 core V genes contribute to more than 99% of the heavy chain repertoire. We further found that genetic background is sufficient but not necessary to determine usage of V, D, and J genes. Although gene usage pattern is not affected by age, we observed a significant sex preference for 24 V genes, 9 D genes and 5 J genes, but found no positional bias for V-D and D-J recombination. In addition, we found that the number of observed clones that were shared between any two repertoires followed a linear model and noted that the mutability of hot/cold spots and single nucleotides within antibody genes suggested a strand-specific somatic hypermutation mechanism. This population-level analysis resolves some critical characteristics of the antibody repertoire and thus may serve as a reference for research aiming to unravel B cell-related biology or diseases. The metrics revealed here will be of significant value to the large cadre of scientists who study the antibody repertoire.