bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex Feed-Forward and Feedback Mechanisms Underlie the Relationship Between Traumatic Brain Injury and the Gut–Microbiota–Brain Axis
Authors: Patterson T. Tyler , Nicholson Susannah , Wallace David , Hawryluk Gregory W.J. , Grandhi Ramesh 
Published: October 2018

ABSTRACT
Traumatic brain injury (TBI) contributes to nearly 1 in 3 injury-related deaths in the United States and accounts for a substantial public health burden and cost. The current literature reports that physiologic responses in the gastrointestinal system after TBI include, but are not limited to, epithelial barrier dysfunction, microbiota changes, and immunologic transformations. Recent evidence suggests gut alterations after TBI modify the homeostasis of the bidirectional gut–microbiota–brain axis, resulting in altered immune responses in the periphery and the brain. This cascade possibly contributes to impaired central nervous system (CNS) healing. Although attention to the gut–brain–microbiota axis has been increasing in the literature, the precise mechanisms underlying the changes observed after TBI remain unclear. The purpose of this review are to describe our current understanding regarding alterations to the gut–microbiota–brain axis after TBI, highlight the pathophysiologic changes involved, and evaluate how these variations modify healing in the CNS or even contribute to secondary injury. We also discuss current investigations into potential medical therapies directed at the gut–microbiota–brain axis, which might offer improved outcomes after TBI.
A Comparison of Sacrospinous Hysteropexy Augmented With Polypropylene Mesh Versus Human Dermis at 12-Month Follow-up: An Ambidirectional Study
Authors: Seitz Miriam , Jirschele Kelly , Tran Alexis , Iyer Shilpa , Gafni-Kane Adam , Tomezsko Janet , Botros Sylvia M. , Sand Peter K. 
Published: October 2018

Background
Suture-based hysteropexy is performed for pelvic organ prolapse with varying results. Graft augmentation may improve outcomes.

Objective
The aim of this study was to determine whether vaginal hysteropexy with mesh reduces recurrence at 1-year postoperative examination compared with hysteropexy with allograft.

Methods
Data were collected for patients who underwent vaginal hysteropexy with either mesh “Uphold” (referred to as “mesh”) or a cadaveric allograft “Axis or Repliform” (referred to as “dermal”). The primary outcome was anatomic success defined as no prolapse Pelvic Organ Prolapse Quantification System stage II or less at 12 months postoperative. The secondary outcomes were recurrence to the hymen and a composite score (any positive response to the 20-item Pelvic Floor Distress Inventory question 3 and cervix ≥ −1/2 total vaginal length at rest or as reference point 3 cm proximal to or above the hymenal ring anteriorly [Ba] ≥0) measured at 12 months.

Results
Two hundred seventy-four patients returned for their 1-year postoperative examination: 93.5% of the mesh group (231/247 subjects) and 95.5% of the dermal group (43/45 subjects). The mesh group had fewer recurrences to or beyond Pelvic Organ Prolapse Quantification System stage II (mesh 18% vs dermal 29%, P = 0.03), to the hymen (2.6% vs 9.3%, P = 0.007), or based on composite score (19 vs 33%, P = 0.007). Questionnaire data improved more in the mesh group (P < 0.0001). The exposure rate was 5.75% (13/247) in the mesh group. Reoperation rate was greater in the dermal group (mesh 4.3%vs dermal 7.3%, P = 02).

Conclusions
Hysteropexy augmented with mesh reduced the recurrence at 1 year compared with hysteropexy with allograft. Fewer patients in the mesh group felt a bulge at 1 year (4.5% vs 20.9%, P < 0.0001). These findings need to be weighed against the mesh exposure rate of 5.75%.
International Liver Transplantation Society Asian Consensus on the Management of Hepatitis C Virus Infection in Resource Limited Setting—From Noncirrhotic to Decompensated Disease and After Liver Transplantation
Authors: Charlton Michael R. , Gane Edward J. , Shukla Aakash , Dashtseren Bekhbold , Duger Davaadorj , Muljono David H. , Payawal Diana A. , Jargalsaikhan Ganbolor , Purnomo Hery D. , Cua Ian H. , Hasan Irsan , Sollano Jose , Win Khin Maung , Lesmana Laurentius A. , Salih Mohammad , Thi Thu Thuy Pham , Shankar Ravi , Saraswat Vivek A. 
Published: October 2018

Background.
The population of Asia exceeds 4.4 billion people. Chronic hepatitis C virus (HCV) infection in Asia is characterized by specific distribution of genotypes, lack of access to specific therapeutic agents, relatively high cost of treatment, and lack of experienced healthcare providers. Clear consensus on the diagnosis, management, and monitoring of HCV infection specific to the Asian region is a major unmet need. The consensus guidelines documents that have been published to date by major medical societies presume access to an array of direct acting antiviral agents and diagnostic tests that are not broadly applicable to resource limited settings, including Asia.

Methods.
To address the lack of an Asia-specific set of HCV treatment guidelines, we assembled a panel of 15 HCV experts in the field of hepatology from India, Indonesia, Myanmar, Vietnam, Pakistan, Philippines, and Mongolia convened in April 2017 to review the updated literature and provide recommendations on the diagnosis and management of chronic HCV infection that reflects local conditions.

Results.
An evidence-based comprehensive compilation of the literature supported by the graded recommendations from the expert panel for the optimization of the diagnosis, pretreatment, on treatment, and posttreatment assessments, and management of chronic HCV infection has been presented in this article.

Conclusions.
With the evolving treatment landscape and addition of several new direct-acting antiviral agents and combination regimens into the therapeutic armamentarium, the current article may serve as a guide to the clinicians in optimizing the diagnosis and treatment selection for the management of chronic HCV infection in resource-limited settings.
Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation
Authors: Younossi Zobair M. , Marchesini Giulio , Pinto-Cortez Helena , Petta Salvatore 
Published: October 2018

Abstract
Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population with a range of 13.5% in Africa and 31.8% in the Middle East. Nonalcoholic fatty liver disease is closely associated with a constellation of metabolic comorbidities which include: obesity, type 2 diabetes mellitus, hypertension, and hypercholesteremia. In fact, the increasing number of metabolic comorbidities not only increases the prevalence of NAFLD but also places patients at higher risk for progressive liver disease. As such, NAFLD is presently among the top etiologies for hepatocellular carcinoma and an indication for liver transplantation (LT) in the United States. Therefore, the following recommendations are made based on our current knowledge of NAFLD and its consequences: (1) the evaluation of the risk of liver disease progression can be affected by patient's ethnic origin and sex; (2) fibrosis in NAFLD is the most important predictor of mortality; (3) we recommend that individuals who present with features of metabolic syndrome in the presence of elevated liver enzymes should be screened for NAFLD and, more importantly, nonalcoholic steatohepatitis (NASH); (4) we recommend that NAFLD patients, especially those with multiple risk factors, should be screened for cardiovascular diseases and managed accordingly; (5) comorbidities in NAFLD/NASH patients who are considered for LT need to be assessed in the pretransplant and posttransplant settings because these factors can affect waitlist mortality, resource utilization, as well as posttransplant complications, morbidity, and perhaps, mortality; (6) any attempt to decrease the incidence of NAFLD should ideally address the development of obesity in childhood and early adulthood, favoring the adoption of healthy lifestyles through comprehensive health policy programs.
Clinical Significance of Microvascular Inflammation in the Absence of Anti-HLA DSA in Kidney Transplantation
Authors: Parajuli Sandesh , Redfield Robert R. , Garg Neetika , Aziz Fahad , Mohamed Maha , Astor Brad C. , Zhong Weixong , Djamali Arjang , Mandelbrot Didier A. 
Published: October 2018

Background.
Limited information exists about outcomes of HLA donor-specific antibody (DSA) negative (DSA−) microvascular inflammation (MVI).

Methods.
We report our experience with 25 DSA− patients with MVI compared to 155 DSA+ patients who met Banff 2013 criteria for antibody-mediated rejection (AMR). We also compared outcomes to 228 DSA+ patients whose biopsies were negative for rejection and served as a negative control.

Results.
There were no significant differences in the baseline characteristics between the DSA− MVI and DSA+ AMR groups. At the time of diagnosis, both groups had similar graft function. The DSA− group had higher MVI scores but lower C4d scores. At last follow-up, renal function was similar between the groups. There were 12 (48%) graft failures in the DSA− group and 59 (38%) graft failures in the DSA+ group, which was not statistically different. Similar results were found after matching for the MVI scores, C4d, and treatment between 2 groups. We also found similar outcomes between DSA− and DSA+ patients when only including those who would have met Banff 2017 criteria for AMR. In univariate Cox regression analyses, estimated glomerular filtration rate at time of biopsy, glomerulitis, rituximab, diabetes, v score, allograft glomerulopathy, fibrous intimal thickening, tubular atrophy, and interstitial fibrosis scores were associated with graft failure. In multivariate analysis, only estimated glomerular filtration rate was protective. Both groups had significantly worse outcomes than the DSA+-negative controls without AMR.

Conclusions.
Our findings suggest that outcomes and response to treatment with HLA DSA− MVI patients are similarly poor to those with DSA+ MVI patients, supporting a critical role for MVI in the diagnosis of AMR.
Quadriceps Muscle Strength and Body Mass Index Are Associated With Estimates of Physical Activity Postheart Transplantation
Authors: Kelly Rebecca L. , Walsh James R. , Paratz Jennifer D. , Yerkovich Stephanie T. , McKenzie Scott C. , Morris Norman R. 
Published: October 2018

Background.
Although exercise capacity improves postheart transplantation (HTx), it remains unclear if the level of physical activity (PA) shows similar improvement. The purpose of this study was to (1) describe PA levels and (2) identify factors which may be associated with levels of PA post-HTx.

Methods.
A prospective observational cross-sectional study was conducted at a single center HTx outpatient clinic. Medically stable adult recipients 6 months or longer post-HTx were recruited. Physical activity level (PAL) and average daily time spent at least moderately active (≥3 metabolic equivalents) were estimated using a multisensor device. Factors investigated were demographic (age, sex, body mass index [BMI], time post-HTx, and reason for HTx), corticosteroid use, exercise capacity (6-min walk distance), and quadriceps muscle strength corrected for body weight (QS%).

Results.
The mean post-HTx time of the 75 participants was 9.2 ± 7.0 years (0.5–26 y). Twenty-seven (36%) participants were classified as extremely inactive (PAL, <1.40), 26 (34.6%) sedentary (1.40 ≤ PAL ≤ 1.69), and 22 (29.3%) active (PAL, ≥1.70). Multivariable analysis showed greater QS% (β = 0.004 (0.002–0.006) P = 0.001) to be independently associated with increased PAL. For increased time, 3 or more metabolic equivalents both greater QS% (β = 0.0164 [0.003–0.029]; P = 0.014) and lower BMI (β = −0.0626 [−0.115 to −0.0099]; P = 0.021) were independently associated.

Conclusions.
The degree of observed sedentary behavior post-HTx is surprising, with the majority of participants not reaching levels of PA recommended for health benefits. QS% and BMI were the only factors found to be independently associated with estimates of PA. Further quality trials are required to demonstrate the long-term benefits of regular PA and investigate ways of increasing adherence to PA post-HTx.
NAFLD and Liver Transplantation in Children—Working Group Report From the ILTS Single Topic Conference on NAFLD
Authors: Cananzi Mara , Vajro Pietro , Rela Mohamed , Dhawan Anil 
Published: October 2018

Background
Nonalcoholic fatty liver disease (NAFLD) has now become a common cause of chronic liver disease in children; however, unlike adults liver transplantation is rarely required as treatment. It is important that in children presenting with NAFLD, secondary causes of fatty liver particularly inherited metabolic defects should be excluded.

Methods
A pediatric working group comprised of 3 hepatologists and a liver transplant surgeon was tasked with a set of questions to address the current state of evidence and knowledge about NAFLD in children with particular focus on liver transplantation. A systematic review of the English literature regarding pediatric NAFLD (from birth to 18 years of age) published in the last 2 decades (2000-2018) was carried out. The evidence was evaluated by the subgroup members and further discussed with the wider workshop faculty leading to the recommendations for best practice.

Results
Given the paucity of literature on the subject good quality of evidence was only available on risk factors for NAFLD and medical treatment where the group could make recommendation with high/moderate strength. The evidence on natural history and indications for liver transplantation was poor hence group could not make any recommendations.

Conclusions
Based on the existing literature and subgroups, collective experience NAFLD unlike in adults is a very rare indication for liver transplantation in children. No definitive recommendations could be made about the natural history, indications, and outcome of liver transplantation for NAFLD in children.
Outcomes of Living-donor Liver Transplantation Using Grafts Heterozygous for α-1 Antitrypsin Gene Mutations
Authors: Doshi Sahil D. , Wood Linda , Abt Peter L. , Olthoff Kim M. , Shaked Abraham , Goldberg David S. , Bittermann Therese 
Published: October 2018

Background.
Patients heterozygous for an abnormal α-1 antitrypsin (A1AT) mutation may have an increased risk of liver disease in the setting of a secondary contributing factor.

Methods.
This single-center retrospective cohort study compared donor and recipient outcomes of A1AT heterozygous versus normal phenotype adult living-donor liver transplants (LDLTs).

Results.
Between 2010 and 2016, 11 A1AT heterozygous donors and 10 recipients were compared to 57 normal donors and 41 recipients. There were no significant differences in sex, age, or race/ethnicity by A1AT phenotype. Heterozygous donors had significantly lower serum A1AT (median 100 mg/dL versus 131 mg/dL; P < 0.001). Median liver volume at 3 months post-LDLT was not different among donors or their recipients (1164 mm3 in heterozygous versus 1257 mm3 in normal [P = 0.449] for donors; 1563 mm3 versus 1606 mm3 [P = 0.387], respectively, for recipients). Recipient serum alkaline phosphatase at 1 month and 1 year post-LDLT was significantly higher in recipients of A1AT heterozygous grafts (160 U/L versus 99.5 U/L; P = 0.025 at 1 mo) but did not persist at 2 years. In addition, there was no association between A1AT level and liver volume at 3 months posttransplant in donors or recipients.

Conclusions.
Patients with a heterozygous A1AT mutation should be considered for living-liver donation.
Deep Convolutional modeling of human face selective columns reveals their role in pictorial face representation
Authors: Grossman Shany , Gaziv Guy , Yeagle Erin M , Harel Michal , Mégevand Pierre , Groppe David M , Khuvis Simon , Herrero Jose L , Irani Michal , Mehta Ashesh D , Malach Rafael 
Published: October 2018

AbstractDespite the massive accumulation of systems neuroscience findings, their functional meaning remains tentative, largely due to the absence of realistically performing models. The discovery that deep convolutional networks achieve human performance in realistic tasks offers fresh opportunities for such modeling. Here we show that the face-space topography of face-selective columns recorded intra-cranially in 32 patients significantly matches that of a DCNN having human-level face recognition capabilities. Three modeling aspects converge in pointing to a role of human face areas in pictorial rather than person identification: First, the match was confined to intermediate layers of the DCNN. Second, identity preserving image manipulations abolished the brain to DCNN correlation. Third, DCNN neurons matching face-column tuning displayed view-point selective receptive fields. Our results point to a “convergent evolution” of pattern similarities in biological and artificial face perception. They demonstrate DCNNs as a powerful modeling approach for deciphering the function of human cortical networks.
LuxRep: a technical replicate-aware method for bisulfite sequencing data analysis
Authors: Malonzo Maia , Halla-aho Viivi , Konki Mikko , Lund Riikka J. , Lähdesmäki Harri 
Published: October 2018

AbstractDNA methylation is measured using bisulfite sequencing (BS-seq). Bisulfite conversion can have low efficiency and a DNA sample is then processed multiple times generating DNA libraries with different bisulfite conversion rates. Libraries with low conversion rates are excluded from analysis resulting in reduced coverage and increased costs. We present a method and software, LuxRep, that accounts for technical replicates from different bisulfite-converted DNA libraries. We show that including replicates with low bisulfite conversion rates generates more accurate estimates of methylation levels and differentially methylated sites.AvailabilityAn implementation of the method is available at https://github.com/tare/LuxGLM/tree/master/LuxRepContactmaia.malonzo@aalto.fi
Loss of Kat2A Enhances Transcriptional Noise and Depletes Acute Myeloid Leukemia Stem-Like Cells
Authors: Domingues Ana Filipa , Kulkarni Rashmi , Giotopoulos George , Gupta Shikha , Tan Shengjiang , Foerner Elena , Adao Rita Romano , Zeka Keti , Huntly Brian J. , Prabakaran Sudhakaran , Pina Cristina 
Published: October 2018

ABSTRACTAcute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution.
Focusing on what matters: Modulation of the human hippocampus by relational attention
Authors: Córdova Natalia I. , Turk-Browne Nicholas B. , Aly Mariam 
Published: October 2018

AbstractHippocampal episodic memory is fundamentally relational, consisting of links between events and the spatial and temporal contexts in which they occurred. Such relations are also important over much shorter time periods, during online visual perception. For example, how do we assess the relative spatial positions of objects, their temporal order, or the relationship between their features? Here, we investigate the role of the hippocampus in such online relational processing by manipulating visual attention to different kinds of relations in a dynamic display. While undergoing high-resolution fMRI, participants viewed two images in rapid succession on each trial and performed one of three relational tasks, judging the images’ relative: spatial positions, temporal onsets, or sizes. As a control, they sometimes also judged whether one image was tilted, irrespective of the other; this served as a baseline item task with no demands on relational processing. All hippocampal regions of interest (CA1, CA2/3/DG, subiculum) showed reliable deactivation when participants attended to relational vs. item information. Attention to temporal relations was associated with more robust deactivation than the other conditions. One possible interpretation of such deactivation is that it reflects hippocampal disengagement. If true, there should be reduced information content and noisier, less reliable patterns of activity in the hippocampus for the temporal vs. other tasks. Instead, analyses of multivariate activity patterns revealed more stable hippocampal representations in the temporal task. Additional analyses showed that this increased pattern similarity was not simply a reflection of the lower univariate activity. Thus, the hippocampus differentiates between relational and item processing even during online visual perception, and its representations of temporal relations in particular are robust and stable. Together, these findings suggest that the relational computations of the hippocampus, known to be important for memory, extend beyond this purpose, enabling the rapid online extraction of relational information in visual perception.
Klebsiella pneumonia, one of potential chief culprits of non-alcoholic fatty liver disease: through generation of endogenous ethanol
Authors: Wei Xiao , Zhao Xiangna , Chen Chen , Lu Jing , Cheng Weiwei , Li Boxin , Li Huan , Lin Weishi , Tian Changyu , Zhao Jiangtao , An Daizhi , Han Juqiang , Ma Xuejun , Li Wei , Wang Xuesong , Chen Xiao , Zhang Zheng , Zeng Hui , Sun Ying , Yang Ruifu , Liu Di , Yuan Jing 
Published: October 2018

AbstractNon-alcoholic fatty liver disease (NAFLD), a prelude of cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. NAFLD has been considerated to be associated with the composition of gut microbiota. However, causal relationship between change of gut microbiome and NAFLD remains unclear. Here we show that Klebsiella pneumoniae was significantly associated with NAFLD through inducing generation of endogenous ethanol. A strain of high alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) was initially isolated from fecal samples of patient with non-alcoholic steatohepatitis (NASH) accompanied with auto-brewery syndrome (ABS). Gavage of HiAlc Kpn was capable of inducing murine model of fatty liver disease (FLD) in which had typical pathological changes of hepatic steatosis and similar liver gene expression profiles to those of alcohol intake in mice. Data derived from germ-free mice by gnotobiotic gavage further demonstrated that the HiAlc Kpn is the major cause of the changes in FLD mice. Furthermore, using proteomic and metabolitic analysis, we found that HiAlc Kpn induced generation of endogenous alcohol through the 2,3-butanediol fermentation pathway. More interestingly, the blood alcohol concentration was elevated in FLD mice induced by HiAlc Kpn after glucose intake. Clinical analysis showed that HiAlc Kpn were observed in up to 60% of patients with NAFLD. Our results suggested that HiAlc Kpn make important contribution to NAFLD, possibly through generation of the endogenous alcohol. Thus, targeting these bacteria might provide a novel therapeutic for clinical treatment of NAFLD.In BriefFatty liver disease induced by high alcohol-producing Klebsiella pneumoniaeCompeting Financial Interest StatementThe authors declare no conflicts of interest.