bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Follow-up of Intracapsular Schwannoma Excision
Authors: Niepel Albert Laurenz , Steinkellner Lara , Sokullu Fuat , Hellekes Dirk , Kömürcü Fercan 
Published: January 2019

Introduction
The current criterion-standard treatment for schwannomas is intracapsular excision. This study was designed as a long-term follow-up to investigate postoperative symptoms, nervous impairment, and recurrence rate.

Methods
We performed a long-term follow-up of 18 subjects who underwent intracapsular schwannoma excision. We evaluated preoperative versus postoperative 2-point discrimination (2-PD) in the affected dermatome, pain (visual analog scale [VAS] from 0–10), Hoffmann-Tinel sign, and thermoreceptor response. For reasons of comparison, all examinations were done on both the healthy and affected extremity.

Results
Last postoperative follow-up was done on average after approximately 50.4 months. Comparison between preoperative and postoperative sensibility testing (2-PD) in the affected dermatome showed a significant improvement of 22.7% after surgery (5-mm 2-PD; P = 0.02). Compared with the healthy nonoperated extremity preoperatively, subjects showed a significant sensory deficit of 40.9% (9-mm 2-PD; P < 0.000). Postoperatively, 12 of 18 subjects still showed a deficit in 2-PD. However, deficiency was decreased to 23.5% (mean, 4-mm 2-PD; P = 0.003). Through intracapsular schwannoma excision, subjects could drastically improve their pain (from VAS 6.7 to VAS 4.0).
During our examination, we clinically suspected recurrence in 3 subjects, which were sent to magnetic resonance imaging to rule out or confirm a recurrent tumor.

Discussion
Many subjects reported ongoing pain and sensory deficits after intracapsular excision of schwannomas. Symptoms right after surgery may be due to iatrogenic nerve injury or residual deficits from compression damage of the tumor mass. As schwannomas are usually growing at a slow rate, early symptoms after a symptom-free period might possibly indicate scarring of soft tissue, which may cause signs of recurrent neurological deficits or pain. Patients with a late onset of symptoms are at the highest risk of having a true recurrence of schwannoma. None of the 3 suspected subjects showed radiological evidence for a recurrent schwannoma, but rather scarring and soft tissue adhesions to the nerve, which could explain the clinical findings.
Intracapsular removal of schwannomas is relatively easy to perform, does not cause any additional damage to the nerve in most cases, and is therefore an excellent method for treatment of symptomatic schwannoma patients.
N-Acetylcysteine Ameliorates Gentamicin-Induced Nephrotoxicity by Enhancing Autophagy and Reducing Oxidative Damage in Miniature Pigs
Authors: Cui Jing , Tang Li , Hong Quan , Lin Shupeng , Sun Xuefeng , Cai Guangyan , Bai Xue-Yuan , Chen Xiangmei 
Published: January 2019

ABSTRACT
The clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. Adult mini pigs were divided into isotonic saline solution, gentamicin, and gentamicin plus NAC combination treatment groups. Gentamicin-induced histopathological changes, including inflammatory cell infiltration and tubular necrosis, were attenuated by NAC. NAC ameliorated the gentamicin-induced decreases in the levels of autophagy-related proteins, such as LC3 (microtubule-associated protein 1 light chain 3), PINK1 (phosphatase and tensin homologue deleted on chromosome10-induced kinase 1), phospho-parkin, AMBRA1 (activatingmolecule in Beclin 1-regulated autophagy), p62/SQSTM1 (sequestosome protein 1), and polyubiquitinated protein aggregates. NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls, γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2′-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These results suggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.
Cost-effectiveness Evaluation of Laparoscopic Versus Robotic Minimally Invasive Colectomy
Authors: Simianu Vlad V. , Gaertner Wolfgang B. , Kuntz Karen , Kwaan Mary R. , Lowry Ann C. , Madoff Robert D. , Jensen Christine C. 
Published: January 2019

Objective:
Evaluate the cost-effectiveness of open, laparoscopic, and robotic colectomy.

Background:
The use of robotic-assisted colon surgery is increasing. Robotic technology is more expensive and whether a robotically assisted approach is cost-effective remains to be determined.

Methods:
A decision-analytic model was constructed to evaluate the 1-year costs and quality-adjusted time between robotic, laparoscopic, and open colectomy. Model inputs were derived from available literature for costs, quality of life (QOL), and outcomes. Results are presented as incremental cost-effectiveness ratios (ICERs), defined as incremental costs per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were performed to test the effect of clinically reasonable variations in the inputs on our results.

Results:
Open colectomy cost more and achieved lower QOL than robotic and laparoscopic approaches. From the societal perspective, robotic colectomy costs $745 more per case than laparoscopy, resulting in an ICER of $2,322,715/QALY because of minimal differences in QOL. From the healthcare sector perspective, robotics cost $1339 more per case with an ICER of $4,174,849/QALY. In both models, laparoscopic colectomy was more frequently cost-effective across a wide range of willingness-to-pay thresholds. Sensitivity analyses suggest robotic colectomy becomes cost-effective at $100,000/QALY if robotic disposable instrument costs decrease below $1341 per case, robotic operating room time falls below 172 minutes, or robotic hernia rate is less than 5%.

Conclusions:
Laparoscopic and robotic colectomy are more cost-effective than open resection. Robotics can surpass laparoscopy in cost-effectiveness by achieving certain thresholds in QOL, instrument costs, and postoperative outcomes. With increased use of robotic technology in colorectal surgery, there is a burden to demonstrate these benefits.
Effects of Telmisartan and Candesartan on the Metabolism of Lipids and Glucose in Kidney Transplant Patients: A Prospective, Randomized Crossover Study
Authors: Miura Yoshifumi , Noguchi Hiroshi , Okabe Yasuhiro , Masutani Kosuke , Tokunaga Shoji , Nakamura Masafumi 
Published: January 2019

Background
The risk of cardiovascular events remains after kidney transplantation (KT). Abnormal glucose metabolism and hyperlipidemia contribute partly to this risk. Among angiotensin II type-1 receptor blockers, telmisartan alone has been shown to ameliorate these effects on glucose and lipid metabolism (GLM). We investigated the effects of telmisartan on GLM in KT patients.

Methods
This trial had a crossover design. Forty-six KT patients with well-controlled hypertension under angiotensin II type-1 receptor blockers were randomized into telmisartan and candesartan groups. After a 12-week treatment, crossover was initiated, and additional 12-week treatment was administered without a washout period. We examined the laboratory parameters of GLM, blood pressure and graft function before and after each treatment period.

Results
Forty patients completed the scheduled treatment regimen. Serum levels of triglyceride were significantly lower (114.3 ± 50.8 mg/dL vs 136.5 ± 66.8 mg/dL; P = 0.019), and the estimated glomerular filtration rate was significantly higher (50.4 ± 15.1 mL/min per 1.73 m2 vs 48.5 ± 12.5 mL/min per 1.73 m2; P = 0.038) after telmisartan treatment than after candesartan treatment. There were no significant differences between the 2 treatment groups with regard to the other parameters studied (including serum adiponectin levels and parameters of glucose metabolism).

Conclusions
These data suggest that telmisartan can improve serum triglyceride levels and graft function for KT patients better than candesartan.
Are high-frequency oscillations better biomarkers of the epileptogenic zone than spikes?
Authors: Roehri Nicolas , Bartolomei Fabrice 
Published: January 2019

Purpose of review
Precise localization of the epileptogenic zone is imperative for the success of resective surgery of drug-resistant epileptic patients. To decrease the number of surgical failures, clinical research has been focusing on finding new biomarkers. For the past decades, high-frequency oscillations (HFOs, 80–500 Hz) have ousted interictal spikes – the classical interictal marker – from the research spotlight. Many studies have claimed that HFOs were more linked to epileptogenicity than spikes. This present review aims at refining this statement in light of recent studies.

Recent findings
Analysis based on single-patient characteristics has not been able to determine which of HFOs or spikes were better marker of epileptogenic tissues. Physiological HFOs are one of the main obstacles to translate HFOs to clinical practice as separating them from pathological HFOs remains a challenge. Fast ripples (a subgroup of HFOs, 250–500 Hz) which are mostly pathological are not found in all epileptogenic tissues.

Summary
Quantified measures of HFOs and spikes give complementary results, but many barriers still persist in applying them in clinical routine. The current way of testing HFO and spike detectors and their performance in delineating the epileptogenic zone is debatable and still lacks practicality. Solutions to handle physiological HFOs have been proposed but are still at a preliminary stage.
Assessing the anterior visual pathway in optic neuritis: recent experimental and clinical aspects
Authors: Dietrich Michael , Aktas Orhan , Hartung Hans-Peter , Albrecht Philipp 
Published: January 2019

Purpose of review
Multiple sclerosis (MS) and related autoimmune disorders of the central nervous system such as neuromyelitis optica spectrum disorders (NMOSD) are characterized by chronic disability resulting from autoimmune neuroinflammation, with demyelination, astrocyte damage, impaired axonal transmission and neuroaxonal loss. Novel therapeutics stopping or reversing the progression of disability are still urgently warranted. This review addresses research on optic neuritis in preclinical experimental models and their translation to clinical trials.

Recent findings
Optic neuritis can be used as paradigm for an MS relapse which can serve to evaluate the efficacy of novel therapeutics in clinical trials with a reasonable duration and cohort size. The advantage is the linear structure of the visual pathway allowing the assessment of visual function and retinal structure as highly sensitive outcome parameters. Experimental autoimmune encephalomyelitis is an inducible, inflammatory and demyelinating central nervous system disease extensively used as animal model of MS. Optic neuritis is part of the clinicopathological manifestations in a number of experimental autoimmune encephalomyelitis models. These have gained increasing interest for studies evaluating neuroprotective and/or remyelinating substances as longitudinal, visual and retinal readouts have become available.

Summary
Translation of preclinical experiments, evaluating neuroprotective or remyelinating therapeutics to clinical studies is challenging. In-vivo readouts like optical coherence tomography, offers the possibility to transfer experimental study designs to clinical optic neuritis trials.
PerMemDB: a database for eukaryotic peripheral membrane proteins
Authors: Nastou Katerina C. , Tsaousis Georgios N. , Hamodrakas Stavros J. , Iconomidou Vassiliki A. 
Published: January 2019

AbstractThe majority of all proteins in cells interact with membranes either permanently or temporarily. Peripheral membrane proteins form transient complexes with membrane proteins and/or lipids, via non-covalent interactions and are of outmost importance, due to numerous cellular functions in which they participate. In an effort to collect data regarding this heterogeneous group of proteins we designed and constructed a database, called PerMemDB. PerMemDB is currently the most complete and comprehensive repository of data for eukaryotic peripheral membrane proteins deposited in UniProt or predicted with the use of MBPpred – a computational method that specializes in the detection of proteins that interact non-covalently with membrane lipids, via membrane binding domains. The first version of the database contains 241173 peripheral membrane proteins from 1216 organisms. All entries have cross-references to other databases, literature references and annotation regarding their interactions with other proteins. Moreover, additional sequence annotation of the characteristic domains that allow these proteins to interact with membranes is available, due to the application of MBPpred. Through the web interface of PerMemDB, users can browse the contents of the database, submit advanced text searches and BLAST queries against the protein sequences deposited in PerMemDB. We expect this repository to serve as a source of information for the development of prediction algorithms regarding peripheral membrane proteins, in addition to proteome-wide analyses.Availabilityhttp://bioinformatics.biol.uoa.gr/permemdbContactveconom@biol.uoa.grSupplementary informationhttp://83.212.109.111:8085/assets/Nastou_Supplement.xlsx
Integrating multi-network topology for gene function prediction using deep neural networks
Authors: Xue Hansheng , Peng Jiajie , Shang Xuequn 
Published: January 2019

AbstractMotivationThe emerging of abundant biological networks, which benefit from the development of advanced high-throughput techniques, contribute to describing and modeling complex internal interactions among biological entities such as genes and proteins. Multiple networks provide rich information for inferring the function of genes or proteins. To extract functional patterns of genes based on multiple heterogeneous networks, network embedding-based methods, aiming to capture non-linear and low-dimensional feature representation based on network biology, have recently achieved remarkable performance in gene function prediction. However, existing methods mainly do not consider the shared information among different networks during the feature learning process. Thus, we propose a novel multi-networks embedding-based function prediction method based on semi-supervised autoencoder and feature convolution neural network, namedDeepMNE-CNN, which captures complex topological structures of multi-networks and takes the correlation among multi-networks into account.ResultsWe design a novel semi-supervised autoencoder method to integrate multiple networks and generate a low-dimensional feature representation. Then we utilize a convolutional neural network based on the integrated feature embedding to annotate unlabeled gene functions. We test our method on both yeast and human dataset and compare with four state-of-the-art methods. The results demonstrate the superior performance of our method over four state-of-the-art algorithms. From the future explorations, we find that semi-supervised autoencoder based multi-networks integration method and CNN-based feature learning methods both contribute to the task of function prediction.AvailabilityDeepMNE-CNNis freely available athttps://github.com/xuehansheng/DeepMNE-CNN
Heterogeneity in surface sensing produces a division of labor inPseudomonas aeruginosapopulations
Authors: Armbruster Catherine R. , Lee Calvin K. , Parker-Gilham Jessica , Anda Jaime de , Xia Aiguo , Tseng Boo Shan , Hoffman Lucas R. , Jin Fan , Harwood Caroline S. , Wong Gerard C. L. , Parsek Matthew R. 
Published: January 2019

AbstractThe second messenger signaling molecule cyclic diguanylate monophosphate (c-di-GMP) drives the transition from planktonic to biofilm growth in many bacterial species.Pseudomonas aeruginosahas two surface sensing systems that produce c-di-GMP in response to surface adherence. The current thinking in the field is that once cells attach to a surface, they uniformly respond with elevated c-di-GMP. Here, we describe how the Wsp system generates heterogeneity in surface sensing, resulting in two physiologically distinct subpopulations of cells. One subpopulation has elevated c-di-GMP and produces biofilm matrix, serving as the founders of initial microcolonies. The other subpopulation has low c-di-GMP and engages in surface motility, allowing for exploration of the surface. We also show that this heterogeneity strongly correlates to surface behavior for descendent cells. Together, our results suggest that after surface attachment,P. aeruginosaengages in a division of labor that persists across generations, accelerating early biofilm formation and surface exploration.
Probabilistic Harmonization and Annotation of Single-cell Transcriptomics Data with Deep Generative Models
Authors: Xu Chenling , Lopez Romain , Mehlman Edouard , Regier Jeffrey , Jordan Michael I. , Yosef Nir 
Published: January 2019

AbstractAs single-cell transcriptomics becomes a mainstream technology, the natural next step is to integrate the accumulating data in order to achieve a common ontology of cell types and states. However, owing to various nuisance factors of variation, it is not straightforward how to compare gene expression levels across data sets and how to automatically assign cell type labels in a new data set based on existing annotations. In this manuscript, we demonstrate that our previously developed method, scVI, provides an effective and fully probabilistic approach for joint representation and analysis of cohorts of single-cell RNA-seq data sets, while accounting for uncertainty caused by biological and measurement noise. We also introduce single-cell ANnotation using Variational Inference (scANVI), a semi-supervised variant of scVI designed to leverage any available cell state annotations — for instance when only one data set in a cohort is annotated, or when only a few cells in a single data set can be labeled using marker genes. We demonstrate that scVI and scANVI compare favorably to the existing methods for data integration and cell state annotation in terms of accuracy, scalability, and adaptability to challenging settings such as a hierarchical structure of cell state labels. We further show that different from existing methods, scVI and scANVI represent the integrated datasets with a single generative model that can be directly used for any probabilistic decision making task, using differential expression as our case study. scVI and scANVI are available as open source software and can be readily used to facilitate cell state annotation and help ensure consistency and reproducibility across studies.
Length of uninterrupted CAG repeats, independent of polyglutamine size, results in increased somatic instability and hastened age of onset in Huntington disease
Authors: Wright Galen E.B. , Collins Jennifer A. , Kay Chris , McDonald Cassandra , Dolzhenko Egor , Xia Qingwen , Bečanović Kristina , Semaka Alicia , Nguyen Charlotte M. , Trost Brett , Richards Fiona , Bijlsma Emilia K. , Squitieri Ferdinando , Scherer Stephen W. , Eberle Michael A. , Yuen Ryan K.C. , Hayden Michael R. 
Published: January 2019

ABSTRACTHuntington disease (HD) is an autosomal dominant neurological disorder that is caused by a CAG repeat expansion, translated into polyglutamine, in the huntingtin (HTT)gene. Although the length of this repeat polymorphism is inversely correlated with age of onset (AOO), it does not fully explain the variability in AOO. Genomic studies have provided evidence for the involvement of DNA repair in modifying this trait, potentially through somatic repeat instability. We therefore assessed genetic variants within the 12bp interrupting sequence between the pathogenic CAG repeat and the polymorphic proline (CCG) tract in theHTTgene and identified variants that result in complete loss of interruption (LOI) between the adjacent CAG/CCG repeats. Analysis of multiple HD pedigrees showed that this variant is associated with dramatically earlier AOO and is particularly relevant to HD patients with reduced penetrance alleles. On average AOO of HD is hastened by an average of 25 years in LOI carriers. This finding indicates that the number of uninterrupted CAG repeats is the most significant contributor to AOO of HD and is more impactful than polyglutamine length, which is not altered in these patients. We show that the LOI variant is associated with increases in both somatic and germline repeat instability, demonstrating a potential mechanism for this effect. Screening individuals from the general population (n=2,674 alleles) suggests that the variant occurs only in expanded CAG repeat alleles. Identification of this modifier has important clinical implications for disease management of HD families, especially for those in the reduced penetrance ranges.
An allele-specific functional SNP associated with two autoimmune diseases modulatesIRF5expression by long-range chromatin loop formation
Authors: Thynn Hlaing Nwe , Chen Xiao-Feng , Hu Wei-Xin , Duan Yuan-Yuan , Zhu Dong-Li , Chen Hao , Wang Nai-Ning , Chen Huan-Huan , Rong Yu , Lu Bing-Jie , Yang Man , Jiang Feng , Dong Shan-Shan , Guo Yan , Yang Tie-Lin 
Published: January 2019

AbstractBoth Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc) are autoimmune diseases sharing similar genetic backgrounds. Genome-wide association studies (GWASs) have constantly disclosed numerous genetic variants conferring to both disease risks at 7q32.1, but the functional mechanisms underlying them are still largely unknown. Through combining fine-mapping and functional epigenomic analyses, we prioritized a potential independent functional SNP (rs13239597) withinTNPO3promoter region, residing in a putative enhancer element. Functional analysis integrating expression quantitative trait locus (eQTL) and high-throughput chromatin interaction (Hi-C) demonstrated thatIRF5is the distal target gene (~118kb) of rs13239597, which is a key regulator of pathogenic autoantibody dysregulation increased risk of both SLE and SSc. We experimentally validated the long-range chromatin interactions between rs13239597 andIRF5using chromosome conformation capture (3C) assay. We further demonstrated that rs13239597-A acted as an allele-specific enhancer regulatingIRF5expression, independently ofTNPO3by using dual-luciferase reporter assays and CRISPR-Cas9. Particularly, the transcription factor EVI1 could preferentially bind to rs13239597-A allele and increase the enhancer activity to regulateIRF5expression. Taken together, our results uncovered the mechanistic insight connecting between a noncoding functional variant with a distal immunologically pathogenic geneIRF5, which might obligate in understanding the complex genetic architectures of SLE and SSc pathogenesis.