bluuebunny/crossref_metadata_2025_split huggingface dataset:
BCrystal: an interpretable sequence-based protein crystallization predictor
Authors: Elbasir Abdurrahman , Mall Raghvendra , Kunji Khalid , Rawi Reda , Islam Zeyaul , Chuang Gwo-Yu , Kolatkar Prasanna R , Bensmail Halima 
Published: October 2019

Abstract

Motivation
X-ray crystallography has facilitated the majority of protein structures determined to date. Sequence-based predictors that can accurately estimate protein crystallization propensities would be highly beneficial to overcome the high expenditure, large attrition rate, and to reduce the trial-and-error settings required for crystallization.

Results
In this study, we present a novel model, BCrystal, which uses an optimized gradient boosting machine (XGBoost) on sequence, structural and physio-chemical features extracted from the proteins of interest. BCrystal also provides explanations, highlighting the most important features for the predicted crystallization propensity of an individual protein using the SHAP algorithm. On three independent test sets, BCrystal outperforms state-of-the-art sequence-based methods by more than 12.5% in accuracy, 18% in recall and 0.253 in Matthew’s correlation coefficient, with an average accuracy of 93.7%, recall of 96.63% and Matthew’s correlation coefficient of 0.868. For relative solvent accessibility of exposed residues, we observed higher values to associate positively with protein crystallizability and the number of disordered regions, fraction of coils and tripeptide stretches that contain multiple histidines associate negatively with crystallizability. The higher accuracy of BCrystal enables it to accurately screen for sequence variants with enhanced crystallizability.

Availability and implementation
Our BCrystal webserver is at https://machinelearning-protein.qcri.org/ and source code is available at https://github.com/raghvendra5688/BCrystal.

Supplementary information
Supplementary data are available at Bioinformatics online.
Cancer classification of single-cell gene expression data by neural network
Authors: Kim Bong-Hyun , Yu Kijin , Lee Peter C W 
Published: October 2019

AbstractMotivationCancer classification based on gene expression profiles has provided insight on the causes of cancer and cancer treatment. Recently, machine learning-based approaches have been attempted in downstream cancer analysis to address the large differences in gene expression values, as determined by single-cell RNA sequencing (scRNA-seq).ResultsWe designed cancer classifiers that can identify 21 types of cancers and normal tissues based on bulk RNA-seq as well as scRNA-seq data. Training was performed with 7398 cancer samples and 640 normal samples from 21 tumors and normal tissues in TCGA based on the 300 most significant genes expressed in each cancer. Then, we compared neural network (NN), support vector machine (SVM), k-nearest neighbors (kNN) and random forest (RF) methods. The NN performed consistently better than other methods. We further applied our approach to scRNA-seq transformed by kNN smoothing and found that our model successfully classified cancer types and normal samples.Availability and implementationCancer classification by neural network.Supplementary informationSupplementary data are available at Bioinformatics online.
SOLart: a structure-based method to predict protein solubility and aggregation
Authors: Hou Qingzhen , Kwasigroch Jean Marc , Rooman Marianne , Pucci Fabrizio 
Published: October 2019

Abstract

Motivation
The solubility of a protein is often decisive for its proper functioning. Lack of solubility is a major bottleneck in high-throughput structural genomic studies and in high-concentration protein production, and the formation of protein aggregates causes a wide variety of diseases. Since solubility measurements are time-consuming and expensive, there is a strong need for solubility prediction tools.

Results
We have recently introduced solubility-dependent distance potentials that are able to unravel the role of residue–residue interactions in promoting or decreasing protein solubility. Here, we extended their construction by defining solubility-dependent potentials based on backbone torsion angles and solvent accessibility, and integrated them, together with other structure- and sequence-based features, into a random forest model trained on a set of Escherichia coli proteins with experimental structures and solubility values. We thus obtained the SOLart protein solubility predictor, whose most informative features turned out to be folding free energy differences computed from our solubility-dependent statistical potentials. SOLart performances are very good, with a Pearson correlation coefficient between experimental and predicted solubility values of almost 0.7 both in cross-validation on the training dataset and in an independent set of Saccharomyces cerevisiae proteins. On test sets of modeled structures, only a limited drop in performance is observed. SOLart can thus be used with both high-resolution and low-resolution structures, and clearly outperforms state-of-art solubility predictors. It is available through a user-friendly webserver, which is easy to use by non-expert scientists.

Availability and implementation
The SOLart webserver is freely available at http://babylone.ulb.ac.be/SOLART/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Freezing of gait: understanding the complexity of an enigmatic phenomenon
Authors: Weiss Daniel , Schoellmann Anna , Fox Michael D , Bohnen Nicolaas I , Factor Stewart A , Nieuwboer Alice , Hallett Mark , Lewis Simon J G 
Published: October 2019

Abstract
Diverse but complementary methodologies are required to uncover the complex determinants and pathophysiology of freezing of gait. To develop future therapeutic avenues, we need a deeper understanding of the disseminated functional-anatomic network and its temporally associated dynamic processes. In this targeted review, we will summarize the latest advances across multiple methodological domains including clinical phenomenology, neurogenetics, multimodal neuroimaging, neurophysiology, and neuromodulation. We found that (i) locomotor network vulnerability is established by structural damage, e.g. from neurodegeneration possibly as result from genetic variability, or to variable degree from brain lesions. This leads to an enhanced network susceptibility, where (ii) modulators can both increase or decrease the threshold to express freezing of gait. Consequent to a threshold decrease, (iii) neuronal integration failure of a multilevel brain network will occur and affect one or numerous nodes and projections of the multilevel network. Finally, (iv) an ultimate pathway might encounter failure of effective motor output and give rise to freezing of gait as clinical endpoint. In conclusion, we derive key questions from this review that challenge this pathophysiological view. We suggest that future research on these questions should lead to improved pathophysiological insight and enhanced therapeutic strategies.
Evolutionary modifications in human brain connectivity associated with schizophrenia
Authors: van den Heuvel Martijn P , Scholtens Lianne H , de Lange Siemon C , Pijnenburg Rory , Cahn Wiepke , van Haren Neeltje E M , Sommer Iris E , Bozzali Marco , Koch Kathrin , Boks Marco P , Repple Jonathan , Pievani Michela , Li Longchuan , Preuss Todd M , Rilling James K 
Published: October 2019

See Vértes and Seidlitz (doi:10.1093/brain/awz353) for a scientific commentary on this article.Is schizophrenia a by-product of human brain evolution? By comparing the human and chimpanzee connectomes, van den Heuvel et al. demonstrate that connections unique to the human brain show greater involvement in schizophrenia pathology. Modifications in service of higher-order brain functions may have rendered the brain more vulnerable to dysfunction.
LncRNA CRNDE acts as an oncogene in cervical cancer through sponging miR-183 to regulate CCNB1 expression
Authors: Bai Xiaoxia , Wang Wendong , Zhao Peng , Wen Jie , Guo Xuedong , Shen Tao , Shen Junhua , Yang Xiaofu 
Published: October 2019

AbstractStudies have identified a series of lncRNAs that contributed to various tumors, although the underlying mechanisms remain largely unclear. We proposed a ceRNA network and investigate relations among lncRNA/miRNA/mRNA in cervical cancer (CC). The genes of differential expression and lncRNA/miRNA/mRNA network were identified by combining TCGA, miRcode, starBase, miRTarBase, miRDB, TargetScan and STRING databases. Meanwhile, the function enrichment was recognized with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Quantitative real time-PCR (qRT-PCR) was performed to determine colorectal neoplasia differentially expressed (CRNDE) expression in CC tissues and cell lines. The effects of CRNDE on the CC biological functions and cyclin B1 (CCNB1) expression were detected by conducting in vitro and in vivo experiments. Quantitative real time-PCR, western blot and dual-luciferase reporter assay were used to predict the target of miR-183. Furthermore, rescue experiments were conducted to further confirm the regulation of CCNB1 by CRNDE. Systematic analyses of bioinformatics from several databases predicted that CRNDE, miR-183 and CCNB1 were in the same network path. Their expressions were up-regulated in CC tissues and cells. Silencing CRNDE-inhibited cell proliferation, migration and invasion, restricted solid tumor growth and promoted cell apoptosis. Moreover, our results suggested that miR-183 targeted the CCNB1 3′UTR and regulated its expression. Additionally, miR-183 mimic could inverse the antitumor function of CRNDE inhibition and partially eliminated the attenuated expression of CCNB1 induced by silencing CRNDE, indicating that CRNDE could positively regulate CCNB1 expression by sponging miR-183. Our study highlighted a role for the CRNDE/miR-183/CCNB1-axis in CC and offered a promising diagnostic strategy for CC treatment.
Key Aspects of Neurovascular Control Mediated by Specific Populations of Inhibitory Cortical Interneurons
Authors: Lee L , Boorman L , Glendenning E , Christmas C , Sharp P , Redgrave P , Shabir O , Bracci E , Berwick J , Howarth C 
Published: October 2019

Abstract
Inhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (nNOS)-expressing interneurons might influence the neurovascular relationship. In mice, specific activation of SST- or nNOS-interneurons was sufficient to evoke hemodynamic changes. In the case of nNOS-interneurons, robust hemodynamic changes occurred with minimal changes in neural activity, suggesting that the ability of blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to reliably reflect changes in neuronal activity may be dependent on type of neuron recruited. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. Prolonged activation of SST-interneurons often resulted in an increase in blood volume in the centrally activated area with an accompanying decrease in blood volume in the surrounding brain regions, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function.
Long-term Memory Upscales Volume of Postsynaptic Densities in the Process that Requires Autophosphorylation of αCaMKII
Authors: Śliwińska Małgorzata Alicja , Cały Anna , Borczyk Malgorzata , Ziółkowska Magdalena , Skonieczna Edyta , Chilimoniuk Magdalena , Bernaś Tytus , Giese K Peter , Radwanska Kasia 
Published: October 2019

Abstract
It is generally accepted that formation and storage of memory relies on alterations of the structure and function of brain circuits. However, the structural data, which show learning-induced and long-lasting remodeling of synapses, are still very sparse. Here, we reconstruct 1927 dendritic spines and their postsynaptic densities (PSDs), representing a postsynaptic part of the glutamatergic synapse, in the hippocampal area CA1 of the mice that underwent spatial training. We observe that in young adult (5 months), mice volume of PSDs, but not the volume of the spines, is increased 26 h after the training. The training-induced growth of PSDs is specific for the dendritic spines that lack smooth endoplasmic reticulum and spine apparatuses, and requires autophosphorylation of αCaMKII. Interestingly, aging alters training-induced ultrastructural remodeling of dendritic spines. In old mice, both the median volumes of dendritic spines and PSDs shift after training toward bigger values. Overall, our data support the hypothesis that formation of memory leaves long-lasting footprint on the ultrastructure of brain circuits; however, the form of circuit remodeling changes with age.
Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls
Authors: Ramendra Rayoun , Isnard Stéphane , Lin John , Fombuena Brandon , Ouyang Jing , Mehraj Vikram , Zhang Yonglong , Finkelman Malcolm , Costiniuk Cecilia , Lebouché Bertrand , Chartrand-Lefebvre Carl , Durand Madeleine , Tremblay Cécile , Ancuta Petronela , Boivin Guy , Routy Jean-Pierre 
Published: October 2019

Abstract

Background
Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation.

Methods
A total of 150 PLWH (79 ART-naive and 71 ART-treated) were compared to 26 without human immunodeficiency virus (HIV) infection (uninfected controls). Plasma markers of HIV disease progression, epithelial gut damage, microbial translocation, nonspecific B-cell activation, anti-CMV and anti–Epstein-Barr virus (EBV) IgG levels, and proinflammatory cytokines were measured.

Results
CMV seropositivity and elevated anti-CMV IgG levels were associated with markers of epithelial gut damage, microbial translocation, and inflammation in PLWH and participants without HIV infection. In contrast, total nonspecific IgG, immunoglobulin M, immunoglobulin A, and anti-EBV IgG levels were not associated with these markers. CMV seropositivity was associated with markers of epithelial gut damage, microbial translocation, and inflammation independent of sociodemographic and behavioral characteristics of the study population.

Conclusions
CMV-seropositive people with and without HIV had increased epithelial gut damage, microbial translocation, and inflammation. Furthermore, anti-CMV IgG levels were independently associated with increased epithelial gut damage and microbial translocation. CMV coinfection may partially explain persistent gut damage, microbial translocation, and inflammation in ART-treated PLWH.
Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections
Authors: Doi Yohei 
Published: October 2019

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.
Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials
Authors: Sax Paul E , Erlandson Kristine M , Lake Jordan E , Mccomsey Grace A , Orkin Chloe , Esser Stefan , Brown Todd T , Rockstroh Jürgen K , Wei Xuelian , Carter Christoph C , Zhong Lijie , Brainard Diana M , Melbourne Kathleen , Das Moupali , Stellbrink Hans-Jürgen , Post Frank A , Waters Laura , Koethe John R 
Published: October 2019

Abstract

Background
Initiation of antiretroviral therapy (ART) often leads to weight gain. While some of this weight gain may be an appropriate return-to-health effect, excessive increases in weight may lead to obesity. We sought to explore factors associated with weight gain in several randomized comparative clinical trials of ART initiation.

Methods
We performed a pooled analysis of weight gain in 8 randomized controlled clinical trials of treatment-naive people living with human immunodeficiency virus (HIV) initiating ART between 2003 and 2015, comprising &gt;5000 participants and 10 000 person-years of follow-up. We used multivariate modeling to explore relationships between demographic factors, HIV disease characteristics, and ART components and weight change following ART initiation.

Results
Weight gain was greater in more recent trials and with the use of newer ART regimens. Pooled analysis revealed baseline demographic factors associated with weight gain including lower CD4 cell count, higher HIV type 1 RNA, no injection drug use, female sex, and black race. Integrase strand transfer inhibitor use was associated with more weight gain than were protease inhibitors or nonnucleoside reverse transcriptase inhibitors (NNRTIs), with dolutegravir and bictegravir associated with more weight gain than elvitegravir/cobicistat. Among the NNRTIs, rilpivirine was associated with more weight gain than efavirenz. Among nucleoside/nucleotide reverse transcriptase inhibitors, tenofovir alafenamide was associated with more weight gain than tenofovir disoproxil fumarate, abacavir, or zidovudine.

Conclusions
Weight gain is ubiquitous in clinical trials of ART initiation and is multifactorial in nature, with demographic factors, HIV-related factors, and the composition of ART regimens as contributors. The mechanisms by which certain ART agents differentially contribute to weight gain are unknown.
Congestion-Free Transient Plane (CFTP) Using Bandwidth Sharing During Link Failures in SDN
Authors: Vanamoorthy Muthumanikandan , Chinnaiah Valliyammai 
Published: October 2019

Abstract
Software-defined networking (SDN) is an emerging trend where the control plane and the data plane are separated from each other, culminating in effective bandwidth utilization. This separation also allows multi-vendor interoperability. Link failure is a major problem in networking and must be detected as soon as possible because when a link fails the path becomes congested and packet loss occurs, delaying the delivery of packets to the destination. Backup paths must be configured immediately when a failure is detected in the network to speed up packet delivery, avoid congestion and packet loss and provide faster convergence. Various SDN segment protection algorithms that efficiently reduce CPU cycles and flow table entries exist, but each has drawbacks. An independent transient plane technique can be used to reduce packet loss but is not as efficient when multiple flows try to share the same link. The proposed work focuses on reducing congestion, providing faster convergence with minimal packet loss and effectively utilizing link bandwidth using bandwidth-sharing techniques. An analysis and related studies show that this method performs better and offers a more reliable network without loss, while simultaneously ensuring the swift delivery of data packets toward the destination without congestion, compared to the other existing schemes.
Post-apocalyptic humanism in Hesiod, Mary Shelley, and Olaf Stapledon
Authors: Payne Mark 
Published: October 2019

AbstractThis paper considers the role of anachronism in large scale narratives of speculative fiction. Mary Shelley's The Last Man and Olaf Stapledon's Last and First Men signal in their titles an ambition to deal with humankind totally and all inclusively. Both authors look to Hesiod as a model for their projects: the Greek poet's account of successive creations and destructions of humankind at the hands of the gods offers a way of narrating human being as both a local cosmic occurrence that has been and one day will be no longer, and as a life form that has persisted with distinctive orientations and commitments through its various local incarnations. The question of anachronism is thus given maximum scope. Rather than a question about accuracy in the representation of local historical details, anachronism emerges as an interrogation of what we recognize and acknowledge as ourselves in the horizon of deep time.
Thymectomy in ocular myasthenia gravis before generalization results in a higher remission rate
Authors: Li Feng , Li Zhongmin , Chen Yanli , Bauer Gero , Uluk Deniz , Elsner Aron , Swierzy Marc , Ismail Mahmoud , Meisel Andreas , Rückert Jens-C 
Published: October 2019

Abstract

OBJECTIVES
This study aimed to compare the outcomes of patients with ocular myasthenia gravis (OMG) who underwent thymectomy before generalization with the outcomes of those who underwent thymectomy after generalization.

METHODS
We retrospectively reviewed patients who underwent robotic thymectomy for myasthenia gravis between January 2003 and February 2018. Patients who presented with purely ocular symptoms at myasthenia gravis onset were eligible for inclusion. Exclusion criteria were patients who were lost to follow-up and patients who underwent re-thymectomy. Patients with OMG who developed generalization before thymectomy were categorized into gOMG group and those who did not were categorized into OMG group. The primary outcome was complete stable remission according to the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS).

RESULTS
One hundred and sixty-five (66 males and 99 females) out of 596 patients with myasthenia gravis were eligible for inclusion. Of these, there were 73 and 92 patients undergoing thymectomy before and after the generalization of OMG, respectively. After propensity score matching, a data set of 130 patients (65 per group) was formed and evaluating results showed no statistical differences between the 2 groups. The estimated cumulative probabilities of complete stable remission at 5 years were 49.5% [95% confidence interval (CI) 0.345–0.611] in the OMG group and 33.4% (95% CI 0.176–0.462) in the gOMG group (P = 0.0053). Similar results were also found in patients with non-thymomatous subgroup [55 patients per group, OMG vs gOMG, 53.5% (95% CI 0.370–0.656) vs 28.9% (95% CI 0.131–0.419), P = 0.0041].

CONCLUSIONS
Thymectomy in OMG before generalization might result in a higher rate of complete stable remission than thymectomy after generalization.