bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Hospital Volume With Respect to Performing Gastric Cancer Resection on Recurrence and Survival
Authors: Claassen Yvette H. M. , van Amelsfoort Romy M. , Hartgrink Henk H. , Dikken Johan L. , de Steur Wobbe O. , van Sandick Johanna W. , van Grieken Nicole C. T. , Cats Annemieke , Boot Henk , Trip Anouk K. , Jansen Edwin P. M. , Kranenbarg Elma Meershoek-Klein , Braak Jeffrey P. B. M. , Putter Hein , van Berge Henegouwen Mark I. , Verheij Marcel , van de Velde Cornelis J. H. 
Published: July 2018

Objective:We examined the association between surgical hospital volume and both overall survival (OS) and disease-free survival (DFS) using data obtained from the international CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial.Summary Background Data:In the CRITICS trial, patients with resectable gastric cancer were randomized to receive preoperative chemotherapy followed by adequate gastrectomy and either chemotherapy or chemoradiotherapy.Methods:Patients in the CRITICS trial who underwent a gastrectomy with curative intent in a Dutch hospital were included in the analysis. The annual number of gastric cancer surgeries performed at the participating hospitals was obtained from the Netherlands Cancer Registry; the hospitals were then classified as low-volume (1–20 surgeries/year) or high-volume (≥21 surgeries/year) and matched with the CRITICS trial data. Univariate and multivariate analyses were then performed to evaluate the hazard ratio (HR) between hospital volume and both OS and DFS.Results:From 2007 through 2015, 788 patients were included in the CRITICS trial. Among these 788 patients, 494 were eligible for our study; the median follow-up was 5.0 years. Five-year OS was 59.2% and 46.1% in the high-volume and low-volume hospitals, respectively. Multivariate analysis revealed that undergoing surgery in a high-volume hospital was associated with higher OS [HR = 0.69, 95% confidence interval (CI) = 0.50–0.94,P= 0.020] and DFS (HR = 0.73, 95% CI: 0.54–0.99,P= 0.040).Conclusions:In the CRITICS trial, hospitals with a high annual volume of gastric cancer surgery were associated with higher overall and DFS. These findings emphasize the value of centralizing gastric cancer surgeries in the Western world.
Penetration Assessment of Dietary Supplements and Drugs through the Blood-Brain Barrier for Potential Treatment of Parkinson ‘s Disease
Authors: Chevalier Roger 
Published: July 2018

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder, affecting 2% of the population over the age of 60. To date, there is no disease modifying drugs to prevent dopaminergic neuron loss and abnormal protein deposition in the brains. There is a strong demand for neuroprotective therapies to prevent or slow down dopaminergic neuron degeneration. An essential prerequisite for a compound designed to affect the central nervous system (CNS) is a satisfactory transport through the blood brain barrier (BBB). Numerous posts on the net suggest that both repositioned drugs molecules and active molecules present in dietary supplements may slow down PD’s progression. The logBB is an index of BBB permeability. Starting from quantitative and qualitative permeability data, this study tries to predict logBB values from various physicochemical properties of molecules, including, among others, molecular size, polar surface area (PSA) and logP values. Quantitative logBB models were implemented using MLP (multiple linear regression), PLS (Partial Least Square), AAKR (Auto Associative Kernel Regression) and ECM (Evolving Cluster Method). Qualitative models were carried out with SVM (Support Vector Method).The paper estimates the BBB permeability of 39 molecules potentially able to slow down PD’s progression and compares the performances of qualitative and quantitative machine learning method used. For information, the current study also gives a short overview of the state of the art on the potential impact of dietary supplements on PD.
Determinants of invasive species policy: print media and agriculture determine United States invasive wild pig policy
Authors: Miller Ryan S. , Opp Susan M. , Webb Colleen T. 
Published: July 2018

AbstractConflicts between wildlife, invasive species, and agricultural producers are increasing. Although direct management actions taken to mitigate these conflicts remain controversial, most stakeholders agree that better policies are needed to balance socio-economic considerations with invasive species management, wildlife conservation, and agriculture. However the interaction between societal and biological drivers that influence human-invasive species-wildlife conflict mitigation policy is poorly understood. We identify factors influencing policy leading to the establishment of a new federal program to control invasive wild pigs in the United States. We fit generalized linear models relating frequency of congressional policy activity, such as congressional hearings and reports, to frequency of print newspaper media and percent of the U.S. agricultural industry co-occurring with invasive wild pigs for 29 years preceding the establishment of the federal program in 2013. Our models explained 89% of the deviance in congressional policy activity indicating a strong linkage between congressional invasive wild pig policy activity and predictors representing the number of negative of newspaper articles, geographic distribution of print media, and percent of agricultural producers co-occurring with invasive wild pigs. These effects translated to 3.7% increase in the number of congressional policy actions for every additional five states with negative news media. Invasive wild pig congressional policy activity increased 6.7% for every additional 10 negative newspaper articles. Increases in co-occurrence of agriculture and invasive wild pigs had the largest effect, for every 1% increase in co-occurrence there was a 41% increase in congressional policy activity. Invasive wild pig congressional policy activity that explicitly addressed livestock increased at nearly twice the rate of policy activity addressing crop agriculture. These results suggest that agriculture and media coverage may act as determinants for invasive species policy. Our approach may provide early insight into emerging policy areas enabling proactive policy development by agencies or early engagement by scientists to find solutions before the policy area becomes grid locked. Our results can also support policy and program evaluation providing a means of determining if the implemented policies match the original policy determinants ensuring best alignment with public, environmental, and stakeholder interests.
FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice
Authors: Findlay Steven , Heath John , Luo Vincent M. , Malina Abba , Morin Théo , Djerir Billel , Li Zhigang , Samiei Arash , Simo-Cheyou Estelle , Karam Martin , Bagci Halil , Rahat Dolev , Grapton Damien , Lavoie Elise G. , Dove Christian , Khaled Husam , Kuasne Hellen , Mann Koren K. , Klein Kathleen Oros , Greenwood Celia M. , Tabach Yuval , Park Morag , Côté Jean-Francois , Maréchal Alexandre , Orthwein Alexandre 
Published: July 2018

SUMMARYDNA double-strand breaks (DSBs) can be repaired by two major pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). DNA repair pathway choice is governed by the opposing activities of 53BP1, in complex with its effectors RIF1 and REV7, and BRCA1. However, it remains unknown how the 53BP1/RIF1/REV7 complex stimulates NHEJ and restricts HR to the S/G2 phases of the cell cycle. Using a mass spectrometry (MS)-based approach, we identify 11 high-confidence REV7 interactors and elucidate the role of a previously undescribed factor, FAM35A/SHDL2, as a novel effector of REV7 in the NHEJ pathway. FAM35A depletion impairs NHEJ-mediated DNA repair and compromises antibody diversification by class switch recombination (CSR) in B-cells. FAM35A accumulates at DSBs in a 53BP1-, RIF1- and REV7-dependent manner and antagonizes HR by limiting DNA end resection. In fact, FAM35A is part of a larger complex composed of REV7 and another previously uncharacterized protein, C20orf196/SHDL1, which promotes NHEJ and limits HR. Together, these results establish FAM35A as a novel effector of REV7 in controlling the decision-making process during DSB repair.
JNK-mediated spindle reorientation in stem cells promotes dysplasia in the aging intestine
Authors: Hu Daniel Jun-Kit , Jasper Heinrich 
Published: July 2018

AbstractHomeostasis in high-turnover tissues depends on precise yet plastic regulation of stem cell daughter fates. In Drosophila, intestinal stem cells (ISCs) respond to unknown signals to switch from asymmetric to symmetric divisions during feeding-induced growth. Here, we show that this switch is controlled by dynamic reorientation of mitotic spindles by a Jun-N-terminal Kinase (JNK) / Wdr62 / Kif1a interaction. JNK promotes Wdr62 localization at the spindle and represses transcription of the kinesin Kif1a. This activity of JNK results in over-abundance of symmetric divisions in stress conditions, and contributes to the loss of tissue homeostasis in the aging animal. Restoring normal ISC spindle orientation by perturbing the JNK/Wdr62/Kif1a axis is sufficient to improve intestinal physiology and extend lifespan. Our findings reveal a critical role for the dynamic control of SC spindle orientation in epithelial maintenance.
Infection of highly insecticide-resistant malaria vector Anopheles coluzzii with an environmentally friendly entomopathogenic bacteria Chromobacterium violaceum reduces its survival, blood feeding propensity and fecundity
Authors: Gnambani Edounou Jacques , Bilgo Etienne , Sanou Adama , Dabiré Roch K. , Diabaté Abdoulaye 
Published: July 2018

AbstractThis is now a concern that malaria eradication will not be achieved without the introduction of novel control tools. Microbiological control might be able to make a greater contribution to vector control in the future. Here, we studied the impact of Chromobacterium violaceum infections isolated from wild caught Anopheles gambiae s.l. mosquitoes in Burkina Faso on mosquito survival, blood feeding and fecundity propensy. C. violaceum kills pyrethroid resistant mosquitoes An. coluzzii (LT80 ~ at 108 bacteria cell/ml of sugar meal). Interestingly, this bacterium had other negative effects on mosquito lifespan by significantly reducing (~59%, P<0.001) the mosquito feeding willingness from day 4-post infection to 9-day post infection. Moreover, C.violaceum considerably jeopardized the mosquito egg laying and hatching of mosquitoes by ~77.93% and ~22 % respectively. Mosquitoes infected with C. violaceum also showed significantly higher retention rates of immature eggs and follicles. These data showed important entomopathogenic properties of Burkina Faso C. violaceum strains. However, additional studies as the sequencing of C. violaceum genome and the potential toxins secreted will certainly provide useful information render it a potential candidate for the biological control strategies of malaria.
Learning from Longitudinal Data in Electronic Health Record and Genetic Data to Improve Cardiovascular Event Prediction
Authors: Zhao Juan , Feng QiPing , Wu Patrick , Lupu Roxana , Wilke Russell A. , Wells Quinn S. , Denny Joshua C. , Wei Wei-Qi 
Published: July 2018

ABSTRACTBackgroundCurrent approaches to predicting Cardiovascular disease rely on conventional risk factors and cross-sectional data. In this study, we asked whether: i) machine learning and deep learning models with longitudinal EHR information can improve the prediction of 10-year CVD risk, and ii) incorporating genetic data can add values to predictability.MethodsWe conducted two experiments. In the first experiment, we modeled longitudinal EHR data with aggregated features and temporal features. We applied logistic regression (LR), random forests (RF) and gradient boosting trees (GBT) and Convolutional Neural Networks (CNN) and Recurrent Neural Networks, using Long Short-Term Memory (LSTM) units. In the second experiment, we proposed a late-fusion framework to incorporate genetic features.ResultsOur study cohort included 109, 490 individuals (9,824 were cases and 99, 666 were controls) from Vanderbilt University Medical Center’s (VUMC) de-identified EHRs. American College of Cardiology and the American Heart Association (ACC/AHA) Pooled Cohort Risk Equations had areas under receiver operating characteristic curves (AUROC) of 0.732 and areas under receiver under precision and recall curves (AUPRC) of 0.187. LSTM, CNN and GBT with temporal features achieved best results, which had AUROC of 0.789, 0.790, and 0.791, and AUPRC of 0.282, 0.280 and 0.285, respectively. The late fusion approach achieved a significant improvement for the prediction performance.ConclusionsMachine learning and deep learning with longitudinal features improved the 10-year CVD risk prediction. Incorporating genetic features further enhanced 10-year CVD prediction performance, underscoring the importance of integrating relevant genetic data whenever available in the context of routine care.
De novoGene Signature Identification from Single-Cell RNA-Seq with Hierarchical Poisson Factorization
Authors: Levitin Hanna Mendes , Yuan Jinzhou , Cheng Yim Ling , Ruiz Francisco J.R. , Bush Erin C. , Bruce Jeffrey N. , Canoll Peter , Iavarone Antonio , Lasorella Anna , Blei David M. , Sims Peter A. 
Published: July 2018

AbstractCommon approaches to gene signature discovery in single cell RNA-sequencing (scRNA-seq) depend upon predefined structures like clusters or pseudo-temporal order, require prior normalization, or do not account for the sparsity of single cell data. We present single cell Hierarchical Poisson Factorization (scHPF), a Bayesian factorization method that adapts Hierarchical Poisson Factorization [1] forde novodiscovery of both continuous and discrete expression patterns from scRNA-seq. scHPF does not require prior normalization and captures statistical properties of single cell data better than other methods in benchmark datasets. Applied to scRNA-seq of the core and margin of a high-grade glioma, scHPF uncovers marked differences in the abundance of glioma subpopulations across tumor regions and subtle, regionally-associated expression biases within glioma subpopulations. scHFP revealed an expression signature that was spatially biased towards the glioma-infiltrated margins and associated with inferior survival in glioblastoma.
SP1433-1438 operon ofStreptococcus pneumoniaeregulates metal homeostasis and cellular metabolism during zinc-stress
Authors: Burcham Lindsey R. , Hill Rebecca A. , Caulkins Rachel C. , Emerson Joseph P. , Nanduri Bindu , Rosch Jason W. , Fitzkee Nicholas C. , Thornton Justin A. 
Published: July 2018

AbstractStreptococcus pneumoniaecolonizes the mucosa of the human nasopharynx and is a leading cause of community-acquired pneumonia, acute otitis media, and bacterial meningitis. Metal ion homeostasis is vital to the survival of this pathogen and contributes significantly to both colonization and invasive disease. Microarray and qRT-PCR analysis revealed an upregulation of an uncharacterized operon (SP1433-1438) in pneumococci subjected to metal-chelation byN,N,N’,N’-tetrakis-(2-Pyridylmethyl)ethylenediamine (TPEN). Supplementation of either zinc or cobalt following TPEN treatment drastically abrogated induction. BLAST analysis predicted this operon to encode two ABC-transporters, sharing homology to a multidrug resistance system (SP1434-1435) and an energy-coupling factor (ECF) transport system (SP1436-1438). Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated changes in intracellular concentrations of iron, zinc, and manganese ions in a Δ1434-8 strain compared to parental T4R. Analysis of the secreted metabolomic profile of the T4R and Δ1434-8 strains identified significant changes in pneumococcal glycolytic pathways, indicating a shift towards increased production of acetate. Additionally, proteomic analysis revealed 41 differentially expressed proteins in the Δ1434-8 strain, with roughly 20% of them regulated by the global catabolite repressor, CcpA. Based on these findings, we propose that theSP1433-1438operon is largely involved in the central metabolism ofS. pneumoniaeduring zinc-limitation.ImportanceMetal sequestration is a common strategy utilized by the host immune response as well as antibiotics such as vancomycin to kill invading bacterial pathogens (1). However, pneumococcus is still able to thrive under zinc-limiting conditions. This study describes a previously uncharacterized operon encoding two ABC transport systems that are strongly induced during zinc-limiting conditions. This operon was found to be regulated by a zinc-dependent regulator (SP1433) that functions independently of the overarching AdcR regulon. We have additionally utilized a 2D-NMR approach to analyze the secreted metabolome and have employed proteomic analysis to identify a role for these systems in the maintenance of cellular metabolism. This study provides new information on howStreptococcus pneumoniaeresponds and adapts to zinc-limiting conditions.
acI Actinobacteria Assemble a Functional Actinorhodopsin with Natively-synthesized Retinal
Authors: Dwulit-Smith Jeffrey R. , Hamilton Joshua J. , Stevenson David M. , He Shaomei , Oyserman Ben O. , Moya-Flores Francisco , Amador-Noguez Daniel , McMahon Katherine D. , Forest Katrina T. 
Published: July 2018

ABSTRACTFreshwater lakes harbor complex microbial communities, but these ecosystems are often dominated by acI Actinobacteria from three clades (acI-A, acI-B, acI-C). Members of this cosmopolitan lineage are proposed to bolster heterotrophic growth using phototrophy because their genomes encode actino-opsins (actR). This model has been difficult to experimentally validate because acI are not consistently culturable. In this study, using genomes from single cells and metagenomes, we provide a detailed biosynthetic route for many acI-A and -B members to synthesize retinal and its carotenoid precursors. Accordingly, these acI should be able to natively assemble light-driven actinorhodopsins (holo-ActR) to pump protons, in contrast to acI-C members and other bacteria that encode opsins but lack retinal-production machinery. Moreover, we show that all acI clades contain genes for a complex carotenoid pathway that starts with retinal precursors. Transcription analysis of acI in a eutrophic lake shows that all retinal and carotenoid pathway operons are transcribed and that actR is among the most highly-transcribed of all acI genes. Furthermore, heterologous expression of retinal pathway genes shows that lycopene, retinal, and ActR can be made. Model cells producing ActR and the key acI retinal-producing β-carotene oxygenase formed acI-holo-ActR and acidified solution during illumination. Our results prove that acI containing both ActR and retinal-production enzymes have the capacity to natively synthesize a green light-dependent outward proton-pumping rhodopsin.IMPORTANCEMicrobes play critical roles in determining the quality of freshwater ecosystems that are vital to human civilization. Because acI Actinobacteria are ubiquitous and abundant in freshwater lakes, clarifying their ecophysiology is a major step in determining the contributions that they make to nitrogen and carbon cycling. Without accurate knowledge of these cycles, freshwater systems cannot be incorporated into climate change models, ecosystem imbalances cannot be predicted, and policy for service disruption cannot be planned. Our work fills major gaps in microbial light utilization, secondary metabolite production, and energy cycling in freshwater habitats.
Quantitative behavior of protein complexes in human cells
Authors: Chalabi Morteza H , Tsiamis Vasileios , Käll Lukas , Vandin Fabio , Schwämmle Veit 
Published: July 2018

AbstractTranslational and post-translational control mechanisms in the cell result in widely observable differences between measured gene transcription and protein abundances. Herein, protein complexes are among the most tightly controlled entities by selective degradation of their individual proteins. They furthermore act as control hubs that regulate highly important processes in the cell and exhibit a high functional diversity due to their ability to change their composition and their structure. To better understand and predict these functional states, extensive characterization of complex composition, behavior, and abundance is necessary. Mass spectrometry provides an unbiased approach to directly determine protein abundances across cell populations and thus to profile a comprehensive abundance map of proteins. We investigated the behavior of protein subunits in known complexes by comparing their abundance profiles across up to 140 cell types available in ProteomicsDB. After thorough assessment of different randomization methods and statistical scoring algorithms, we developed a computational tool to quantify the significance of concurrent profiles within a complex, therefore providing insights into the conservation of their composition across human cell types. We identified the intrinsic structures in complex behavior that allow to determine which proteins orchestrate complex function. This analysis can be extended to investigate common profiles within arbitrary protein groups. With the CoExpresso web service, we offer a potent scoring scheme to assess proteins for their co-regulation and thereby offer insight into their potential for forming functional groups like protein complexes. CoExpresso can be accessed through http://computproteomics/Apps/CoExpresso. Source code and R scripts for database generation are available at https://bitbucket.org/veitveit/coexpresso.Author summaryMany proteins form multi-functional assemblies called protein complexes instead of working as singly units. These complexes control most processes in the cell making the full characterization of their behavior inevitable to understand cellular control mechanisms. Detailed knowledge about complex behavior will elucidate biomarkers and drug targets that exhibit and correct aberrant cell states, respectively. We investigated abundance changes of the protein complex components over more than 100 different human cell types. By using statistical scoring models, we estimated the evidence for the co-regulation of the proteins and revealed which proteins form subunits with impact on complex function and composition. By providing the interactive web service CoExpresso, any combination of proteins can be tested for their co-regulation in human cells.