bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy
Authors: Barceló Catalina , Guidi Monia , Thorball Christian W , Hammer Christian , Chaouch Aziz , Scherrer Alexandra U , Hasse Barbara , Cavassini Matthias , Furrer Hansjakob , Calmy Alexandra , Haubitz Sebastian , Bernasconi Enos , Buclin Thierry , Fellay Jacques , Tarr Philip E , Csajka Chantal ,   Swiss HIV Cohort Study, Anagnostopoulos A , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C R , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S 
Published: January 2020

AbstractObjectiveThere is limited data on abdominal obesity and the influence of genetics on weight change after antiretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) change over time in the Swiss HIV Cohort study (SHCS).MethodsMixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background.ResultsIndividuals with CD4 nadir &lt;100 cells/µL gained 6.4 times more BMI than individuals with ≥200, and 2.8 times more WHR than individuals with ≥100 (P &lt; .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir &lt;100 cells/µL compared to 100–199 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.63–2.74) and ≥200 (OR, 1.69; 95% CI, 1.26–2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir &lt;100 compared to ≥100 (OR, 1.35; 95% CI, 1.17–1.54 [in men]; OR, 1.36; 95% CI, 1.18–1.57 [in women]), persisting after 10 years of ART. No significant differences were found across antiretroviral drug classes or genetic scores.ConclusionsThe risk of general and abdominal obesity increased with CD4 nadir &lt;100 cells/µL. Based on our results, including the genetic background would not improve obesity predictions in HIV-infected individuals.
CGRP Plasma Levels Decrease in Classical Trigeminal Neuralgia Patients Treated with Botulinum Toxin Type A: A Pilot Study
Authors: Zhang Yi , Lian Yajun , Zhang Haifeng , Xie Nanchang , Chen Yuan 
Published: January 2020

Abstract

Objective
The aim of this study was to investigate the changes of calcitonin gene-related peptide (CGRP) plasma levels in patients with classical trigeminal neuralgia (TN) and if plasma CGRP concentrations could be used to predict the response to botulinum toxin type A (BTX-A).

Methods
Forty-seven patients with classical TN were recruited and treated with BTX-A. A patient was considered a responder when the visual analog scale (VAS) score and number of episodes were reduced by at least 50% compared with baseline data. Matched healthy subjects with no headache history served as controls. CGRP levels were measured by the enzyme-linked immunosorbent assay.

Results
A total of 45 patients and 30 healthy controls completed the study. Plasma CGRP concentrations after treatment with BTX-A (median [interquartile range {IQR}] = 28.86 [14.75–61.23] pg/mL) were significantly lower than before treatment (median [IQR] = 55.38 [22.59–71.67] pg/mL, P &lt; 0.001). Plasma CGRP concentrations in responders after treatment with BTX-A (median [IQR] = 28.02 [12.78–57.28] pg/mL) were significantly lower than before treatment (median [IQR] = 50.57 [24.30–70.09] pg/mL, P &lt; 0.001). In nonresponders, there were no significant differences between the levels before and after treatment (P = 0.938). Age, gender, VAS score, taking/not taking carbamazepine, and the number of trigeminal nerve branches involved had no significant influence on the median difference between plasma CGRP concentrations. The concentration of CGRP before treatment was not predictive of the treatment result.

Conclusions
CGRP levels decrease significantly in patients with classical TN after treatment with BTX-A. Plasma levels of CGRP cannot be used to predict the response to BTX-A. This study indicates that CGRP is likely to be involved in the pathophysiology of classical TN. Moreover, the analgesic mechanism of BTX-A may be related to the inhibition of CGRP release.
Practical and measurable definitions of care coordination, care management, and case management
Authors: Williams Mark D 
Published: January 2020

Abstract
Integrated behavioral health is a population-based approach that acknowledges the chronic nature of most mental illnesses and the need for services beyond those delivered in face-to-face visits. These services have been referred to by different and confusing names with over 40 definitions of care coordination concepts in the literature. Kilbourne et al. in a recent article in this journal divided these tasks into three groups: care coordination, care management and case management with associated definitions provided as used in the veterans affairs system. In this commentary, while drawing on over a decade of experience in implementing care management models in the Mayo clinic system of care, I will suggest we need to be even more specific with these definitions. I propose these terms be linked to critical and measurable tasks in the management of chronic conditions, thus allowing those administrating or researching these interventions to better assess fidelity, processes and outcomes when a model is applied to a population of patients with chronic conditions in an integrated setting.
Potential of ToxCast Data in the Safety Assessment of Food Chemicals
Authors: Punt Ans , Firman James , Boobis Alan , Cronin Mark , Gosling John Paul , Wilks Martin F , Hepburn Paul A , Thiel Anette , Fussell Karma C 
Published: January 2020

Abstract
Tox21 and ToxCast are high-throughput in vitro screening programs coordinated by the U.S. National Toxicology Program and the U.S. Environmental Protection Agency, respectively, with the goal of forecasting biological effects in vivo based on bioactivity profiling. The present study investigated whether mechanistic insights in the biological targets of food-relevant chemicals can be obtained from ToxCast results when the chemicals are grouped according to structural similarity. Starting from the 556 direct additives that have been identified in the ToxCast database by Karmaus et al. [Karmaus, A. L., Trautman, T. D., Krishan, M., Filer, D. L., and Fix, L. A. (2017). Curation of food-relevant chemicals in ToxCast. Food Chem. Toxicol. 103, 174–182.], the results showed that, despite the limited number of assays in which the chemical groups have been tested, sufficient results are available within so-called “DNA binding” and “nuclear receptor” target families to profile the biological activities of the defined chemical groups for these targets. The most obvious activity identified was the estrogen receptor-mediated actions of the chemical group containing parabens and structurally related gallates, as well the chemical group containing genistein and daidzein (the latter 2 being particularly active toward estrogen receptor β as a potential health benefit). These group effects, as well as the biological activities of other chemical groups, were evaluated in a series of case studies. Overall, the results of the present study suggest that high-throughput screening data could add to the evidence considered for regulatory risk assessment of food chemicals and to the evaluation of desirable effects of nutrients and phytonutrients. The data will be particularly useful for providing mechanistic information and to fill data gaps with read-across.
Honey bee queen production: Canadian costing case study and profitability analysis
Authors: Bixby Miriam , Hoover Shelley E. , McCallum Robyn , Ibrahim Abdullah , Ovinge Lynae , Olmstead Sawyer , Pernal Stephen F. , Zayed Amro , Foster Leonard J. , Guarna M. Marta 
Published: January 2020

AbstractThe recent decline in honey bee (Hymenoptera: Apidae) colony health worldwide has had a significant impact on the beekeeping industry as well as on pollination-dependent crop sectors in North America and Europe. The pollinator crisis has been attributed to many environmental and anthropological factors including less nutrient rich agricultural monocultures, pesticide exposure, new parasite and pathogen infestations as well as beekeeper management and weather. Canadian beekeepers have indicated that issues with honey bee queens are the most significant factor affecting their colony health. In Canada, beekeepers manage colony losses by relying on the importation of foreign bees, particularly queens from warmer climates, to lead new replacement colonies. Unfortunately, the risks associated with imported queens include the introduction of new and potentially resistant pests and diseases, undesirable genetics including bees with limited adaptations to Canada’s unique climate and bees negatively affected by transportation. Importing a large proportion of our queens each year also creates an unsustainable dependency on foreign bee sources, putting our beekeeping and pollination sectors at an even greater risk in the case of border closures and restrictions. Increasing the domestic supply of queens is one mitigation strategy that could provide Canadian beekeepers, farmers and consumers with a greater level of agricultural stability through locally bred, healthier queens. Our study is the first rigorous analysis of the economic feasibility of Canadian queen production. We present the costs of queen production for three case study operations across Canada over two years as well as the profitability implications. Our results show that for a small to medium sized queen production operation in Canada, producing queen cells and mated queens can be profitable. Using a mated queen market price ranging from $30 to $50, a producer selling mated queens could earn a profit of between $2 and $40 per queen depending on price and the cost structure of his operation. If the producer chose to rear queens for his own operation, the cost savings would also be significant as imported queen prices continue to rise. Our case studies reveal that there is potential for both skilled labour acquisition over time in queen production as well as cost savings from economies of scale. Our queen producers also reduced their production costs by re-using materials year to year. Domestic queen production could be one viable strategy to help address the current pollinator crisis in Canada.
Hybrid dynamic pharmacophore models as effective tools to identify novel chemotypes for anti-TB inhibitor design: A case study with Mtb-DapB
Authors: Choudhury Chinmayee , Bhardwaj Anshu 
Published: January 2020

AbstractAntimicrobial resistance (AMR) is one of the most serious global public health threats as it compromises the successful treatment of deadly infectious diseases like tuberculosis. New therapeutics are constantly needed but it takes a long time and is expensive to explore new biochemical space. One way to address this issue is to repurpose the validated targets and identify novel chemotypes that can simultaneously bind to multiple binding pockets of these targets as a new lead generation strategy. This study reports such a strategy, dynamic hybrid pharmacophore model (DHPM), which represents the combined interaction features of different binding pockets contrary to the conventional approaches, where pharmacophore models are generated from single binding sites. We have considered Mtb-DapB, a validated mycobacterial drug target, as our model system to explore the effectiveness of DHPMs to screen novel unexplored compounds. Mtb-DapB has a cofactor binding site (CBS) and an adjacent substrate binding site (SBS). Four different model systems of Mtb-DapB were designed where, either NADPH/NADH occupies CBS in presence/absence of an inhibitor 2, 6-PDC in the adjacent SBS. Two more model systems were designed, where 2, 6-PDC was linked to NADPH and NADH to form hybrid molecules. The six model systems were subjected to 200ns molecular dynamics simulations and trajectories were analyzed to identify stable ligand-receptor interaction features. Based on these interactions, conventional pharmacophore models (CPM) were generated from the individual binding sites while DHPMs were created from hybrid-molecules occupying both binding sites. A huge library of 15, 63,764 publicly available molecules were screened by CPMs and DHPMs. The screened hits obtained from both types of models were compared based on their Hashed binary molecular fingerprints and 4-point pharmacophore fingerprints using Tanimoto, Cosine, Dice and Tversky similarity matrices. Molecules screened by DHPM exhibited significant structural diversity, better binding strength and drug like properties as compared to the compounds screened by CPMs indicating the efficiency of DHPM to explore new chemical space for anti-TB drug discovery. The idea of DHPM can be applied for a wide range of mycobacterial or other pathogen targets to venture into unexplored chemical space.
CASSPER: A Semantic Segmentation based Particle Picking Algorithm for Single Particle Cryo-Electron Microscopy
Authors: George Blesson , Assaiya Anshul , Roy Robin Jacob , Kembhavi Ajit , Chauhan Radha , Paul Geetha , Kumar Janesh , Philip Ninan Sajeeth 
Published: January 2020

AbstractSingle-particle cryo-electron microscopy has emerged as the method of choice for structure determination of proteins and protein complexes. However, particle identification and selection which is a prerequisite for achieving high-resolution still poses a major bottleneck for automating the steps of structure determination. Here, we present a generalised deep learning tool, CASSPER, for the automated detection and isolation of protein particles in transmission microscope images. This deep learning tool uses Semantic Segmentation and a collection of visually prepared training samples to capture the differences in the transmission intensities of protein, ice, carbon and other impurities found in the micrograph. CASSPER is the first method to do pixel level classification and completely eliminates the need of manual particle picking. Integration of Contrast Limited Adaptive Histogram Equalization (CLAHE) in CASSPER enables high-fidelity particle detection even in micrographs with variable ice thickness and contrast. In addition, our generalized model for cross molecule picking works with high efficiency on unseen datasets and can potentially pick particles on-the-fly, thereby, enabling automation of data processing.
Immunohistochemical Characterization of Phosphorylated Ubiquitin in the Mouse Hippocampus
Authors: Kataoka Kosuke , Bilkei-Gorzo Andras , Zimmer Andreas , Asahi Toru 
Published: January 2020

ABSTRACTMitochondrial autophagy (mitophagy) is an essential and evolutionarily conserved process that maintains mitochondrial integrity via the removal of damaged or superfluous mitochondria in eukaryotic cells. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and Parkin promote mitophagy and function in a common signaling pathway. PINK1-mediated ubiquitin phosphorylation at Serine 65 (Ser65-pUb) is a key event in the efficient execution of PINK1/Parkin-dependent mitophagy. However, few studies have used immunohistochemistry to analyze Ser65-pUb in the mouse. Here, we examined the immunohistochemical characteristics of Ser65-pUb in the mouse hippocampus. Some hippocampal cells were Ser65-pUb positive, whereas the remaining cells expressed no or low levels of Ser65-pUb. PINK1 deficiency resulted in a decrease in the density of Ser65-pUb-positive cells, consistent with a previous hypothesis based onin vitroresearch. Interestingly, Ser65-pUb-positive cells were detected in hippocampi lacking PINK1 expression. The CA3 pyramidal cell layer and the dentate gyrus (DG) granule cell layer exhibited significant reductions in the density of Ser65-pUb-positive cells in PINK1-deficient mice. Moreover, Ser65-pUb immunoreactivity colocalized predominantly with neuronal markers. These findings suggest that Ser65-pUb may serve as a biomarker ofin situPINK1 signaling in the mouse hippocampus; however, the results should be interpreted with caution, as PINK1 deficiency downregulated Ser65-pUb only partially.
Plxdc family members are novel receptors for the rhesus monkey rhadinovirus (RRV)
Authors: Großkopf Anna K. , Schlagowski Sarah , Fricke Thomas , Ensser Armin , Desrosiers Ronald C. , Hahn Alexander S. 
Published: January 2020

ABSTRACTThe rhesus monkey rhadinovirus (RRV), a γ2-herpesvirus of rhesus macaques, shares many biological features with the human pathogenic Kaposi’s sarcoma-associated herpesvirus (KSHV). Both viruses, as well as the more distantly related Epstein-Barr virus, engage cellular receptors from the Eph family of receptor tyrosine kinases (Ephs). However, the importance of the Eph interaction for RRV entry varies between cell types suggesting the existence of Eph-independent entry pathways. We therefore aimed to identify additional cellular receptors for RRV by affinity enrichment and mass spectrometry. We identified an additional receptor family, the Plexin domain containing proteins 1 and 2 (Plxdc1/2) that bind the RRV gH/gL glycoprotein complex. Preincubation of RRV with soluble Plxdc2 decoy receptor reduced infection by approx. 60%, while overexpression of Plxdc1 and 2 dramatically enhanced RRV susceptibility of otherwise marginally permissive Raji cells. While the Plxdc2 interaction is conserved between two RRV strains, 26-95 and 17577, Plxdc1 specifically interacts with RRV 26-95 gH. The Plxdc interaction is mediated by a short motif at the N-terminus of RRV gH that is partially conserved between isolate 26-95 and isolate 17577, but absent in KSHV gH. Mutation of this motif abrogated the interaction with Plxdc1/2 inin vitroassays and reduced RRV infection in a cell-type specific manner. Taken together, our findings characterize Plxdc1/2 as novel interaction partners and entry receptors for RRV and support the concept of the N-terminal domain of the gammaherpesviral gH/gL complex as a multifunctional receptor-binding domain. Further, Plxdc1/2 usage defines an important biological difference between KSHV and RRV.AUTHORS SUMMARYKSHV is the causative agent of a group of malignancies which account for a substantial disease burden in particular in sub-Saharan Africa. RRV, a related virus of rhesus macaques, has shown promise as model system for KSHV and for the development of immunization strategies. To exploit the full potential of the RRV animal model system, detailed knowledge of commonalities and differences between KSHV and RRV is key. Here, we describe the Plexin domain containing proteins 1 and 2 as a novel receptor family which mediates entry of RRV, but not of KSHV. Infection experiments using RRV mutants deleted of the Plxdc interaction motif suggest a cell type-specific contribution of Plxdc receptors to RRV infection. As information on Plxdc1/2 and its biological function is still sparse, analysis of the RRV–Plxdc interaction will help to characterize the physiological and pathophysiological role of this receptor family.
PHENSIM: Phenotype Simulator
Authors: Alaimo Salvatore , Rapicavoli Rosaria Valentina , Marceca Gioacchino P. , La Ferlita Alessandro , Serebrennikova Oksana B. , Tsichlis Philip N. , Mishra Bud , Pulvirenti Alfredo , Ferro Alfredo 
Published: January 2020

AbstractDespite the unprecedented growth in our understanding of cell biology, it still remains challenging to connect it to experimental data obtained with cells and tissues’ physiopathological status under precise circumstances. This knowledge gap often results in difficulties in designing validation experiments, which are usually labor-intensive, expensive to perform, and hard to interpret.Here we propose PHENSIM, a computational tool using a systems biology approach in order to simulate how cell phenotypes are affected by the activation/inhibition of one or multiple biomolecules and does so by exploiting signaling pathways. Our tool’s applications include predicting the outcome of drug administration, knockdown experiments, gene transduction, and exposure to exosomal cargo. Importantly, PHENSIM enables the user to make inferences on well-defined cell lines and includes pathway maps from three different model organisms. To assess our approach’s reliability, we built a benchmark from transcriptomics data gathered from NCBI GEO and performed four case studies on known biological experiments. Our results show high prediction accuracy, thus highlighting the capabilities of this methodology.PHENSIM standalone Java application is available athttps://github.com/alaimos/phensim, along with all data and source codes for benchmarking. A web-based user interface is accessible athttps://phensim.atlas.dmi.unict.it/.
Suitable habitats of fish species in the Barents Sea
Authors: Husson Bérengère , Certain Gregoire , Filin Anatoly , Planque Benjamin 
Published: January 2020

AbstractMany marine species are shifting their distribution poleward in response to climate change. The Barents Sea, as a doorstep to the fast-warming Arctic, is experiencing large scale changes in its environment and its communities. This paper aims at understanding what environmental predictors limit fish species habitats in the Barents Sea and discuss their possible evolution in response to the warming of the Arctic.Species distribution models usually aim at predicting the probability of presence or the average abundance of a species, conditional on environmental drivers. A complementary approach is to determine suitable habitats by modelling the upper limit of a species’ response to environmental factors. Using quantile regressions, we model the upper limit of biomass for 33 fish species in the Barents Sea in response to 10 environmental predictors. Boreal species are mainly limited by temperatures and most of them are expected to be able to expand their distribution in the Barents Sea when new thermally suitable habitats become available, in the limit of bathymetric constraints. Artic species are often limited by several predictors, mainly depth, bottom and surface temperature and ice cover, and future habitats are hard to predict qualitatively. Widespread species like the Atlantic cod are not strongly limited by the selected variables at the scale of the study, and current and future suitable habitats are harder to predict. These models can be used as input to integrative tools like end-to-end models on the habitat preference and tolerance at the species scale to inform resource management and conservation.