bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of an intensive lifestyle intervention on the prevalence of metabolic syndrome and its components among overweight and obese adults
Authors: Guzmán M , Zbella E , Alvarez S Shah , Nguyen J L , Imperial E , Troncale F J , Holub C , Mallhi A K , VanWyk S 
Published: November 2019

AbstractBackgroundDespite the fact that up to a third of the global population has metabolic syndrome (MetS), it has been overlooked in clinical settings. This study assesses the impact of a physician-supervised nonsurgical weight management program on the prevalence of MetS and its key indicators.MethodsFour-hundred seventy-nine overweight and obese participants aged 19 years or older were included in a prospective longitudinal study. Changes in MetS and its key indicators were assessed using the binomial exact, chi-square and Wilcoxon signed-rank tests in an intent-to-treat study population. Differences in age strata were assessed using a generalized linear model.ResultsFifty-two percent of participants (n = 249) had MetS at baseline. Prevalence of MetS decreased steadily with significant changes from baseline observed at weeks 13 (31.8%, P &lt; 0.0001), 26 (28.7%, P &lt; 0.0012) and 39 (21.6%, P &lt; 0.0002); changes from baseline were observed at week 52 as statistically significant (16.7%, P &lt; 0.0012). Improvements in anthropometrics and levels of key indicators of MetS were observed throughout the study.ConclusionThese findings confirm that weight loss is inversely associated with prevalence of MetS and its key indicators among overweight and obese individuals. Future studies may benefit from a larger sample size and better retention (ClinicalTrials.gov ID: NCT03588117).
Beta Risk in the Cross-Section of Equities
Authors: Boloorforoosh Ali , Christoffersen Peter , Fournier Mathieu , Gouriéroux Christian 
Published: November 2019

Abstract
We develop a conditional capital asset pricing model in continuous time that allows for stochastic beta exposure. When beta comoves with market variance and the stochastic discount factor (SDF), beta risk is priced, and the expected return on a stock deviates from the security market line. The model predicts that low-beta stocks earn high returns, because their beta positively comoves with market variance and the SDF. The opposite is true for high-beta stocks. Estimating the model on equity and option data, we find that beta risk explains expected returns on low- and high-beta stocks, resolving the “betting against beta” anomaly.
Authors have furnished code and an Internet Appendix, which are available on the Oxford University Press Web site next to the link to the final published paper online.
Autophagy mediates hepatic GRK2 degradation to facilitate glucagon‐induced metabolic adaptation to fasting
Authors: Cruces‐Sande Marta , Arcones Alba C. , Vila‐Bedmar Rocío , Val‐Blasco Almudena , Sharabi Kfir , Díaz‐Rodríguez Daniel , Puigserver Pere , Mayor Federico , Murga Cristina 
Published: November 2019

AbstractThe liver plays a key role during fasting to maintain energy homeostasis and euglycemia via metabolic processes mainly orchestrated by the insulin/glucagon ratio. We report here that fasting or calorie restriction protocols in C57BL6 mice promote a marked decrease in the hepatic protein levels of G protein‐coupled receptor kinase 2 (GRK2), an important negative modulator of both G protein‐coupled receptors (GPCRs) and insulin signaling. Such downregulation of GRK2 levels is liver‐specific and can be rapidly reversed by refeeding. We find that autophagy, and not the proteasome, represents the main mechanism implicated in fasting‐induced GRK2 degradation in the liver in vivo. Reducing GRK2 levels in murine primary hepatocytes facilitates glucagon‐induced glucose production and enhances the expression of the key gluconeogenic enzyme Pck1. Conversely, preventing full downregulation of hepatic GRK2 during fasting using adenovirus‐driven overexpression of this kinase in the liver leads to glycogen accumulation, decreased glycemia, and hampered glucagon‐induced gluconeogenesis, thus preventing a proper and complete adaptation to nutrient deprivation. Overall, our data indicate that physiological fasting‐induced downregulation of GRK2 in the liver is key for allowing complete glucagon‐mediated responses and efficient metabolic adaptation to fasting in vivo.
MiR‐9‐5p protects from kidney fibrosis by metabolic reprogramming
Authors: Fierro‐Fernández Marta , Miguel Verónica , Márquez‐Expósito Laura , Nuevo‐Tapioles Cristina , Herrero J. Ignacio , Blanco‐Ruiz Eva , Tituaña Jessica , Castillo Carolina , Cannata Pablo , Monsalve María , Ruiz‐Ortega Marta , Ramos Ricardo , Lamas Santiago 
Published: November 2019

AbstractMicroRNAs (miRNAs) regulate gene expression posttranscriptionally and control biological processes (BPs), including fibrogenesis. Kidney fibrosis remains a clinical challenge and miRNAs may represent a valid therapeutic avenue. We show that miR‐9‐5p protected from renal fibrosis in the mouse model of unilateral ureteral obstruction (UUO). This was reflected in reduced expression of pro‐fibrotic markers, decreased number of infiltrating monocytes/macrophages, and diminished tubular epithelial cell injury and transforming growth factor‐beta 1 (TGF‐β1)‐dependent de‐differentiation in human kidney proximal tubular (HKC‐8) cells. RNA‐sequencing (RNA‐Seq) studies in the UUO model revealed that treatment with miR‐9‐5p prevented the downregulation of genes related to key metabolic pathways, including mitochondrial function, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and glycolysis. Studies in human tubular epithelial cells demonstrated that miR‐9‐5p impeded TGF‐β1‐induced bioenergetics derangement. The expression of the FAO‐related axis peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (PGC‐1α)‐peroxisome proliferator‐activated receptor alpha (PPARα) was reduced by UUO, although preserved by the administration of miR‐9‐5p. We found that in mice null for the mitochondrial master regulator PGC‐1α, miR‐9‐5p was unable to promote a protective effect in the UUO model. We propose that miR‐9‐5p elicits a protective response to chronic kidney injury and renal fibrosis by inducing reprogramming of the metabolic derangement and mitochondrial dysfunction affecting tubular epithelial cells.
Olanzapine for the Prevention and Treatment of Nausea and Vomiting Induced by Chemotherapy for Lung Cancer: protocol for a multicenter, double-blind and randomized controlled trial
Authors: Zhou Jian-Guo , Li Pei-Jie , Jin Su-Han , Liu Da-Hai , Huang Lang , Cao Ming-Ze , Zou Yu , Ma Hu 
Published: November 2019

AbstractBackgroundChemotherapy-induced nausea and vomiting (CINV) is frequently observed after the administration of chemotherapy and significantly influences the quality of life (QoL) of patients. Olanzapine has a high control rate of CINV in patients with cancer when combined with the NK-1 receptor antagonist dexamethasone and 5-hydroxytryptamine (5-HT3) receptor antagonists. The efficacy of a regimen without an NK-1 receptor antagonist remains unknown. Therefore, we designed this randomized trial to provide evidence for the management of CINV.Methods and ananlysisThis is a double-blind, multicenter and randomized controlled trial. Patients with histologically confirmed lung cancer will be assessed by physicians based on the inclusion and exclusion criteria, and 156 participants will be enrolled and randomized to a placebo group or experiment group to receive treatment for CINV. The primary endpoint is the incidence of delayed CINV. The secondary endpoints are complete response (CR) of acute CINV, CR of delayed CINV, effective control rate (ECR) of CINV and QoL. During the six days after administration, these endpoints will be evaluated and recorded by physicians.Ethic and disseminationThis study has received approval from the institutional ethical review board of the Affiliated Hospital of Zunyi Medical University (ref approval No. 58). Written informed consent will be signed by all participants prior to enrolling. Participants will be randomly assigned to the experimental group or comparator group by blocked randomization.Article summaryStrengths and limitationsThis study will provide evidence for physicians to find an affordable and effective treatment regimen for CINV through this study.Because of the variety of pharmaceutical companies, medical care and other factors, problem of cost will be further explored in the following studies.Although the study is designed as a double-blind randomized controlled trial, QoL will be measured by a questionnaire that is filled out by patients themselves. This may influence the conclusions.
Porous upconversion nanostructures as bimodal biomedical imaging contrast agents
Authors: Du Ziqing , Gupta Abhishek , Clarke Christian , Cappadana Matt , Clases David , Liu Deming , Yang Zhuoqing , Doble Philip , Price Bill , Xu Xiaoxue 
Published: November 2019

AbstractLanthanide ions doped upconversion nanoparticles (UCNPs) hold great promise as the imaging contrast agent for multimodal medical imaging techniques for diagnosis, including fluorescent bioimaging, magnetic resonance imaging, and computed tomography. However, the maximized signal values of fluorescence and MRI cannot be achieved simultaneously from the same upconversion nanoparticles structures because high specific surface areas can benefit the signal gaining of MRI while big size can induce brighter fluorescent imaging. In this work, we designed and fabricated novel core-porous shell structures for UCNPs with much-enhanced signal values for both fluorescent imaging and MRI. The core-porous shell UCNPs were synthesized via a post-treatment process after an inert shell was coated onto the core UCNPs. The formation mechanism was carefully investigated. The fluorescent and magnetic resonance properties have been detailed characterized and compared from core, core-shell and core-porous UCNPs. Large and bright UCNPs in fluorescence and MRI have been achieved and great potential as the dual-modal contrast agent.
A resource of targeted mutant mouse lines for 5,061 genes
Authors: Birling Marie-Christine , Yoshiki Atsushi , Adams David J , Ayabe Shinya , Beaudet Arthur L , Bottomley Joanna , Bradley Allan , Brown Steve DM , Bürger Antje , Bushell Wendy , Chiani Francesco , Chin Hsian-Jean Genie , Christou Skevoulla , Codner Gemma F , DeMayo Francesco J , Dickinson Mary E , Doe Brendan , Donahue Leah Rae , Fray Martin D , Gambadoro Alessia , Gao Xiang , Gertsenstein Marina , Gomez-Segura Alba , Goodwin Leslie O , Heaney Jason D , Hérault Yann , de Angelis Martin Hrabe , Jiang Si-Tse , Justice Monica J , Kasparek Petr , King Ruairidh E , Kühn Ralf , Lee Ho , Lee Young Jae , Liu Zhiwei , Kent Lloyd K C , Lorenzo Isabel , Mallon Ann-Marie , McKerlie Colin , Meehan Terrence F , Newman Stuart , Nutter Lauryl MJ , Oh Goo Taeg , Pavlovic Guillaume , Ramirez-Solis Ramiro , Rosen Barry , Ryder Edward J , Santos Luis A , Schick Joel , Seavitt John R , Sedlacek Radislav , Seisenberger Claudia , Seong Je Kyung , Skarnes William C , Sorg Tania , Steel Karen P , Tamura Masaru , Tocchini-Valentini Glauco P , Leo Wang Chi-Kuang , Wardle-Jones Hannah , Wattenhofer-Donzé Marie , Wells Sara , Willis Brandon J , Wood Joshua A , Wurst Wolfgang , Xu Ying ,   IMPC Consortium, Teboul Lydia , Murray Stephen A 
Published: November 2019

AbstractThe International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for over 5,000 genes from targeted embryonic stem cells on the C57BL/6N genetic background. This includes 2,850 null alleles for which no equivalent mutant mouse line exists, 2,987 novel conditional-ready alleles, and 4,433 novel reporter alleles. This nearly triples the number of genes with reporter alleles and almost doubles the number of conditional alleles available to the scientific community. When combined with more than 30 years of community effort, the total mutant allele mouse resource covers more than half of the genome. The extensively validated collection is archived and distributed through public repositories, facilitating availability to the worldwide biomedical research community, and expanding our understanding of gene function and human disease.
A Systems Change Framework for Evaluating Academic Equity and Inclusion in an Ecology & Evolution Graduate Program
Authors: Wallace Kelly J , York Julia M 
Published: November 2019

AbstractWhile academia is moving forward in terms of diversifying recruitment of undergraduate and graduate students, diverse representation is still not found across the academic hierarchy. At the graduate level, new discussions are emerging around efforts to improve the experiences of women and underrepresented minorities through inclusive graduate programming. Inclusive graduate programs are that which actively center and prioritize support for diverse experiences, identities, career goals, and perspectives, from recruitment through graduation. Establishing regular and rigorous evaluation of equity and inclusion efforts and needs is a critical component of this work. This is recognized by funding agencies that increasingly require reporting on inclusion efforts; here we suggest use of a systems change framework for these evaluations.A systems change approach emphasizes three levels: explicit change (e.g. policies), semi-explicit change (e.g. power dynamics), and implicit change (e.g. biases). We use the Ecology, Evolution, and Behavior (EEB) PhD Program at the University of Texas at Austin in an exercise to (1) identify areas of concern regarding inclusive programming voiced by graduate students, (2) categorize efforts to address these concerns, and (3) integrating and evaluating which areas of the systems change framework show the greatest progress or potential for progress. We argue this framework is particularly useful for academic systems as they are complex, composed of variable individuals, and must address diverse stakeholder needs.
Gene-flow from steppe individuals into Cucuteni-Trypillia associated populations indicates long-standing contacts and gradual admixture
Authors: Immel Alexander , Țerna Stanislav , Simalcsik Angela , Susat Julian , Šarov Oleg , Sîrbu Ghenadie , Hofmann Robert , Müller Johannes , Nebel Almut , Krause-Kyora Ben 
Published: November 2019

AbstractThe Cucuteni-Trypillia complex (CTC) flourished in eastern Europe for over two millennia (5100 – 2800 BCE) from the end of the Neolithic to the Early Bronze Age. Its vast distribution area encompassed modern-day eastern Romania, Moldova and western/central Ukraine. Due to a lack of existing burials throughout most of this time, only little is known about of the people associated with this complex and their genetic composition. Here, we present genome-wide data generated from the skeletal remains of four females that were excavated from two Late CTC sites in Moldova (3500 – 3100 BCE). All individuals carried a large Neolithic-derived ancestry component and were genetically more closely related to Linear Pottery than to Anatolian farmers. Three of the specimens also showed considerable amounts of steppe-related ancestry, suggesting influx into the CTC gene-pool from people affiliated with, for instance, the Ukraine Mesolithic. The latter scenario is supported by archaeological evidence. Taken together, our results confirm that the steppe component had arrived in eastern Europe farming communities maybe as early as 3500 BCE. In addition, they are in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations.
Stromal cell-contact dependent PI3K and APRIL induced NF-κB signaling complement each other to prevent mitochondrial- and endoplasmic reticulum stress induced cell death of bone marrow plasma cells
Authors: Cornelis Rebecca , Hahne Stefanie , Taddeo Adriano , Petkau Georg , Malko Darya , Durek Pawel , Thiem Manja , Heiberger Lukas , Mohr Elodie , Klaeden Cora , Tokoyoda Koji , Siracusa Francesco , Hoyer Bimba Franziska , Hiepe Falk , Mashreghi Mir-Farzin , Melchers Fritz , Chang Hyun-Dong , Radbruch Andreas 
Published: November 2019

SummaryPersistence of long-lived, memory plasma cells in the bone marrow depends on survival factors available in the bone marrow, provided in niches organized by stromal cells. Here we describe thatex vivowe can prevent apoptosis of bone marrow plasma cells by supplying direct cell contact with stromal cells and the soluble cytokine APRIL. Integrin-mediated contact of bone marrow plasma cells with stromal cells activates the PI3K signaling pathway, leading to critical inactivation of FoxO1/3 and preventing the activation of mitochondrial stress-associated effector caspases 3 and 7. Likely, inhibition of PI3K signalingin vivoablates bone marrow plasma cells. APRIL signaling, via the NF-κB pathway, blocks activation of the endoplasmic reticulum stress-associated initiator caspase 12. Thus, stromal cell-contact induced PI3K and APRIL-induced NF-κB signaling provide necessary and complementary signals to maintain bone marrow memory plasma cells.
Biomarker2vec: Attribute- and Behavior-driven Representation for Multi-type Relationship Prediction between Various Biomarkers
Authors: Guo Zhen-Hao , You Zhu-Hong , Wang Yan-Bin , Yi Hai-Cheng 
Published: November 2019

AbstractThe explosive growth of genomic, chemical and pathological data provides new opportunities and challenges to re-recognize life activities within human cells. However, there exist few computational models that aggregate various biomarkers to comprehensively reveal the physical and functional landscape of the biology system. Here, we construct a graph called Molecular Association Network (MAN) and a representation method called Biomarker2vec. Specifically, MAN is a heterogeneous attribute network consists of 18 kinds of edges (relationships) among 8 kinds of nodes (biomarkers). Biomarker2vec is an algorithm that represents the nodes as vectors by integrating biomarker attribute and behavior. After the biomarkers are described as vectors, random forest classifier is applied to carry out the prediction task. Our approach achieved promising performance on 18 relationships, with AUC of 0.9608 and AUPR of 0.9572. We also empirically explored the contribution of attribute and behavior feature of biomarkers to the results. In addition, a drug-disease association prediction case study was performed to validate our method’s ability on a specific object. These results strongly prove that MAN is a network with rich topological and biological information and Biomarker2vec can indeed adequately characterize biomarkers. Generally, our method can achieve simultaneous prediction of both single-type and multi-type relationships, which bring beneficial inspiration to relevant scholars and expand the medical research paradigm.
Rqc1 and other yeast proteins containing highly positively charged sequences are not targets of the RQC complex
Authors: Barros Géssica C. , Requião Rodrigo D. , Carneiro Rodolfo L. , Masuda Claudio A. , Moreira Mariana H. , Rossetto Silvana , Domitrovic Tatiana , Palhano Fernando L. 
Published: November 2019

ABSTRACTHighly positively charged protein segments are known to result in poor translation efficiency. This effect is explained by ribosome stalling caused by electrostatic interactions between the nascent peptide and the negatively charged ribosome exit tunnel, leading to translation termination followed by protein degradation mediated by the RQC complex. These polybasic sequences are mainly studied in the context of artificial reporter systems. Examples of endogenous yeast proteins targeted by the RQC complex are Rqc1, a protein essential for RQC function, and Sdd1. Both contain polybasic sequences that are thought to activate the RQC, leading to protein down-regulation. Here, we investigated whether the RQC complex regulates other endogenous proteins with polybasic sequences. We show by bioinformatics, ribosome profiling data analysis, and western blot that endogenous proteins containing polybasic sequences similar to, or even more positively charged than those of Rqc1 and Sdd1, are not targeted by the RQC complex suggesting that endogenous polybasic sequences are not sufficient to induce this type of regulation. Finally, our results also suggest that Rqc1 is regulated post-translationally by the E3 component of the RQC complex Ltn1, in a manner independent of the RQC complex.
Complexin suppresses spontaneous exocytosis by capturing the membrane-proximal regions of VAMP2 and SNAP25
Authors: Malsam J. , Bärfuss S. , Trimbuch T. , Zarebidaki F. , Sonnen A.F.-P. , Wild K. , Scheutzow A. , Sinning I. , Briggs J.A.G. , Rosenmund C. , Söllner T.H. 
Published: November 2019

SummaryThe neuronal protein complexin contains multiple domains that exert both clamping and facilitatory functions to tune spontaneous and action potential triggered synaptic release. We address the clamping mechanism and show that the accessory helix of complexin arrests the assembly of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that forms the core machinery of intracellular membrane fusion. In a reconstituted fusion assay, site- and stage-specific photo-cross-linking reveals that prior to fusion the complexin accessory helix laterally binds the membrane-proximal C-terminal ends of SNAP25 and VAMP2. Corresponding complexin interface mutants selectively increase spontaneous release of neurotransmitter in living neurons, implying that the accessory helix suppresses final zippering/assembly of the SNARE four-helix bundle by restraining VAMP2 and SNAP25.
GraphProt2: A graph neural network-based method for predicting binding sites of RNA-binding proteins
Authors: Uhl Michael , Tran Van Dinh , Heyl Florian , Backofen Rolf 
Published: November 2019

AbstractCLIP-seq is the state-of-the-art technique to experimentally determine transcriptome-wide binding sites of RNA-binding proteins (RBPs). However, it relies on gene expression which can be highly variable between conditions, and thus cannot provide a complete picture of the RBP binding landscape. This creates a demand for computational methods to predict missing binding sites. Here we present GraphProt2, a computational RBP binding site prediction framework based on graph convolutional neural networks (GCNs). In contrast to current CNN methods, GraphProt2 offers native support for the encoding of base pair information as well as variable length input, providing increased flexibility and the prediction of nucleotide-wise RBP binding profiles. We demonstrate its superior performance compared to GraphProt and two CNN-based methods on single as well as combined CLIP-seq datasets. Conceived as an end-to-end method, GraphProt2 includes all necessary functionalities, from dataset generation over model training to the evaluation of binding preferences and binding site prediction. Various input types and features are supported, accompanied by comprehensive statistics and visualizations to inform the user about datatset characteristics and learned model properties. All this makes GraphProt2 the most versatile and complete RBP binding site prediction method available so far.