bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collaborative Behavior of Urea and KI in Denaturing Protein Native Structure
Authors: Shao Qiang , Wang Jinan , Zhu Weiliang 
Published: January 2020

AbstractIn this work, the combined influence of urea and KI on protein native structure is quantitatively investigated through the comparative molecular dynamics simulations on the structural dynamics of a polypeptide of TRPZIP4 in a series of urea/KI mixed solutions (urea concentration: 4M, KI salt concentration: 0M-6M). The observed enhanced denaturing ability of urea/KI mixture can be explained by direct interactions of urea/K+/water towards protein (electrostatic and vdW interactions from urea and electrostatic interactions from K+and water) and indirect influence of KI on the strengthened interaction of urea towards protein backbone and side-chain. The latter indirect influence is fulfilled through the weakening of hydrogen bonding network among urea and water by the appearance of K+–water and I—urea interactions. As a result, the denaturing ability enhancement of urea and KI mixed solution is induced by the collaborative behavior of urea and KI salt.
Galantamine alleviates oxidative stress alongside anti-inflammatory and cardio-metabolic effects in subjects with the metabolic syndrome in a randomized trial
Authors: Sangaleti Carine Teles , Katayama Keyla Yukari , De Angelis Kátia , de Moraes Tércio Lemos , Araújo Amanda Aparecida , Lopes Heno F. , Camacho Cleber , Bortolotto Luiz Aparecido , Michelini Lisete Compagno , Irigoyen Maria Cláudia , Barnaby Douglas P. , Tracey Kevin J. , Pavlov Valentin A. , Consolim Colombo Fernanda Marciano 
Published: January 2020

AbstractBackgroundThe metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.MethodsThe effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.ResultsGalantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.ConclusionLow-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.
Evaluating the performance of the WHO international reference standard for osteoporosis diagnosis in postmenopausal women of varied polygenic score and race
Authors: Wu Qing , Xiao Xiangxue , Xu Yingke 
Published: January 2020

AbstractBackgroundWhether the bone mineral density (BMD) T-score performs differently in osteoporosis classification in women of different genetic profiling and race background remains unclear.MethodsThe genomic data in the Women’s Health Initiative study was analyzed (n=2,417). The polygenic score (PGS) was calculated from 63 BMD-associated single nucleotide polymorphisms (SNPs) for each participant. The World Health Organization’s (WHO) definition of osteoporosis (BMD T-score≤-2.5) was used to estimate the cumulative incidence of fracture.ResultsT-score classification significantly underestimated the risk of major osteoporotic fracture (MOF) in the WHI study. An enormous underestimation was observed in African American women (POR: 0.52, 95% CI: 0.30-0.83) and in women with low PGS (predicted/observed ratio [POR]: 0.43, 95% CI: 0.28-0.64). Compared to Caucasian women, African American, African Indian, and Hispanic women respectively had a 59%, 41%, and 55% lower hazard of MOF after the T-score was adjusted for. The results were similar when used for any fractures.ConclusionsOur study suggested the BMD T-score performance varies significantly by race in postmenopausal women.
Classification of glomerular pathological findings using deep learning and nephrologist–AI collective intelligence approach
Authors: Uchino Eiichiro , Suzuki Kanata , Sato Noriaki , Kojima Ryosuke , Tamada Yoshinori , Hiragi Shusuke , Yokoi Hideki , Yugami Nobuhiro , Minamiguchi Sachiko , Haga Hironori , Yanagita Motoko , Okuno Yasushi 
Published: January 2020

AbstractBackgroundAutomated classification of glomerular pathological findings is potentially beneficial in establishing an efficient and objective diagnosis in renal pathology. While previous studies have verified the artificial intelligence (AI) models for the classification of global sclerosis and glomerular cell proliferation, there are several other glomerular pathological findings required for diagnosis, and the comprehensive models for the classification of these major findings have not yet been reported. Whether the cooperation between these AI models and clinicians improves diagnostic performance also remains unknown. Here, we developed AI models to classify glomerular images for major findings required for pathological diagnosis and investigated whether those models could improve the diagnostic performance of nephrologists.MethodsWe used a dataset of 283 kidney biopsy cases comprising 15888 glomerular images that were annotated by a total of 25 nephrologists. AI models to classify seven pathological findings: global sclerosis, segmental sclerosis, endocapillary proliferation, mesangial matrix accumulation, mesangial cell proliferation, crescent, and basement membrane structural changes, were constructed using deep learning by fine-tuning of InceptionV3 convolutional neural network. Subsequently, we compared the agreement to truth labels between majority decision among nephrologists with or without the AI model as a voter.ResultsOur model for global sclerosis showed high performance (area under the curve: periodic acid-Schiff, 0.986; periodic acid methenamine silver, 0.983); the models for the other findings also showed performance close to those of nephrologists. By adding the AI model output to majority decision among nephrologists, the sensitivity and specificity were significantly improved in 9 of 14 constructed models compared to those of nephrologists alone.ConclusionOur study showed a proof-of-concept for the classification of multiple glomerular findings in a comprehensive method of deep learning and suggested its potential effectiveness in improving diagnostic accuracy of clinicians.
Interprofessional Learning in Immediate Life Support training improves simulated patient related outcomes
Authors: Morse Jeremy Charles , Brown Craig William 
Published: January 2020

AbstractAim of the studyTo assess team performance in implementing time critical key interventions during a simulated resuscitation after participating in either an interprofessional-learning (IPL) or uniprofessional-learning (UPL) Immediate Life Support training course (ILS).IntroductionMuch of the published work on team-based simulation training has measured the lower levels of Kirkpatrick’s hierarchy of evidence and effectiveness. This study aimed to ascertain if interprofessional team training could improve a higher level of outcome such as behaviour and patient outcomes.MethodsA retrospective quantitative analysis of time critical points in a simulated cardiac arrest resuscitation, from a previous randomised study on the effects of Interprofessional Learning in ILS. The video recordings from the original study consisting of medical (n=48) and nursing (n=48) students were analysed to mark when either the IPL or UPL team performed a time critical intervention.ResultsFive time-critical points for interventions were identified; confirmation of cardiac arrest, commencement of initial CPR, rhythm check, time to 1st shock and delay in restarting CPR. Parametric testing of each of these time-based criteria were subjected to an independent sample t-test with statistically significant findings in three of the five criteria in favour of those who had undertaken the interprofessional learning.ConclusionOur results demonstrate that through an IPL approach in ILS there was a statistically different improvement in mean times to performing time-critical interventions, which if transferred to the clinical environment could improve and impact on both change of behaviour and patient outcomes in Kirkpatrick’s higher levels of evidence and effectiveness.Though this study shows that team behaviour and performing time-critical interventions can improve in the short-term, we acknowledge that further longitudinal studies are required to ascertain the effect of such improvement over time. So that both as researchers and educators we can make healthcare teams work safer and more efficiently to improve patient outcomes.What this paper addsWhat is already knownLike simulation, intuitively we know that Interprofessional Learning and Team training should make a difference to clinical practice for those involved. The majority of research reported, is measured at the lower levels of Kirkpatrick’s hierarchy. This retrospective video analysis of a previous study aimed to look at the functioning between interprofessionally and uni-professionally trained teams in performing time-critical interventions in a simulated cardiac arrest.What this study addsOur study suggests that the use of Interprofessional Learning in resuscitation training does have an effect on performance during the management of a simulated cardiac arrest which could improve and impact on both change of behaviour and patient outcomes in Kirkpatrick’s higher levels of evidence and effectiveness.
A new incidence peak of childhood narcolepsy type 1 in 2013: a new perspective on the role of influenza virus?
Authors: Zhang Zhongxing , Gool Jari , Fronczek Rolf , Bassetti Claudio L. , Dauvilliers Yves , Mayer Geert , Plazzi Giuseppe , Pizza Fabio , Santamaria Joan , Partinen Markku , Overeem Sebastiaan , Peraita-Adrados Rosa , da Silva Antonio Martins , Sonka Karel , Rio-Villegas Rafael del , Heinzer Raphael , Wierzbicka Aleksandra , Young Peter , Högl Birgit , Manconi Mauro , Feketeova Eva , Mathis Johannes , Paiva Teresa , Canellas Francesca , Lecendreux Michel , Baumann Christian R. , Barateau Lucie , Pesenti Carole , Antelmi Elena , Gaig Carles , Iranzo Alex , Lillo-Triguero Laura , Medrano-Martínez Pablo , Haba-Rubio José , Gorban Corina , Lammers Gert-Jan , Khatami Ramin 
Published: January 2020

AbstractIncreased incidence rates of narcolepsy type 1 (NT1) after the 2009-2010 H1N1 influenza pandemic (pH1N1) have been reported world-wide. While some European countries found an association between the NT1 increase and H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus rather than Pandemrix to be linked with the increase of new NT1 cases. We analyzed the number of de-novo NT1 cases in the last two decades until 2016 using the European Narcolepsy Network (EU-NN) database. Using robust data-driven modelling approaches we confirmed the peak of NT1 incidence in 2009-2010 pH1N1 and identified a new peak in 2013 that is age-specific for children/adolescents. Most of these de-novo cases showed a subacute disease onset consistent with an immune-mediated type of narcolepsy, which is most likely not related to Pandemrix vaccination that was used in 2009-2010, but may have been triggered by some new epidemiological event in Europe. Our finding of an unexpected peak in de-novo children narcolepsy in 2013 provides a unique opportunity to develop new hypotheses, such as considering other (influenza) viruses to further investigate the pathophysiology of immune-mediated narcolepsy.
Molecular Diversity Among Adult Human Hippocampal and Entorhinal Cells
Authors: Franjic Daniel , Choi Jinmyung , Skarica Mario , Xu Chuan , Li Qian , Ma Shaojie , Tebbenkamp Andrew T. N. , Santpere Gabriel , Arellano Jon I. , Gudelj Ivan , Jankovic-Rapan Lucija , Sousa Andre M. M. , Rakic Pasko , Sestan Nenad 
Published: January 2020

SUMMARYThe hippocampal-entorhinal system is comprised of functionally distinct subregions collectively critical for cognition, and selectively vulnerable to aging and pathological processes. To gain insights into neuronal and non-neuronal populations within this system, we performed single-nucleus transcriptional profiling from five human hippocampal-entorhinal subregions. We found that transcriptomic diversity of excitatory neurons across these subregions reflected the molecular transition from three-layered archicortex to six-layered neocortex. Additionally, mRNA and protein for DCX, an immature neuron marker, were clearly detected in some cells, but not in dentate granule cells, the cell-type predicted to be generated in adult neurogenesis. We also found that previously functionally uncharacterized METTL7B was enriched in human and non-human primate neuronal subtypes less vulnerable to initial Alzheimer’s disease pathology. Proteomic and biochemical assays revealed METTL7B interacts with Alzheimer’s disease-related proteins, including APP, and its overexpression reduced amyloid-beta generation. These results reveal cell type-specific molecular properties relevant for hippocampal-entorhinal physiology and dysfunction.
GeneMark-EP and -EP+: eukaryotic gene prediction with self-training in the space of genes and proteins
Authors: Brůna Tomáš , Lomsadze Alexandre , Borodovsky Mark 
Published: January 2020

We have made several steps towards creating a fast and accurate algorithm for gene prediction in eukaryotic genomes. First, we introduced an automated method for efficientab initiogene finding, GeneMark-ES, with parameters trained in iterativeunsupervisedmode. Next, in GeneMark-ET we proposed a method of integration of unsupervised training with information on intron positions revealed by mapping short RNA reads.Now we describe GeneMark-EP, a tool that utilizes another source of external information, a protein database, readily available prior to a start of a sequencing project. A new specialized pipeline, ProtHint, initiates massive protein mapping to genome and extracts hints to splice sites and translation start and stop sites of potential genes. GeneMark-EP uses the hints to improve estimation of model parameters as well as to adjust co-ordinates of predicted genes if they disagree with the most reliable hints (the -EP+ mode).Tests of GeneMark-EP and -EP+ demonstrated improvements in gene prediction accuracy in comparison with GeneMark-ES, while the GeneMark-EP+ showed higher accuracy than GeneMark-ET. We have observed that the most pronounced improvements in gene prediction accuracy happened in large eukaryotic genomes.
Tau avoids the GTP cap at growing microtubule plus ends
Authors: Castle Brian T. , McKibben Kristen M. , Rhoades Elizabeth , Odde David J. 
Published: January 2020

AbstractPlus-end tracking proteins (+TIPs) are a group of proteins that associate with the growing end of microtubules and mediate important cellular functions including neural development and cell division. Work in recent years has shown that the majority of +TIPs are directed to the plus-end through a family of end binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present during microtubule growth, versus weaker binding to GDP-tubulin in the proximal microtubule. One question yet to be addressed is whether there may exist other microtubule associated proteins (MAPs) that preferentially bind specific nucleotide states of tubulin. Here we report that the neuronal MAP tau, which is enriched in axons where it promotes microtubule growth and bundling, preferentially binds GDP-tubulin (KD= 0.26 µM) over GMPCPP-tubulin (KD= 1.1 µM)in vitroas well as GTP-tubulin at the tips of growing microtubulesin vitroandin vivo. This nucleotide preference causes tau binding to lag behind the growing microtubule plus-end by about 100-200 nm bothin vitroand in live cells. Thus, tau is a microtubule tip avoiding protein, establishing a new class of tip avoiding MAPs, and acts primarily by suppressing microtubule shortening rather than promoting growth. We speculate that neurological disease-relevant tau mutations may exert their phenotype by their failure to properly recognize GDP-tubulin, thus displacing +TIPs, such as EB3, and their associated activities into abnormal locations in the neuron.
Differences in Characteristics of Medicare Patients Treated by Ophthalmologists and Optometrists
Authors: Miller Darby D. , Stewart Michael W. , Gagne Joshua J. , Wagner Alan L. , Lee Aaron Y. 
Published: January 2020

AbstractPurposeTo quantify differences in the age, gender, race, and clinical complexity of Medicare beneficiaries treated by ophthalmologists and optometrists in each of the United States.DesignCross-sectional study based on publicly accessible Medicare payment and utilization data from 2012 to 2017.MethodsFor each ophthalmic and optometric provider, demographic information of treated Medicare beneficiaries was obtained from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services (CMS) for the years 2012 to 2017. Clinical complexity was defined using Hierarchical Condition Category (HCC) coding.ResultsFrom 2012 to 2017, ophthalmologists in every state treated significantly older beneficiaries, with the greatest difference (4.99 years in 2014) between provider groups seen in Rhode Island. In most states, there was no gender difference among patients treated by the providers, but in 46 states ophthalmologists saw significantly more racially diverse groups of beneficiaries. HCC risk score analysis demonstrated that ophthalmologists in all 50 states saw more medically complex beneficiaries and the differences were statistically significant in 47 states throughout all six years.ConclusionsAlthough there are regional variations in the characteristics of patients treated by ophthalmologists and optometrists, ophthalmologists throughout the United States manage older, more racially diverse, and more medically complex Medicare beneficiaries.
Hyaluronic Acid on the Urokinase Sustained Release with a Hydrogel System Composed of Poloxamer 407
Authors: Hsieh Hao-Ying , Lin Wei-Yang , Lee An Li , Li Yi-Chen , Chen Yi-Jane , Chen Ke-Cheng , Young Tai-Horng 
Published: January 2020

AbstractPleural empyema is an inflammatory condition characterized by accumulation of pus inside the pleural cavity, which is usually followed by bacterial pneumonia. During the disease process, the pro-inflammatory and pro-fibrotic cytokines in the purulent pleural effusion cause proliferation of fibroblasts and deposition of extracellular matrix, which lead to fibrin deposition and fibrothorax. Urokinase instillation therapy through a chest drainage tube is frequently used for fibrinolysis in patients with empyema. However, urokinase treatment requires multiple instillation (2-3 times per day, for 4-8 days) and easily flows out from the chest drainage tube due to its high water solubility. In this in vitro study, we developed a thermo-responsive hydrogel based on poloxamer 407 (P407) combined with hyaluronic acid (HA) for optimal loading and release of urokinase. Our results show that the addition of HA to poloxamer gels provides a significantly more compact microstructure, with smaller pore sizes (**p < 0.001). The differential scanning calorimetry (DSC) profile revealed no influence on the micellization intensity of poloxamer gel by HA. The 25% poloxamer-based gel was significantly superior to the 23% poloxamer-based gel, with slower gel erosion when comparing the 16th hour residual gel weight of both gels (*p < 0.05; **p < 0.001). The 25% poloxamer-HA gel also exhibited a superior urokinase release profile and longer release time. A Fourier-transform infrared spectroscopy (FT-IR) study of the P407/HA hydrogel showed no chemical interactions between P407 and HA in the hydrogel system. The thermoresponsive P407/HA hydrogel may have a promising potential in the loading and delivery of hydrophilic drugs. On top of that, in vitro toxicity test of this combination demonstrates a lower toxicity.
Consensus Features Nested Cross-Validation
Authors: Parvandeh Saeid , Yeh Hung-Wen , Paulus Martin P. , McKinney Brett A. 
Published: January 2020

AbstractMotivationFeature selection can improve the accuracy of machine learning models, but appropriate steps must be taken to avoid overfitting. Nested cross-validation (nCV) is a common approach that chooses the classification model and features to represent a given outer fold based on features that give the maximum inner-fold accuracy. Differential privacy is a related technique to avoid overfitting that uses a privacy preserving noise mechanism to identify features that are stable between training and holdout sets.MethodsWe develop consensus nested CV (cnCV) that combines the idea of feature stability from differential privacy with nested CV. Feature selection is applied in each inner fold and the consensus of top features across folds is a used as a measure of feature stability or reliability instead of classification accuracy, which is used in standard nCV. We use simulated data with main effects, correlation, and interactions to compare the classification accuracy and feature selection performance of the new cnCV with standard nCV, Elastic Net optimized by CV, differential privacy, and private Evaporative Cooling (pEC). We also compare these methods using real RNA-Seq data from a study of major depressive disorder.ResultsThe cnCV method has similar training and validation accuracy to nCV, but cnCV has much shorter run times because it does not construct classifiers in the inner folds. The cnCV method chooses a more parsimonious set of features with fewer false positives than nCV. The cnCV method has similar accuracy to pEC and cnCV selects stable features between folds without the need to specify a privacy threshold. We show that cnCV is an effective and efficient approach for combining feature selection with classification.AvailabilityCode available athttps://github.com/insilico/cncv.Contactbrett.mckinney@utulsa.eduSupplementary information: