bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of an in silico prediction system of human renal excretion and clearance from chemical structure information incorporating fraction unbound in plasma as a descriptor
Authors: Watanabe Reiko , Ohashi Rikiya , Esaki Tsuyoshi , Kawashima Hitoshi , Natsume-Kitatani Yayoi , Nagao Chioko , Mizuguchi Kenji 
Published: December 2019

AbstractPrediction of pharmacokinetic profiles of new chemical entities is essential in drug development to minimize the risks of potential withdrawals. The excretion of unchanged compounds by the kidney constitutes a major route in drug elimination and plays an important role in pharmacokinetics. Herein, we created in silico prediction models of the fraction of drug excreted unchanged in the urine (fe) and renal clearance (CLr), with datasets of 411 and 401 compounds using freely available software; notably, all models require chemical structure information alone. The binary classification model for fe demonstrated a balanced accuracy of 0.74. The two-step prediction system for CLr was generated using a combination of the classification model to predict excretion-type compounds and regression models to predict the CLr value for each excretion type. The accuracies of the regression models increased upon adding a descriptor, which was the observed and predicted fraction unbound in plasma (fu,p); 78.6% of the samples in the higher range of renal clearance fell within 2-fold error with predicted fu,p value. Our prediction system for renal excretion is freely available to the public and can be used as a practical tool for prioritization and optimization of compound synthesis in the early stage of drug discovery.
5D Flow Tensor MRI to Efficiently Map Reynolds Stresses of Aortic Blood Flow In-Vivo
Authors: Walheim Jonas , Dillinger Hannes , Gotschy Alexander , Kozerke Sebastian 
Published: December 2019

AbstractDiseased heart valves perturb normal blood flow with a range of hemodynamic and pathologic consequences. In order to better stratify patients with heart valve disease, a comprehensive characterization of blood flow including turbulent contributions is desired. In this work we present a framework to efficiently quantify velocities and Reynolds stresses in the aorta in-vivo. Using a highly undersampled 5D Flow MRI acquisition scheme with locally low-rank image reconstruction, multipoint flow tensor encoding in short and predictable scan times becomes feasible (here, 10 minutes), enabling incorporation of the protocol into clinical workflows. Based on computer simulations, a 19-point 5D Flow Tensor MRI encoding approach is proposed. It is demonstrated that, for in-vivo resolution and signal-to-noise ratios, sufficient accuracy and precision of velocity and turbulent shear stress quantification is achievable. In-vivo proof of concept is demonstrated on patients with a bio-prosthetic heart valve and healthy controls. Results demonstrate that aortic turbulent shear stresses and turbulent kinetic energy are elevated in the patients compared to the healthy subjects. Based on these data, it is concluded that 5D Flow Tensor MRI holds promise to provide comprehensive flow assessment in patients with heart valve diseases.
Crowdsourcing and the feasibility of manual gene annotation: A pilot study in the nematode Pristionchus pacificus
Authors: Rödelsperger Christian , Athanasouli Marina , Lenuzzi Maša , Theska Tobias , Sun Shuai , Dardiry Mohannad , Wighard Sara , Hu Wen , Sharma Devansh Raj , Han Ziduan 
Published: December 2019

AbstractNematodes such asCaenorhabditis elegansare powerful systems to study basically all aspects of biology. Their species richness together with tremendous genetic knowledge fromC. elegansfacilitate the evolutionary study of biological functions using reverse genetics. However, the ability to identify orthologs of candidate genes in other species can be hampered by erroneous gene annotations. To improve gene annotation in the nematode model organismPristionchus pacificus, we performed a genome-wide screen forC. elegansgenes with potentially incorrectly annotatedP. pacificusorthologs. We initiated a community-based project to manually inspect more than two thousand candidate loci and to propose new gene models based on recently generated Iso-seq and RNA-seq data. In most cases, misannotation ofC. elegansorthologs was due to artificially fused gene predictions and completely missing gene models. The community-based curation raised the gene count from 25,517 to 28,036 and increased the single copy ortholog completeness level from 86% to 97%. This pilot study demonstrates how even small-scale crowdsourcing can drastically improve gene annotations. In future, similar approaches can be used for other species, gene sets, and even larger communities thus making manual annotation of large parts of the genome feasible.
Inactivation of Interferon Regulatory Factor 1 Causes Susceptibility to Colitis-Associated Colorectal Cancer
Authors: Jeyakumar Thiviya , Fodil Nassima , Van Der Kraak Lauren , Meunier Charles , Cayrol Romain , McGregor Kevin , Langlais David , Greenwood Celia M. T. , Beauchemin Nicole , Gros Philippe 
Published: December 2019

AbstractThe mechanisms linking chronic inflammation of the gut (IBD) and increased colorectal cancer susceptibility are poorly understood. IBD risk is influenced by genetic factors, including the IBD5 locus (human 5q31), that harbors the IRF1 gene. A cause-to-effect relationship between chronic inflammation and colorectal cancer, and a possible role of IRF1 were studied in Irf1-/- mice in a model of colitis-associated colorectal cancer (CA-CRC) induced by azoxymethane and dextran sulfate. Loss of Irf1 causes hyper-susceptibility to CA-CRC, with early onset and increased number of tumors leading to rapid lethality. Transcript profiling (RNA-seq) and immunostaining of colons shows heightened inflammation and enhanced enterocyte proliferation in Irf1−/− mutants, prior to appearance of tumors. Considerable infiltration of leukocytes is seen in Irf1−/− colons at this early stage, and is composed primarily of proinflammatory Gr1+ Cd11b+ myeloid cells and other granulocytes, as well as CD4+ lymphoid cells. Differential susceptibility to CA-CRC of Irf1−/− vs. B6 controls is fully transferable through hematopoietic cells as observed in bone marrow chimera studies. Transcript signatures seen in Irf1−/− mice in response to AOM/DSS are enriched in clinical specimens from patients with IBD and with colorectal cancer. In addition, IRF1 expression in the colon is significantly decreased in late stage colorectal cancer (stages 3, 4) and is associated with poorer prognosis. This suggests that partial or complete loss of IRF1 expression alters the type, number, and function of immune cells in situ during chronic inflammation, possibly via the creation of a tumor-promoting environment.
Polymorphism in the LASP1 gene promoter region alters cognitive functions of patients with schizophrenia
Authors: Lin Chieh-Hsin , Yang Sheng , Huang Yu-Jhen , Lane Hsien-Yuan 
Published: December 2019

AbstractSchizophrenia’s pathogenesis remains elusive. Cognitive dysfunction is the endophenotype and outcome predictor of schizophrenia. The LIM and SH3 domain protein (LASP1) protein, a component of CNS synapses and dendritic spines, has been related to the N-methyl-D-aspartate receptor (NMDAR) dysfunction hypothesis and schizophrenia. A single-nucleotide polymorphism (rs979607) in the LASP1 gene promoter region has been also implicated in schizophrenia susceptibility. The aim of this study was to investigate the role of the LASP1 rs979607 polymorphism in the cognitive functions of patients with schizophrenia. Two hundred and ninety-one Han Taiwanese patients with schizophrenia were recruited. Ten cognitive tests and two clinical rating scales were assessed. The scores of cognitive tests were standardized to T-scores. The genotyping of the LASP1 rs979607 polymorphism was performed using TaqMan assay. Among the 291 patients, 85 were C/C homozygotes of rs979607, 141 C/T heterozygotes, and 65 T/T homozygotes, which fitted the Hardy-Weinberg equilibrium. After adjusting age, gender, and education with general linear model, the C/C homozygotes performed better than C/T heterozygotes in overall composite score (p = 0.023), Category Fluency test (representing processing speed and semantic memory) (p = 0.045), and Wechsler Memory Scale (WMS)-III backward Spatial Span test (p = 0.025), albeit without correction for multiple comparisons for the latter two individual tests. To the best of our knowledge, this is the first study suggesting that the genetic variation of LASP1 may be associated with global cognitive function, category verbal fluency, and spatial working memory of patients with schizophrenia. The finding also lends support to the NMDAR dysfunction hypothesis of schizophrenia. More studies with longitudinal designs are warranted.
NMDA attenuates the neurovascular response to hypercapnia in the neonatal cerebral cortex
Authors: Remzső Gábor , Németh János , Tóth-Szűki Valéria , Varga Viktória , Kovács Viktória , Domoki Ferenc 
Published: December 2019

AbstractCortical spreading depolarization (SD) involves activation of NMDA receptors and elicit neurovascular unit dysfunction. NMDA cannot trigger SD in newborns, thus its effect on neurovascular function is not confounded by other aspects of SD. The present study investigated if NMDA affected hypercapnia-induced microvascular and electrophysiological responses in the cerebral cortex of newborn pigs. Anesthetized piglets were fitted with cranial windows over the parietal cortex to study hemodynamic and electrophysiological responses to graded hypercapnia before/after topically applied NMDA assessed with laser-speckle contrast imaging and recording of local field potentials (LFP)/neuronal firing, respectively. NMDA increased cortical blood flow (CoBF), suppressed LFP power in most frequency bands but evoked a 2.5 Hz δ oscillation. The CoBF response to hypercapnia was abolished after NMDA and the hypercapnia-induced biphasic changes in δ and θ LFP power were also altered. MK-801 prevented NMDA-induced increases in CoBF and the attenuation of microvascular reactivity to hypercapnia. The neuronal nitric oxide synthase (nNOS) inhibitor (N-(4 S)-4-amino-5-[aminoethyl]aminopentyl-N′-nitroguanidin) also significantly preserved the CoBF response to hypercapnia after NMDA, although it didn’t reduce NMDA-induced increases in CoBF. In conclusion, excess activation of NMDA receptors alone can elicit SD-like neurovascular unit dysfunction involving nNOS activity.
Open source automated insulin delivery: addressing the challenge
Authors: Oliver Nick , Reddy Monika , Marriott Claire , Walker Tomas , Heinemann Lutz 
Published: December 2019

AbstractDo-it-yourself automated insulin delivery systems for people living with type 1 diabetes use commercially available continuous glucose sensors and insulin pumps linked by unregulated open source software. Uptake of these systems is increasing, with growing evidence suggesting that positive glucose outcomes may be feasible. Increasing interest from people living with, or affected by, type 1 diabetes presents challenges to healthcare professionals, device manufacturers and regulators as the legal, governance and risk frameworks for such devices are not defined. We discuss the data, education, policy, technology and medicolegal obstacles to wider implementation of DIY systems and outline the next steps required for a co-ordinated approach to reducing variation in access to a technology that has potential to enable glucose self-management closer to target.
T cell fate following Salmonella infection is determined by a STING-IRF1 signaling axis in mice
Authors: Park Sung-Moo , Omatsu Tatsushi , Zhao Yun , Yoshida Naohiro , Shah Pankaj , Zagani Rachid , Reinecker Hans-Christian 
Published: December 2019

AbstractThe innate immune response following infection with entero-invasive bacterial species is triggered upon release of cyclic di-guanylate monophosphate (c-di-GMP) into the host cell cytosol. Bacterial c-di-GMP activates the intracellular Sensor Stimulator of Interferon Genes (STING), encoded by Tmem173 in mice. Here we identify Interferon Regulatory Factor (IRF) 1 as a critical effector of STING-mediated microbial DNA sensing that is responsible for TH17 cell generation in the mucosal immune system. We find that STING activation induces IRF1-dependent transcriptional programs in dendritic cells (DCs) that define T cell fate determination, including induction of Gasdermin D, IL-1 family member cytokines, and enzymes for eicosanoid synthesis. Our results show that IRF1-dependent transcriptional programs in DCs are a prerequisite for antigen-specific TH17 subspecification in response to microbial c-di-GMP and Salmonella typhimurium infection. Our identification of a STING-IRF1 signaling axis for adaptive host defense control will aid further understanding of infectious disease mechanisms.
Patient-Centered Outcomes in Critical Illness: Will My Patient Be Functionally and Cognitively Intact?
Authors: Geer Jacqueline H. , Qi Wei , Ferrante Lauren E. 
Published: December 2019

AbstractSurvival in the intensive care unit (ICU) has steadily increased over the past several decades; millions of patients now survive a critical illness every year. ICU survivors are at a significantly increased risk of impairments in physical function, cognitive function, and mental health. These patient-centered outcomes are among the most meaningful to patients. Landmark studies concerning treatment preferences have demonstrated that patients value functional and cognitive outcomes over mortality. In this chapter, we discuss the determinants of functional and cognitive outcomes post critical illness to address the question, “Will my ICU patient be functionally and cognitively intact?”
Translational Research in Intensive Care Unit: Novel Approaches for Drug Development and Personalized Medicine
Authors: Samanta Romit J. , Summers Charlotte 
Published: December 2019

AbstractThe major clinical presentations seen by critical care physicians are sepsis and acute respiratory distress syndrome (ARDS), both of which are heterogeneous clinical syndromes rather than specific diagnoses. The current diagnostic criteria provide little insight into the mechanisms underlying these heterogeneous syndromes and minimal progress has been made with regard to the development of therapies, despite many large randomized controlled trials being undertaken. This review outlines the advances made in improved characterization of critically-ill patients, using ARDS as an exemplar, and highlights the need for this improved patient characterization to be coupled with mechanistic science to develop therapies that target specific pathomechanisms.
Potential for Increased Epilepsy Awareness: Impact of Health Education Program in School on Teachers and Children
Authors: Murthy Meena Kolar Sridara , Rajaram Prakashi , Mudiyanuru Kannappa Shetty , Marimuthu P , Govindappa Lakshmana , Dasgupta Madhuporna 
Published: December 2019

Abstract

Background Although epilepsy is a common disorder, it is highly stigmatized. Not only public but even teachers are not free from stigmatization and cultural barriers. Under this condition, children with epilepsy are more vulnerable for stigmatization, social isolation, lack of support, and psychological and emotional problems. At the same time, there is an immediate need of literature focusing on intervention studies to change the attitudes of school teachers and children.

Materials and Methods The study was conducted with the objectives to evaluate knowledge, attitude, and practices about epilepsy among school teachers and children; provide educational training program to teachers; and check the efficacy of training program imparted by teacher and trainer.

Results Repeated measure of analysis of variance shows that knowledge (F = 1134.875, p < 0.001), attitude (F = 2429.909, p < 0.001), and practice (F = 2205.122, p < 0.001) are significantly different between pre- and posttest indicated by Pillai’s trace test. Similarly, from the Pillai’s test knowledge (F = 49.317, p < 0.001), attitude (F = 125.304, p < 0.001) and practice (F = 178.697, p < 0.001) are significantly different among the teachers, trainer imparted training group of children, and teachers imparted training group of children groups. It is seen that knowledge, attitude, and practice scores significantly differ between two time points and across three groups. Among all the groups, teachers imparted training group children had high level of practice.

Conclusion Inclusion of health education programs in the textbooks and health education schemes for teachers and school children is a crucial way to bring a change in their attitude, behavior, and practices.
Effect of Pregabalin on Postcraniotomy Pain in Patients Undergoing Supratentorial Tumor Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Lamsal Ritesh , Mahajan Charu , Chauhan Vikas , Gupta Nidhi , Mishra Nitasha , Rath Girija Prasad 
Published: December 2019

Abstract
Background and Objectives Suboptimal management of postcraniotomy pain causes sympathetic and hemodynamic perturbations, leading to deleterious effects on the neurological system and overall patient outcome. Opioids are the mainstay of postoperative pain management but have various problems when given in high doses, or for prolonged durations in neurosurgical patients. The ideal method of pain control following craniotomy generally relies on a combination of various drugs. Oral pregabalin may be an attractive alternative in these patients.
Materials and Methods Sixty, American Society of Anesthesiologists class I and II patients posted for elective supratentorial craniotomy, aged 18 and 60 years, were randomly assigned into three groups of 20 each to receive oral placebo (Group A), pregabalin 75 mg (Group B), or pregabalin 150 mg (Group C) before the induction of anesthesia. At the end of the surgery, patient-controlled analgesia was started with intravenous fentanyl. Visual analog scale (VAS) score was recorded every 2 hours for 24 hours, along with total postoperative fentanyl requirement.
Results There were no differences in sex, duration of surgery or anesthesia and total intraoperative fentanyl administered among the three groups. The median postoperative VAS score (Group A—18.0, Group B—20, and Group C—22.0; p = 0.63) was similar in all the groups. However, postoperative fentanyl requirement over 24 hours was least in the group that received 150 mg pregabalin (Group A—190 μg, Group B—240 μg, and Group C—100 μg; p = 0.03).
Conclusions Even though pain scores were not significantly different, patients receiving 150 mg oral pregabalin required the least amount of postoperative opioids.
Effectiveness of a Web-Based Tobacco Product use Prevention Videogame Intervention on Young Adolescents’ Beliefs and Knowledge
Authors: Hieftje Kimberly D. , Fernandes Claudia-Santi F. , Lin I-Hsin , Fiellin Lynn E. 
Published: December 2019

Background Preventing tobacco product initiation in youth is a critical need. While cigarette smoking among youth has been on the decline, tobacco use in other forms, such as e-cigarettes and vaping, continue to be a major concern. The purpose of this study was to conduct a real-world, quasi-experimental test of the effectiveness of a web-based videogame, smokeSCREEN, aimed at developing healthy beliefs and knowledge associated with tobacco product use prevention, including electronic cigarettes. Methods Adolescents ( N = 560) aged 10–16 years were enrolled from schools and afterschool programs in a single-group pre–post study. Measures included a pre- and post-survey of beliefs and knowledge about tobacco product use. At post-survey, participants were asked questions regarding their gameplay experience. Paired responses for the tobacco product use in the beliefs and knowledge survey before and after the smokeSCREEN videogame intervention were compared using McNemar's test. Descriptive statistics were generated to assess overall participant gameplay experience. Results McNemar's test showed significant differences in the proportions of correct answers before (pre-survey) and after (post-survey) the intervention in seven out of eight belief questions ( p < . 0001). It also suggested significant differences in the proportions of correct answers before (pre-survey) and after (post-survey) the intervention in all six knowledge questions ( p < . 0001). Several gender and age differences were noted for belief and knowledge questions related to e-cigarettes and vaping. There was no association between gameplay duration at post-survey or to the answers of the beliefs or knowledge questions. Overall, participants reported that they enjoyed playing the game. Conclusions Findings suggest that the videogame intervention, smokeSCREEN, has a promising effect on participants’ beliefs and knowledge about tobacco product use, including electronic cigarettes and vaping, and is well accepted by adolescents.
Single trajectory characterization via machine learning
Authors: Muñoz-Gil Gorka , Garcia-March Miguel Angel , Manzo Carlo , Martín-Guerrero José D , Lewenstein Maciej 
Published: December 2019

Abstract
In order to study transport in complex environments, it is extremely important to determine the physical mechanism underlying diffusion and precisely characterize its nature and parameters. Often, this task is strongly impacted by data consisting of trajectories with short length (either due to brief recordings or previous trajectory segmentation) and limited localization precision. In this paper, we propose a machine learning method based on a random forest architecture, which is able to associate single trajectories to the underlying diffusion mechanism with high accuracy. In addition, the algorithm is able to determine the anomalous exponent with a small error, thus inherently providing a classification of the motion as normal or anomalous (sub- or super-diffusion). The method provides highly accurate outputs even when working with very short trajectories and in the presence of experimental noise. We further demonstrate the application of transfer learning to experimental and simulated data not included in the training/test dataset. This allows for a full, high-accuracy characterization of experimental trajectories without the need of any prior information.
Total phase shift of terahertz wave in a rectangular waveguide with zero-refractive index metamaterial
Authors: Ghaffari Amir Hosein , Zandi Hesam 
Published: December 2019

Abstract
In many applications, appropriate spatial phase shifts in propagation of a THz wave are desired. Serving this purpose, a rectangular waveguide with two-dimensional photonic crystal zero-refractive index metamaterial is studied. In this structure, additional phase shift is computed in a numerical method in comparison with the same waveguide without zero-refractive index metamaterial. Modelling the characteristics of this waveguide, relations are presented which are shown to be compatible with numerical results. Then getting in inverse direction, a procedure is introduced in which, equivalent photonic crystals can be designed in terms of an arbitrary given phase shift with estimated errors of less than 1 degree. We also have calculated the sensitivity of additional phase difference with respect to the refractive index of rods, which showed relatively high dependence.