bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuated strain of CVB3 with a mutation in the CAR-interacting region protects against both myocarditis and pancreatitis
Authors: Lasrado Ninaad , Gangaplara Arunakumar , Massilamany Chandirasegaran , Arumugam Rajkumar , Shelbourn Allison , Rasquinha Mahima T. , Basavalingappa Rakesh H. , Delhon Gustavo , Xiang Shi-Hua , Pattnaik Asit K. , Steffen David , Reddy Jay 
Published: June 2021

AbstractCoxsackievirus B3 (CVB3), is commonly implicated in myocarditis, which can lead to dilated cardiomyopathy, in addition to causing acute pancreatitis and meningitis. Yet, no vaccines are currently available to prevent this infection. Here, we describe the derivation of a live attenuated vaccine virus, termed mutant (Mt) 10, encoding a single amino acid substitution H790A within the viral protein 1, that prevents CVB3 infection in mice and protects from both myocarditis and pancreatitis in challenge studies. We noted that animals vaccinated with Mt 10 developed virus-neutralizing antibodies, predominantly containing IgG2a and IgG2b, and to a lesser extent IgG3 and IgG1. Furthermore, by using major histocompatibility complex class II dextramers and tetramers, we demonstrated that Mt 10 induces antigen-specific T cell responses that preferentially produce interferon-γ. Finally, neither vaccine recipients nor those challenged with the wild-type virus revealed evidence of autoimmunity or cardiac injury as determined by T cell response to cardiac myosin and measurement of circulating cardiac troponin I levels, respectively. Together, our data suggest that Mt 10 is a vaccine candidate that prevents CVB3 infection through the induction of neutralizing antibodies and antigen-specific T cell responses, the two critical components needed for complete protection against virus infections in vaccine studies.
Olive leaf extract prevents obesity, cognitive decline, and depression and improves exercise capacity in mice
Authors: Mikami Toshio , Kim Jimmy , Park Jonghyuk , Lee Hyowon , Yaicharoen Pongson , Suidasari Sofya , Yokozawa Miki , Yamauchi Ken 
Published: June 2021

AbstractObesity is a risk factor for development of metabolic diseases and cognitive decline; therefore, obesity prevention is of paramount importance. Neuronal mitochondrial dysfunction induced by oxidative stress is an important mechanism underlying cognitive decline. Olive leaf extract contains large amounts of oleanolic acid, a transmembrane G protein-coupled receptor 5 (TGR5) agonist, and oleuropein, an antioxidant. Activation of TGR5 results in enhanced mitochondrial biogenesis, which suggests that olive leaf extract may help prevent cognitive decline through its mitochondrial and antioxidant effects. Therefore, we investigated olive leaf extract’s effects on obesity, cognitive decline, depression, and endurance exercise capacity in a mouse model. In physically inactive mice fed a high-fat diet, olive leaf extract administration suppressed increases in fat mass and body weight and prevented cognitive declines, specifically decreased working memory and depressive behaviors. Additionally, olive leaf extract increased endurance exercise capacity under atmospheric and hypoxic conditions. Our study suggests that these promising effects may be related to oleanolic acid’s improvement of mitochondrial function and oleuropein’s increase of antioxidant capacity.
Childhood overeating is associated with adverse cardiometabolic and inflammatory profiles in adolescence
Authors: Hübel Christopher , Herle Moritz , Santos Ferreira Diana L. , Abdulkadir Mohamed , Bryant-Waugh Rachel , Loos Ruth J. F. , Bulik Cynthia M. , Lawlor Deborah A. , Micali Nadia 
Published: June 2021

AbstractChildhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers.
Severe protein deficiency induces hepatic expression and systemic level of FGF21 but inhibits its hypothalamic expression in growing rats
Authors: Moro Joanna , Chaumontet Catherine , Even Patrick C. , Blais Anne , Piedcoq Julien , Gaudichon Claire , Tomé Daniel , Azzout-Marniche Dalila 
Published: June 2021

AbstractTo study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.
Major ocean currents may shape the microbiome of the topshell Phorcus sauciatus in the NE Atlantic Ocean
Authors: Sousa Ricardo , Vasconcelos Joana , Vera-Escalona Iván , Delgado João , Freitas Mafalda , González José A. , Riera Rodrigo 
Published: June 2021

AbstractStudies on microbial communities are pivotal to understand the role and the evolutionary paths of the host and their associated microorganisms in the ecosystems. Meta-genomics techniques have proven to be one of the most effective tools in the identification of endosymbiotic communities of host species. The microbiome of the highly exploited topshell Phorcus sauciatus was characterized in the Northeastern Atlantic (Portugal, Madeira, Selvagens, Canaries and Azores). Alpha diversity analysis based on observed OTUs showed significant differences among regions. The Principal Coordinates Analysis of beta-diversity based on presence/absence showed three well differentiated groups, one from Azores, a second from Madeira and the third one for mainland Portugal, Selvagens and the Canaries. The microbiome results may be mainly explained by large-scale oceanographic processes of the study region, i.e., the North Atlantic Subtropical Gyre, and specifically by the Canary Current. Our results suggest the feasibility of microbiome as a model study to unravel biogeographic and evolutionary processes in marine species with high dispersive potential.
Inter-vendor performance of deep learning in segmenting acute ischemic lesions on diffusion-weighted imaging: a multicenter study
Authors: Alis Deniz , Yergin Mert , Alis Ceren , Topel Cagdas , Asmakutlu Ozan , Bagcilar Omer , Senli Yeseren Deniz , Ustundag Ahmet , Salt Vefa , Dogan Sebahat Nacar , Velioglu Murat , Selcuk Hakan Hatem , Kara Batuhan , Oksuz Ilkay , Kizilkilic Osman , Karaarslan Ercan 
Published: June 2021

AbstractThere is little evidence on the applicability of deep learning (DL) in the segmentation of acute ischemic lesions on diffusion-weighted imaging (DWI) between magnetic resonance imaging (MRI) scanners of different manufacturers. We retrospectively included DWI data of patients with acute ischemic lesions from six centers. Dataset A (n = 2986) and B (n = 3951) included data from Siemens and GE MRI scanners, respectively. The datasets were split into the training (80%), validation (10%), and internal test (10%) sets, and six neuroradiologists created ground-truth masks. Models A and B were the proposed neural networks trained on datasets A and B. The models subsequently fine-tuned across the datasets using their validation data. Another radiologist performed the segmentation on the test sets for comparisons. The median Dice scores of models A and B were 0.858 and 0.857 for the internal tests, which were non-inferior to the radiologist’s performance, but demonstrated lower performance than the radiologist on the external tests. Fine-tuned models A and B achieved median Dice scores of 0.832 and 0.846, which were non-inferior to the radiologist's performance on the external tests. The present work shows that the inter-vendor operability of deep learning for the segmentation of ischemic lesions on DWI might be enhanced via transfer learning; thereby, their clinical applicability and generalizability could be improved.
Extraction of Preisach model parameters for fluorite-structure ferroelectrics and antiferroelectrics
Authors: Wang Zheng , Hur Jae , Tasneem Nujhat , Chern Winston , Yu Shimeng , Khan Asif 
Published: June 2021

AbstractFlourite-structure ferroelectrics (FEs) and antiferroelectrics (AFEs) such as HfO2 and its variants have gained copious attention from the semiconductor community, because they enable complementary metal-oxide-semiconductor (CMOS)-compatible platforms for high-density, high-performance non-volatile and volatile memory technologies. While many individual experiments have been conducted to characterize and understand fluorite-structure FEs and AFEs, there has been little effort to aggregate the information needed to benchmark and provide insights into their properties. We present a fast and robust modeling framework that automatically fits the Preisach model to the experimental polarization ($$Q_{FE}$$

Q

FE

) versus electric field ($$E_{FE}$$

E

FE

) hysteresis characterizations of fluorite-structure FEs. The modifications to the original Preisach model allow the double hysteresis loops in fluorite-structure antiferroelectrics to be captured as well. By fitting the measured data reported in the literature, we observe that ferroelectric polarization and dielectric constant decrease as the coercive field rises in general.
Neuroprotective effect of selumetinib on acrolein-induced neurotoxicity
Authors: Huang Hui-Ju , Wang Hsiang-Tsui , Yeh Ting-Yu , Lin Bo-Wei , Shiao Young-Ji , Lo Yu-Li , Lin Anya Maan-Yuh 
Published: June 2021

AbstractAbnormal accumulation of acrolein, an α, β unsaturated aldehyde has been reported as one pathological cause of the CNS neurodegenerative diseases. In the present study, the neuroprotective effect of selumetinib (a MEK–ERK inhibitor) on acrolein-induced neurotoxicity was investigated in vitro using primary cultured cortical neurons. Incubation of acrolein consistently increased phosphorylated ERK levels. Co-treatment of selumetinib blocked acrolein-induced ERK phosphorylation. Furthermore, selumetinib reduced acrolein-induced increases in heme oxygenase-1 (a redox-regulated chaperone protein) and its transcriptional factor, Nrf-2 as well as FDP-lysine (acrolein-lysine adducts) and α-synuclein aggregation (a pathological biomarker of neurodegeneration). Morphologically, selumetinib attenuated acrolein-induced damage in neurite outgrowth, including neuritic beading and neurite discontinuation. Moreover, selumetinib prevented acrolein-induced programmed cell death via decreasing active caspase 3 (a hallmark of apoptosis) as well as RIP (receptor-interacting protein) 1 and RIP3 (biomarkers for necroptosis). In conclusion, our study showed that selumetinib inhibited acrolein-activated Nrf-2-HO-1 pathway, acrolein-induced protein conjugation and aggregation as well as damage in neurite outgrowth and cell death, suggesting that selumetinib, a MEK–ERK inhibitor, may be a potential neuroprotective agent against acrolein-induced neurotoxicity in the CNS neurodegenerative diseases.
Mantle-derived helium released through the Japan trench bend-faults
Authors: Park Jin-Oh , Takahata Naoto , Jamali Hondori Ehsan , Yamaguchi Asuka , Kagoshima Takanori , Tsuru Tetsuro , Fujie Gou , Sun Yue , Ashi Juichiro , Yamano Makoto , Sano Yuji 
Published: June 2021

AbstractPlate bending-related normal faults (i.e. bend-faults) develop at the outer trench-slope of the oceanic plate incoming into the subduction zone. Numerous geophysical studies and numerical simulations suggest that bend-faults play a key role by providing pathways for seawater to flow into the oceanic crust and the upper mantle, thereby promoting hydration of the oceanic plate. However, deep penetration of seawater along bend-faults remains controversial because fluids that have percolated down into the mantle are difficult to detect. This report presents anomalously high helium isotope (3He/4He) ratios in sediment pore water and seismic reflection data which suggest fluid infiltration into the upper mantle and subsequent outflow through bend-faults across the outer slope of the Japan trench. The3He/4He and4He/20Ne ratios at sites near-trench bend-faults, which are close to the isotopic ratios of bottom seawater, are almost constant with depth, supporting local seawater inflow. Our findings provide the first reported evidence for a potentially large-scale active hydrothermal circulation system through bend-faults across the Moho (crust-mantle boundary) in and out of the oceanic lithospheric mantle.
Systematic analysis of safety profile for darunavir and its boosted agents using data mining in the FDA Adverse Event Reporting System database
Authors: Tian Xiaojiang , Yao Yao , He Guanglin , Jia Yuntao , Wang Kejing , Chen Lin 
Published: June 2021

AbstractThis current investigation was aimed to generate signals for adverse events (AEs) of darunavir-containing agents by data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS). All AE reports for darunavir, darunavir/ritonavir, or darunavir/cobicistat between July 2006 and December 2019 were identified. The reporting Odds Ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) were used to detect the risk signals. A suspicious signal was generated only if the results of the three algorithms were all positive. A total of 10,756 reports were identified commonly observed in hepatobiliary, endocrine, cardiovascular, musculoskeletal, gastrointestinal, metabolic, and nutrition system. 40 suspicious signals were generated, and therein 20 signals were not included in the label. Severe high signals (i.e. progressive extraocular muscle paralysis, acute pancreatitis, exfoliative dermatitis, acquired lipodystrophy and mitochondrial toxicity) were identified. In pregnant women, umbilical cord abnormality, fetal growth restriction, low birth weight, stillbirth, premature rupture of membranes, premature birth and spontaneous abortion showed positive signals. Darunavir and its boosted agents induced AEs in various organs/tissues, and were shown to be possibly associated with multiple adverse pregnant conditions. This study highlighted some novel and severe AEs of darunavir which need to be monitored prospectively.
Natural human postural oscillations enhance the empathic response to a facial pain expression in a virtual character
Authors: Treal Thomas , Jackson Philip L. , Jeuvrey Jean , Vignais Nicolas , Meugnot Aurore 
Published: June 2021

AbstractVirtual reality platforms producing interactive and highly realistic characters are being used more and more as a research tool in social and affective neuroscience to better capture both the dynamics of emotion communication and the unintentional and automatic nature of emotional processes. While idle motion (i.e., non-communicative movements) is commonly used to create behavioural realism, its use to enhance the perception of emotion expressed by a virtual character is critically lacking. This study examined the influence of naturalistic (i.e., based on human motion capture) idle motion on two aspects (the perception of other’s pain and affective reaction) of an empathic response towards pain expressed by a virtual character. In two experiments, 32 and 34 healthy young adults were presented video clips of a virtual character displaying a facial expression of pain while its body was either static (still condition) or animated with natural postural oscillations (idle condition). The participants in Experiment 1 rated the facial pain expression of the virtual human as more intense, and those in Experiment 2 reported being more touched by its pain expression in the idle condition compared to the still condition, indicating a greater empathic response towards the virtual human’s pain in the presence of natural postural oscillations. These findings are discussed in relation to the models of empathy and biological motion processing. Future investigations will help determine to what extent such naturalistic idle motion could be a key ingredient in enhancing the anthropomorphism of a virtual human and making its emotion appear more genuine.
A genome-wide portrait of pervasive drug contaminants
Authors: Ogbede Joseph Uche , Giaever Guri , Nislow Corey 
Published: June 2021

AbstractUsing a validated yeast chemogenomic platform, we characterized the genome-wide effects of several pharmaceutical contaminants, including three N-nitrosamines (NDMA, NDEA and NMBA), two related compounds (DMF and 4NQO) and several of their metabolites. A collection of 4800 non-essential homozygous diploid yeast deletion strains were screened in parallel and the strain abundance was quantified by barcode sequencing. These data were used to rank deletion strains representing genes required for resistance to the compounds to delineate affected cellular pathways and to visualize the global cellular effects of these toxins in an easy-to-use searchable database. Our analysis of the N-nitrosamine screens uncovered genes (via their corresponding homozygous deletion mutants) involved in several evolutionarily conserved pathways, including: arginine biosynthesis, mitochondrial genome integrity, vacuolar protein sorting and DNA damage repair. To investigate why NDMA, NDEA and DMF caused fitness defects in strains lacking genes of the arginine pathway, we tested several N-nitrosamine metabolites (methylamine, ethylamine and formamide), and found they also affected arginine pathway mutants. Notably, each of these metabolites has the potential to produce ammonium ions during their biotransformation. We directly tested the role of ammonium ions in N-nitrosamine toxicity by treatment with ammonium sulfate and we found that ammonium sulfate also caused a growth defect in arginine pathway deletion strains. Formaldehyde, a metabolite produced from NDMA, methylamine and formamide, and which is known to cross-link free amines, perturbed deletion strains involved in chromatin remodeling and DNA repair pathways. Finally, co-administration of N-nitrosamines with ascorbic or ferulic acid did not relieve N-nitrosamine toxicity. In conclusion, we used parallel deletion mutant analysis to characterize the genes and pathways affected by exposure to N-nitrosamines and related compounds, and provide the data in an accessible, queryable database.
Musical novices perform with equal accuracy when learning to drum alone or with a peer
Authors: Schiavio Andrea , Stupacher Jan , Xypolitaki Elli , Parncutt Richard , Timmers Renee 
Published: June 2021

AbstractThe capacity of expert musicians to coordinate with each other when playing in ensembles or rehearsing has been widely investigated. However, little is known about the ability of novices to achieve satisfactory coordinated behaviour when making music together. We tested whether performance accuracy differs when novices play a newly learned drumming pattern with another musically untrained individual (duo group) or alone (solo group). A comparison between musical outcomes of the two groups revealed no significant differences concerning performative accuracy. An additional, exploratory examination of the degree of mutual influence between members of the duos suggested that they reciprocally affected each other when playing together. These findings indicate that a responsive auditory feedback involving surprises introduced by human errors could be part of pedagogical settings that employ repetition or imitation, thereby facilitating coordination among novices in a less prescribed fashion.
Sensitive detection and quantification of SARS-CoV-2 in saliva
Authors: Abasiyanik Mustafa Fatih , Flood Blake , Lin Jing , Ozcan Sefika , Rouhani Sherin J. , Pyzer Athalia , Trujillo Jonathan , Zhen Chaojie , Wu Ping , Jumic Stephen , Wang Andrew , Gajewski Thomas F. , Wang Peng , Hartley Madeline , Ameti Bekim , Niemiec Rachael , Fernando Marian , Mishra Vasudha , Savage Peter , Aydogan Bulent , Bethel Cindy , Matushek Scott , Beavis Kathleen G. , Agrawal Nishant , Segal Jeremy , Tay Savaş , Izumchenko Evgeny 
Published: June 2021

AbstractSaliva has significant advantages as a test medium for detection of SARS-CoV-2 infection in patients, such as ease of collection, minimal requirement of supplies and trained personnel, and safety. Comprehensive validation in a large cohort of prospectively collected specimens with unknown SARS-CoV-2 status should be performed to evaluate the potential and limitations of saliva-based testing. We developed a saliva-based testing pipeline for detection of SARS-CoV-2 nucleic acids using real-time reverse transcription PCR (RT-PCR) and droplet digital PCR (ddPCR) readouts, and measured samples from 137 outpatients tested at a curbside testing facility and 29 inpatients hospitalized for COVID-19. These measurements were compared to the nasal swab results for each patient performed by a certified microbiology laboratory. We found that our saliva testing positively detects 100% (RT-PCR) and 93.75% (ddPCR) of curbside patients that were identified as SARS-CoV-2 positive by the Emergency Use Authorization (EUA) certified nasal swab testing assay. Quantification of viral loads by ddPCR revealed an extremely wide range, with 1 million-fold difference between individual patients. Our results demonstrate for both community screening and hospital settings that saliva testing reliability is on par with that of the nasal swabs in detecting infected cases, and has potential for higher sensitivity when combined with ddPCR in detecting low-abundance viral loads that evade traditional testing methods.