bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing Endothelial Dysfunction in COVID-19: A Pilot, Double-Blind, Placebo-Controlled, Randomized Clinical Trial at the Lebanese American University Medical Center - Rizk Hospital (MEDIC-LAUMCRH)
Authors: Matli Kamal , Al Kotob Abdulrahman , Jamaleddine Wassim , Al Osta Soad , Salameh Pascale , Tabbikha Rami , Chamoun Nibal , Moussawi Ahmad , Saad Jean-Michel , Atwi Gibran , Saad Tarik Abu , Jamal Omar , Mokhbat Jacques , Ghanem Georges 
Published: February 2022

AbstractBackgroundCoronavirus disease 2019 (Covid-19) is associated with endothelial dysfunction. Pharmacologically targeting the different mechanisms of endothelial dysfunction may improve clinical outcomes and lead to reduced morbidity and mortalityMethodsIn this pilot, double-blind, placebo-controlled, randomized clinical trial we assigned patients who were admitted to the hospital with mild, moderate, or severe COVID-19 infection to receive, on top of optimal medical therapy, either an endothelial protocol consisting of (Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin) or placebo for up to 14 days. The primary outcome was time to recovery, measured by an 8 category ordinal scale and defined by the time to being discharged from the hospital or hospitalized for infection-control or other nonmedical reasons. Secondary outcomes included the composite outcome of ICU admission or the need for mechanical ventilation, all-cause mortality, and the occurrence of side effectsResultsOf 42 randomized patients, 37 were included in the primary analysis. The mean age of the patients was 57 years; the mean BMI of study participants was 29.14. History of hypertension was present in 27% of the patients, obesity in 45%, and Diabetes Mellitus in 21.6%. The median(Interquartile range) time to recovery was not significantly different between the endothelial protocol group (6 [4-12] days) and the placebo group (6 [5-8]days)(p-value = 0.854). Furthermore, there were no statistically significant differences in the need for mechanical ventilation or ICU admission, all-cause mortality, and the occurrence of side effects between the endothelial protocol group and the placebo group.ConclusionAmong patients hospitalized with mild, moderate, or severe COVID-19 infection, targeting endothelial dysfunction by administering Nicorandil, L-arginine, Folate, Nebivolol, and Atorvastatin on top of optimal medical therapy did not decrease time to recovery. However, this treatment protocol was associated with an excellent safety profile. Adequately sized prospective randomized controlled trials are needed for the evaluation of the role of treating endothelial dysfunction in COVID-19 infection.
Artificial intelligence-driven meta-analysis of brain gene expression identifies novel gene candidates and a role for mitochondria in Alzheimer’s Disease
Authors: Finney Caitlin A. , Delerue Fabien , Gold Wendy A. , Brown David A. , Shvetcov Artur 
Published: February 2022

AbstractAlzheimer’s disease (AD) is the most common form of dementia. There is no treatment and AD models have focused on a small subset of genes identified in familial AD. Microarray studies have identified thousands of dysregulated genes in the brains of patients with AD yet identifying the best gene candidates to both model and treat AD remains a challenge. We performed a meta-analysis of microarray data from the frontal cortex (n = 697) and cerebellum (n = 230) of AD patients. A two-stage artificial intelligence approach, with both unsupervised and supervised machine learning, combined with a functional network analysis was used to identify functionally connected and biologically relevant novel gene candidates in AD. We found that in the frontal cortex, genes involved in mitochondrial energy, ATP, and oxidative phosphorylation, were the most significant dysregulated genes. In the cerebellum, dysregulated genes were involved in mitochondrial cellular biosynthesis (mitochondrial ribosomes). There was little overlap between dysregulated genes between the frontal cortex and cerebellum. A further functional network analysis of these genes identified that two downregulated genes, ATP5L and ATP5H, which both encode subunits of ATP synthase (mitochondrial complex V) may play a role in AD. Combined, our results suggest that mitochondrial dysfunction, particularly a deficit in energy homeostasis, may play an important role in AD.
Real world performance of inactivated SARS-CoV-2 vaccine (CoronaVac) against infection, hospitalization and death due to COVID-19 in adult population in Indonesia
Authors: Suryatma Anton , Anasi Raras , Hananto Miko , Hermawan Asep , Ramadhany Ririn , Indalao Irene Lorinda , Agustiningsih Agustiningsih , Fikriyah Ely Hujjatul , Tobing Kristina Lumban , Tejayanti Teti , Rustika Rustika , Dhewantara Pandji Wibawa 
Published: February 2022

AbstractBackgroundInactivated SARS-CoV-2 vaccine has been included in the national COVID-19 vaccination program in Indonesia since January 2021. The study aims to assess the impacts of inactivated COVID-19 vaccine on infection, hospitalization, and death among adult population aged ≥18 years in Bali, Indonesia.MethodsTest-negative, case control study was conducted by linking SARS-CoV-2 laboratory records, vaccination, and health administrative data for the period of January 13 to June 30, 2021. Case-subjects were defined as individuals who had a positive RT-PCR test for SARS-CoV-2 during the period; they were matched with controls (tested negative) (1:1) based on age, sex, district of residence, and week of testing. We estimated the odds of vaccination in PCR confirmed, hospitalization and death due to COVID-19, accounting for the presence of comorbidities and prior infection. Vaccine effectiveness was estimated as (1-odds ratio) x 100%.ResultsTotal 109,050 RT-PCR test results were retrieved during the January 13 to June 30, 2021. Of these, 14,168 subjects were eligible for inclusion in the study. Total 5518 matched case-control pairs were analyzed. Adjusted vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection was 14.5% (95% confidence interval -11 to 34.2) at 0-13 days after the first dose; 66.7% (95% CI: 58.1-73.5) at ≥14 days after the second dose. The adjusted effectiveness against hospitalization and COVID-19-associated death was 71.1% (95% CI: 62.9-77.6) and 87.4% (95% CI: 65.1-95.4%) at ≥14 days after receiving the second dose, respectively.ConclusionsTwo-dose of inactivated CoronaVac vaccine showed high effectiveness against laboratory confirmed COVID-19 infection, hospitalization, and death associated with COVID-19 among adults aged ≥18 years.
The outer-hair-cell RC time constant: A feature, not a bug, of the mammalian cochlea
Authors: Altoè Alessandro , Shera Christopher A. 
Published: February 2022

AbstractThe cochlea of the mammalian inner ear includes an active, hydromechanical amplifier thought to arise via the piezoelectric action of the outer hair cells (OHCs). A classic problem of cochlear biophysics is that the long resistance-capacitance (RC) time constant of the hair-cell membrane produces an effective cut-off frequency much lower than that of most audible sounds. The long RC time constant implies that the OHC receptor potential—and hence its electromotile response—decreases by several orders of magnitude over the frequency range of hearing. This “RC problem” is often invoked to question the role of cycle-by-cycle OHC-based amplification in mammalian hearing. Here, we use published data and simple physical reasoning to show that the RC problem is, in practice, a relatively minor physical issue whose importance has been unduly magnified by viewing it through the wrong lens. Indeed, our analysis indicates that the long RC time constant is actually beneficial for hearing, reducing noise and distortion while increasing the fidelity of cochlear amplification.
High resolution micro-CT imaging in mice stroke models: from 3D detailed infarct characterization to automatic area segmentation
Authors: Pinto Raquel , Matula Jan , Gomez-Lazaro Maria , Sousa Mafalda , Zikmund Tomas , Kaiser Jozef , Gomes João R. 
Published: February 2022

ABSTRACTCharacterization of brain infarct lesion in rodent models of stroke is crucial to assess the outcome of stroke therapies and to study the disease pathophysiology. However, so far it has been mostly performed by: 1) histological methods, a time-consuming process that lead to significant flaws and tissue distortion; or 2) via MRI imaging, which is faster, yielding 3D information but at high costs. High-resolution micro-CT imaging became, in the last decade, a simple, fast, and cheaper solution, allowing 3D analysis of samples. Here, we describe that high-resolution micro-CT, either using iodine/OsO4 as contrast agents, can be successfully applied for fine quantification and localization of lesion size and edema volume in preclinical stroke models. We successfully correlated this new approach with the standard histological method TTC. In transient MCAO mouse stroke model, we were able to identify/quantify large lesioned areas (segmented in core and penumbra), up to degenerated finer striatal myelinated fibers in a transient ischemic attack (TIA) mouse model, at different timepoints post-ischemia, through manual and automatic segmentation approaches (deep learning). Furthermore, 3D reconstructions of the whole brain allow for brain atlas co-registration of the specific affected brain areas. Hence, the presented methodology, through iodine/OsO4 micro-CT imaging, constitutes a valuable advance in tools for precise and detailed assessment of stroke outcomes in preclinical animal studies.
patcHwork: A user-friendly pH sensitivity analysis web server for protein sequences and structures
Authors: Schmitz Mirko , Schultze Anne , Vanags Raimonds , Voigt Karsten , Di Ventura Barbara , Öztürk Mehmet Ali 
Published: February 2022

AbstractpH regulates protein function and interactions by altering the charge of individual residues causing the loss or gain of intra-molecular non-covalent bonds, which may additionally lead to structural rearrangements. While tools to analyze residue-specific charge distribution of protein sequences and structures at a given pH exist, currently no tool is available to investigate non-covalent bond changes at two different pH values. In an effort to make protein pH sensitivity analysis more accessible to researchers without computational structural biology background, we developed patcHwork, a web server that combines the identification of amino acids undergoing a charge shift with the determination of affected non-covalent bonds at two user-defined pH values. At the sequence-only level, patcHwork applies the Henderson-Hasselbalch equation to determine pH-sensitive residues. When the 3D protein structure is available, patcHwork can be employed to gain a deeper mechanistic understanding of the effect of pH on a protein of interest. This is achieved using the PDB2PQR and PROPKA tools and non-covalent bond determination algorithms. A user-friendly interface allows visualizing pH-sensitive residues as well as affected salt bridges, hydrogen bonds and aromatic (pi-pi and cation-pi) interactions. Importantly, patcHwork can be used to identify patches, a new concept we propose of pH-sensitive residues in close proximity on the protein structure, which may have a major impact on function. We demonstrate the attractiveness of patcHwork studying experimentally investigated pH-sensitive proteins. (Access:https://patchwork.biologie.uni-freiburg.de/)Graphical abstract
Deep Immunophenotyping Reveals Endometriosis is Marked by Dysregulation of the Mononuclear Phagocytic System in Endometrium and Peripheral Blood
Authors: Vallvé-Juanico Júlia , George Ashley F. , Sen Sushmita , Thomas Reuben , Shin Min-Gyoung , Kushnoor Divyashree , Vásquez Joshua J. , Vo Kim Chi , Irwin Juan C. , Roan Nadia R. , Combes Alexis J. , Giudice Linda C. 
Published: February 2022

AbstractBackgroundEndometriosis is a chronic, estrogen-dependent disorder where inflammation contributes to disease-associated symptoms of pelvic pain and infertility. Immune dysfunction includes insufficient immune lesion clearance, a pro-inflammatory endometrial environment, and systemic inflammation. Comprehensive understanding of endometriosis immune pathophysiology in different hormonal milieu and disease severity has been hampered by limited direct characterization of immune populations in endometrium, blood, and lesions. Simultaneous deep phenotyping at single cell resolution of complex tissues has transformed our understanding of the immune system and its role in many diseases. Herein, we report mass cytometry and high dimensional analyses to study immune cell phenotypes, abundance, activation states, and functions in endometrium and blood of women with and without endometriosis in different cycle phases and disease stages.MethodsA case-control study was designed. Endometrial biopsies and blood (n=60 total) were obtained from women with (n=20, n=17, respectively) and without (n=14, n=9) endometriosis in the proliferative and secretory cycle phases of the menstrual cycle. Two mass cytometry panels were designed; one broad panel and one specific for mononuclear phagocytic cells (MPC), and all samples were multiplexed to characterize both endometrium and blood immune composition at unprecedented resolution. We combined supervised and unsupervised analyses to finely define the immune cell subsets with an emphasis on MPC. Then, association between cell types, protein expression, disease status, and cycle phase were performed.ResultsThe broad panel highlighted a significant modification of MPC in endometriosis; thus, they were studied in detail with an MPC-focused panel. Endometrial CD91+ macrophages overexpressed SIRPα (phagocytosis inhibitor) and CD64 (associated with inflammation) in endometriosis, and they were more abundant in mild versus severe disease. In blood, classical and intermediate monocytes were less abundant in endometriosis, whereas plasmacytoid dendritic cells and non-classical monocytes were more abundant. Non-classical monocytes were higher in severe versus mild disease.ConclusionsA greater inflammatory phenotype and decreased phagocytic capacity of endometrial macrophages in endometriosis are consistent with defective clearance of endometrial cells shed during menses and in tissue homeostasis, with implications in endometriosis pathogenesis and pathophysiology. Different proportions of monocytes and plasmacytoid dendritic cells in blood from endometriosis suggest systemically aberrant functionality of the myeloid system opening new venues for the study of biomarkers and therapies for endometriosis.
Movement characteristics impact decision-making and vice versa
Authors: Carsten Thomas , Fievez Fanny , Duque Julie 
Published: February 2022

AbstractPrevious studies suggest that humans are capable of coregulating the speed of decisions and movements if promoted by task incentives. It is unclear however whether such behavior is inherent to the process of translating decisional information into movements, beyond posing a valid strategy in some task contexts. Therefore, in a behavioral online study we imposed time constraints to either decision or movement -phases of a sensorimotor task, ensuring that coregulating decisions and movements was not promoted by task incentives. We found that participants indeed moved faster when fast decisions were promoted and decided faster when subsequent movements had to be executed swiftly. Furthermore, inflicting faster movements seems to alter decision-making in a similar fashion as conditions promoting faster decisions: In both fast-decision and fast-movement blocks, decisions relied more strongly on information presented shortly rather than long before movement onset. Taken together, these findings suggest that decisions not only impact movement characteristics, but that properties of movement impact the time and manner with which decisions are made. We interpret these behavioral results in the context ofembodied decision-making, whereby shared neural mechanisms may not only enable faster movements but also assist in making decisions in less time.
Trait divergence and trade-offs among Brassicaceae species differing in elevational distribution
Authors: Maccagni Alessio , Willi Yvonne 
Published: February 2022

AbstractSpecies have restricted geographic distributions and the causes are still largely unknown. Temperature has long been associated with distribution limits, suggesting that there are ubiquitous constraints to the evolution of the climate niche. Here we investigated the traits involved in such constraints by macroevolutionary comparisons involving around 100 Brassicaceae species differing in elevational distribution. Plants were grown under three temperature treatments (regular frost, mild, regular heat) and phenotyped for phenological, morphological and thermal resistance traits. Trait values were analysed by assessing the effect of temperature and elevational distribution, by comparing models of evolutionary trajectories, and by correlative approaches to identify trade-offs. Analyses pointed to size, leaf morphology and growth under heat as among the most discriminating traits between low- and high-elevation species, with high-elevation species growing faster under the occurrence of regular heat bouts, at the cost of much reduced size. Mixed models and evolutionary models supported adaptive divergence for these traits, and correlation analysis indicated their involvement in moderate trade-offs. Finally, we found asymmetry in trait evolution, with evolvability across traits being 50% less constrained under regular frost. Overall, results suggest that trade-offs between traits under adaptive divergence contribute to the disparate distribution of species along the elevational gradient.
Top-down control of the left visual field bias in cued visual spatial attention
Authors: Meyyappan Sreenivasan , Rajan Abhijit , Mangun George R , Ding Mingzhou 
Published: February 2022

AbstractA left visual field (LVF) bias in perceptual judgements, response speed and discrimination accuracy are well documented in humans. However, LVF bias can be modulated by perceptual and task demands. For example, cuing spatial attention can reduce or eliminate the LVF bias, suggesting that attentional control can compensate for the LVF bias. We investigated this possibility directly by recording pupillometry together with fMRI in a cued visual spatial attention task. Prior to the onset of a task-relevant target stimulus, we observed that the pupil was significantly more dilated following attend-right than attend-left cues even though task performance did not differ. This difference in pupil dilation was inversely related to the corresponding difference in later target-evoked pupil dilation and in the reaction times to those targets, suggesting that an increased attentional effort was triggered by the attend-right cues, and this offset the LVF bias, equating behavioral performance. The differences in pupil dilation to the right versus left hemifield were correlated with corresponding fMRI differences primarily in the right hemisphere, supporting the idea that the increased attentional effort for rightward attention is mediated by activity in right hemisphere networks, which illuminates how attentional control mediates attentional biases in vision.
A novel rhesus macaque model of Huntington’s disease recapitulates key neuropathological changes along with progressive motor and cognitive decline
Authors: Weiss Alison R. , Liguore William A. , Brandon Kristin , Wang Xiaojie , Liu Zheng , Domire Jacqueline S. , Button Dana , Kroenke Christopher D. , McBride Jodi L. 
Published: February 2022

ABSTRACTWe created a new nonhuman primate model of the genetic neurodegenerative disorder, Huntington’s disease (HD), by injecting a mixture of recombinant adeno-associated viral vectors, serotypes AAV2 and AAV2.retro, each expressing a fragment of human mutant HTT (mHTT) into the caudate and putamen of adult rhesus macaques. This novel modeling strategy results in robust expression of mutant huntingtin protein (mHTT) in the injected brain regions, as well as dozens of other cortical and subcortical brain regions that are also affected in human HD patients. We queried the disruption of cortico-basal ganglia circuitry for 20-months post-surgery using a variety of behavioral and imaging readouts. Compared to controls, mHTT-treated macaques developed progressive working memory decline and motor impairment. Multimodal imaging revealed circuit-wide white and gray matter degenerative processes in several key brain regions affected in HD. This novel model will aid in the development of disease biomarkers and therapeutic strategies for this devastating disorder.
Comparative evaluation of Oral lesions: “Tale - the Covid 19 Tells”
Authors: Bhavasar Rashmi , Ajith Namratha A. , Bhavasar Rahul , Shah Arti , Vaswani Vivek 
Published: February 2022

AbstractIntroduction & ObjectivesThe COVID-19 pandemic has been raging across the globe since early January 2020. India has reported over 27 million cases and more than 3, 00,000 deaths. This study was planned to analyze the differences in demographic, clinical features and oral manifestations of COVID 19 patients hospitalized during COVID-19 pandemic.MethodsThis observational pilot study had total 36 participants, 12 each of mild, moderate and severe RT-PCR positive COVID cases hospitalized during COVID 19 pandemic. All demographic, clinical features, treatment details and oral manifestations were noted from first day of admission to hospital till treatment completion with follow up of minimum 7 days.ResultsMean age of the patients was 39.44 ±9.13 years with M: F ratio of 5:4. Most common clinical presentation was fever, shortness of breath and treatment involved was symptomatic with supplemental oxygen & mechanical ventilation. Most common oral site involved was tongue & oral lesions observed were herpes labialis, mucositis, burning sensation, dryness of oral cavity, angular chelitis, aphthous ulcers, geographic tongue, fissuring of tongue, candidiasis, coated tongue, sublingual varicosity, & scalloped tongue.Interpretation and ConclusionAll demographic, clinical and oral manifestations were significantly different in mild, moderate and severe cases of covid hospitalized patients. Though clinical symptoms were improved, oral lesions were worsened. Oral Lesions seen in covid patients were associated with multiple drug therapy for illness along with poor oral hygiene, but further etiology for lesions needs to be evaluated. Sublingual varicosity was observed in our hospitalised covid patients, but large sample observation is required for confirmation of findings and may be an early oral feature for covid detection. Prevention is always better than cure, so all patients positive for Covid should have a full mouth examination. Oral health should be priority during overall management of COVID patients and dentists should be a part of Covid management team.