bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of transcranial direct current stimulation on post-stroke fatigue
Authors: De Doncker William , Ondobaka Sasha , Kuppuswamy Annapoorna 
Published: November 2020

AbstractBackgroundFatigue is one of the most commonly reported symptoms post-stroke, which has a severe impact on quality of life. Post-stroke fatigue is associated with reduced motor cortical excitability, specifically of the affected hemisphere.ObjectiveThe aim of this exploratory study was to assess whether fatigue symptoms can be reduced by increasing cortical excitability using anodal transcranial direct current stimulation (tDCS).MethodsIn this sham-controlled, double-blind intervention study, tDCS was applied bilaterally over the primary motor cortex in a single session in thirty stroke survivors with high severity of fatigue. A questionnaire-based measure of trait fatigue (primary outcome) was obtained before, after a week and a month post stimulation. Secondary outcome measures of state fatigue, motor cortex neurophysiology and perceived effort were also assessed pre, immediately post, a week and a month post stimulation.ResultsAnodal tDCS significantly improved fatigue symptoms a week after real stimulation when compared to sham stimulation. There was also a significant change in motor cortex neurophysiology of the affected hemisphere and perceived effort, a week after stimulation. The degree of improvement in fatigue was associated with baseline anxiety levels.ConclusionA single session of anodal tDCS improves fatigue symptoms with the effect lasting up to a week post stimulation. tDCS may therefore be a useful tool for managing fatigue symptoms post-stroke.
Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients
Authors: Boshier Florencia A.T. , Pang Juanita , Penner Justin , Hughes Joseph , Parker Matthew , Shepherd James , Alders Nele , Bamford Alasdair , Grandjean Louis , Grunewald Stephanie , Hatcher James , Best Timothy , Dalton Caroline , Bynoe Patricia Dyal , Frauenfelder Claire , Köeglmeier Jutta , Myerson Phoebe , Roy Sunando , Williams Rachel ,   The COVID-19 Genomics UK (COG-UK) consortium, Thomson Emma C , de Silva Thushan I , Goldstein Richard A. , Breuer Judith 
Published: November 2020

AbstractWhile changes in SARS-CoV-2 viral load over time have been documented, detailed information on the impact of remdesivir and how it might alter intra-host viral evolution is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 recovered from the upper respiratory tract of hospitalised children revealed that remdesivir treatment suppressed viral RNA levels in one patient but not in a second infected with an identical strain. Evidence of drug resistance to explain this difference was not found. Reduced levels of subgenomic (sg) RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication that is independent of viral RNA levels. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. We conclude that these are likely to have arisen from within-host evolution, and not co-transmission, although superinfection cannot be excluded in one case. Sample-to-sample heterogeneity in the abundances of variant genotypes is best explained by the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalisation is well described in serious lung infections caused by influenza and Mycobacterium tuberculosis and has been associated with poor drug penetration, suboptimal treatment and drug resistance. Our data provide evidence that remdesivir is able to suppress SARS-CoV-2 replication in vivo but that its efficacy may be compromised by factors reducing penetration into the lung. Based on data from influenza and Mycobacterium tuberculosis lung infections we conclude that early use of remdesivir combined with other agents should now be evaluated.Summary SentenceDeep sequencing of longitudinal samples from SARS-CoV-2 infected paediatric patients identifies evidence of remdesivir-associated inhibition of viral replication in vivo and uncovers evidence of within host evolution of distinct viral genotypes.
Causal effects of circulating cytokine concentrations on risk of Alzheimer’s disease: A bidirectional two-sample Mendelian randomization study
Authors: Pagoni Panagiota , Howe Laura D , Smith George Davey , Ben-Shlomo Yoav , Stergiakouli Evie , Anderson Emma L 
Published: November 2020

ABSTRACTBackgroundThere is considerable interest in the role of neuroinflammation in the pathogenesis of Alzheimer’s disease. Evidence from observational studies suggests an association between cytokine concentrations and Alzheimer’s disease. However, establishing a causal role of cytokine concentrations on risk of Alzheimer’s disease is challenging due to bias from reverse causation and residual confounding.MethodsWe used two-sample MR to explore causal effects of circulating cytokine concentrations on Alzheimer’s disease and vice versa, employing genetic variants associated with cytokine concentrations (N=8,293) and Alzheimer’s disease (71,880 cases / 383,378 controls) from the largest non-overlapping genome-wide association studies (GWAS) of European ancestry.ResultsThere was weak evidence to suggest that 1 standard deviation (SD) increase in levels of CTACK (CCL27) (OR= 1.09 95%CI: 1.01 to 1.19, p=0.03) increased risk of Alzheimer’s disease. There was also weak evidence of a causal effect of 1 SD increase in levels of MIP-1b (CCL4) (OR=1.04 95%CI: 0.99 to 1.09, p=0.08), Eotaxin (OR=1.08 95%CI: 0.99 to 1.17, p =0.10), GROa (CXCL1) (OR=1.04 95%CI: 0.99 to 1.10, p=0.15), MIG (CXCL9) (OR=1.17 95%CI: 0.97 to 1.41, p=0.10), IL-8 (Wald Ratio: OR=1.21 95%CI: 0.97 to 1.51, p=0.09) and IL-2 (Wald Ratio: OR=1.21 95%CI: 0.94 to 1.56, p=0.14) on greater risk of Alzheimer’s disease. There was little evidence of a causal effect of genetic liability to Alzheimer’s disease on circulating cytokine concentrations.ConclusionsOur study provides some evidence supporting a causal role of cytokines in the pathogenesis of Alzheimer’s disease. However, more studies are needed to elucidate the specific mechanistic pathways via which cytokines alter the risk of Alzheimer’s disease.
Lipidomics and Dietary Assessment of Infant Formulas Reveal High Intakes of Major Cholesterol Oxidative Product (7-ketocholesterol)
Authors: Kilvington Alice , Barnaba Carlo , Rajasekaran Surender , Leimanis Mara L. , Medina-Meza Ilce Gabriela 
Published: November 2020

AbstractApproximately two-thirds of US infants receive infant formula (IF) as a primary or sole nutritional source during the first six months of life. IF is available in a variety of commercial presentations, although from a manufacturing standpoint, they can be categorized in powder-(PIF) or liquid-(LIF) based formulations. Herein, thirty commercial IFs were analyzed in their oxidative and non-oxidative lipidomics profiles. Results show that LIFs have a characteristic lipidomic fingerprint, enriched in an oxidated form of cholesterol, and a lower load of phytosterols. We identified 7-ketocholesterol – a major end-product of cholesterol oxidation – as a potential biomarker of IF manufacturing. Our data allowed re-classification of IF based on their metabolomic fingerprint, resulting in three groups assigned with low-to-high oxidative status. Finally, we modeled the dietary intake for cholesterol, sterols, and 7-ketocholesterol in the first year of life. The database provided in this study will be instrumental for scientists interested in infant nutrition, to establish bases for epidemiological studies aimed to find connections between nutrition and diet-associated diseases, such as sitosterolemia.
Investigating Blunt Force Trauma to the Larynx: The Role of Inferior-Superior Vocal Fold Displacement on Phonation
Authors: Stewart Molly E. , Erath Byron D. 
Published: November 2020

AbstractBlunt force trauma to the larynx, which may result from motor vehicle collisions, sports activities, etc., can cause significant damage, often leading to displaced fractures of the laryngeal cartilages, thereby disrupting vocal function. Current surgical interventions primarily focus on airway restoration to stabilize the patient, with restoration of vocal function usually being a secondary consideration. Due to laryngeal fracture, asymmetric vertical misalignment of the left or right vocal fold (VF) in the inferior-superior direction often occurs. This affects VF closure and can lead to a weak, breathy voice requiring increased vocal effort. It is unclear, however, how much vertical VF misalignment can be tolerated before voice quality degrades significantly. To address this need, the influence of inferior-superior VF displacement on phonation is investigated in 1.0 mm increments using synthetic, self-oscillating VF models in a physiologically-representative facility. Acoustic (SPL, frequency, H1-H2, jitter, and shimmer), kinematic (amplitude and phase differences), and aerodynamic parameters (flow rate and subglottal pressure) are investigated as a function of inferior-superior vertical displacement. Significant findings include that once the inferior-superior medial length of the VF is surpassed, sustained phonation degrades significantly, becoming severely pathological. If laryngeal reconstruction approaches can ensure VF contact is maintained during phonation (i.e., vertical displacement doesn’t surpass VF medial length), better vocal outcomes are expected.
Chemoproteomics Maps Glycolytic Targetome in Cancer Cells
Authors: Tian Yang , Wan Ning , Ding Ming , Shao Chang , Wang Nian , Bao Qiuyu , Lu Wenjie , Hu Haiyang , Sun Huiyong , Yang Chenxi , Zhou Kun , Chen Shuai , Wang Guangji , Ye Hui , Hao Haiping 
Published: November 2020

ABSTRACTHyperactivated glycolysis, favoring uncontrolled growth and metastasis by producing essential metabolic intermediates engaging bioenergetics and biosynthesis, is a metabolic hallmark of most cancer cells. Although sporadic information has revealed glycolytic metabolites also possess non-metabolic function as signaling molecules, it remains largely elusive how these metabolites interact with and functionally regulate their binding targets. Here we introduce a Target Responsive Accessibility Profiling (TRAP) approach that measures ligand binding-induced steric hindrance in protein targets via global profiling accessibility changes in reactive lysines, and mapped 913 target candidates and 2,487 interactions for 10 major glycolytic metabolites in cancer cells via TRAP. The elucidated targetome uncovers diverse regulatory modalities of glycolytic metabolites involving the direct perturbation of carbohydrate metabolism enzymes, intervention of transcriptional control, modulation of proteome-level acetylation and protein complex assemblies. The advantages gained from glycolysis by cancer cells are expanded by discovering lactate as a ligand for an orphan transcriptional regulator TRIM 28 that promotes p53 degradation, and by identifying pyruvate acting against a cell apoptosis inducer trichostatin A via attenuating protein acetylation. Lastly, the inhibition of glycolytic key enzymes led to identify an intrinsically active glycolytic intermediate glyceraldehyde 3-phosphate that elicits its cytotoxicity by engaging with ENO1 and MTHFD1. Collectively, the glycolytic targetome depicted by TRAP constitutes a fertile resource for understanding how glycolysis finely tunes metabolism and signaling in support of cancer cells, and fostering the exploitation of glycolytic targetome as promising nodes for anti-cancer therapeutics development.
Detecting SARS-CoV-2 variants with SNP genotyping
Authors: Harper Helen , Burridge Amanda J. , Winfield Mark , Finn Adam , Davidson Andrew D. , Matthews David , Hutchings Stephanie , Vipond Barry , Jain Nisha , Edwards Keith J ,   The COVID-19 Genomics UK (COG-UK) consortium, Barker Gary 
Published: November 2020

AbstractTracking genetic variations from positive SARS-CoV-2 samples yields crucial information about the number of variants circulating in an outbreak and the possible lines of transmission but sequencing every positive SARS-CoV-2 sample would be prohibitively costly for population-scale test and trace operations. Genotyping is a rapid, high-throughput and low-cost alternative for screening positive SARS-CoV-2 samples in many settings. We have designed a SNP identification pipeline to identify genetic variation using sequenced SARS-CoV-2 samples. Our pipeline identifies a minimal marker panel that can define distinct genotypes. To evaluate the system we developed a genotyping panel to detect variants-identified from SARS-CoV-2 sequences surveyed between March and May 2020- and tested this on 50 stored qRT-PCR positive SARS-CoV-2 clinical samples that had been collected across the South West of the UK in April 2020. The 50 samples split into 15 distinct genotypes and there was a 76% probability that any two randomly chosen samples from our set of 50 would have a distinct genotype. In a high throughput laboratory, qRT-PCR positive samples pooled into 384-well plates could be screened with our marker panel at a cost of < £1.50 per sample. Our results demonstrate the usefulness of a SNP genotyping panel to provide a rapid, cost-effective, and reliable way to monitor SARS-CoV-2 variants circulating in an outbreak. Our analysis pipeline is publicly available and will allow for marker panels to be updated periodically as viral genotypes arise or disappear from circulation.
SARS-CoV-2 infection suppresses ACE2 function and antiviral immune response in the upper respiratory tract of infected patients
Authors: Gutiérrez-Chamorro Lucía , Riveira-Muñoz Eva , Barrios Clara , Palau Vanesa , Massanella Marta , Garcia-Vidal Edurne , Badia Roger , Pedreño Sònia , Senserrich Jordi , Rodríguez Eva , Clotet Bonaventura , Cabrera Cecilia , Mitjà Oriol , Crespo Marta , Pascual Julio , Riera Marta , Ballana Ester 
Published: November 2020

AbstractThere is an urgent need to elucidate the molecular mechanisms underlying the transmissibility and pathogenesis of SARS-CoV-2. ACE2 is a host ectopeptidase with well-described anti-inflammatory and tissue protective functions and the receptor for the virus. Understanding SARS-CoV-2-ACE2 interaction and the expression of antiviral host genes in early infection phase is crucial for fighting the pandemic. We tested the significance of soluble ACE2 enzymatic activity longitudinally in positive nasopharyngeal swabs at two time points after symptom consultation, along with gene expression profiles ofACE2, its proteases,ADAM17andTMPRRS2, and interferon-stimulated genes (ISGs),DDX58,CXCL10andIL-6. Soluble ACE2 activity decreased during infection course, in parallel toACE2gene expression. On the contrary, SARS-CoV-2 infection induced expression of the ISG genes in positive SARS-CoV-2 samples at baseline compared to negative control subjects, although this increase wanes with time. These changes positively correlated with viral load. Our results demonstrate the existence of mechanisms by which SARS-CoV-2 suppressACE2expression and function casting doubt on the IFN-induced upregulation of the receptor. Moreover, we show that initial intracellular viral sensing and subsequent ISG induction is also rapidly downregulated. Overall, our results offer new insights into ACE2 dynamics and inflammatory response in the human upper respiratory tract that may contribute to understand the early antiviral host response to SARS-CoV-2 infection.
Mortality rates in matched cohort, pseudo-randomised and randomised trials of convalescent plasma given to COVID-19 patients
Authors: Ahmad Amar , Salsabil Marwa , Oliver Tim 
Published: November 2020

AbstractIntroductionFor more than 80 years convalescent or immune sera has been used in severe life threatening infections. Since March of this year a rapidly increasing number of publications have reported series of Convalescent plasma (CP) investigations in severely ill COVID-19 patients.Objectivea brief CP scoping review focusing on early mortalityMethodsWe searched available data bases. Three randomised trials, two pseudo-randomised observations and twelve matched cohort studies were identified. Random-effects meta-analyses were performed on extracted dataResultsA total of 2,378 CP treated and 5188 “controls” in 17 studies. Individually only two studies were significant for reduction of deaths to 30 days, but all showed a similar percentage reduction. When pooled, meta-analysis was undertaken. It showed that the overall reduction of death was significant for all series RR 0.710 (p=0.00001), all matched cohort series RR = 0.610 (p-value = 0.001) and the two pseudo-randomised series RR 0.747 (p=0.005) but not the three technically inadequate randomised trials, RR 0.825 (p=0.397). In two of these randomised trials, there was faster clearance of Viral DNA at 72 hours after CP than placeboConclusionIt is hoped the significance of this less than perfect data will increase interest in completing the delayed randomised trials as the results suggest they could be better than currently licenced drugs. Given increasing published evidence of increased risk of both diagnosis and death from COVID-19 in patients with severe Vitamin-D deficiency, future studies should also study influence of Vitamin-D status of donor and recipient on outcome.
COVID-19: how the pandemic impacted the emergency department and urgent surgical activity in a medium-size Italian hospital
Authors: Pinotti Enrico , Carissimi Francesca , Baronio Gianluca , Montuori Mauro , Ongaro Deborah , Vasino Michele Ciocca 
Published: November 2020

ABSTRACTBackgroundsCOVID-19 has grown rapidly in Lombardy, particularly in the province of Bergamo. To deal with the pressure the pandemic has exerted on the Italian health system; many hospitals have had to reorganize their medical and surgical activities. The aim of this study was to evaluate how the pandemic influenced the emergency department and urgent surgical activity in a medium-size hospital in the province of Bergamo.MethodsIn this retrospective observational study, we analyzed the number of admissions to the medical and surgical Emergency Room and their severity compared with those in the same period in previous years (2011-2019). Admission in the medical and surgical department and urgent surgical operation was also assessed.ResultsFrom March 7th to April 5th, 2020, we observe a reduction in emergency department access (−53%) when compared with the corresponding period of previous years. The number of medical admissions was similar to the past years (+0.9%), we observed a drastic reduction of surgical patients (−82.5%). We experienced a significant increase in hospitalizations in the medical department (+359%) and a reduction of admission in the surgical department (−71.2%).ConclusionSARS-CoV2 disease has spread so suddenly and severely that it has stressed Italian health system, in particular the Lombard one. Our data show the rise of critical medical ER accesses and the significant expansion in hospitalisation in the medical department with the necessary hospital reorganisation to face COVID-19 emergency. We also observed a reduction in both surgical ER accesses and urgent surgical activity.
Unmasking Seasonal Cycles in Human Fertility: How holiday sex and fertility cycles shape birth seasonality
Authors: Symul L. , Hsieh P. , Shea A. , Moreno CRC. , Skene D.J. , Holmes S. , Martinez M 
Published: November 2020

AbstractThe mechanisms of human birth seasonality have been debated for over 150 years1. In particular, the question of whether sexual activity or fertility variations drive birth seasonality has remained open and challenging to test without large-scale data on sexual activity2,3. Analyzing data from half-a-million users worldwide collected from the female health tracking app Clue combined with birth records, we inferred that birth seasonality is primarily driven by seasonal fertility, yet increased sexual activity around holidays explains minor peaks in the birth curve. Our data came from locations in the Northern Hemisphere (UK, US, and France) and the Southern Hemisphere (Brazil). We found that fertility peaks between the autumn equinox and winter solstice in the Northern Hemisphere locations and shortly following the winter solstice in the Southern Hemisphere locations.
Aberrant gliogenesis and excitation in MEF2C autism patient hiPSC-neurons and cerebral organoids
Authors: Trudler Dorit , Ghatak Swagata , Parker James , Talantova Maria , Grabauskas Titas , Noveral Sarah Moore , Teranaka Mayu , Luevanos Melissa , Dolatabadi Nima , Bakker Clare , Lopez Kevin , Sultan Abdullah , Chan Agnes , Choi Yongwook , Kawaguchi Riki , Schork Nicholas , Stankiewicz Pawel , Garcia-Bassets Ivan , Kozbial Piotr , Rosenfeld Michael G. , Nakanishi Nobuki , Geschwind Daniel H. , Chan Shing Fai , Ambasudhan Rajesh , Lipton Stuart A. 
Published: November 2020

AbstractMEF2C has been shown to be a critical transcription factor for neurodevelopment, whose loss-of-function mutation in humans results in MEF2C haploinsufficiency syndrome (MHS), a severe form of autism spectrum disorder (ASD)/intellectual disability (ID). Here, we use patient hiPSC-derived cerebrocortical neurons and cerebral organoids to characterize MHS deficits. Unexpectedly, we found an aberrant micro-RNA-mediated gliogenesis pathway that contributes to decreased neurogenesis. We also demonstrate network-level hyperexcitability in neurons, as evidenced by excessive synaptic and extrasynaptic activity contributing to excitatory/inhibitory (E/I) imbalance. Notably, the extrasynaptic NMDA receptor antagonist, NitroSynapsin, corrects this aberrant electrical activity associated with abnormal phenotypes. During neurodevelopment, MEF2C regulates many ASD-associated gene networks suggesting that our approach may lead to personalized therapy for multiple forms of ASD.One sentence summaryAutism-like MEF2C+/-patient hiPSC models show miRNA-mediated overproduction of astrocytes and hyperactivity of neurons.
Abrupt light transitions in illuminance and CCT result in different temporal dynamics and interindividual variability for sensation, comfort and alertness
Authors: Kompier M.E. , Smolders K.C.H.J. , de Kort Y.A.W. 
Published: November 2020

AbstractDetailed insights in both visual effects of light and effects beyond vision due to manipulations in illuminance and correlated color temperature (CCT) are needed to optimize study protocols as well as to design light scenarios for practical applications. This study investigated temporal dynamics and interindividual variability in subjective evaluations of sensation, comfort and mood as well as subjective and objective measures of alertness, arousal and thermoregulation following abrupt transitions in illuminance and CCT in a mild cold environment. The effects could be uniquely attributed to changes in illuminance or CCT and no interaction effects of illuminance and CCT were found for any of these markers. Responses to the abrupt transitions in illuminance and CCT always occurred immediately and exclusively amongst the subjective measures. Most of these responses diminished over time within the 45-minute light manipulation. In this period, no responses were found for objective measures of vigilance, arousal nor thermoregulation. Significant interindividual variability occurred only in the visual comfort evaluation in response to changes in the intensity of the light. The results indicate that the design of dynamic light scenarios aimed to enhance human alertness and vitality requires tailoring to the individual to create visually comfortable environments.