bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemosensory dysfunctions induced by COVID-19 can persist up to 7 months: A study of over 700 healthcare workers
Authors: Bussière Nicholas , Mei Jie , Lévesque-Boissonneault Cindy , Blais Mathieu , Carazo Sara , Gros-Louis Francois , De Serres Gaston , Dupré Nicolas , Frasnelli Johannes 
Published: July 2021

AbstractSeveral studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivity have improved.
The penetrance of age-related monogenic disease depends on ascertainment context
Authors: Mirshahi Uyenlinh L , Colclough Kevin , Wright Caroline F , Wood Andrew R , Beaumont Robin N , Tyrrell Jessica , Laver Thomas W , Stahl Richard , Golden Alicia , Goehringer Jessica M , Frayling Timothy F , Hattersley Andrew T , Carey David J , Weedon Michael N , Patel Kashyap A 
Published: July 2021

AbstractBACKGROUNDAccurate penetrance of monogenic disorders is often unknown due to a phenotype-first approach to genetic testing. Here, we use a genotype-first approach in four large cohorts with different ascertainment contexts to accurately estimate penetrance of the three commonest causes of monogenic diabetes, Maturity Onset Diabetes of the Young (MODY). We contrastHNF1A-MODY /HNF4A-MODY which causes an age-related progressive diabetes andGCK-MODY, which causes life-long mild hyperglycaemia.METHODSWe analysed clinical and genetic sequencing data from four different cohorts: 1742 probands referred for clinical MODY testing; 2194 family members of the MODY probands; 132,194 individuals from an American hospital-based cohort; and 198,748 individuals from a UK population-based cohort.RESULTSAge-related penetrance of diabetes for pathogenic variants inHNF1AandHNF4Awas substantially lower in the clinically unselected cohorts compared to clinically referred probands (ranging from 32% to 98% at age 40yrs forHNF1A, and 21% to 99% forHNF4A). The background rate of diabetes, but not clinical features or variant type, explained the reduced penetrance in the unselected cohorts. In contrast, penetrance of mild hyperglycaemia for pathogenicGCKvariants was similarly high across cohorts (ranging from 89 to 97%) despite substantial variation in the background rates of diabetes.CONCLUSIONSAscertainment context is crucial when interpreting the consequences of monogenic variants for age-related variably penetrant disorders. This finding has important implications for opportunistic screening during genomic testing.
Post COVID-19 sequelae: A prospective observational study from Northern India
Authors: Naik Shivdas , Soneja Manish , Haldar Soumendra , Mundadan Netto George , Garg Prerna , Mittal Ankit , Desai Devashish , Trilangi Praveen Kumar , Chakraborty Sayan , Begam Nazneen Nahar , Bhattacharya Bisakh , Maher Ganesh , Kumar Swathi S , Kirthana J , Arunan Bharathi , Gupta Ankesh , Mahishi Niranjan , Rajanna Chaitra , Parsoon Prateek , Kumar Nikhil A , Maharatna Sayan , Bhattacharya Akashneel , Keri Vishakh C , Samed Sameer A , Adarsh AK , Shareef Imtiyaz , Ravela Neeren , Swain Satish , Sarda Radhika , Kadnur Harshith B , Dudhwal Ashok , Agarwal Ayush , Vedula Kartik , Gupta Ashish , Agarwal Shubham , Anand R , Lalikar Pratima , Jagtap Pallavi , Premjeet B , Kodan Parul , Sethi Prayas , Ray Animesh , Jorwal Pankaj , Kumar Arvind , Nischal Neeraj , Sinha Sanjeev , Biswas Ashutosh , Wig Naveet 
Published: July 2021

AbstractBackgroundLong COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection.AimTo describe the clinical details and risk factors of post-COVID sequelae in the North Indian population.MethodThis prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms.ResultsOf 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease.ConclusionMost often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered patients.
Flying in the Face of Adversity: A Drosophila-based Virtual CURE Provides Semester-long Authentic Research Opportunity to the Flipped Classroom
Authors: Waddell Edward A. , Ruiz-Whalen Dara , O’Reilly Alana M. , Fried Nathan T. 
Published: July 2021

AbstractA call for the integration of research experiences into all biology curricula has been a major goal for educational reform efforts nationally. Course-Based Undergraduate Research Experiences (CUREs) have been the predominant method of accomplishing this, but their associated costs and complex design can limit their wide adoption. In 2020, the COVID-19 pandemic forced programs to identify unique ways to still provide authentic research experiences while students were virtual. We report here a full guide for the successful implementation of a semester-long virtual CURE that uses Drosophila behavioral assays to explore the connection between pain and addiction with the use of a “lab-in-a-box” sent home to students. Individual components were piloted across three semesters and launched as a 100-level introductory course with 19 students. We found that this course increased science identity and successfully improved key research competencies as per the Undergraduate Research Student Self-Assessment (URSSA) survey. This course is ideal for flipped classrooms ranging from introductory biology to upper-level neuroscience courses and can be integrated directly into the lecture period without the need for building a new course. Given the low cost, recent comfort with virtual learning environments, and the current proliferation of flipped biology classrooms following the 2020 pandemic, this curriculum could serve as an ideal project-based active-learning tool for equitably increasing access to authentic research experiences.
A joint distribution framework to improve presence-only species distribution models by exploiting opportunistic surveys
Authors: Escamilla Molgora Juan M. , Sedda Luigi , Diggle Peter , Atkinson Peter M. 
Published: July 2021

Abstract◦AimWe propose a Bayesian framework for modelling species distributions using presence-only biodiversity occurrences obtained from historical opportunistic surveys.◦LocationGlobal applicability with two case studies in south-east Mexico.◦MethodsThe framework defines a bivariate spatial process separable into ecological and sampling effort processes that jointly generate occurrence observations of biodiversity records. Presence-only data are conceived as incomplete observations where some presences have been filtered out. A choosing principle is used to separate out presences, missing data and absences relative to the species of interest and the sampling observations. The framework provides three modelling alternatives for accounting the spatial autocorrelation structure: independent latent variables (model I); common latent spatial random effect (model II); and correlated latent spatial random effects (model III).The framework was compared against the Maximum Entropy (MaxEnt) algorithm in two case studies: one for the prediction of pines (Class: Pinopsida), using botanical records as sampling observations and another for the prediction of Flycatchers (Family: Tyranidae), using bird sightings as sampling records.◦ăResultsIn both case studies, at least one of the proposed models achieved higher predictive accuracy than MaxEnt. The model with correlated spatial effects fit best when the sampling effort was informative, while the one with a shared spatial effect was more suitable in cases with high proportion of non sampled sites.◦Main ConclusionsOur approach provides a flexible framework for presence-only SDMs aided by a sampling effort process informed by the accumulated observations of independent and heterogeneous surveys. For the two case studies, the framework provided a model with a higher predictive accuracy than an optimised version MaxEnt.
Design, synthesis, and characterization of [18F]mG2P026 as a high contrast PET imaging ligand for metabotropic glutamate receptor 2
Authors: Yuan Gengyang , Dhaynaut Maeva , Guehl Nicolas J. , Afshar Sepideh , Huynh Dalena , Moon Sung-Hyun , Iyengar Suhasini , Kang Hye Jin , Ondrechen Mary Jo , Fakhri Georges El , Normandin Marc D. , Brownell Anna-Liisa 
Published: July 2021

ABSTRACTAn array of triazolopyridines based on JNJ-46356479 (6) were synthesized as potential PET imaging ligands for metabotropic glutamate receptor 2 (mGluR2) in the brain. The selected candidates 8-11 featured an enhanced positive allosteric modulator (PAM) activity (37-fold max.) and an apparent mGluR2 agonist activity (25-fold max.) compared to compound 6. Radiolabeling of compounds 8 and 9 (also named mG2P026) was achieved via the Cu(I)-mediated radiofluorination in the automated TRACERLabTM FXF-N platform. Both [18F]8 and [18F]9 were obtained with satisfactory radiochemical yields (> 5%, non-decay corrected), high molar activity (> 180 GBq/μmol), and excellent chemical and radiochemical purities (> 98%). Preliminary characterization of [18F]8 and [18F]9 in rats confirmed their excellent brain permeability with [18F]9 showing better brain heterogeneity and favorable binding kinetics. Pretreatment with different classes of PAMs enhanced the radioactivity uptake for both [18F]8 and [18F]9 at the regions of interest by 20.3-40.9% and 16.7-81.6%, respectively, due to their pharmacological effects. Further evaluation of [18F]9 in a nonhuman primate confirmed its superior brain heterogeneity in mapping mGlu2 receptors and its higher specific binding than [18F]6. Pretreatment with 0.5 mg/kg BINA led (2) to an enhanced brain uptake of [18F]9 by 3% in high tracer uptake regions that was consistent with the rat studies. Therefore, [18F]9 has the potential to be translated for human studies.
Unrevealing water and carbon relations during and after heat and hot drought stress in Pinus sylvestris
Authors: Rehschuh Romy , Ruehr Nadine K. 
Published: July 2021

AbstractForests are increasingly affected by heatwaves, often co-occurring with drought, with consequences for water and carbon (C) cycling. However, our ability to project the resilience of trees to an intensification of hot droughts remains limited. Here, we used single tree cuvettes (n=18) allowing us to investigate transpiration (E), net assimilation (Anet), root respiration (Rroot) and stem diameter change in Scots pine seedlings during gradually intensifying heat or drought-heat stress (max. 42°C), and post-stress. Further, we assessed indicators of stress impacts and recovery capacities.Under heat stress, well-watered seedlings prevented overheating of leaves effectively via increased E, while under drought-heat leaf temperatures increased to 46°C. However, leaf electrolyte leakage was negligible, but F’v/F’m declined alongside Anet moderately in heat but strongly in drought-heat seedlings, in which respiration exceeded C uptake. Further, the decrease of needle water potential (ψNeedle) to −2.7 MPa and relative needle water content (RWCNeedle) under drought-heat reflected a decline of leaf hydraulic conductance (KLeaf) by 90% and stem hydraulic conductivity (KS) by 25%. Alongside, we observed pronounced stem diameter shrinkage.Heat stress alone resulted in low functional impairment and all measured parameters recovered fast. In contrast, larger impacts following combined heat and drought led to the incomplete recovery of KLeaf and KS. Despite Anet tended to be reduced albeit F’v/F’m had recovered, the seedlings’ net C balance reached control values 2 d after stress release and stem growth rates exceeded control rates in the 2nd week post-stress. This indicates that a new equilibrium of C uptake and release was maintained at the tree level, slowly supporting regaining of stress-induced losses.In summary, we highlight that under moderate heatwaves with low functional impairment, recovery is fast in Scots pine, while in combination with drought hydraulic and thermal stress are intensified, resulting in functional damage and delayed recovery processes. The incomplete recovery of hydraulic conductance indicates limited water transport capacities that could become critical under repeated heat events.
TACSTD2 upregulation is an early reaction to lung infection
Authors: Lenárt Sára , Lenárt Peter , Knopfová Lucia , Kotasová Hana , Pelková Vendula , Sedláková Veronika , Čan Vladimír , Šmarda Jan , Souček Karel , Hampl Aleš , Beneš Petr 
Published: July 2021

AbstractTACSTD2encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate thatTACSTD2level consistently increases in lungs infected with miscellaneous pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source ofTACSTD2transcript are lung epithelial cells and their progenitors and thatTACSTD2is induced directly in lung epithelial cells following infection. This increase may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.
The Role of Action Potential Waveform in Failure of Excitation Contraction Coupling
Authors: Wang Xueyong , Nawaz Murad , Burke Steve R.A. , Bannister Roger , Foy Brent D. , Voss Andrew A. , Rich Mark M. 
Published: July 2021

AbstractExcitation contraction coupling (ECC) is the process by which electrical excitation of muscle is converted into force generation. Depolarization of skeletal muscle resting potential contributes to failure of ECC in diseases such as periodic paralysis, ICU acquired weakness and possibly fatigue of muscle during vigorous exercise. When extracellular K+is raised to depolarize the resting potential, failure of ECC occurs suddenly, over a range of several mV of resting potential. While some studies have hypothesized the sudden failure of ECC is due to all-or-none failure of excitation, other studies suggest failure of excitation is graded. Intracellular recordings of action potentials (APs) in individual fibers during depolarization revealed that APs do not fail in an all-or-none manner. Simultaneous imaging of Ca2+transients during depolarization revealed failure over a narrow range of resting potentials. An AP property that closely correlated with the sudden failure of the Ca2+transient was the integral of AP voltage with respect to time. We hypothesize the close correlation is due to the combined dependence on time and voltage of Ca2+release from the sarcoplasmic reticulum. The quantitative relationships established between resting potential, APs and Ca2+transients provide the foundation for future studies of depolarization-induced failure of ECC in diseases such as periodic paralysis.
Extent, impact, and mitigation of batch effects in tumor biomarker studies using tissue microarrays
Authors: Stopsack Konrad H. , Tyekucheva Svitlana , Wang Molin , Gerke Travis A. , Vaselkiv J. Bailey , Penney Kathryn L. , Kantoff Philip W. , Finn Stephen P. , Fiorentino Michelangelo , Loda Massimo , Lotan Tamara L. , Parmigiani Giovanni , Mucci Lorelei A. 
Published: July 2021

AbstractTissue microarrays (TMAs) have been used in thousands of cancer biomarker studies. To what extent batch effects, measurement error in biomarker levels between slides, affects TMA-based studies has not been assessed systematically. We evaluated 20 protein biomarkers on 14 TMAs with prospectively collected tumor tissue from 1,448 primary prostate cancers. In half of the biomarkers, more than 10% of biomarker variance was attributable to between-TMA differences (range, 1–48%). We implemented different methods to mitigate batch effects (R package batchtma), tested in plasmode simulation. Biomarker levels were more similar between mitigation approaches compared to uncorrected values. For some biomarkers, associations with clinical features changed substantially after addressing batch effects. Batch effects and resulting bias are not an error of an individual study but an inherent feature of TMA-based protein biomarker studies. They always need to be considered during study design and addressed analytically in studies using more than one TMA.
Mapping of the fibrinogen-binding site on the staphylocoagulase C-terminal repeat region
Authors: Maddur Ashoka A. , Voehler Markus , Panizzi Peter , Meiler Jens , Bock Paul E. , Verhamme Ingrid M. 
Published: July 2021

AbstractThe N-terminus ofS. aureusstaphylocoagulase (SC) triggers activation of host prothrombin (ProT), and the SC·ProT* complex cleaves host fibrinogen (Fbg) to form fibrin (Fbn) deposits, a hallmark of SC-positive endocarditis. The C-terminal domain of the prototypical Newman D2 Tager 104 SC contains 1 pseudo-repeat (PR) and 7 repeats (R1→R7) that bind Fbg/Fbn Fragment D (Frag D). This work defines affinities and stoichiometries of Frag D binding to single- and multi-repeat C-terminal constructs, using fluorescence equilibrium binding, NMR titration, Ala scanning, and native PAGE. Constructs containing PR and each single repeat bound Frag D withKD~50 - 130 nM and a 1:1 stoichiometry, indicating a conserved binding site shared between PR and each repeat. NMR titration of PR-R7 with Frag D revealed that residues 22-49, bridging PR and R7, constituted the minimal peptide (MP) required for binding, corroborated by Ala scanning, and binding of labeled MP to Frag D. MP alignment with the PR-repeat and inter-repeat junctions identified conserved residues critical for binding. Labeled PR-(R1→R7) bound Frag D withKD~7 - 32 nM and stoichiometry of 1:5; and PR-R1R2R3, PR-R1R6R7, PR-R3R4R7, and PR-R3R6R7 competed with PR-(R1→R7) for Frag D binding, with a 1:3 stoichiometry andKD~7 - 42 nM. These findings are consistent with binding at the PR-R junctions with modest inter-repeat sequence variability. Circular dichroism of PR-R7 and PR-(R1→R7) suggested a largely disordered structure and conformational flexibility, allowing binding of multiple fibrin(ogen) molecules. This property facilitates pathogen localization on host fibrin networks.
Proper control of R-loop homeostasis is required for maintenance of gene expression and neuronal function during aging
Authors: Jauregui-Lozano Juan , Escobedo Spencer , Easton Alyssa , Lanman Nadia A. , Weake Vikki M. , Hall Hana 
Published: July 2021

ABSTRACTAge-related loss of cellular function and increased cell death are characteristic hallmarks of aging. While defects in gene expression and RNA metabolism have been linked with age-associated human neuropathies, it is not clear how the changes that occur in aging neurons contribute to loss of gene expression homeostasis. R-loops are RNA-DNA hybrids that typically form co-transcriptionally via annealing of the nascent RNA to the template DNA strand, displacing the non-template DNA strand. Dysregulation of R-loop homeostasis has been associated with both transcriptional impairment and genome instability. Importantly, a growing body of evidence links R-loop accumulation with cellular dysfunction, increased cell death and chronic disease onset. Here, we characterized the R-loop landscape in agingDrosophila melanogasterphotoreceptor neurons and showed that bulk R-loop levels increased with age. Further, genome-wide mapping of R-loops revealed that transcribed genes accumulated R-loops over gene bodies during aging, which correlated with decreased expression of long and highly expressed genes. Importantly, while photoreceptor-specific down-regulation of Top3β, a DNA/RNA topoisomerase associated with R-loop resolution, lead to decreased visual function, overexpression of Top3β or nuclear-localized RNase H1, which resolves R-loops, enhanced positive light response during aging. Together, our studies highlight the functional link between dysregulation of R-loop homeostasis, gene expression and visual function during aging.