bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence, characteristics, and predictors of Long COVID among diagnosed cases of COVID-19
Authors: Arjun M. C. , Singh Arvind Kumar , Pal Debkumar , Das Kajal , Gajjala Alekhya , Venkateshan Mahalingam , Mishra Baijayantimala , Patro Binod Kumar , Mohapatra Prasanta Raghab , Subba Sonu Hangma 
Published: January 2022

AbstractBackgroundLong COVID or long-term complication after COVID-19 has the ability to affect health and quality of life. Knowledge about the burden and predictors could aid in their prevention and management. Most of the studies are from high-income countries and focus on severe cases. We did this study to estimate the prevalence and identify the characteristics and predictors of Long COVID among our patients.MethodologyWe recruited adult (≥18 years) patients who were diagnosed as Reverse Transcription Polymerase Chain Reaction (RTPCR) confirmed SARS-COV-2 infection and were either hospitalized or tested on outpatient basis. Eligible participants were followed up telephonically after four weeks of diagnosis of SARS-COV-2 infection to collect data on sociodemographic, clinical history, vaccination history, Cycle threshold (Ct) values during diagnosis and other variables. Characteristics of Long COVID were elicited, and multivariable logistic regression was done to find the predictors of Long COVID.ResultsWe have analyzed 487 individual data with a median follow-up of 44 days (Inter quartile range (IQR): 39,47). Overall, Long COVID was reported by 29.2% (95% Confidence interval (CI): 25.3%,33.4%) participants. Prevalence of Long COVID among patients with mild/moderate disease (n = 415) was 23.4% (95% CI: 19.5%,27.7%) as compared to 62.5% (95% CI: 50.7%,73%) in severe/critical cases(n=72). The most common Long COVID symptom was fatigue (64.8%) followed by cough (32.4%). Statistically significant predictors of Long COVID were - Pre-existing medical conditions (Adjusted Odds ratio (aOR)=2.00, 95% CI: 1.16,3.44), having a more significant number of symptoms during acute phase of COVID-19 disease (aOR=11.24, 95% CI: 4.00,31.51), two doses of COVID-19 vaccination (aOR=2.32, 95% CI: 1.17,4.58), the severity of illness (aOR=5.71, 95% CI: 3.00,10.89) and being admitted to hospital (Odds ratio (OR)=3.89, 95% CI: 2.49,6.08).ConclusionA considerable proportion of COVID-19 cases reported Long COVID symptoms. More research is needed in Long COVID to objectively assess the symptoms and find the biological and radiological markers.
basicsynbio and the BASIC SEVA collection: Software and vectors for an established DNA assembly method
Authors: Haines Matthew C. , Carling Benedict , Marshall James , Shenshin Vasily A. , Baldwin Geoff S. , Storch Marko , Freemont Paul 
Published: January 2022

AbstractStandardized DNA assembly methods utilizing modular components provide a powerful framework to explore design spaces and iterate through Design-Build-Test-Learn cycles. Biopart Assembly Standard for Idempotent Cloning (BASIC) DNA assembly uses modular parts and linkers, is highly accurate, easy to automate, free for academic and commercial use, while enabling simple hierarchical assemblies through an idempotent format. These features facilitate various applications including pathway engineering, ribosome binding site tuning, fusion protein engineering and multiplexed gRNA expression. In this work we present basicsynbio, an open-source software encompassing a Web App (https://basicsynbio.web.app/) and Python Package (https://github.com/LondonBiofoundry/basicsynbio). With basicsynbio, users can access commonly used BASIC parts and linkers while robustly designing new parts and assemblies with exception handling for common design errors. Users can export sequence data and create build instructions for manual or acoustic liquid-handling platforms. The generation of build instructions relies on the BasicBuild Open Standard which is easily parsed for bespoke workflows and is serializable in Java Script Object Notation for transfer and storage. We demonstrate basicsynbio by assembling a collection of 30 vectors using various sequences including modules from the Standard European Vector Architecture (SEVA). The BASIC SEVA collection is compatible with BASIC and Golden Gate using BsaI. It encompasses vectors containing six antibiotic resistance markers and five origins of replication from different compatibility groups, including a temperature-sensitive variant. To make the collection accessible we deposited it on Addgene under an OpenMTA agreement. Furthermore, vector sequences are accessible from within the basicsynbio application programming interface along with other collections of parts and linkers, providing an ideal environment to design assemblies for bioengineering applications using BASIC.
Loss-of-function of OTUD7A in the schizophrenia-associated 15q13.3 deletion impairs synapse development and function in human neurons
Authors: Kozlova Alena , Zhang Siwei , Kotlar Alex V. , Jamison Brendan , Zhang Hanwen , Shi Serena , Forrest Marc P. , McDaid John , Cutler David J. , Epstein Michael P. , Zwick Michael E. , Pang Zhiping P. , Sanders Alan R. , Warren Stephen T. , Gejman Pablo V. , Mulle Jennifer G. , Duan Jubao 
Published: January 2022

ABSTRACTIdentifying causative gene(s) within disease-associated large genomic regions of copy number variants (CNVs) is challenging. Here, by targeted sequencing of genes within schizophrenia (SZ)-associated CNVs in 1,779 SZ cases and 1,418 controls, we identified three rare putative loss-of-function (LoF) mutations in OTU deubiquitinase 7A (OTUD7A) within the 15q13.3 deletion in cases, but none in controls. To tie OTUD7A LoF with any SZ-relevant cellular phenotypes, we modeled the OTUD7A LoF mutation, rs757148409, in human induced pluripotent stem cell (hiPSC)-derived induced excitatory neurons (iNs) by CRISPR/Cas9 engineering. The mutant iNs showed a ∼50% decrease in OTUD7A expression without undergoing nonsense-mediated mRNA decay. The mutant iNs also exhibited marked reduction of dendritic complexity, density of synaptic proteins GluA1 and PSD-95, and neuronal network activity. Congruent with the neuronal phenotypes in mutant iNs, our transcriptomic analysis showed that the set of OTUD7A LoF-downregulated genes was enriched for those relating to synapse development and function, and was associated with SZ and other neuropsychiatric disorders. These results suggest that OTUD7A LoF impairs synapse development and neuronal function in human neurons, providing mechanistic insight into the possible role of OTUD7A in driving neuropsychiatric phenotypes associated with the 15q13.3 deletion.
Phylogenomics reveals the evolutionary origins of lichenization in chlorophyte algae
Authors: Puginier Camille , Libourel Cyril , Otte Juergen , Skaloud Pavel , Haon Mireille , Grisel Sacha , Petersen Malte , Berrin Jean-Guy , Delaux Pierre-Marc , Dal Grande Francesco , Keller Jean 
Published: January 2022

AbstractMutualistic symbioses have contributed to major transitions in the evolution of life. Here, we investigate the evolutionary history and the molecular innovations at the origin of lichens, which are a symbiosis established between fungi and green algae or cyanobacteria. Wede novosequence the genomes or transcriptomes of 12 lichen algal symbiont (LAS) and closely related non-symbiotic algae (NSA) to improve the genomic coverage of Chlorophyte algae. We then perform ancestral state reconstruction and comparative phylogenomics. We identify at least three independent gains of the ability to engage in the lichen symbiosis, one in Trebouxiophyceae and two in Ulvophyceae, confirming the convergent evolution of the lichen symbioses. A carbohydrate-active enzyme from the glycoside hydrolase 8 (GH8) family was identified as a top candidate for the molecular-mechanism underlying lichen symbiosis in Trebouxiophyceae. This GH8 was acquired in lichenizing Trebouxiophyceae by horizontal gene transfer, concomitantly with the ability to associate with lichens fungal symbionts (LFS) and is able to degrade polysaccharides found in the cell wall of LFS. These findings indicate that a combination of gene family expansion and horizontal gene transfer provided the basis for lichenization to evolve in chlorophyte algae.
CHDbase: A Comprehensive Knowledgebase for Congenital Heart Disease-related Genes and Clinical Manifestations
Authors: Zhou Wei-Zhen , Li Wenke , Shen Huayan , Wang Ruby W. , Chen Wen , Zhang Yujing , Zeng Qingyi , Wang Hao , Yuan Meng , Zeng Ziyi , Cui Jinhui , Li Chuan-Yun , Ye Fred Y. , Zhou Zhou 
Published: January 2022

AbstractCongenital heart disease (CHD) is the most common cause of major birth defects, with a prevalence of 1%. Although an increasing number of studies reporting the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase with CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124 susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of study were integrated with each item of research record. We also integrated functional annotations through parsing ~50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach, and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibility, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org/.
Climate Surveys of Biomedical PhD Students and Training Faculty Members in the Time of Covid
Authors: Ramadoss Deepti , McCord Meghan , Horn John P. 
Published: January 2022

AbstractIn July 2020, four months into the disruption of normal life caused by the Covid-19 pandemic, we assessed the institutional climate within the School of Medicine. Voluntary surveys were completed by 135 graduate students in 11 PhD-granting programs and by 83 members of the graduate training faculty. Several themes emerged. PhD students work hard, but the number of hours spent on research-related activities has declined during the pandemic. The students are worried about the pandemic’s impact on their research productivity, consequent delays in their graduation, and diminished future job prospects. Many late stage PhD students feel they do not have adequate time or resources to plan for their future careers. Symptoms of anxiety and/or depression are prevalent in 51% of the students, based on answers to standardized questions. Most students report they have strong mentoring relationships with their faculty advisors and like their programs, but they identify to a lesser extent with the medical school as a whole. Faculty think highly of their graduate students and are also worried about the pandemic’s impact upon productivity and the welfare of students. Students are interested in access to an Ombuds office, which is currently being organized by the medical school. Moving forward, the school needs to address issues of bias, faculty diversity, support for mentor training, professional development, and the imposter syndrome. We must also work to create a climate in which many more graduate students feel that they are valued members of the academic medicine community.
Thermal characterization and interaction of the subunits from the multimeric bacteriophage endolysin PlyC
Authors: Hoopes J. Todd , Heselpoth Ryan D. , Schwarz Frederick P. , Nelson Daniel C. 
Published: January 2022

AbstractBacteriophage endolysins degrade the bacterial peptidoglycan and are considered enzymatic alternatives to small molecule antibiotics. In particular, the multimeric streptococcal endolysin PlyC has appealing antibacterial properties. However, a comprehensive thermal analysis of PlyC is lacking, which is necessary for evaluating long-term stability and downstream therapeutic potential. Biochemical and kinetic-based methods were used in combination with differential scanning calorimetry to investigate the structural, kinetic and thermodynamic stability of PlyC and its various subunits and domains. The PlyC holoenzyme structure is irreversibly compromised due to partial unfolding and aggregation at 46°C. Unfolding of the catalytic subunit, PlyCA, instigates this event, resulting in the kinetic inactivation of the endolysin. In contrast to PlyCA, the PlyCB octamer (the cell wall binding domain) is thermostable, denaturing at ∼75°C. Isolation of PlyCA or PlyCB alone altered their thermal properties. Contrary to the holoenzyme, PlyCA alone unfolds uncooperatively and is thermodynamically destabilized whereas the PlyCB octamer reversibly dissociates into monomers and forms an intermediate state at 74°C in phosphate buffered saline, with each subunit subsequently denaturing at 92°C. Adding folded PlyCA to an intermediate state PlyCB, followed by cooling, allowed forin vitroreconstitution of the active holoenzyme.
Fluid-structure interaction analysis of eccentricity and leaflet rigidity on thrombosis biomarkers in bioprosthetic aortic valve replacements
Authors: Oks David , Vázquez Mariano , Houzeaux Guillaume , Butakoff Constantine , Samaniego Cristóbal 
Published: January 2022

AbstractThis work introduces the first 2-way fluid-structure interaction (FSI) computational model to study the effect of aortic annulus eccentricity on the performance and thrombogenic risk of cardiac bioprostheses. The model predicts that increasing eccentricities yield lower geometric orifice areas (GOAs) and higher normalized transvalvular pressure gradients (TPGs) for healthy cardiac outputs during systole, agreeing with in vitro experiments. Regions with peak values of residence time and shear rate are observed to grow with eccentricity in the sinus of Valsalva, indicating an elevated risk of thrombus formation for eccentric configurations. In addition, the computational model is used to analyze the effect of varying leaflet rigidity on both performance, thrombogenic and calcification risks with applications to tissue-engineered prostheses, observing an increase in systolic and diastolic TPGs, and decrease in systolic GOA, which translates to decreased valve performance for more rigid leaflets. An increased thrombogenic risk is detected for the most rigid valves. Peak solid stresses are also analyzed, and observed to increase with rigidity, elevating risk of valve calcification and structural failure. The immersed FSI method was implemented in a high-performance computing multi-physics simulation software, and validated against a well known FSI benchmark. The aortic valve bioprosthesis model is qualitatively contrasted against experimental data, showing good agreement in closed and open states. To the authors’ knowledge this is the first computational FSI model to study the effect of eccentricity or leaflet rigidity on thrombogenic biomarkers, providing a novel tool to aid device manufacturers and clinical practitioners.
Impact of adolescent intermittent ethanol exposure on interneurons and their surrounding perineuronal nets in adulthood
Authors: Dannenhoffer Carol A. , Gómez-A Alexander , Macht Victoria A. , Jawad Rayyanoor , Sutherland E. Blake , Vetreno Ryan P. , Crews Fulton T. , Boettiger Charlotte A. , Robinson Donita L. 
Published: January 2022

AbstractBackgroundBinge alcohol exposure during adolescence results in long-lasting alterations in brain and behavior. For example, adolescent intermittent ethanol (AIE) exposure in rodents results in long-term loss of functional connectivity among prefrontal cortex (PFC) and striatal regions as well as a variety of neurochemical, molecular, and epigenetic alterations. Interneurons in the PFC and striatum play critical roles in behavioral flexibility and functional connectivity. For example, parvalbumin (PV) interneurons are known to contribute to neural synchrony, and cholinergic interneurons contribute to strategy selection. Furthermore, extracellular perineuronal nets (PNNs) surround some interneurons, particularly PV+ interneurons, to further regulate cellular plasticity. The effect of AIE exposure on expression of these markers within the PFC is not well understood.MethodsThe present study tested the hypothesis that AIE exposure reduces expression of PV+ and ChAT+ interneurons in the adult PFC and striatum and increases related expression of PNNs (marked by binding ofWisteria Floribundaagglutinin lectin; WFA) in adulthood. Male rats were exposed to AIE (5 g/kg/day, 2-days-on/2-days-off,i.g., P25-P54) or water (CON), and brain tissue was harvested in adulthood (> P80). Immunohistochemistry and co-immunofluorescence were used to assess expression of ChAT, PV, and WFA labeling within the adult PFC and striatum following AIE exposure.ResultsChAT and PV interneuron numbers in the striatum and PFC were unchanged after AIE exposure. However, WFA labeling in the PFC of AIE-exposed rats was increased compared to CON rats. Moreover, significantly more PV neurons were surrounded by WFA labeling in AIE-exposed subjects relative to controls in both PFC subregions assessed: the orbitofrontal cortex (CON = 34%; AIE = 40%) and the medial PFC (CON = 10%; AIE = 14%).ConclusionsThese findings indicate that while PV interneuron expression in the adult PFC and striatum is unaltered following AIE exposure, PNNs surrounding these neurons (indicated by extracellular WFA binding) are increased. This increase in PNNs may restrict plasticity of the ensheathed neurons, thus contributing to impaired microcircuitry in frontostriatal connectivity and related behavioral impairments.
Molecular convergence by differential domain acquisition is a hallmark of chromosomal passenger complex evolution
Authors: Komaki Shinichiro , Tromer Eelco C. , De Jaeger Geert , De Winne Nancy , Heese Maren , Schnittger Arp 
Published: January 2022

AbstractThe chromosomal passenger complex (CPC) is a heterotetrameric regulator of eukaryotic cell division, consisting of an Aurora-type kinase and a scaffold built of INCENP, Borealin and Survivin. While most CPC components are conserved across eukaryotes, orthologs of the chromatin reader Survivin have previously only been found in animals and fungi, raising the question of how its essential role is carried out in other eukaryotes. By characterizing proteins that bind to the Arabidopsis Borealin ortholog, we identified BOREALIN RELATED INTERACTOR 1 and 2 (BORI1 and BORI2) as redundant Survivin-like proteins in the context of the CPC in plants. Loss of BORI function is lethal and a reduced expression of BORIs causes severe developmental defects. Similar to Survivin, we find that the BORIs bind to phosphorylated histone H3, relevant for correct CPC association with chromatin. However, this interaction is not mediated by a BIR domain as in previously recognized Survivin orthologs, but by an FHA domain, a widely conserved phosphate-binding module. We propose that the unifying criterion of Survivin-type proteins is a helix that facilitates complex formation with the other two scaffold components, and that the addition of a phosphate-binding domain, necessary for concentration at the inner centromere, evolved in parallel in different eukaryotic groups. Using sensitive similarity searches, we indeed find conservation of this helical domain between animals and plants, and identify the missing CPC component in most eukaryotic supergroups. Interestingly, we also detect Survivin orthologs without a defined phosphate-binding domain, possibly reflecting the situation in the last eukaryotic common ancestor.Significance StatementThe identification of two SURVIVIN-type genes in the model plant Arabidopsis unfolded the evolutionary trajectories of this central chromosomal passenger complex component and led to the identification of SURVIVIN orthologs in almost the entire eukaryotic kingdom. Our work indicates that the central most aspect of the SURVIVIN gene family is a helix to make contact with two other core chromosomal passenger complex members whereas the addition of a phosphate-binding domain shown to bind to chromatin in animals and plants evolved in parallel at least 3 times in different eukaryotic branches.
Separable roles for RNAi in regulation of transposable elements and viability in the fission yeast Schizosaccharomyces japonicus
Authors: Chapman Elliott , Taglini Francesca , Bayne Elizabeth H. 
Published: January 2022

ABSTRACTRNA interference (RNAi) is a conserved mechanism of small RNA-mediated genome regulation commonly involved in suppression of transposable elements (TEs) through both post-transcriptional silencing, and transcriptional repression via heterochromatin assembly. The fission yeast Schizosaccharomyces pombe has been extensively utilised as a model for studying RNAi pathways. However, this species is somewhat atypical in that TEs are not major targets of RNAi, and instead small RNAs correspond primarily to non-coding pericentromeric repeat sequences, reflecting a specialised role for the pathway in promoting heterochromatin assembly in these regions. In contrast, in the related fission yeast Schizosaccharomyces japonicus, sequenced small RNAs correspond primarily to TEs. This suggests there may be fundamental differences in the operation of RNAi pathways in these two related species. To investigate these differences, we probed RNAi function in S. japonicus. Unexpectedly, and in contrast to S. pombe, we found that RNAi is essential in this species. Moreover, viability of RNAi mutants can be rescued by mutations implicated in enhanching RNAi-independent heterochromatin propagation. These rescued strains retain heterochromatic marks on TE sequences, but exhibit derepression of TEs at the post-transcriptional level. Our findings indicate that S. japonicus retains the ancestral role of RNAi in facilitating suppression of TEs via both post-transcriptional silencing and heterochromatin assembly, with specifically the heterochromatin pathway being essential for viability, likely due to a function in genome maintenance. The specialised role of RNAi in heterochromatin assembly in S. pombe appears to be a derived state that emerged after the divergence of S. japonicus.