bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Side effects of Vero cell vaccination against Covid-19 among medical students of Nepalgunj Medical College”-A Post Vaccination survey
Authors: Rupak KC , Malla Sibika , Pandey Aashish , Shrestha Merina , Siddiqui Saharoj , Adhikari Suraj , Niranjan KC , Rumi KC 
Published: December 2022

AbstractBackground and aimsSevere Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) is a highly transmissible virus causing Coronavirus disease (COVID-19). Its symptoms include fever, dry cough, and shortness of breath. Vaccine plays a significant role in controlling infectious disease and lesser health resources are used, and there is increased allocation of those resources for disease management. Vero Cell is an inactivated vaccine against COVID-19 manufactured by Sinopharm Company of China and recommended for people above 18 years by the World Health Organization. It is administered in two doses of 0.5 ml, 14-28 days apart. The goal of our study was to determine post-vaccination side effects of both the first(1st) and the second(2nd) dose among participants of Nepalgunj Medical College Teaching Hospital (NGMCTH), Kohalpur, Banke, Nepal.MethodsA prospective cross-sectional study was conducted among undergraduate medical students and intern doctors of Nepalgunj Medical College. A comprehensive structured questionnaire was designed and distributed following each dose of vaccination. Data were collected from 6thJanuary 2022 to 6thApril 2022 and entered in Microsoft Excel and analyzed using the statistical package for social sciences (SPSS) version 22. Analyzed data were presented using simple descriptive statistics with appropriate tables.ResultsOut of 156 participants, the majority were males (66.7%), within the age group of 21-24. The most frequently encountered symptom was pain at the injection site, predominantly seen in males. Among all the tested variables, the second dose of vaccination showed a significant association with sex. All the predominant symptoms exhibited a significant association following vaccination, except for pain at the injection site (p-value <0.05).ConclusionsVaccine has proven to be a lifesaving breakthrough during the peak of the COVID-19 outbreak and has been precisely efficacious in a developing country like Nepal.
Proteome sampling with e-biopsy enables differentiation between cutaneous squamous cell carcinoma and basal cell carcinoma
Authors: Vitkin Edward , Wise Julia , Berl Ariel , Shir-az Ofir , Gabay Batel , Singh Amrita , Kravtsov Vladimir , Yakhini Zohar , Shalom Avshalom , Golberg Alexander 
Published: December 2022

AbstractClinical misclassification between cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) affects treatment plans and carries risks of potential for recurrence, metastases morbidity and mortality. We report the development of a novel tissue sampling approach with molecular biopsy using electroporation. The methods, coined e-biopsy, enables non-thermal permeabilization of cells in the skin for efficient vacuum-assistant extraction of informative biomolecules for rapid diagnosis. We used e-biopsy forex vivoproteome extraction from 3 locations per patient in 21 cSCC and 21 BCC pathologically validated human tissue samples. The total 126 extracted proteomes were profiled using LC/MS/MS. The obtained mass spectra presented significantly different proteome profiles for cSCC and BCC with several hundreds of proteins significantly differentially expressed in each tumor in comparison to the other. Notably, 17 proteins were uniquely expressed in BCC and 7 were uniquely expressed in cSCC patients. Statistical analysis of differentially expressed proteins found 31 cellular processes, 23 cellular functions and 10 cellular components significantly different between cSCC and BCC. Machine Learning classification models constructed on the sampled proteomes enabled the separation of cSCC patients from BCC with average cross-validation accuracy of 81%, cSCC prediction positive predictive value (PPV) of 78.7% and sensitivity of 92.3%, which is comparable to initial diagnostics in a clinical setup. Finally, the protein-protein interaction analysis of the 11 most informative proteins, derived from Machine Learning framework, enabled detection of a novel protein-protein interaction network valuable for further understanding of skin tumors. Our results provide evidence that the e-biopsy approach could potentially be used as a tool to support cutaneous tumors classification with rapid molecular profiling.
Subsumption, Vectorization, Heat Maps, and Word Clouds Support the Visualization of Orphadata Neurology Phenotypes
Authors: Hier Daniel B. , Yelugam Raghu , Carrithers Michael D. , Wunsch Donald C. 
Published: December 2022

ABSTRACTDisease phenotypes are characterized by signs (what a physician observes during the examination of a patient) and symptoms (the complaints of a patient to a physician). Large repositories of disease phenotypes are accessible through the Online Mendelian Inheritance of Man, Human Phenotype Ontology, and Orphadata initiatives. Many of the diseases in these datasets are neurologic. For each repository, the phenotype of a neurologic disease is represented as a variable-length list of concepts selected from a suitable ontology. Visualizations of these lists are not provided. We address this limitation by using subsumption to collapse the number of descriptive features from 2,946 classes into thirty superclasses. Phenotype feature lists of variable lengths were converted into fixed-length numerical vectors. Phenotype vectors can be aggregated into matrices and visualized as heat maps that allow side-by-side disease comparisons. Individual diseases (representing a row in the matrix) can be visualized as word clouds. We illustrate the utility of this approach with a use case based on 32 dystonic diseases in Orphadata. The use of subsumption to collapse phenotype features into superclasses, the conversion of phenotype lists into vectors, and the visualization of phenotypes vectors as heat maps and word clouds contribute to the improved visualization of neurology phenotypes in Orphadata.
Human coronaviruses activate and hijack the proteostasis guardian HSF1 to enhance viral replication
Authors: Pauciullo Silvia , Riccio Anna , Rossi Antonio , Santopolo Silvia , Piacentini Sara , Santoro M. Gabriella 
Published: December 2022

ABSTRACTOrganisms respond to proteotoxic stress by activating a cellular defense mechanism, known as the heat shock response (HSR), that triggers the expression of cytoprotective heat shock proteins (HSP) to counteract the damaging effects of proteostasis disruption. The HSR is regulated by a family of transcription factors (heat shock factors, HSFs); among six human HSFs, HSF1 acts as a proteostasis guardian regulating acute and severe stress-driven transcriptional responses. Seasonal coronaviruses HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 (sHCoV) are globally circulating in the human population. Although sHCoV generally cause only mild upper respiratory diseases in immunocompetent hosts, severe complications may occur in specific populations. There is no effective treatment for sHCoV infections, also due to the limited knowledge on sHCoV biology. We now show that bothAlpha- andBeta-sHCoV are potent inducers of HSF1, selectively promoting HSF1 phosphorylation at serine-326 residue and nuclear translocation, and triggering a powerful HSF1-driven transcriptional response in infected cells at late stages of infection. Despite the coronavirus-mediated shut-down of the host cell translational machinery, high levels of selected canonical and non-canonical HSF1-target genes products, including HSP70, HSPA6 and the zinc-finger AN1-type domain-2a gene/AIRAP, were found in HCoV-infected cells. Interestingly, silencing experiments demonstrate that HSR activation does not merely reflect a cellular defense response to viral infection, but that sHCoV activate and hijack the HSF1-pathway for their own gain. Notably, nuclear HSF1 pools depletion via Direct-Targeted HSF1 inhibitor (DTHIB) treatment was highly effective in hindering sHCoV replication in lung cells. Altogether the results open new scenarios for the search of innovative antiviral strategies in the treatment of coronavirus infections.
High robustness of cytosolic glutathione redox potential under combined salt and osmotic stress in barley as revealed by the biosensor Grx1-roGFP2
Authors: Bohle Finja , Klaus Alina , Tegethof Hendrik , Schwarzländer Markus , Hochholdinger Frank , Meyer Andreas J. , Acosta Ivan F. , Müller-Schüssele Stefanie J. 
Published: December 2022

AbstractBarley is a staple crop of major global importance and relatively resilient to a wide range of stress factors in the field. Transgenic reporter lines to investigate physiological parameters during stress treatments remain scarce.We generated and characterized stable homozygous barley lines (cv. Golden Promise Fast) expressing the genetically-encoded biosensor Grx1-roGFP2, which indicates the redox potential of the major antioxidant glutathione in the cytosol.Our results demonstrate functionality of the sensor in living barley plants. We determined the glutathione redox potential (EGSH) of the cytosol to be in the range of −308 to −320 mV.EGSHwas robust against a combined NaCl (150 mM) and water deficit treatment (−0.8 MPa) that caused growth retardation and showed only a minor oxidation after 96 h of treatment.We conclude that the generated reporter lines are a novel resource to study stress resilience in barley.One sentence summaryGeneration and characterization of barley plants stably expressing Grx1-roGFP2 reveal high robustness of cytosolic glutathione redox potential (EGSH) under combined salt and osmotic stress.
Usefulness of docking and molecular dynamics in selecting tumor neoantigens to design personalized cancer vaccines:a proof of concept
Authors: Amaya-Ramirez Diego , Martinez-Enriquez Laura Camila , Parra-López Carlos 
Published: December 2022

AbstractPersonalized cancer vaccines are presented as a new and promising treatment alternative for cancer, especially in those cases where effective treatments do not yet exist. However, multiple challenges remain to be resolved so that this type of immunotherapy can be used in the clinical setting. Among these, the effective identification of immunogenic peptides stands out, since thein-silicotools currently used generate a significant portion of false positives. This is where molecular simulation techniques can play an important role when it comes to refining the results produced by these tools. In the present work, we explore the use of molecular simulation techniques such as docking and molecular dynamics to study the relationship between stability of peptide-HLA complexes and their immunogenicity using two HLA-A2-restricted neoantigens that have already been evaluatedin vitro. The results obtained agreed with thein vitroimmunogenicity of the immunogenic neoantigen ASTN1 the only one that remains bound at both ends to the HLA-A2 molecule. Additionally, molecular dynamics indicates that position 1 of the peptide has a more important role in stabilizing the N-terminal part than previously assumed. Likewise, the results suggest that the mutations may have a “delocalized” effect on the peptide-HLA interaction, that is, they may modulate the intensity of the interactions of other amino acids in the peptide. These results highlight the suitability of this type ofin silicostrategy to identify peptides that form stable complexes with HLA proteins that are highly immunogenic for CD8+ T cells.
HEIP1 is required for efficient meiotic crossover implementation and is conserved from plants to humans
Authors: Singh Dipesh Kumar , Lian Qichao , Durand Stephanie , Chambon Aurelie , Hurel Aurelie , Walkemeier Birgit , Solier Victor , Kumar Rajeev , Mercier Raphaёl 
Published: December 2022

AbstractCrossovers (CO) shuffle genetic information and physically connect homologous chromosome pairs, ensuring their balanced segregation during meiosis. COs arising from the major class I pathway require the activity of a well-conserved ZMMs group of proteins which, in conjunction with MLH1, facilitate the maturation of DNA recombination intermediates specifically into COs. The HEIP1 protein was identified in rice and proposed to be a new, plant-specific member of the ZMM group. Here we establish and decipher the function of theArabidopsis thalianaHEIP1 homolog in meiotic crossover formation and report its wide conservation in eukaryotes. We show that the loss of Arabidopsis HEIP1 elicits a marked reduction in meiotic COs and their redistribution towards chromosome ends. Epistasis analysis showed thatAtHEIP1acts specifically in the class I CO pathway. Further, we show that HEI1P acts both prior to crossover designation, as the number of MLH1 foci is reduced inheip1, and at the maturation step of MLH1-marked sites into COs. Despite the HEIP1 protein being predicted to be primarily unstructured and very divergent at the sequence level, we identified homologs of HEIP1 in an extensive range of eukaryotes, including mammals.
Identification of novel coloboma candidate genes through conserved gene expression analyses across four vertebrate species
Authors: Trejo-Reveles Violeta , Owen Nicholas , Chan Brian Ho Ching , Toms Maria , Schoenebeck Jeffrey J , Moosajee Mariya , Rainger Joe 
Published: December 2022

AbstractOcular coloboma (OC) is a failure of complete optic fissure closure during embryonic development and presents as a tissue defect along the proximal distal axis of the ventral eye. It is classed as part of the clinical spectrum of structural eye malformations with microphthalmia and anophthalmia, collectively abbreviated to MAC. Despite deliberate attempts to identify causative variants in MAC, many patients remain without a genetic diagnosis. To reveal potential candidate genes, we utilised transcriptomes experimentally generated from embryonic eye tissues derived from human, mouse, zebrafish, and chicken at stages coincident with optic fissure closure. Our in-silico analyses found 10 genes with optic fissure specific enriched expression:ALDH1A3, BMPR1B, EMX2, EPHB3, NID1, NTN1, PAX2, SMOC1, TENM3, andVAX1. In situ hybridization revealed that all 10 genes were broadly expressed ventrally in the developing eye, but that onlyPAX2andNTN1were expressed in cells at the edges of the optic fissure margin. Of these conserved optic fissure genes,EMX2, NID1, andEPHB3have not previously been associated with human MAC cases. Targeted genetic manipulation in zebrafish embryos using CRISPR/Cas9 caused the developmental MAC phenotype foremx2andephb3. We scrutined available whole genome sequencing datasets from MAC patients and identified a range of variants with plausible causality. In combination our data suggest that expression of genes involved in ventral eye development are conserved across a range of vertebrate species, and thatEMX2, NID1, andEPHB3are candidate loci that should be adopted into clinical diagnostic screens for patients with structural eye malformations.
Automated Workflow for Instant Labeling and Real-Time Monitoring of Monoclonal Antibody N-Glycosylation
Authors: Gyorgypal Aron , Potter Oscar , Chaturvedi Antash , Powers David N. , Chundawat Shishir P. S. 
Published: December 2022

AbstractWith the transition toward continuous bioprocessing, process analytical technology (PAT) is becoming necessary for rapid and reliable in-process monitoring during biotherapeutics manufacturing. Bioprocess 4.0 is looking to build an end-to-end bioprocesses that includes PAT-enabled real-time process control. This is especially important for drug product quality attributes that can change during bioprocessing, such as protein N-glycosylation, a critical quality attribute for most monoclonal antibody (mAb) therapeutics. Glycosylation of mAbs is known to influence their efficacy as therapeutics and is regulated for a majority of mAb products on the market today. Currently, there is no method to truly measure N-glycosylation using on-line PAT, hence making it impractical to design upstream process control strategies. We recently described the N-GLYcanyzer: an integrated PAT unit that measures mAb N-glycosylation within 3 hours of automated sampling from a bioreactor. Here, we integrated Agilent’s Instant PC (IPC) based chemistry workflow into the N-GLYcanzyer PAT unit to allow for nearly 10x faster mAb glycoforms analysis. Our methodology is explained in detail to allow for replication of the PAT workflow as well as present a case study demonstrating use of this PAT to autonomously monitor a mammalian cell perfusion process at the bench-scale to gain increased knowledge of mAb glycosylation dynamics during continuous biomanufacturing of biologics using Chinese Hamster Ovary (CHO) cells.Graphical Abstract
Vascular ultrasound forin vivoassessment of arterial pathologies in a murine model of atherosclerosis and aortic aneurysm
Authors: Hof Alexander , Guthoff Henning , Ahdab Maysam , Landerer Max , Schäkel Jasper , Niehues Jana , Schorscher Max , Winkels Holger , Geißen Simon , Adam Matti , Mollenhauer Martin , Mehrkens Dennis 
Published: December 2022

AbstractBackgroundVascular diseases like atherosclerosis or aortic aneurysms are common pathologies in the western world, promoting various, potentially fatal conditions. Hence, a plethora of animal models have been developed to investigate underlying mechanisms and potential therapeutics. Here we evaluate high resolution (HR) ultrasound in mouse models of atherosclerosis and abdominal aortic aneurysm (AAA) for noninvasive monitoring of morphological and functional vascular changesin vivo.MethodsEight-week-oldApoE-/-mice were used for disease models. For induction of atherosclerosis, mice were fed a western diet over 12 weeks. To trigger AAA development, osmotic minipumps were implanted, permanently releasing Angiotensin II continuously for 28 days. All animals were on C57Bl6/J background. HR vascular ultrasound of the carotid artery or the abdominal aorta was performed, respectively. Images obtained were analyzed by a speckle tracking algorithm (VevoVasc software) and were correlated with histological analyses by Picro Sirius Red staining and automated collagen quantification.ResultsArterial wall distensibility and global radial strain (GRS) as measures of arterial wall elasticity were reduced in the carotids of atherosclerotic mice as well as in the aortas of AAA mice. Pulse wave velocity (PWV) was elevated in both disease models. Intima-media thickness (IMT) was significantly increased in the atherosclerosis model. Matching those findings, area of the tunica media was enlarged inApoE-/-mice fed a western diet, and in Angiotensin II treated mice as measured by automated image analysis, depicting higher collagen depositions in diseased arteries. Simple regression analysis revealed a strong correlation of media collagen content and area in AAA with IMT and GRS, respectively. In atherosclerosis, media collagen content significantly correlated with PWV and GRS, whereas wall distensibility was associated with the size of media area.ConclusionVascular imaging using latest generation HR ultrasound devices is suitable to trace changes of arterial wall properties in murine models of atherosclerosis and AAA. Obtained results not only correlate with histological findings but deliver information on functional parameters which may be used as early disease and risk markers in a longitudinal experimental approach.
Deep Generative Design of Epitope-Specific Binding Proteins by Latent Conformation Optimization
Authors: Eguchi Raphael R. , Choe Christian A. , Parekh Udit , Khalek Irene S. , Ward Michael D. , Vithani Neha , Bowman Gregory R. , Jardine Joseph G. , Huang Po-Ssu 
Published: December 2022

AbstractDesigningde novobinding proteins against arbitrary epitopes using a single scaffold, as seen with natural antibodies, remains an unsolved challenge in protein design. Current design methods are unable to capture the structural dynamics of flexible loops nor search loop conformational space in a principled way. Here we present Sculptor, a deep generative design algorithm that creates epitope-specific protein binders. The Sculptor algorithm constitutes a joint search over the positions, interactions, and generated conformations of a fold, and crafts a backbone to complement a user-specified epitope. Sequences are designed onto generated backbones using a combination of a residue-wise interaction database, a convolutional sequence design module, and Rosetta. Instead of relying on static structures, we capture the local conformational landscape of a single fold using molecular dynamics, and demonstrate that a model trained on such dense conformational data can generate backbones tailor-fit to an epitope. We use Sculptor to design binders against a conserved epitope on venom toxins implicated in neuromuscular paralysis, and obtain a multi-toxin binder from a small naïve library – a promising step towards creating broadly neutralizing binders. This study constitutes a novel application of deep generative modeling for epitope-targeted design, leveraging conformational dynamics to achieve function.
Artificial neural network in soft HR performance management: new insights from a large organizational dataset
Authors: Roedenbeck Marc , Poljsak-Rosinski Petra 
Published: December 2022

PurposeThis study investigates whether the artificial neural network approach, when used on a large organizational soft HR performance dataset, results in a better (R2/RMSE) model compared to the linear regression. With the use of predictive modelling, a more informed base for managerial decision making within soft HR performance management is offered.Design/methodology/approachThe study builds on a dataset (n > 43 k) stemming from an annual employee MNC survey. It covers several soft HR performance drivers and outcomes (such as engagement, satisfaction and others) that either have evidence of a dual-role nature or non-linear relationships. This study applies the framework for artificial neural network analysis in organization research (Scarborough and Somers, 2006).FindingsThe analysis reveals a substantial artificial neural network model performance (R2 > 0.75) with an excellent fit statistic (nRMSE <0.10) and all drivers have the same relative importance (RMI [0.102; 0.125]). This predictive analysis revealed that the organization has to increase six of the drivers, keep two on the same level and decrease one.Originality/valueUp to date, this study uses the largest dataset in soft HR performance management. Additionally, the predictive results reveal that specific target values lay below the current levels to achieve optimal performance.