bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Stem Cell Therapy in Fetuses With Myelomeningocele: A Systematic Review and Meta-Analysis
Authors: Kunpalin Yada , Subramaniam Sindhu , Perin Silvia , Gerli Mattia F. M. , Bosteels Jan , Ourselin Sebastien , Deprest Jan , De Coppi Paolo , David Anna L. 
Published: August 2021

(Abstracted from Prenatal Diagnosis 2021;41:283–300)
Myelomeningocele (MMC) is a congenital malformation of the central nervous system that is caused by an incomplete closure of the neural tube during the third to fourth week of embryonic development. An MMC can be seen in some cases by prenatal ultrasound in the first trimester, although most cases are diagnosed during the second trimester.
A Multidisciplinary Approach and Review of Safety Recommendations for Plastic Surgeons during the COVID-19 Pandemic: Are N95 Masks Enough?
Authors: Jalisi Scharukh , Chen Austin D. , Gomez Ernest , Chigurupati Radhika , Cauley Ryan , Olbricht Suzanne , Lee Bernard T. , Lin Samuel J. 
Published: August 2021

Summary:
The novel coronavirus disease of 2019 pandemic presents a unique challenge to the field of plastic and reconstructive surgery. Although plastic surgeons may be postponing elective operations, there are still a number of emergent or urgent procedures that may need to be performed, and surgeons may be facing the reality of returning to a new normalcy of operating with coronavirus disease of 2019. These procedures, consisting of those such as head and neck reconstruction or maxillofacial trauma, largely require a multidisciplinary approach and may be considered of higher risk to health care workers because of the involvement of areas of the body identified as sources for viral transmission. Moreover, viral transmission may potentially extend beyond respiratory secretions, which has been the main focus of most safety precautions. The authors aim to present the scope of these procedures and the means of viral transmission, and to provide safety precaution recommendations for plastic surgery and its related disciplines.
Evaluation of Broadly Neutralizing Antibody Sensitivity by Genotyping and Phenotyping for Qualifying Participants to HIV Clinical Trials
Authors: Moldt Brian , Parvangada Aiyappa , Martin Ross , Pace Craig , Balakrishnan Mini , Thomsen Nathan D. , E. Collins Sean , Kuster Herbert , Braun Dominique L. , Günthard Huldrych F. , Geleziunas Romas , Callebaut Christian 
Published: August 2021

Background:
HIV envelope (env) diversity represents a significant challenge for the use of broadly neutralizing antibodies (bNAbs) in HIV treatment and cure studies. Screening for viral sensitivity to bNAbs to select eligible trial participants will be important to improve clinical efficacy; however, no universal approach has been established.

Methods:
Pre-antiretroviral therapy plasma virus from participants in the Zurich Primary HIV Infection (ZPHI) study was genotyped and phenotyped for sensitivity to the bNAbs elipovimab (EVM, formerly GS-9722) and 3BNC117. The genotyping and phenotyping assessments were performed following the Clinical Laboratory Improvement Amendments of 1988 guidelines as required for entry into clinical trials. The genotypic-based prediction of bNAb sensitivity was based on HIV env amino acid signatures identified from a genotypic–phenotypic correlation algorithm using a subtype B database.

Results:
Genotyping the plasma virus and applying env sensitivity signatures, ZPHI study participants with viral sensitivity to EVM and 3BNC117 were identified. ZPHI study participants with virus sensitive to EVM and 3BNC117 were also identified by phenotyping the plasma virus. Comparison of the genotypic and phenotypic sensitivity assessments showed strong agreement between the 2 methodologies.

Conclusions:
The genotypic assessment was found to be as predictive as the direct measurement of bNAb sensitivity by phenotyping and may, therefore, be preferred because of more rapid turnaround time and assay simplicity. A significant number of the participants were predicted to have virus sensitive to EVM and 3BNC117 and could, thus, be potential participants for clinical trials involving these bNAbs.
Potential for combining semantics and data analysis in the context of digital twins
Authors: Vogel-Heuser Birgit , Ocker Felix , Weiß Iris , Mieth Robert , Mann Frederik 
Published: August 2021

Modern production systems can benefit greatly from integrated and up-to-date digital representations. Their applications range from consistency checks during the design phase to smart manufacturing to maintenance support. Such digital twins not only require data, information and knowledge as inputs but can also be considered integrated models themselves. This paper provides an overview of data, information and knowledge typically available throughout the lifecycle of production systems and the variety of applications driven by data analysis, expert knowledge and knowledge-based systems. On this basis, we describe the potential for combining data analysis and knowledge-based systems in the context of production systems and describe two feasibility studies that demonstrate how knowledge-based systems can be created using data analysis.This article is part of the theme issue ‘Towards symbiotic autonomous systems’.
Comparative genomic and pan-genomic characteristion of Staphylococcus epidermidis from different sources unveils the molecular basis and potential biomarkers of pathogenic strains
Authors: Lin Shudan , Sun Bianjin , Shi Xinrui , Xu Yi , Gu Yunfeng , Gu Xiaobin , Ma Xueli , Wan Tian , Xu Jie , Su Jianzhong , Lou Yongliang , Zheng Meiqin 
Published: August 2021

AbstractCoagulase-negative Staphylococcus (CoNS) is the most common pathogen causing traumatic endophthalmitis, Staphylococcus epidermidis is the most common species which colonizes human skin, eye surfaces and nasal cavity and is the main cause of nosocomial infection, specially foreign body-related bloodstream infections (FBR-BSIs). Although some studies have reported the genome characteristics of S. epidermidis, a comprehensive understanding of its pathogenicity and the genome of ocular trauma-sourced strains is still lacking. In this study, we sequenced, analyzed and reported the whole genomes of 11 ocular trauma-sourced samples of S. epidermidis that caused traumatic endophthalmitis. By integrating publicly available genomes, we obtained a total of 187 S. epidermidis samples from healthy and diseased eyes, skin, respiratory tract and blood. Combined with pangenome, phylogenetic and comparative genomic analyses, our study supported that S. epidermidis, regardless of niche source, exhibits two founder lineages with different pathogenicities. Moreover, we identified potential biomarkers associated with the virulence of S. epidermidis, namely, essD, uhpt, sdrF, sdrG, fbe and icaABCDR. The essD and uhpt genes have high homology with esaD and hpt in Staphylococcus aureus, showing that the genomes of S. epidermidis and S. aureus may have communicated during evolution, while the sdrF, sdrG, fbe, and icaABCDR genes are related to biofilm formation. Compared to S. epidermidis from blood sources, ocular-sourced strains causing intraocular infection had no direct relationship with biofilm formation. In conclusion, this study not only provided additional data resources for studies on S. epidermidisis, but also improved understanding of the evolution and pathogenicity of different source strains.ImportantsIn this study, we comprehensively analysied and reported the whole genome sequence (WGS) of the strains that caused traumatic endophthalmitis. Through comparative genomic analyses among 187 S. epidermidis samples from healthy and diseased eyes, skin, respiratory tract and blood, we identified 10 potential biomarkers of pathogenic strains. Finally, we revealed S. epidermidis-induced traumatic endophthalmitis may be independent of biofilm formation. Overall, our data may facilitate comparative research of S. epidermidis and provide clinical value for identifying pathogenic or contaminating strains.
Gait as a Quantitative Translational Outcome Measure in Angelman Syndrome
Authors: Petkova Stela P. , Duis Jessica D. , Silverman Jill L. 
Published: August 2021

AbstractAngelman Syndrome (AS) is a genetic neurodevelopmental disorder characterized by developmental delay, lack of speech, seizures, intellectual disability, and walking and balance disorders. Recently, motor ability became an interesting outcome measure in AS, as it is broad including ataxia, hypotonia, delayed and abnormal walking and postural movements and affects nearly every individual with AS. We predict that gait presents a strong opportunity for rigorous, reliable, and quantitative metrics with direct translation to evaluate pharmacological, dietary, and genetic therapies. Numerous motoric deficits have been identified clinically. In this study, we used an innovative, automated gait analysis as well as gold standard motor behavioral assays to further delineate components of motor, coordination, balance, and gait impairments in an AS mouse model across development. Our study demonstrated marked global motoric deficits in AS mice, corroborating many previous reports. Uniquely, this is the first report of nuanced and pertinent aberrations in quantitative spatial and temporal components of gait between AS and wildtype littermate controls, that are analogous in AS individuals. These metrics were followed longitudinally to observe the progression of maladaptive gait in AS, a clinical phenotype. This has not been reported previously and contributes a substantial novel metric for therapeutic development. Taken together, these findings demonstrate the robust translational value in the study of nuanced motor outcomes, i.e., gait, for AS, as well as similar genetic syndromes, in the endeavor of therapeutic screening.Lay AbstractMotor behaviors, like ambulation, gross and fine motor skills, coordination and balance, are easily quantifiable and readily translational between humans and preclinical rodent models for neurodevelopmental and neurodegenerative disorders, than other domains of behavior. To that end, we investigated gait across development in a mouse model for Angelman Syndrome and elucidated onset, progression, and decline of motor deficits in innovative, nuanced, and clinically relevant manner.
The ability of bumblebees Bombus terrestris (Hymenoptera: Apidae) to detect floral humidity is dependent upon environmental humidity
Authors: Harrison Amy S. , Rands Sean A. 
Published: August 2021

ABSTRACTFlowers produce local humidity that is often greater than that of the surrounding environment, and studies have shown that insect pollinators may be able to use this humidity difference to locate and identify suitable flowers. However, environmental humidity is highly heterogeneous, and is likely to affect the detectability of floral humidity, potentially constraining the contexts in which it can be used as a salient communication pathway between plants and their pollinators. In this study, we use differential conditioning techniques on bumblebees Bombus terrestris audax (Harris) to explore the detectability of an elevated floral humidity signal when presented against different levels of environmental noise. Artificial flowers were constructed that could be either dry or humid, and individual bumblebees were presented with consistent rewards in either the humid or dry flowers presented in an environment with four levels of constant humidity, ranging from low (∼20% RH) to highly saturated (∼95% RH). Ability to learn was dependent upon both the rewarding flower type and the environment: the bumblebees were able to learn rewarding dry flowers in all environments, but their ability to learn humid rewarding flowers was dependent on the environmental humidity, and they were unable to learn humid rewarding flowers when the environment was highly saturated. This suggests that floral humidity might be masked from bumblebees in humid environments, suggesting that it may be a more useful signal to insect pollinators in arid environments.
Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome
Authors: Berg Elizabeth L. , Petkova Stela P. , Born Heather A. , Adhikari Anna , Anderson Anne E. , Silverman Jill L. 
Published: August 2021

AbstractBackgroundAngelman Syndrome (AS) is a rare neurodevelopmental disorder for which there is currently no cure or effective therapeutic. Since the genetic cause of AS is known to be dysfunctional expression of the maternal allele of ubiquitin protein ligase E3A (UBE3A), several genetic animal models of AS have been developed. Both the Ube3a maternal deletion mouse and rat models of AS reliably demonstrate behavioral phenotypes of relevance to AS and therefore offer suitable in vivo systems in which to test potential therapeutics. One promising candidate treatment is insulin-like growth factor-2 (IGF-2), which has recently been shown to ameliorate behavioral deficits in the mouse model of AS and improve cognitive abilities across model systems.MethodsWe used both the Ube3a maternal deletion mouse and rat models of AS to evaluate the ability of IGF-2 to improve electrophysiological and behavioral outcomes.ResultsAcute systemic administration of IGF-2 had an effect on electrophysiological activity in the brain and on a metric of motor ability, however the effects were not enduring or extensive. Additional metrics of motor behavior, learning, ambulation, and coordination were unaffected and IGF-2 did not improve social communication, seizure threshold, or cognition.LimitationsThe generalizability of these results to humans is difficult to predict and it remains possible that dosing schemes (i.e., chronic or subchronic dosing), routes, and/or post-treatment intervals other than that used herein may show more efficacy.ConclusionsDespite a few observed effects of IGF-2, our results taken together indicate that IGF-2 treatment does not profoundly improve behavioral deficits in mice or rat models of AS. These findings shed cautionary light on the potential utility of acute systemic IGF-2 administration in the treatment of AS.
Spatio-temporally efficient coding assigns functions to hierarchical structures of the visual system
Authors: Sihn Duho , Kim Sung-Phil 
Published: August 2021

AbstractHierarchical structures constitute a wide array of brain areas, including the visual system. One of the important questions regarding visual hierarchical structures is to identify computational principles for assigning functions that represent the external world to hierarchical structures of the visual system. Given that visual hierarchical structures contain both bottom-up and top-down pathways, the derived principles should encompass these bidirectional pathways. However, existing principles such as predictive coding do not provide an effective principle for bidirectional pathways. Therefore, we propose a novel computational principle for visual hierarchical structures as spatio-temporally efficient coding underscored by the efficient use of given resources in both neural activity space and processing time. This coding principle optimises bidirectional information transmissions over hierarchical structures by simultaneously minimising temporal differences in neural responses and maximising entropy in neural representations. Simulations demonstrated that the proposed spatio-temporally efficient coding was able to assign the function of appropriate neural representations of natural visual scenes to visual hierarchical structures. Furthermore, spatio-temporally efficient coding was able to predict well-known phenomena, including deviations in neural responses to unlearned inputs and bias in preferred orientations. Our proposed spatio-temporally efficient coding may facilitate deeper mechanistic understanding of the computational processes of hierarchical brain structures.
In silico design of bioactive chimeric peptide from archaeal antimicrobial peptides
Authors: Banerjee Souvik , Chakraborty Soham , Majumder Kaustav 
Published: August 2021

AbstractNovel peptide therapeutics have been the cardinal part of modern-day research. Such therapies are being incorporated to prevent the adverse effects of globally emerging multi-drug resistant bacteria and various chronic human diseases which pose a great risk to the present world. In this study, we have designed a novel peptide therapy involving archaeal antimicrobial peptides. In silico predictions assign the peptide construct to be antigenic, non-allergenic, non-toxic and having stable physicochemical properties. The secondary and tertiary structures of the construct were predicted. The tertiary structure was refined for improving the quality of the predicted model. Computational tools predicted intracellular receptors in Escherichia coli, Klebsiella pneumoniae and the human body to be possible binding targets of the construct. In silico docking of modelled peptide with predicted targets, showed prominent results against targets for complex human diseases and that of bacterial infections. The stability of those docked complexes was confirmed with computational studies of conformational dynamics. Certainly, the designed peptide could be a potent therapeutic against multi-drug resistant bacteria as well as several human diseases.
Cutting epitopes to survive: the case of lambda variant
Authors: Pascarella Stefano , Ciccozzi Massimo , Bianchi Martina , Benvenuto Domenico , Cauda Roberto , Cassone Antonio 
Published: August 2021

AbstractThis manuscript concisely reports an in-silico study on the potential impact of the Spike protein mutations on immuno-escape ability of SARS-CoV-2 lambda variant. Biophysical and bioinformatics data suggest that a combination of shortening immunogenic epitope loops and generation of potential N-glycosylation sites may be a viable adaptation strategy potentially allowing this emerging viral variant escaping host immunity.
Gender Distribution of Organizing Committees and Invited Speakers at the International Conferences on Emergency Medicine
Authors: Galletta Gayle , Subhan Imron , Marathe Priyadarshini 
Published: August 2021

AbstractBackgroundIt has been documented that women are under-represented as speakers at emergency medicine conferences globally. This lack of opportunity is likely contributing to the gender gap of women in academic and leadership positions.MethodsThe Gender-Specific Issues Special Interest Group (GSI-SIG) of the International Federation of Emergency Medicine (IFEM) has analyzed the gender distribution of invited speakers, plenary speakers, and organizing committees from its last three International Conferences on Emergency Medicine in 2016, 2018, and 2019.ResultsMen comprised 75% (range 57-92%) of organizing committees, 69% (67-70%) of plenary speakers, and 78% (range 75-81%) of invited speakers.ConclusionThe percentage of women speakers at IFEM’s International Conferences on Emergency Medicine is low; even below the percentage of women emergency medicine physicians. By understanding these data and their consequences, changes can be made to close this gender gap and create more equitable opportunities for women and their career advancement.Strengths and Limitations of this studyThe gender breakdown of local organizing committee members and invited speakers at three consecutive International Conferences on Emergency Medicine heavily favoured men over women.Having women on the host country’s local organizing committee had no effect on the gender distribution of speakers.As these conferences draw speakers and participants from a diverse, international audience, the results are generalizable.The organizing committee and speakers’ backgrounds (MD, RN, paramedic) were not delineated, and may have skewed the results.Gender non-conforming individuals were not identified.
Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR
Authors: Szeto Christopher , Nguyen Andrea T. , Lobos Christian A. , Chatzileontiadou Dimitra S.M. , Jaya-singhe Dhilshan , Grant Emma J. , Riboldi-Tunnicliffe Alan , Smith Corey , Gras Stephanie 
Published: August 2021

AbstractThe data currently available on how the immune system recognizes the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus, we are lacking data on how T cells are able to recognize this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.
Estimating tumor mutational burden from RNA-sequencing without a matched-normal sample
Authors: Katzir Rotem , Yizhak Keren 
Published: August 2021

AbstractDetection of somatic point mutations using patients sequencing data has many clinical applications, including the identification of cancer driver genes, detection of mutational signatures, and estimation of tumor mutational burden (TMB). In a recent work we developed a tool for detection of somatic mutations using tumor RNA and matched-normal DNA. Here, we further extend it to detect somatic mutations from RNA sequencing data without a matched-normal sample. This is accomplished via a machine learning approach that classifies mutations as either somatic or germline based on various features. When applied to RNA-sequencing of >450 melanoma samples high precision and recall are achieved, and both mutational signatures and driver genes are correctly identified. Finally, we show that RNA-based TMB is significantly associated with patient survival, with similar or superior performance to DNA-based TMB. Our pipeline can be utilized in many future applications, analyzing novel and existing datasets where only RNA is available.