bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-House Viral Transport Medium (VTM) Manufacture in the Time of Shortage, Supply and Crisis of COVID-19 at Veteran Affairs Medical Center (VAMC)
Authors: Petersen J M , Dalal S , Jhala D 
Published: October 2020

Abstract

Introduction/Objective
With the outbreak of COVID-19 caused by SARS-CoV-2, there have been challenges in the maintenance of adequate supplies both in terms of PPE and for testing. The shortage of commercial VTM for the transport of specimens for PCR testing has created a situation in which laboratories would need to manufacture their own in-house VTM as commonly used commercial VTM is unavailable. However, there is sparse literature on the emergency manufacture of VTM. Here, we describe the VAMC experience in manufacturing/quality control on its own VTM.

Results
VTM was manufactured by pathology and laboratory medicine using strict aseptic technique with Hanks Balanced Salt Solution (HBSS) 500 ml bottle with phenol red, sterile heat-inactivated fetal bovine serum (FBS) gentamicin sulfate (50 mg/mL) and amphotericin B (250 ug/ml). First, 50 ml of amphotericin B and 50 ml of gentamicin sulfate were mixed. Then 10 ml of FBS was mixed with the HBSS bottle and then 2 ml of the gentamicin/amphotericin B mixture was also mixed into the HBSS bottle. 3 ml aliquots were made from this mixture to constitute individual tubes of VTM for clinical use. Sterility for each batch (after 24-hour incubation at 37o C in the CO2 incubator) was assessed visually and by culture on a blood agar, chocolate agar, and thioglycolate mediums. An efficacy check was performed for each batch by spiking positive and negative controls into the VTM aliquots; RT-PCR for SARS-CoV-2 was executed to verify the medium did not degrade viral RNA and produced expected results for room temperature, refrigerated, and frozen samples. Previously manufactured VTM without phenol red also underwent sterility and efficacy checks.

Results
VTM was successfully manufactured in-house, allowing testing to continue despite the shortage. Sterility and efficacy checks on all lots and bottles from which the VTM aliquots were made passed with no growth detected and efficacy passing with all expected positives and negatives resulting as expected.

Conclusion
To the author’s knowledge, this represents the first published abstract on VTM manufacture in this most unprecedented crisis involving COVID-19. In this national emergency with corresponding shortage of testing supplies including commercial VTM, the in-house manufacture of VTM is both feasible and prudent to ensure continuity of testing and quality patient/laboratory care.
Do Deeper Levels of Cervical Biopsies Preceded by a Pap Smear Diagnosis of LSIL, ASCUS, or NILM/HPV+ Increase the Yield of Identifying Clinically Significant Lesions?
Authors: Manjee K G , Watkin W G 
Published: October 2020

Abstract

Introduction/Objective
Cervical biopsy is performed following an abnormal pap smear or positive HPV testing in an attempt to uncover clinically significant lesions [HSIL/invasive carcinoma (HSIL+)]. An excisional procedure is considered if biopsy confirms HSIL+. When preceded by pap smear of LSIL, ASCUS, NILM/HPV+ or persistent HPV, continued surveillance is recommended for biopsies showing no SIL or LSIL. In our laboratory, cervical biopsies are routinely sectioned at 3 levels. Deeper levels are often ordered when initial sections are non-diagnostic. p16 immunohistochemistry, with or without deeper levels, is often ordered to confirm HSIL, or to differentiate HSIL from mimics. In this study, we examine whether and in what clinical situations does obtaining additional levels uncover clinically significant lesions.

Methods
430 cervical biopsies between January-May 2018, with recent cytology of LSIL, ASCUS or NILM/HPV+ were identified in the pathology database. HPV status (if known), final biopsy diagnosis and past history of LSIL/HSIL were recorded. For each biopsy, orders for additional levels and/or p16 immunohistochemistry were recorded resulting in 4 categories: C1-no additional levels or p16, C2-deeper only, C3-deeper+p16 and C4-p16 only. Final diagnoses were divided into HSIL+, LSIL and no SIL.

Results
There was no significant difference in prior history of LSIL/HSIL and HPV status between all categories. Biopsy results were as follows:
HSIL+: 11/222 (5%) C1; 1/78 (1%) C2; 7/43 (16%) C3; 15/87 (17%) C4
LSIL: 91/222 (41%) C1; 7/78 (9%) C2; 16/43 (37%) C3; 35/87 (40%) C4
No SIL: 120/222 (54%) C1; 70/78 (90%) C2; 20/43 (46%) C3; 37/87 (42%) C4
The average number of additional levels in C2 and C3 was 3.8 and 1.8, respectively.

Conclusion
Deeper levels alone did not enhance the detection of HSIL+. Almost all LSIL/HSIL were detected when initial levels were diagnostic or suspicious and supported by p16 immunohistochemistry. 3 levels are adequate to detect clinically significant lesions.
Sero-Epidemiology And Pattern Of Transfusion-Transmissible Infectious Diseases Among Family Replacement And Voluntary Blood Donors In Lagos University Teaching Hospital (2018-2019), South-West Nigeria
Authors: Otokiti O E 
Published: October 2020

Abstract

Introduction/Objective
Despite innovations and giant strides achieved in medicine, blood transfusion has continually remained an integral aspect of patient care and management. Currently, blood and blood products are part of the World Health Organisation (WHO) model list of Essential Medicine (EML). However, despite being a ‘life saver’, potential risks of transfusion of fatal infections (TTI) are associated with its use, hence this study to evaluate the trend of TTI in blood donors.

Methods
In this study, 21,464 donors were screened for HIV, HBV, HCV and Syphilis between 2018 and 2019 via 4 th generation ELISA. Retrospective data was gotten from records. The results were read using a spectrophotometer.
Optical Density was calculated for positive and negative controls and only results from runs in which controls had passed were used and released.

Results
Of the 21,464donors tested, 3818 (17%) were voluntary blood donors (VBD) and 17,646 (83%) were family replacement donors (FRP). Total number of TTI was 1928 (0.1%) of units donated. Of the screened units positive for TTI, HBV accounted for the highest prevalence 1031 (54%), HCV 498 (26%), HIV 246 (13%) and Syphilis 147 (8%). A much higher incidence of TTI sero-positivity was observed in FRP (85%) as compared with voluntary blood donors (15%). Cumulative discard rate from TTI was approximately 0.1%.

Conclusion
Our results in this study showed that FRP are more likely to transmit TTI than VBD. Blood transfusion services should work more on replacing family replacement donors with voluntary donors. This can be achieved by reinforcing the culture of voluntary blood donation through the media, secondary and higher institutions as well as through advocacy. Indeed the WHO recommends 100% voluntary blood donations for all nations.
A Structured Approach to Evaluating Life-Course Hypotheses: Moving Beyond Analyses of Exposed Versus Unexposed in the -Omics Context
Authors: Zhu Yiwen , Simpkin Andrew J , Suderman Matthew J , Lussier Alexandre A , Walton Esther , Dunn Erin C , Smith Andrew D A C 
Published: October 2020

AbstractThe structured life-course modeling approach (SLCMA) is a theory-driven analytical method that empirically compares multiple prespecified life-course hypotheses characterizing time-dependent exposure-outcome relationships to determine which theory best fits the observed data. In this study, we performed simulations and empirical analyses to evaluate the performance of the SLCMA when applied to genomewide DNA methylation (DNAm). Using simulations (n = 700), we compared 5 statistical inference tests used with SLCMA, assessing the familywise error rate, statistical power, and confidence interval coverage to determine whether inference based on these tests was valid in the presence of substantial multiple testing and small effects—2 hallmark challenges of inference from -omics data. In the empirical analyses (n = 703), we evaluated the time-dependent relationship between childhood abuse and genomewide DNAm. In simulations, selective inference and the max-|t|-test performed best: Both controlled the familywise error rate and yielded moderate statistical power. Empirical analyses using SLCMA revealed time-dependent effects of childhood abuse on DNAm. Our findings show that SLCMA, applied and interpreted appropriately, can be used in high-throughput settings to examine time-dependent effects underlying exposure-outcome relationships over the life course. We provide recommendations for applying the SLCMA in -omics settings and encourage researchers to move beyond analyses of exposed versus unexposed individuals.
Highly accurate diagnosis of papillary thyroid carcinomas based on personalized pathways coupled with machine learning
Authors: Park Kyoung Sik , Kim Seong Hoon , Oh Jung Hun , Kim Sung Young 
Published: October 2020

AbstractThyroid nodules are neoplasms commonly found among adults, with papillary thyroid carcinoma (PTC) being the most prevalent malignancy. However, current diagnostic methods often subject patients to unnecessary surgical burden. In this study, we developed and validated an automated, highly accurate multi-study-derived diagnostic model for PTCs using personalized biological pathways coupled with a sophisticated machine learning algorithm. Surprisingly, the algorithm achieved near-perfect performance in discriminating PTCs from non-tumoral thyroid samples with an overall cross-study-validated area under the receiver operating characteristic curve (AUROC) of 0.999 (95% confidence interval [CI]: 0.995–1) and a Brier score of 0.013 on three independent development cohorts. In addition, the algorithm showed excellent generalizability and transferability on two large-scale external blind PTC cohorts consisting of The Cancer Genome Atlas (TCGA), which is the largest genomic PTC cohort studied to date, and the post-Chernobyl cohort, which includes PTCs reported after exposure to radiation from the Chernobyl accident. When applied to the TCGA cohort, the model yielded an AUROC of 0.969 (95% CI: 0.950–0.987) and a Brier score of 0.109. On the post-Chernobyl cohort, it yielded an AUROC of 0.962 (95% CI: 0.918–1) and a Brier score of 0.073. This algorithm also is robust against other various types of clinical scenarios, discriminating malignant from benign lesions as well as clinically aggressive thyroid cancer with poor prognosis from indolent ones. Furthermore, we discovered novel pathway alterations and prognostic signatures for PTC, which can provide directions for follow-up studies.
Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach
Authors: Alam Aftab , Khan Arbaaz , Imam Nikhat , Siddiqui Mohd Faizan , Waseem Mohd , Malik Md Zubbair , Ishrat Romana 
Published: October 2020

Abstract
The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80\hbox{--} 90\%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.
CATH functional families predict functional sites in proteins
Authors: Das Sayoni , Scholes Harry M , Sen Neeladri , Orengo Christine 
Published: October 2020

Abstract

Motivation
Identification of functional sites in proteins is essential for functional characterization, variant interpretation and drug design. Several methods are available for predicting either a generic functional site, or specific types of functional site. Here, we present FunSite, a machine learning predictor that identifies catalytic, ligand-binding and protein–protein interaction functional sites using features derived from protein sequence and structure, and evolutionary data from CATH functional families (FunFams).

Results
FunSite’s prediction performance was rigorously benchmarked using cross-validation and a holdout dataset. FunSite outperformed other publicly available functional site prediction methods. We show that conserved residues in FunFams are enriched in functional sites. We found FunSite’s performance depends greatly on the quality of functional site annotations and the information content of FunFams in the training data. Finally, we analyze which structural and evolutionary features are most predictive for functional sites.

Availabilityand implementation
https://github.com/UCL/cath-funsite-predictor.

Supplementary information
Supplementary data are available at Bioinformatics online.
PathExt: a general framework for path-based mining of omics-integrated biological networks
Authors: Sambaturu Narmada , Pusadkar Vaidehi , Hannenhalli Sridhar , Chandra Nagasuma 
Published: October 2020

Abstract

Motivation
Transcriptomes are routinely used to prioritize genes underlying specific phenotypes. Current approaches largely focus on differentially expressed genes (DEGs), despite the recognition that phenotypes emerge via a network of interactions between genes and proteins, many of which may not be differentially expressed. Furthermore, many practical applications lack sufficient samples or an appropriate control to robustly identify statistically significant DEGs.

Results
We provide a computational tool—PathExt, which, in contrast to differential genes, identifies differentially active paths when a control is available, and most active paths otherwise, in an omics-integrated biological network. The sub-network comprising such paths, referred to as the TopNet, captures the most relevant genes and processes underlying the specific biological context. The TopNet forms a well-connected graph, reflecting the tight orchestration in biological systems. Two key advantages of PathExt are (i) it can extract characteristic genes and pathways even when only a single sample is available, and (ii) it can be used to study a system even in the absence of an appropriate control. We demonstrate the utility of PathExt via two diverse sets of case studies, to characterize (i) Mycobacterium tuberculosis response upon exposure to 18 antibacterial drugs where only one transcriptomic sample is available for each exposure; and (ii) tissue-relevant genes and processes using transcriptomic data for 39 human tissues. Overall, PathExt is a general tool for prioritizing context-relevant genes in any omics-integrated biological network for any condition(s) of interest, even with a single sample or in the absence of appropriate controls.

Availabilityand implementation
The source code for PathExt is available at https://github.com/NarmadaSambaturu/PathExt.

Supplementary information
Supplementary data are available at Bioinformatics online.
RNANet: an automatically built dual-source dataset integrating homologous sequences and RNA structures
Authors: Becquey Louis , Angel Eric , Tahi Fariza 
Published: October 2020

Abstract

Motivation
Applied research in machine learning progresses faster when a clean dataset is available and ready to use. Several datasets have been proposed and released over the years for specific tasks such as image classification, speech-recognition and more recently for protein structure prediction. However, for the fundamental problem of RNA structure prediction, information is spread between several databases depending on the level we are interested in: sequence, secondary structure, 3D structure or interactions with other macromolecules. In order to speed-up advances in machine-learning based approaches for RNA secondary and/or 3D structure prediction, a dataset integrating all this information is required, to avoid spending time on data gathering and cleaning.

Results
Here, we propose the first attempt of a standardized and automatically generated dataset dedicated to RNA combining together: RNA sequences, homology information (under the form of position-specific scoring matrices) and information derived by annotation of available 3D structures (including secondary structure, canonical and non-canonical interactions and backbone torsion angles). The data are retrieved from public databases PDB, Rfam and SILVA. The paper describes the procedure to build such dataset and the RNA structure descriptors we provide. Some statistical descriptions of the resulting dataset are also provided.

Availability and implementation
The dataset is updated every month and available online (in flat-text file format) on the EvryRNA software platform (https://evryrna.ibisc.univ-evry.fr/evryrna/rnanet). An efficient parallel pipeline to build the dataset is also provided for easy reproduction or modification.

Supplementary information
Supplementary data are available at Bioinformatics online.
Glans inflation morphology and female cloaca copulatory interactions of the male American alligator phallus†
Authors: Moore Brandon C , Brennan Patricia L R , Francis Rachel , Penland Samuel , Shiavone Kelsie , Wayne Kathryn , Woodward Allan R , Does Mark D , Kim Dong Kyu , Kelly Diane A 
Published: October 2020

AbstractThe phallic glans of the American alligator (Alligator mississippiensis) is the distal termination of the semen-conducting sulcus spermaticus and during copulation has the closest, most intimate mechanical interactions with the female urodeum, the middle cloacal chamber that contains the opening to the vaginal passages and oviducts. However, the details of this interface leading to insemination and gamete uptake are unclear. Here, we: (1) histologically characterize the underlying tissue types and morphologically quantify the shape changes associated with glans inflation into the copulatory conformation, (2) digitally reconstruct from MRI the 3D shape of functional tissue compartments, and (3) diffusible iodine-based contrast-enhanced computed tomography image the copulatory fit between male phallus and female cloaca. We discuss these results in relation to tissue type material properties, the transfer on intromittent forces, establishing potential copulatory lock, inflated glans volume scaling with body mass/length, the mechanics of semen targeting and insemination, and potential female cryptic choice impacting multiple clutch paternity. In part, this study further clarifies the phallic morphological variation observed among crocodylians and begins to investigate the role(s) these divergent male forms play during copulation interacting with female cloacal forms to increase reproductive success.
Mesenchymal stromal cell-derived extracellular vesicle therapy prevents preeclamptic physiology through intrauterine immunomodulation†
Authors: Taglauer Elizabeth S , Fernandez-Gonzalez Angeles , Willis Gareth R , Reis Monica , Yeung Vincent , Liu Xianlan , Mitsialis S Alex , Kourembanas Stella 
Published: October 2020

AbstractHuman umbilical cord-derived mesenchymal stromal cells (MSCs) are a widely recognized treatment modality for a variety of preclinical disease models and have been transitioned to human clinical trials. We have previously shown in neonatal lung disease that the therapeutic capacity of MSCs is conferred by their secreted extracellular vesicles (MEx), which function primarily through immunomodulation. We hypothesize that MEx have significant therapeutic potential pertinent to immune-mediated gestational diseases. Of particular interest is early-onset preeclampsia, which can be caused by alterations of the maternal intrauterine immune environment. Using a heme-oxygenase-1 null mouse model of pregnancy loss with preeclampsia-like features, we examined the preventative effects of maternal MEx treatment early in pregnancy. Heme oxygenase-1 null females (Hmox1−/−) or wild-type control females were bred in homozygous matings followed by evaluation of maternal and fetal parameters. A single dose of MEx was administered intravenously on gestational day (GD)1 to Hmox1−/− females (Hmox1−/− MEx). Compared with untreated Hmox1−/− females, Hmox1−/− MEx-treated pregnancies showed significant improvement in fetal loss, intrauterine growth restriction, placental spiral artery modification, and maternal preeclamptic stigmata. Biodistribution studies demonstrated that MEx localize to a subset of cells in the preimplantation uterus. Further, mass cytometric (CyTOF) evaluation of utero-placental leukocytes in Hmox1−/− MEx versus untreated pregnancies showed alteration in the abundance, surface marker repertoire, and cytokine profiles of multiple immune populations. Our data demonstrate the therapeutic potential of MEx to optimize the intrauterine immune environment and prevent maternal and fetal sequelae of preeclamptic disease.
Bio-equivalence tests in functional data by maximum deviation
Authors: Dette Holger , Kokot Kevin 
Published: October 2020

Summary
We study the problem of testing equivalence of functional parameters, such as the mean or the variance function, in the two-sample functional data setting. In contrast to previous work where the functional problem is reduced to a multiple testing problem for the equivalence of scalar data by comparing the functions at each point, our approach is based on an estimate of a distance measuring the maximum deviation between the two functional parameters. Equivalence is claimed if the estimate for the maximum deviation does not exceed a given threshold. We propose a bootstrap procedure for obtaining quantiles of the distribution of the test statistic, and we prove consistency of the corresponding test in the large-sample scenario. As the methods proposed here avoid the use of the intersection-union principle, they are less conservative and more powerful than currently available approaches.