bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplexviruses successfully adapt to their host by fine-tuning immune responses
Authors: Mozzi Alessandra , Cagliani Rachele , Pontremoli Chiara , Forni Diego , Saulle Irma , Saresella Marina , Pozzoli Uberto , Clerici Mario , Biasin Mara , Sironi Manuela 
Published: July 2020

AbstractPrimate herpes simplex viruses are relatively harmless to their natural hosts, whereas cross-species transmission can result in severe disease. We performed a genome-wide scan for signals of adaptation of simplexviruses to hominins. We found evidence of positive selection in three glycoproteins, with selected sites located in antigenic determinants. Positively selected non-core proteins were involved in different immune-escape mechanisms. By expressing mutants of one of these proteins (ICP47), we show that the amino acid status at the positively selected sites is sufficient to induce HLA-G. HSV-1/HSV-2 ICP47 induced HLA-G when mutated to recapitulate residues in B virus, whereas the mutated version of B virus ICP47 failed to determine HLA-G expression. Thus, the evolution of ICP47 in HSV-1/HSV-2 determined the loss of an immunosuppressive effect, suggesting that simplexviruses tune immune responses to promote successful co-existence with their hosts. These results also help explain the high pathogenicity of B virus in humans.
Determinants of SARS-CoV-2 infection in Italian healthcare workers: a multicenter study
Authors: Boffetta Paolo , Violante Francesco , Durando Paolo , Palma Giuseppe De , Pira Enrico , Vimercati Luigi , Cristaudo Alfonso , Icardi Giancarlo , Sala Emma , Coggiola Maurizio , Tafuri Silvio , Gattini Vittorio , Apostoli Pietro , Spatari Giovanna ,   Working Group on SARS-CoV-2 infection in Italian healthcare workers.
Published: July 2020

AbstractBackgroundHealthcare workers (HCW) are at increased risk of being infected with SARS-CoV-2, yet limited information is available on risk factors of infection.MethodsWe pooled data on occupational surveillance of 10,654 HCW who were tested for SARS-CoV-2 infection in six Italian centers. Information was available on demographics, job title, department of employment, source of exposure, use of personal protective equipment (PPE), and COVID-19-related symptoms. We fitted multivariable logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI).FindingsThe prevalence of infection varied across centers and ranged from 3.0% to 22.0%, being strongly correlated with that of the respective areas. Women were at lower risk of infection compared to men. Fever, cough, dyspnea and malaise were the symptoms most strongly associated with infection, together with anosmia and ageusia. No differences in the risk of infection were detected between job titles, or working in a COVID-19 designated department. Reported contact with a patient inside or outside the workplace was a risk factor. Use of a mask was strongly protective against risk of infection as was use of gloves. The use of a mask by the source of exposure (patient or colleague) had an independent effect in reducing infection risk.
Trans-ethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals shared but also ethnicity-specific disease associations
Authors: Degenhardt Frauke , Mayr Gabriele , Wendorff Mareike , Boucher Gabrielle , Ellinghaus Eva , Ellinghaus David , ElAbd Hesham , Rosati Elisa , Hübenthal Matthias , Juzenas Simonas , Abedian Shifteh , Vahedi Homayon , BK Thelma , Yang Suk-Kyun , Ye Byong Duk , Cheon Jae Hee , Datta Lisa Wu , Daryani Naser Ebrahim , Ellul Pierre , Esaki Motohiro , Fuyuno Yuta , McGovern Dermot PB , Haritunians Talin , Hong Myhunghee , Juyal Garima , Jung Eun Suk , Kubo Michiaki , Kugathasan Subra , Lenz Tobias L. , Leslie Stephen , Malekzadeh Reza , Midha Vandana , Motyer Allan , Ng Siew C , Okou David T , Raychaudhuri Soumya , Schembri John , Schreiber Stefan , Song Kyuyoung , Sood Ajit , Takahashi Atsushi , Torres Esther A , Umeno Junji , Alizadeh Behrooz Z. , Weersma Rinse K , Wong Sunny H , Yamazaki Keiko , Karlsen Tom H , Rioux John D , Brant Steven R ,   for the MAAIS Recruitment Center, Franke Andre ,   for the International IBD Genetics Consortium
Published: July 2020

ABSTRACTInflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD, and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such a delineation could not be made due to tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a trans-ethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9,272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40,691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analysed the physico-chemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we identified consistent associations across different ethnicities but also identified population-specific signals. We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids such. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.
Evidence favouring the efficacy of convalescent plasma for COVID-19 therapy
Authors: Joyner Michael J. , Klassen Stephen A. , Senefeld Jonathon W. , Johnson Patrick W. , Carter Rickey E. , Wiggins Chad C. , Shoham Shmuel , Grossman Brenda J. , Henderson Jeffrey P. , Musser James , Salazar Eric , Hartman William R. , Bouvier Nicole M. , Liu Sean T. H. , Pirofski Liise-anne , Baker Sarah E. , van Helmond Noud , Wright R. Scott , Fairweather DeLisa , Bruno Katelyn A. , Paneth Nigel S. , Casadevall Arturo 
Published: July 2020

AbstractTo determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from randomized clinical trials, matched control, case series, and case report studies. Fixed-effects analyses demonstrated that hospitalized COVID-19 patients transfused with convalescent plasma exhibited a ~57% reduction in mortality rate (10%) compared to matched-patients receiving standard treatments (22%; OR: 0.43,P< 0.001). These data provide evidence favouring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized COVID-19 patients.
Deep skin dysbiosis in vitiligo patients: link with mitochondrial and immune changes
Authors: Bzioueche Hanene , Simonyté Sjödin Kotryna , West Christina E , Khemis Abdallah , Rocchi Stéphane , Passeron Thierry , Tulic Meri K 
Published: July 2020

ABSTRACTRationaleVitiligo is an autoimmune-disease characterized by patchy, white skin due to melanocyte loss. Commensal cutaneous or gut dysbiosis have been linked to various dermatological disorders. Here, we studied skin and gut microbiota of vitiligo patients compared to healthy controls.MethodsWe recruited 20 subjects and obtained swabs and biopsies from lesional and non-lesional skin, stool and blood from each individual (total 100 samples).ResultsWe detected reduced richness and distribution of microbiota in stool of vitiligo subjects compared to controls (P<0.01). Skin swabs had greater alpha-diversity than skin biopsies (P<0.001), however only trends were seen between groups when examining microbiota at the skin surface. This was in contrast to sampling deeper layers of skin from the same patients which showed decreased richness and distribution of species (P<0.01) but greater phylogenetic diversity (P<0.01) in lesional compared to non-lesional sites. Biopsy microbiota from the lesional skin had distinct microbiota composition which was depleted of protective Bifidobacterium and enriched in Terenicutes, Streptococcus, Mycoplasma and mitochondrial DNA (P<0.001); the latter was linked with increased innate immunity and stress markers in the blood of the same patients (P<0.05).ConclusionThese data describe vitiligo-specific cutaneous and gut microbiota and, for the first time in humans, a link between mitochondrial alteration, innate immunity and skin microbiota.
Readmission Rates and Medication Selection for Patients with Heart Failure Preserved Ejection Fraction
Authors: Kramer Troy , Vogler Carrie , Robinson Robert , Bhattarai Mukul 
Published: July 2020

AbstractPurposeHeart failure with preserved ejection fraction (HFpEF) has less guideline driven treatment options due to a lack of trials demonstrating medications with improved clinical outcomes for this patient population. The primary objective of this study is to determine which medications and dosages are related to high readmission rates for HFpEF patients.MethodsA retrospective, single center, chart review was performed on patients with HFpEF at an academic medical center. Heart failure patients ages between 18-89 with an ejection fraction ≥45% from a transthoracic echocardiogram (TTE) were included. Primary outcomes include 30-day all cause readmission rates, prescribing patterns, and avoidance of potentially harmful medications. Descriptive statistics and multivariate logistic regression were used to assess potential risk factors.ResultsThis study analyzed 455 patient admissions. Univariate analysis shows patients who were not readmitted were more likely to be on furosemide (54% vs 42%; p = 0.019). Conversely, readmitted patients were more likely to be taking bumetanide (4% vs 1%; p = 0.039). Lisinopril was the only angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) associated with lower readmission rates (p = 0.036). Multivariate logistic regression showed bumetanide on admission (OR 14.6, p = 0.001), discharged on rosuvastatin (OR 6.29, p = 0.003) and meloxicam therapy (OR 6.33, p = 0.003) to be independent predictors of hospital readmission.ConclusionThree independent pharmacologic predictors for 30-day readmissions for patients with HFpEF were therapy with bumetanide, meloxicam, or rosuvastatin. Further research is needed to clarify the significance of these results.
Efficacy and safety of treating symptomatic, primary focal osteochondral lesions of the patella with a combination of intra-articular injection of hyaluronic acid (HAi) and radial extracorporeal shock wave therapy (rESWT) or HAi alone: a retrospective two-cohort study
Authors: Cao Jin , Huang Heqin , Zhang Changgui , Yang Liu , Schmitz Christoph , Duan Xiaojun 
Published: July 2020

ABSTRACTBackgroundThis study tested the hypothesis that a combination of intra-articular injection of hyaluronic acid (HAi) and radial extracorporeal shock wave therapy (rESWT) is more effective than HAi alone in the treatment of symptomatic, primary focal osteochondral lesions of the patella (sPFOLP).MethodsWe performed a retrospective analysis of n=81 subjects with unilateral sPFOLP who were treated with respectively HAi+rESWT (n=36) or HAi alone (n=45) at the outpatient department of our hospital between January 1st, 2014 and January 31th, 2018. Subjects in both cohorts also received education with special attention to reduction of going up and down the stairs, squatting and specific activities, as well as non-opioid analgesics if necessary. Efficacy was assessed using the pain visual analogue scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, which were examined at baseline (BL) and six weeks (W6), three months (M3) and six months (M6) after BL, as well as during a last follow-up examination (LE) which was performed at 37.6 ± 1.7 (mean ± standard error of the mean) months after BL (range, 12-59 months). In addition, measurements of the area of the patellar bone marrow edema (PBME) on sagittal, fat suppression sequence magnetic resonance imaging (MRI) scans of the knee were performed at BL, M3, M6 and LE.ResultsSubjects who were treated with HAi+rESWT showed significantly smaller mean VAS pain scores at W6, M3 and M6, significantly smaller mean WOMAC scores at W6, M3 and LE and significantly smaller mean PBME areas at M3, M6 and LE than subjects who were treated with HAi alone. No severe adverse events were observed.DiscussionThe results of this study suggest that HAi+rESWT is safe and more effective than HAi alone in the treatment of sPFOLP. This result should be verified in adequate randomized controlled trials.Level of evidenceLevel III; retrospective two-cohort study.
Performance of Abbott Architect, Ortho Vitros, and Euroimmun Assays in Detecting Prior SARS-CoV-2 Infection
Authors: Mahajan Shiwani , Redlich Carrie A. , Wisnewski Adam V. , Fazen Louis E. , Rao Lokinendi V. , Kuppusamy Karthik , Ko Albert I. , Krumholz Harlan M. 
Published: July 2020

ABSTRACTBackgroundSeveral serological assays have been developed to detect anti-SARS-CoV-2 IgG antibodies, but evidence about their comparative performance is limited. We sought to assess the sensitivity of four anti-SARS-CoV-2 IgG enzyme-linked immunosorbent assays (ELISA) in individuals with evidence of prior SARS-CoV-2 infection.MethodsWe obtained sera from 36 individuals with PCR-confirmed SARS-CoV-2 infection between March and May 2020. We evaluated samples collected at around 21 days (±14 days) after their initial PCR test using 3 commercially available ELISA assays, two anti-spike (Ortho- Clinical Diagnostics Vitros, and Euroimmun) and one anti-nucleocapsid (Abbott Architect), and a Yale-developed anti-spike ELISA test. We determined the sensitivity of the tests and compared their results. The Euroimmun and Yale ELISA had an equivocal and indeterminate category, which were considered as both negative and positive.ResultsAmong the 36 individuals with SARS-CoV-2 infection, mean age was 43 (±13) years and 19 (53%) were female. The sensitivities of the tests were not significantly different (Abbott Architect, Ortho Vitros, Euroimmmun, and Yale assays: 86% (95% confidence interval [CI], 71– 95), 94% (95% CI, 81–99), 86% (95% CI, 71–95), and 94% (95% CI, 81–99), respectively; p- value=0.464). The sensitivities of the Euroimmun and Yale ELISA tests increased when the equivocal/indeterminate results were considered positive (97% [95% CI, 85–100] and 100% [95% CI, 90–100], respectively), but were not significantly different from other tests (p=0.082). The cross-correlation coefficient ranged from 0.85–0.98 between three anti-spike protein assays (Ortho Vitros, Euroimmun, Yale) and was 0.58–0.71 between the three anti-spike protein assays and the anti-nucleocapsid assay (Abbott).ConclusionThe sensitivities of four anti-SARS-CoV-2 protein assays did not significantly differ, although the sample size was small. Sensitivity also depended on the interpretation of equivocal and indeterminate results. The strongest correlations were present for the three anti- spike proteins assays. These findings suggest that individual test characteristics and the correlation between different tests should be considered when comparing or aggregating data across different populations studies for serologic surveillance of past SARS-CoV-2 infection.
Eye-tracking for low vision with virtual reality (VR): testing status quo usability of the HTC Vive Pro Eye
Authors: Sipatchin Alexandra , Wahl Siegfried , Rifai Katharina 
Published: July 2020

AbstractBackgroundAdding an eye tracker inside a head-mounted display (HMD) can offer a variety of novel functions in virtual reality (VR). Promising results point towards its usability as a flexible and interactive tool for low vision assessments and research of low vision functional impairment. Visual field (VF) perimetry performed using VR methodologies evidenced a correlation between the reliability of visual field testing in VR and the Humphrey test. The simulation of visual loss in VR is a powerful method used to investigate the impact and the adaptation to visual diseases. The present study presents a preliminary assessment of the HTC Vive Pro Eye for its potential use for these applications.MethodsWe investigated data quality over a wide visual field and tested the effect of head motion. An objective direct end-to-end temporal precision test simulated two different scenarios: the appearance of a pupil inside the eye tracker and a shift in pupil position, known as artificial saccade generator. The technique is low-cost thanks to a Raspberry Pi system and automatic.ResultsThe target position on the screen and the head movement limit the HTC Vive Pro Eye’s usability. All the simulated scenarios showed a system’s latency of 58.1 milliseconds (ms).ConclusionThese results point towards limitations and improvements of the HTC Vive Pro Eye’s status quo for visual loss simulation scenarios and visual perimetry testing.
Estradiol Action at the Median Preoptic Nucleus is Necessary and Sufficient for Sleep Suppression in Female Rats
Authors: Smith Philip C. , Cusmano Danielle M. , Viechweg Shaun S. , Schwartz Michael D. , Mong Jessica A. 
Published: July 2020

AbstractTo further our understanding of how gonadal steroids impact sleep biology, we sought to address the mechanism by which proestrus levels of cycling ovarian steroids, particularly estradiol (E2), suppress sleep in female rats. We showed that steroid replacement of proestrus levels of E2 to ovariectomized female rats, suppressed sleep to similar levels as those reported by endogenous ovarian hormones. We further showed that this suppression is due to the high levels of E2 alone, and that progesterone did not have a significant impact on sleep behavior. We found that E2 action within the Median Preoptic Nucleus (MnPO), which contains estrogen receptors (ERs), is necessary for this effect; antagonism of ERs in the MnPO attenuated the E2-mediated suppression of both non-Rapid Eye Movement (NREM) and Rapid Eye Movement (REM) sleep. Finally, we found E2 action at the MnPO is also sufficient for sleep suppression, as direct infusion of E2 into the MnPO suppressed sleep. Based on our findings, we predict proestrus levels of E2 alone, acting at the MnPO, mediate sex-hormone driven suppression of sleep in female rats.Competing Interest StatementMDS is now an employee of Jazz Pharmaceuticals; the views expressed in this manuscript are solely the authors’ and do not reflect the views, policies or procedures of Jazz Pharmaceuticals.
Glycosylation of bioactive C13-apocarotenols inNicotiana benthamianaandMentha × piperita
Authors: Sun Guangxin , Putkaradze Natalia , Bohnacker Sina , Jonczyk Rafal , Fida Tarik , Hoffmann Thomas , Bernhardt Rita , Härtl Katja , Schwab Wilfried 
Published: July 2020

SummaryC13-apocarotenoids (norisoprenoids) are carotenoid-derived oxidation products, which perform important physiological functions in plants. Although their biosynthetic pathways have been extensively studied, their metabolism including glycosylation remains elusive. Candidate uridine-diphosphate glycosyltransferase genes (UGTs) were selected for their high transcript abundance in comparison with otherUGTsin vegetative tissues ofNicotiana benthamianaandMentha × piperita, as these tissues are rich sources of apocarotenoid glucosides. Hydroxylated C13-apocarotenol substrates were produced by P450-catalyzed biotransformation and microbial/plant enzyme systems were established for the synthesis of glycosides. Natural substrates were identified by physiological aglycone libraries prepared from isolated plant glycosides. In total, we identified six UGTs that catalyze the unprecedented glucosylation of C13-apocarotenols, where glucose is bound either to the cyclohexene ring or butane side chain. MpUGT86C10 is a superior novel enzyme that catalyzes the glucosylation of allelopathic 3-hydroxy-α-damascone, 3-oxo-α-ionol, 3-oxo-7,8-dihydro-α-ionol (Blumenol C) and 3-hydroxy-7,8-dihydro-β-ionol, while a germination test demonstrated the higher phytotoxic potential of a norisoprenoid glucoside in comparison to its aglycone. Glycosylation of C13-apocarotenoids has several functions in plants, including increased allelopathic activity of the aglycone, facilitating exudation by roots and allowing symbiosis with arbuscular mycorrhizal fungi. The results enable in-depth analyses of the roles of glycosylated norisoprenoid allelochemicals, the physiological functions of apocarotenoids during arbuscular mycorrhizal colonization and the associated maintenance of carotenoid homeostasis.One-sentence summaryWe identified six transferases inNicotiana benthamianaandMentha x piperita, two rich sources of glycosylated apocarotenoids that catalyze the unprecedented glycosylation of a range of hydroxylated α- and β-ionone/ionol derivatives and were able to modify bioactivity by glucosylation.
Benchmarking full-length transcript single cell mRNA sequencing protocols
Authors: Probst Victoria , Pacheco Felix , Nielsen Finn Cilius , Bagger Frederik Otzen 
Published: July 2020

AbstractSingle cell mRNA sequencing technologies have transformed our understanding of cellular heterogeneity and identity. For sensitive discovery or clinical marker estimation where high transcript capture per cell is needed only plate-based techniques currently offer sufficient resolution. Here, we present a performance evaluation of three different plate-based scRNA-seq protocols. Our evaluation is aimed towards applications requiring high gene detection sensitivity, reproducibility between samples, and minimum hands-on time, as is required, for example, in clinical use. We included two commercial kits, NEBNext®Single Cell/ Low Input RNA Library Prep Kit (NEB®), SMART-seq®HT kit (Takara®), and the non-commercial protocol Genome & Transcriptome sequencing (G&T). G&T delivered the highest detection of genes per single cell, at the absolute lowest price. Takara®kit presented similar high gene detection per single cell, and high reproducibility between sample, but at the absolute highest price. NEB®delivered a lower detection of genes but remain an alternative to more expensive commercial kits.
The effect of grape juice dilution on oenological fermentation
Authors: Gardner Jennifer Margaret , Walker Michelle Elisabeth , Boss Paul Kenneth , Jiranek Vladimir 
Published: July 2020

AbstractThe impact of water addition to grape juice in winemaking, on both alcoholic and malolactic fermentation duration and outcome has been examined using commercial wine yeasts, Lalvin EC1118™ and Lalvin R2™ and malolactic bacteria Lalvin VP41™. As expected, dilution with water did not impede fermentation, instead resulted in shortened duration, or in the case of malolactic fermentation enabled completion in these conditions. Addition of complex organic nutrient further shortened alcoholic fermentation by Lalvin R2™ and in some conditions also reduced the duration of malolactic fermentation. In general, volatile compounds and some major yeast metabolites were present at lower concentrations at the end of fermentation where juices were diluted and the addition of organic complex nutrient also influenced the concentration of some compounds in wine. These findings are significant to commercial winemaking, highlighting that winemakers should consider potential impacts of juice dilution on processing efficiencies along with wine flavour and aroma.Highlights: Gardner et al. The effect of grape juice dilution on fermentationGrape juice dilution shortened both alcoholic and malolactic fermentationIn some conditions addition of commercial nutrient decreased fermentation durationIn general wine volatiles decrease with grape juice dilutionIsoamyl acetate can be decreased in wine by grape juice dilution