bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small Fiber Polyneuropathy Is Associated With Non–Bladder-Centric Interstitial Cystitis/Bladder Pain Syndrome Patients
Authors: Overholt Tyler L. , Matthews Catherine A. , Evans Robert J. , Badlani Gopal , Ahn Christine , Simon Trang , Walker Stephen J. 
Published: October 2020

Objectives
Interstitial cystitis/bladder pain syndrome (IC/BPS) comprises at least 2 phenotypes. Bladder centric patients typically demonstrate low bladder capacity (BC), often with Hunner lesion (HL), whereas non–bladder-centric patients typically have normal cystoscopic findings and more co-occurring nonurologic symptoms/syndromes (NUS), contributing to widespread pain beyond the bladder. Small fiber polyneuropathy (SFPN) is significantly associated with fibromyalgia, a frequent IC/BPS codiagnosis and may play an etiologic role in IC/BPS. We assessed SFPN status in bladder-centric versus non–bladder-centric IC/BPS patients.

Methods
Distal leg biopsies were obtained from 11 IC/BPS patients after therapeutic hydrodistention. Specimens were embedded/sectioned per standard protocol and stained for protein gene product 9.5, an intraepidermal nerve fiber marker. To determine SFPN status, intraepidermal nerve fiber density was calculated and compared with normative reference values stratified by age/sex. The SFPN prevalence and reported comorbidities were compared between low BC and/or HL-positive (bladder-centric) versus non–low BC, HL (non–bladder-centric) patients.

Results
Seven patients (63.6%) were SFPN positive. Non–bladder-centric patients demonstrated significantly more SFPN (6/7, 85.7%) compared with bladder-centric patients (1/4, 25.0%; P = 0.027). Non–bladder-centric patients also reported more comorbid NUS overall (1.25 ± 0.83 vs 5.86 ± 2.47; P = 0.003), including fibromyalgia (P = 0.010), migraines (P = 0.035), anxiety/panic disorder (P = 0.035), allergies (P = 0.027), and asthma (P = 0.035).

Conclusions
In this pilot study, SFPN was significantly more common in non–bladder-centric IC/BPS, that is, those patients who also reported greater prevalence of NUS, including fibromyalgia, migraines, anxiety/panic disorders, allergies, and asthma. These findings suggest that SFPN may have an etiologic role in a larger, systemic pain syndrome and should be explored further.
Engineered phage endolysin eliminates Gardnerella in bacterial vaginosis without damaging the healthy vaginal microbiome
Authors: Landlinger Christine , Tisakova Lenka , Oberbauer Vera , Schwebs Timo , Latka Agnieszka , Van Simaey Leen , Vaneechoutte Mario , Guschin Alexander , Swidsinski Sonja , Swidsinski Alexander , Corsini Lorenzo 
Published: October 2020

BackgroundBacterial vaginosis is characterized by an imbalance of the vaginal microbiome in which the normally predominant lactobacilli are replaced by other bacterial species. Initiated by strains of the bacterium Gardnerella, a characteristic biofilm forms on the vaginal epithelium, explaining the typical presence of clue cells. This biofilm contributes to the resilience of the bacteria to antibiotic treatment, which may explain the frequent recurrence of BV.ObjectiveIn this study, we investigate whether a therapy based on bacteriophage endolysins which specifically lyse Gardnerella, in particular the drug candidate PM-477, might be a promising alternative to broad-spectrum antibiotics and antiseptics.Study designTo identify Gardnerella specific endolysins, we searched for endolysin-encoding sequences in regions of Gardnerella genomes that are of prophage origin. This search identified fourteen homologous genes predicted to encode 1,4-beta-N-acetylmuramidase-type endolysins. When expressed in Escherichia coli and purified, the recombinant proteins demonstrated strong bactericidal activity against four different Gardnerella species. By shuffling the N-terminal catalytic domains and C-terminal cell wall-binding domains between the homologues, we produced 81 chimeric endolysins. These endolysins were tested for their activity and specificity in vitro and ex-vivo on vaginal samples from fifteen BV positive patients. Fluorescence in situ hybridization was used for visualization.ResultsSeveral engineered endolysins were 10-fold more active than the most active wild-type enzymes. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13–8 µg/ml. PM-477 had no effect on Lactobacillus strains or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested on vaginal samples from fifteen patients with either first time or recurring bacterial vaginosis. In fourteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome.ConclusionThe high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising drug candidate and an alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence.
Brain Network Connectivity in Adolescents At Risk for Alcohol Use Problems
Authors: Baker Simon T. E. , Yücel Murat , Fornito Alex , Zalesky Andrew , Whittle Sarah , Allen Nicholas B. , Lubman Dan I. 
Published: October 2020

AbstractImaging studies of young people with a family history of alcohol use disorder (AUD) have found structural and/or functional differences within and between anatomically distributed and functionally specialised systems throughout the brain. Differences in brain connectivity among adolescents with a family history of AUD may account for the increased risk of later alcohol use problems; however, to date, no prospective studies have directly examined this hypothesis across the entire connectome in a regionally unbiased way. Our analysis included 52 adolescents (Mage = 16.5 years ± 0.6 SD) assessed with diffusion-weighted magnetic resonance imaging, of whom 20 had a family history of AUD and 32 did not. All participants were followed-up 2.3 years later and completed a questionnaire measuring past year alcohol use and alcohol-related harms. Subject-specific connectomic maps of structural connectivity were constructed using two parcellation schemes (82-node anatomical and 530-node random) and five measures of connectivity weight (streamline count, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity), and a connectome-wide network-based statistic analysis was used to compare group differences at each and every connection between adolescents with and without a family history of AUD. Baseline connectivity measures did not differentiate these groups, and we did not find an association between baseline connectivity measures and alcohol outcomes at follow-up. These findings suggest that atypical inter-regional structural connectivity may not contribute to the risk of developing alcohol use problems in this particular age group, or during this particular period of development.
Analytical and clinical evaluation of four anti-SARS-CoV-2 serologic (IgM, IgG, and total) immunoassays
Authors: Higgins Victoria , Fabros Anselmo , Wang Xiao Yan , Bhandari Maria , Daghfal David J. , Kulasingam Vathany 
Published: October 2020

AbstractIntroductionCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is diagnosed by molecular-based detection of SARS-CoV-2 RNA. Serologic testing detects antibodies specific to SARS-CoV-2 and IgM specifically may serve as an adjunct test to PCR early in disease. We evaluated the Abbott anti-SARS-CoV-2 IgM and IgG assays along with DiaSorin anti-SARS-CoV-2 IgG and Roche anti-SARS-CoV-2 Total.MethodsSpecimens from 175 PCR-positive patients and 107 control specimens were analyzed using Abbott IgM and IgG, DiaSorin IgG, and Roche Total (IgA, IgG, IgM) assays. Sensitivity, specificity, cross-reactivity, concordance between assays, trends over time, positive predictive value (PPV), and negative predictive value (NPV) were determined.ResultsAbbott IgM sensitivity was 63.6% at 0 days post-PCR positivity, 76.5% at 1-5d, 76.3% at 6-14d, 85.2% at 15-30d, and 63.6% at >30d. All assays exhibited highest sensitivity 15-30d post-PCR positivity (83.3-85.2%). Combining Abbott IgM and IgG improved sensitivity by 22.7% compared to IgG alone when tested 0d post-PCR positivity. All assays had a specificity of 100% and only Abbott IgG exhibited cross-reactivity (anti-dsDNA). Cohen’s kappa varied between 0.86-0.93. Time to seroconversion from PCR positivity was lowest for Abbott IgM and highest for Abbott IgG. NPV was highest for Abbott IgM <14 days post-PCR positivity and Abbott IgG ≥14 days.ConclusionThe Abbott IgM assay exhibited the earliest response and greatest signal in most patients evaluated for serial sampling and had the highest NPV <14 days post-PCR positivity, suggesting its potential utility as an adjunct test to PCR early in disease course.
Standard Blood Laboratory as a Clinical Support Tool to Distinguish between SARS-CoV-2 Positive and Negative Patients
Authors: Thell Rainer , Zimmermann Jascha , Szell Marton , Tomez Sabine , Eisenburger Philip , Haugk Moritz , Kreil Anna , Spiel Alexander , Blaschke Amelie , Klicpera Anna , Janata Oskar , Krugluger Walter , Sebesta Christian , Herkner Harald , Laky Brenda 
Published: October 2020

ABSTRACTBackgroundCoronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is current pandemic disease. Acute polymerase-chain-reaction is the gold standard test for this disease, is not available everywhere. Standard blood laboratory parameters may have diagnostic potential.MethodsWe evaluated standard blood laboratory parameters of 655 COVID-19 patients suspected to be infected with SARS-CoV-2, who underwent PCR testing in one of five hospitals in Vienna, Austria. Additionally, clinical characteristics and 28-day outcome were obtained from medical records. We compared standard blood laboratory parameters, clinical characteristics, and outcomes between positive and negative PCR-tested patients and evaluated the ability of those parameters to distinguish between groups.ResultsOf the 590 study patients including 276 females and 314 males, aged between 20 and 100 years, 208 were tested positive by means of PCR. Patients with positive compared to negative PCR-tests had significantly lower levels of leukocytes, basophils, eosinophils, monocytes, and thrombocytes; while significantly higher levels were detected with hemoglobin, C-reactive-protein (CRP), neutrophil-to-lymphocyte ratio (NLR), activated-partial-thromboplastin-time (aPTT), creatine-kinase (CK), lactate-dehydrogenase (LDH), alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), and lipase. Our multivariate model correctly classified 83.9% of cases with a sensitivity of 78.4%, specificity of 87.3%, positive predictive value of 79.5%, and negative predictive value of 86.6%. Decreasing leucocytes and eosinophils and increasing hemoglobin and CRP were significantly associated with an increased likelihood of being COVID-19 positive tested.ConclusionsOur findings suggest that especially leucocytes, eosinophils, hemoglobin, and CRP are helpful to distinguish between COVID-19 positive and negative tested patients and that a certain blood pattern is able to predict PCR-results.SummaryDecreasing leucocytes and eosinophils and increasing hemoglobin and CRP were significantly associated with an increased likelihood of being COVID-19 positive tested. Each single parameter showed either a high sensitivity (leucocytes, eosinophils, CRP, monocytes, thrombocytes) or specificity (NLR, CK, ALT, lipase), or a sensitivity and specificity around 60% (Hb, LDH, AST).
Characteristics and outcomes of hospitalized adult COVID-19 patients in Georgia
Authors: Tsertsvadze Tengiz , Ezugbaia Marina , Endeladze Marina , Ratiani Levani , Javakhishvili Neli , Mumladze Lika , Khotchava Manana , Janashia Maiko , Zviadadze Diana , Gopodze Levan , Gokhelashvili Alex , Metchurchtlishvili Revaz , Abutidze Akaki , Chkhartishvili Nikoloz 
Published: October 2020

AbstractObjectiveDescribe presenting characteristics of hospitalized patients and explore factors associated with in-hospital mortality during the first wave of pandemic in Georgia.MethodsThis retrospective study included 582 adult patients admitted to 9 dedicated COVID-19 hospitals as of July 30, 2020 (72% of all hospitalizations). Data were abstracted from medical charts. Factors associated with mortality were evaluated in multivariable Poisson regression analysis.ResultsAmong 582 adults included in this analysis 14.9% were 65+ years old, 49.1% were women, 59.3% had uni- or bi-lateral lung involvement on chest computed tomography, 27.1% had any co-morbidity, 13.2% patients had lymphopenia, 4.1% had neutophilosis, 4.8% had low platelet count, 37.6% had d-dimer levels of >0.5 mcg/l. Overall mortality was 2.1% (12/582). After excluding mild infections, mortality among patients with moderate-to-critical disease was 3.0% (12/399), while among patients with severe-to-critical disease mortality was 12.7% (8/63). Baseline characteristics associated with increased risk of mortality in multivariate regression analysis included: age ≥65 years (RR: 10.38, 95% CI: 1.30-82.75), presence of any chronic co-morbidity (RR: 20.71, 95% CI: 1.58-270.99), lymphopenia (RR: 4.76, 95% CI: 1.52-14.93), neutrophilosis (RR: 7.22, 95% CI: 1.27-41.12), low platelet count (RR: 6.92, 95% CI: 1.18-40.54), elevated d-dimer (RR: 4.45, 95% CI: 1.48-13.35), elevated AST (RR: 6.33, 95% CI: 1.18-33.98).ConclusionIn-hospital mortality during the first wave of pandemic in Georgia was low. We identified several risk factors (older age, co-morbidities and laboratory abnormalities) associated with poor outcome that should provide guidance for planning health sector response as pandemic continues to evolve.
Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences
Authors: Ganel Liron , Chen Lei , Christ Ryan , Vangipurapu Jagadish , Young Erica , Das Indraniel , Kanchi Krishna , Larson David , Regier Allison , Abel Haley , Kang Chul Joo , Scott Alexandra , Havulinna Aki , Chiang Charleston W. K. , Service Susan , Freimer Nelson , Palotie Aarno , Ripatti Samuli , Kuusisto Johanna , Boehnke Michael , Laakso Markku , Locke Adam , Stitziel Nathan O. , Hall Ira M. 
Published: October 2020

AbstractMitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell type composition. Here, we studied MT-CN variation in blood-derived DNA from 19,184 Finnish individuals using a combination of genome (N = 4,163) and exome sequencing (N = 19,034) data as well as imputed genotypes (N = 17,718). We identified two loci significantly associated with MT-CN variation: a common variant at the MYB-HBS1L locus (P = 1.6×10−8), which has previously been associated with numerous hematological parameters; and a burden of rare variants in the TMBIM1 gene (P = 3.0×10−8), which has been reported to protect against non-alcoholic fatty liver disease. We also found that MT-CN is strongly associated with insulin levels (P = 2.0×10−21) and other metabolic syndrome (metS) related traits. Using a Mendelian randomization framework, we show evidence that MT-CN measured in blood is causally related to insulin levels. We then applied an MT-CN polygenic risk score (PRS) derived from Finnish data to the UK Biobank, where the association between the PRS and metS traits was replicated. Adjusting for cell counts largely eliminated these signals, suggesting that MT-CN affects metS via cell type composition. These results suggest that measurements of MT-CN in blood-derived DNA partially reflect differences in cell-type composition and that these differences are causally linked to insulin and related traits.
A Randomised, Double-Blind, Sham-Controlled Trial of Deep Brain Stimulation of the Bed Nucleus of the Stria Terminalis for Treatment-Resistant Obsessive-Compulsive Disorder
Authors: Mosley Philip E. , Windels François , Morris John , Coyne Terry , Marsh Rodney , Giorni Andrea , Mohan Adith , Sachdev Perminder , O’Leary Emily , Boschen Mark , Sah Pankaj , Silburn Peter A. 
Published: October 2020

1ABSTRACTDeep brain stimulation (DBS) is a promising treatment for severe, treatment-resistant obsessive-compulsive disorder (OCD). Here, nine participants (four females, mean age 47.9 ±10.7 years) were implanted with DBS electrodes bilaterally in the bed nucleus of the stria terminalis (BNST). Following a one-month postoperative recovery phase, participants entered a three-month randomised, double-blind, sham-controlled phase before a twelve-month period of open-label stimulation incorporating a course of cognitive behavioural therapy (CBT). The primary outcome measure was OCD symptoms as rated with the Yale-Brown Obsessive-Compulsive Scale (YBOCS). In the blinded phase, there was a significant benefit of active stimulation over sham (p = 0.025, mean difference 4.9 points). After the open phase, the mean reduction in YBOCS was 16.6 ±1.9 points (Χ2 (11) = 39.8, p = 3.8 × 10−5), with seven participants classified as responders. CBT resulted in an additive YBOCS reduction of 4.8 ±3.9 points (p = 0.011). There were two serious adverse events related to the DBS device, the most severe of which was an infection during the open phase necessitating device explantation. There were no psychiatric adverse events related to stimulation. An analysis of the structural connectivity of each participant’s individualised stimulation field isolated right-hemispheric fibres associated with YBOCS reduction. These included subcortical tracts incorporating the amygdala, hippocampus and stria terminalis, in addition to cortical regions in the ventrolateral and ventromedial prefrontal cortex, parahippocampal, parietal and extrastriate visual cortex. In conclusion, this study provides further evidence supporting the efficacy and tolerability of DBS for individuals with otherwise treatment-refractory OCD and identifies a connectivity fingerprint associated with clinical benefit.
Increasing SARS-CoV-2 RT-qPCR testing capacity by sample pooling
Authors: Alcoba-Florez Julia , Gil-Campesino Helena , de Artola Diego García-Martínez , Díez-Gil Oscar , Valenzuela-Fernández Agustín , González-Montelongo Rafaela , Ciuffreda Laura , Flores Carlos 
Published: October 2020

AbstractObjectivesLimited testing capacity has characterized the ongoing COVID-19 pandemic in Spain, hampering a timely control of outbreaks and the possibilities to reduce the escalation of community transmissions. Here we investigated the potential of using pooling of samples followed by one-step retrotranscription and quantitative PCR (RT-qPCR) to increase SARS-CoV-2 testing capacity.MethodsWe first evaluated different sample pooling (1:5, 1:10 and 1:15) prior to RNA extractions followed by standard RT-qPCR for SARS-CoV-2/COVID-19 diagnosis. The pool size achieving reproducible results in independent tests was then used for assessing nasopharyngeal samples in a tertiary hospital during August 2020.ResultsWe found that pool size of five samples achieved the highest sensitivity compared to pool sizes of 10 and 15, showing a mean (± SD) Ct shift of 3.5 ± 2.2 between the pooled test and positive samples in the pool. We then used a pool size of five to test a total of 895 pools (4,475 prospective samples) using two different RT-qPCR kits available at that time. The Real Accurate Quadruplex corona-plus PCR Kit (PathoFinder) reported the lowest mean Ct (± SD) shift (2.2 ± 2.4) among the pool and the individual samples. The strategy allows detecting individual samples in the positive pools with Cts in the range of 16.7-39.4.ConclusionsWe found that pools of five samples combined with RT-qPCR solutions helped to increase SARS-CoV-2 testing capacity with minimal loss of sensitivity compared to that resulting from testing the samples independently.
Burden and Predictors of Underweight among Preschool Orphan Children in Southern Ethiopia
Authors: Tesfaye Adane , Wete Andnet Tadesse , Negassa Belay , Chane Yawkal , Ejajo Tekle , Molla Abebaw , Mingude Alemu Basazin , Getacher Lemma 
Published: October 2020

ABSTRACTBackgroundUnderweight is one of the public health problems in Ethiopia. Underweight children had lower resistance to diseases, lower school performance, and poor quality of life. In Ethiopia, most of the available evidences are related to the general community children, which had different risks and severity level than orphan children. Even though under-five orphan children had a higher risk of underweight, they are the most neglected population. Therefore, the aim of the study to determine the burden and predictors of underweight among preschool orphan children in Dilla Town, Southern Ethiopia.MethodA community-based cross-sectional study was conducted among 367 orphans from December 5, 2017 to January 30, 2018. The survey data were entered into EPi-info version 3.5.4 software and exported to SPSS version 20 for analysis. The burden of underweight was assessed by calculating the percentages using ENA SMART software was used for anthropometric data management using WHO standard cutoff point below-2 S.D using z-scores. All variables with a p-value of < 0.25 during bivariate logistic regression analysis were entered into a multivariate analysis to identify predictors variables independently associated with underweight at a p-value of 0.05 with 95% CI.ResultsIn this study, the burden of underweight among orphan children was 27.4%. The main predictors of underweight were sex of child (AOR = 5.29, 95% CI (2.83-9.92)), type of first complementary food (AOR = 2.47; 95% CI (1.24-4.94)), household food security (AOR = 1.98; 95% CI (1.23-3.21)) and age of child (AOR = 7.19; 95% CI (3.81-13.60)).ConclusionUnderweight is a public health problem in the study area. Sex of a child, type of first complimentary food, household food security status, and child age were the predictors of underweight. Therefore, dietary appropriate intervention, nutrition education of mothers, and increase food security status of orphan children are highly recommended.