bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point-of-care molecular testing and antiviral treatment of influenza in residents of homeless shelters in Seattle, WA: study protocol for a stepped-wedge cluster-randomized controlled trial
Authors:   on behalf of Seattle Flu Study Investigators, Newman Kira L. , Rogers Julia H. , McCulloch Denise , Wilcox Naomi , Englund Janet A. , Boeckh Michael , Uyeki Timothy M. , Jackson Michael L. , Starita Lea , Hughes James P. , Chu Helen Y. 
Published: November 2020

Abstract
Introduction
Influenza is an important public health problem, but data on the impact of influenza among homeless shelter residents are limited. The primary aim of this study is to evaluate whether on-site testing and antiviral treatment of influenza in residents of homeless shelters reduces influenza spread in these settings.

Methods and analysis
This study is a stepped-wedge cluster-randomized trial of on-site testing and antiviral treatment for influenza in nine homeless shelter sites within the Seattle metropolitan area. Participants with acute respiratory illness (ARI), defined as two or more respiratory symptoms or new or worsening cough with onset in the prior 7 days, are eligible to enroll. Approximately 3200 individuals are estimated to participate from October to May across two influenza seasons. All sites will start enrollment in the control arm at the beginning of each season, with routine surveillance for ARI. Sites will be randomized at different timepoints to enter the intervention arm, with implementation of a test-and-treat strategy for individuals with two or fewer days of symptoms. Eligible individuals will be tested on-site with a point-of-care influenza test. If the influenza test is positive and symptom onset is within 48 h, participants will be administered antiviral treatment with baloxavir or oseltamivir depending upon age and comorbidities. Participants will complete a questionnaire on demographics and symptom duration and severity. The primary endpoint is the incidence of influenza in the intervention period compared to the control period, after adjusting for time trends.

Trial registration
ClinicalTrials.gov NCT04141917. Registered 28 October 2019. Trial sponsor: University of Washington.
Letter to the editor: Study Summary - Randomized Control Trial of Omega-3 Fatty Acid Supplementation for the Treatment of COVID-19 Related Olfactory Dysfunction
Authors: Lerner David , Garvey Katherine , Arrighi-Allisan Annie , Filimonov Andrey , Filip Peter , Liu Katherine , Ninan Sen , Schaberg Madeleine , Colley Patrick , Del Signore Anthony , Govindaraj Satish , Iloreta Alfred Marc 
Published: November 2020

Abstract
Objectives
To evaluate a therapeutic role for omega-3 fatty acid supplementation in the treatment of olfactory dysfunction associated with COVID-19 infection

Trial design
Randomized, double-blinded, placebo-controlled trial

Participants
Eligible patients are adults with self-reported new-onset olfactory dysfunction of any duration associated with laboratory-confirmed or clinically suspected COVID-19 patients. Exclusion criteria include patients with pre-existing olfactory dysfunction, history of chronic rhinosinusitis or history of sinus surgery, current use of nasal steroid sprays or omega-3 supplementation, fish allergy, or inability to provide informed consent for any reason. The trial is conducted at Mount Sinai Hospital

Intervention and comparator
The intervention group will receive 2000 mg daily of omega-3 supplementation in the form of two “Fish Oil, Ultra Omega-3” capsules (product of Pharmavite®) daily. The comparator group will take 2 placebo capsules of identical size, shape, and odor daily for 6 weeks.

Main outcomes
Each subject will take a Brief Smell Identification Test at study enrolment and completion after 6 weeks. The primary outcome will be change in Brief Smell Identification Test over the 6-week period.

Randomisation
Patients will be randomized by the Investigational Drug Pharmacy at the Icahn School of Medicine at Sinai via a computer-generated sequence in a 1:1 allocation to treatment or control arms.

Blinding (masking)
Both participants and researchers will be blinded.

Numbers to be randomised (sample size)
There will be 88 participants randomized to each group. A total of 176 participants will be randomized.

Trial Status
Protocol Version 1, 8/3/2020
Recruitment is ongoing, started 8/5/2020 with estimated completion 11/30/2020.

Trial registration
The trial is registered on ClinicalTrials.gov with Protocol Identifier: NCT04495816.
Trial registration: ClinicalTrials.gov, NCT04495816. Registered 3 August 2020

Full protocol
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).
First report on the phylogenetic relationship, genetic variation of Echinococcus shiquicus isolates in Tibet Autonomous Region, China
Authors: Zhu Guo-Qiang , Yan Hong-Bin , Li Li , Ohiolei John Asekhaen , Wu Yan-Tao , Li Wen-Hui , Zhang Nian-Zhang , Fu Bao-Quan , Jia Wan-Zhong 
Published: November 2020

Abstract
Background
Cystic or alveolar echinococcosis caused by the larval stages of Echinococcus spp. is a very severe zoonotic helminth infection. Echinococcus shiquicus is a newly discovered species that has only been reported in the Qinghai and Sichuan provinces of the Qinghai-Tibet plateau, China where, to date, it has only been confirmed in Tibetan foxes and wild small mammal populations of the Tibetan plateau. Information on its genetic and evolutionary diversity is scanty. The aim of this study was to investigate the prevalence of E. shiquicus in plateau pikas (Ochotona curzoniae), a known intermediate host, and to determine the genetic variation and phylogenetic relationship of the E. shiquicus population in the Tibet region of China based on mitochondrial DNA.

Methods
Echinococcus shiquicus samples were collected from Damxung and Nyêmo counties (located in Tibet Autonomous Region, China). The mitochondrial cox1 and nad1 gene sequences were analyzed, and the genetic diversity and epidemiology of E. shiquicus in the region were discussed based on the results.

Results
The prevalence of E. shiquicus in pikas in Damxung and Nyêmo counties was 3.95% (6/152) and 6.98% (9/129), respectively. In combination with previous public sequence data, the haplotype analysis revealed 12 haplotypes (H) characterized by two distinct clusters (I and II), and a sequence distance of 99.1–99.9% from the reference haplotype (H1). The diversity and neutrality indices for the entire E. shiquicus populations were: haplotype diversity (Hd) ± standard deviation (SD) 0.862 ± 0.035; nucleotide diversity (Hd ± SD) 0.0056 ± 0.0003; Tajima's D 0.876 (P > 0.05); and Fu’s F 6.000 (P > 0.05).

Conclusions
This was the first analysis of the newly discovered E. shiquicus in plateau pikas in the Tibet Autonomous Region of China. The neutrality indices suggest a deficiency of alleles, indicative of a recent population bottleneck.

Graphical Abstract
Influence of environmental factors on the detection of blood in sheep faeces using visible–near-infrared spectroscopy as a measure of Haemonchus contortus infection
Authors: Kho Elise A. , Fernandes Jill N. , Kotze Andrew C. , Fox Glen P. , Sikulu-Lord Maggy T. , Beasley Anne M. , Moore Stephen S. , James Peter J. 
Published: November 2020

AbstractBackgroundExisting diagnostic methods for the parasitic gastrointestinal nematode,Haemonchus contortus, are time consuming and require specialised expertise, limiting their utility in the field. A practical, on-farm diagnostic tool could facilitate timely treatment decisions, thereby preventing losses in production and flock welfare. We previously demonstrated the ability of visible–near-infrared (Vis–NIR) spectroscopy to detect and quantify blood in sheep faeces with high accuracy. Here we report our investigation of whether variation in sheep type and environment affect the prediction accuracy of Vis–NIR spectroscopy in quantifying blood in faeces.MethodsVisible–NIR spectra were obtained from worm-free sheep faeces collected from different environments and sheep types in South Australia (SA) and New South Wales, Australia and spiked with various sheep blood concentrations. Spectra were analysed using principal component analysis (PCA), and calibration models were built around the haemoglobin (Hb) wavelength region (387–609 nm) using partial least squares regression. Models were used to predict Hb concentrations in spiked faeces from SA and naturally infected sheep faeces from Queensland (QLD). Samples from QLD were quantified using Hemastix® test strip and FAMACHA© diagnostic test scores.ResultsPrincipal component analysis showed that location, class of sheep and pooled versus individual samples were factors affecting the Hb predictions. The models successfully differentiated ‘healthy’ SA samples from those requiring anthelmintic treatment with moderate to good prediction accuracy (sensitivity 57–94%, specificity 44–79%). The models were not predictive for blood in the naturally infected QLD samples, which may be due in part to variability of faecal background and blood chemistry between samples, or the difference in validation methods used for blood quantification. PCA of the QLD samples, however, identified a difference between samples containing high and low quantities of blood.ConclusionThis study demonstrates the potential of Vis–NIR spectroscopy for estimating blood concentration in faeces from various types of sheep and environmental backgrounds. However, the calibration models developed here did not capture sufficient environmental variation to accurately predict Hb in faeces collected from environments different to those used in the calibration model. Consequently, it will be necessary to establish models that incorporate samples that are more representative of areas whereH. contortusis endemic.Graphical Abstract
Increased frequency of intermetatarsal and submetatarsal bursitis in early rheumatoid arthritis: a large case-controlled MRI study
Authors: Dakkak Yousra J. , Niemantsverdriet Ellis , van der Helm-van Mil Annette H. M. , Reijnierse Monique 
Published: November 2020

AbstractBackgroundThe forefoot is a preferential location for joint and tendon sheath inflammation in rheumatoid arthritis (RA). It also contains bursae, of which the intermetatarsal bursae have a synovial lining. Some small imaging studies suggested that intermetatarsal bursitis (IMB) and submetatarsal bursitis (SMB) are involved in RA, but their association has not been thoroughly explored. Healthy control studies suggested that lesion size might be relevant. We studied the relation between IMB and SMB in early RA, compared to other arthritides and healthy controls, and the relevance of lesion sizes.MethodsSix hundred and thirty-four participants were studied: 157 consecutive patients presenting with early RA, 284 other arthritides, and 193 healthy controls. All underwent unilateral contrast-enhanced MRI of the forefoot at presentation. Two readers independently scored IMB and SMB and measured transverse and dorsoplantar diameters, blinded to clinical data. Subsequently, consensus was reached. Intra-reader ICC was 0.89. Logistic regression models were used, and test characteristics were calculated.ResultsIMB and SMB associated with RA independent of each other (P < 0.001) and independent of age, gender, BMI, RA-MRI inflammation, and anti-CCP-antibodies (P = 0.041). Sensitivity for RA of IMB was 69%, and for SMB 25%. Specificity for IMB was 70% compared to other arthritides, and 84% compared to healthy controls. For SMB, this was 94% and 97% respectively. Regarding lesion size, the groups had considerable overlap: no cut-off size for RA could be distinguished with high sensitivity and specificity.ConclusionIntermetatarsal and submetatarsal bursitis associated with early rheumatoid arthritis, contributing to the emerging evidence that inflammation of juxta-articular soft tissues is an early feature of RA.
Chebulinic acid is a safe and effective antiangiogenic agent in collagen-induced arthritis in mice
Authors: Lu Kai , Iwenofu O. Hans , Mitra Rita , Mo Xiaokui , Dasgupta Partha Sarathi , Basu Sujit 
Published: November 2020

Abstract
Background
Although vascular endothelial growth factor-A (VEGF)-induced angiogenesis has been reported to play an important role in the pathogenesis of rheumatoid arthritis (RA), serious side effects, mainly grade 2–3 hypertension, which is commonly observed with currently available anti-VEGF agents, can be detrimental for RA patients due to hypertension and associated cardiovascular complications seen in these patients. Thus, identification of anti-VEGF molecules that do not increase blood pressure could be useful for the treatment of RA. Chebulinic acid (CI), a water-soluble small-molecule tannin, can inhibit the actions of VEGF, and a report suggested that CI might not increase blood pressure due to its compensatory effects on the cardiovascular system. Therefore, the effects of CI on blood pressure in mice and the progression of the disease in a murine collagen-induced arthritis (CIA) model were investigated.

Methods
CIA was induced in DBA/1J mice with type II collagen. The effects of CI in these animals were then evaluated by determination of clinical, histopathological, and immunohistochemical parameters. The effects of CI on VEGF-induced proangiogenic genes and signaling pathways were examined in vitro and in vivo.

Results
Significant CD31 and VEGF expressions were detected in the synovial tissues of mice with CIA, similar to their expressions observed in human RA patients. However, treatment with CI significantly inhibited paw swelling, decreased the mean articular index and joint pathology scores in these animals through inhibition of VEGF-induced proangiogenic gene expressions and signaling pathways that regulate angiogenesis. Unlike currently used antiangiogenic agents, CI at a dose that inhibits VEGF actions did not increase blood pressure in mice.

Conclusion
CI can act as a safe and potent anti-VEGF antiangiogenic agent for the treatment of types of inflammatory arthritis, such as RA.
Dynamic changes in chromatin accessibility, altered adipogenic gene expression, and total versus de novo fatty acid synthesis in subcutaneous adipose stem cells of normal-weight polycystic ovary syndrome (PCOS) women during adipogenesis: evidence of cellular programming
Authors: Leung Karen L. , Sanchita Smriti , Pham Catherine T. , Davis Brett A. , Okhovat Mariam , Ding Xiangming , Dumesic Phillip , Grogan Tristan R. , Williams Kevin J. , Morselli Marco , Ma Feiyang , Carbone Lucia , Li Xinmin , Pellegrini Matteo , Dumesic Daniel A. , Chazenbalk Gregorio D. 
Published: November 2020

Abstract
Background
Normal-weight polycystic ovary syndrome (PCOS) women exhibit adipose resistance in vivo accompanied by enhanced subcutaneous (SC) abdominal adipose stem cell (ASC) development to adipocytes with accelerated lipid accumulation per cell in vitro. The present study examines chromatin accessibility, RNA expression and fatty acid (FA) synthesis during SC abdominal ASC differentiation into adipocytes in vitro of normal-weight PCOS versus age- and body mass index-matched normoandrogenic ovulatory (control) women to study epigenetic/genetic characteristics as well as functional alterations of PCOS and control ASCs during adipogenesis.

Results
SC abdominal ASCs from PCOS women versus controls exhibited dynamic chromatin accessibility during adipogenesis, from significantly less chromatin accessibility at day 0 to greater chromatin accessibility by day 12, with enrichment of binding motifs for transcription factors (TFs) of the AP-1 subfamily at days 0, 3, and 12. In PCOS versus control cells, expression of genes governing adipocyte differentiation (PPARγ, CEBPα, AGPAT2) and function (ADIPOQ, FABP4, LPL, PLIN1, SLC2A4) was increased two–sixfold at days 3, 7, and 12, while that involving Wnt signaling (FZD1, SFRP1, and WNT10B) was decreased. Differential gene expression in PCOS cells at these time points involved triacylglycerol synthesis, lipid oxidation, free fatty acid beta-oxidation, and oxidative phosphorylation of the TCA cycle, with TGFB1 as a significant upstream regulator. There was a broad correspondence between increased chromatin accessibility and increased RNA expression of those 12 genes involved in adipocyte differentiation and function, Wnt signaling, as well as genes involved in the triacylglycerol synthesis functional group at day 12 of adipogenesis. Total content and de novo synthesis of myristic (C14:0), palmitic (C16:0), palmitoleic (C16:1), and oleic (C18:1) acid increased from day 7 to day 12 in all cells, with total content and de novo synthesis of FAs significantly greater in PCOS than controls cells at day 12.

Conclusions
In normal-weight PCOS women, dynamic chromatin remodeling of SC abdominal ASCs during adipogenesis may enhance adipogenic gene expression as a programmed mechanism to promote greater fat storage.
Acute respiratory failure as initial manifestation of conventional osteosarcoma rich in giant cells: a case report
Authors: Mosquera-Salas Laura , Salazar-Falla Nathalia , Perez Bladimir , Sangiovanni Saveria , Sua Luz F. , Fernández-Trujillo Liliana 
Published: November 2020

Abstract
Background
Osteosarcoma is a malignant tumor of the bone. The giant cell-rich osteosarcoma (GCRO) is a rare histological variant of the conventional osteosarcoma, accounting for 3% of all osteosarcomas. It has a variable clinical presentation, ranging from asymptomatic to multiple pathological fractures, mainly involving long bones, and less frequently the axial skeleton and soft tissues.

Case presentation
We present the case of a 25-year-old Hispanic woman, previously healthy, with a 1-month history of dyspnea on exertion, intermittent dry cough, hyporexia, and intermittent unquantified fever. She presented to the emergency department with a sudden increase in dyspnea during which she quickly entered ventilatory failure and cardiorespiratory arrest with pulseless electrical activity. Resuscitation maneuvers and orotracheal intubation were initiated, but effective ventilation was not achieved despite intubation and she was transferred to the intensive care unit of our institution. The chest radiograph showed a mediastinal mass that occluded and displaced the airway. The chest tomography showed a large mediastinal mass that involved the pleura and vertebral bodies. A thoracoscopic biopsy was performed that documented a conventional giant cell-rich osteosarcoma. The patient was considered to be inoperable due to the size and extent of the tumor and subsequently died.

Conclusions
The giant cell-rich osteosarcoma is a very rare histological variant of conventional osteosarcoma. Few cases of this type of osteosarcoma originating from the spine have been reported in the literature, and to our knowledge none of the reported cases included invasion to the chest cavity with airway compression and fatal acute respiratory failure that was present our case. Radiological and histological features of the GCRO must be taken into account to make a prompt diagnosis.
Sex differences in clinical characteristics and long-term outcomes in patients with vasospastic angina: results from the VA-Korea registry, a prospective multi-center cohort
Authors: Kim Hack-Lyoung , Jo Sang-Ho , Kim Hyun-Jin , Lee Min-Ho , Seo Won-Woo , Baek Sang Hong 
Published: November 2020

Abstract
Background
Sex differences in clinical characteristics and prognosis of vasospastic angina (VA) have not been well elucidated. This study was performed to investigate sex-specific characteristics and predictors for long-term clinical outcomes in patients with VA.

Methods
We analyzed 1838 patients (55 years and 62% male) who were diagnosed with definite (n = 680) or intermediate (n = 1212) VA in ergonovine provocation test from a nation-wide VA registry. The primary study end-point was composite events including cardiac death, acute coronary syndrome, ventricular tachycardia or fibrillation, and atrioventricular block during clinical follow-up.

Results
Male patients were younger, and there were more smokers and alcohol drinkers in male patients than in female patients. During the median follow-up period of 760 days (interquartile range, 336–1105 days), there were 73 cases (3.97%) of composite events. There was no sex difference in the occurrence of composite events (log-rank p = 0.649). Concomitant significant (≥ 50%) organic coronary stenosis was associated with worse clinical outcomes in both male (hazard ration [HR], 1.97; 95% confidence interval [CI], 1.01–3.85; p = 0.047) and female (HR, 3.26; 95% CI, 1.07–9.89; p = 0.037) patients. Obesity (body mass index ≥ 25 kg/m2) was associated with better prognosis in female VA patients (HR, 0.22; 95% CI, 0.07–0.68; p = 0.008). Even when only patients with definite diagnosis of VA were considered, there was no significant sex difference in clinical outcomes (log-rank p = 0.876).

Conclusions
In VA patients, there were several different clinical characteristics according to sex; however, long-term clinical outcome was similar between sexes. Significant organic coronary stenosis in both sexes and low body mass index (< 25 kg/m2) in females were associated with worse prognosis in VA patients.
Infection of bovine well-differentiated airway epithelial cells by Pasteurella multocida: actions and counteractions in the bacteria–host interactions
Authors: Su Ang , Tong Jie , Fu Yuguang , Müller Sandy , Weldearegay Yenehiwot Berhanu , Becher Paul , Valentin-Weigand Peter , Meens Jochen , Herrler Georg 
Published: November 2020

AbstractPasteurella (P.) multocida is a zoonotic pathogen, which is able to cause respiratory disorder in different hosts. In cattle, P. multocida is an important microorganism involved in the bovine respiratory disease complex (BRDC) with a huge economic impact. We applied air–liquid interface (ALI) cultures of well-differentiated bovine airway epithelial cells to analyze the interaction of P. multocida with its host target cells. The bacterial pathogen grew readily on the ALI cultures. Infection resulted in a substantial loss of ciliated cells. Nevertheless, the epithelial cell layer maintained its barrier function as indicated by the transepithelial electrical resistance and the inability of dextran to get from the apical to the basolateral compartment via the paracellular route. Analysis by confocal immunofluorescence microscopy confirmed the intactness of the epithelial cell layer though it was not as thick as the uninfected control cells. Finally, we chose the bacterial neuraminidase to show that our infection model is a sustainable tool to analyze virulence factors of P. multocida. Furthermore, we provide an explanation, why this microorganism usually is a commensal and becomes pathogenic only in combination with other factors such as co-infecting microorganisms.