bluuebunny/crossref_metadata_2025 huggingface dataset:
Interferon β-1a (IFNβ-1a) in COVID-19 patients (INTERCOP): study protocol for a randomized controlled trial
Authors: Bosi Emanuele , Bosi Carlo , Rovere Querini Patrizia , Mancini Nicasio , Calori Giliola , Ruggeri Annalisa , Canzonieri Cecilia , Callegaro Luciano , Clementi Massimo , De Cobelli Francesco , Filippi Massimo , Bregni Marco
Published: November 2020

Background

Pharmacological therapies of proven efficacy in coronavirus disease 2019 (COVID-19) are still lacking. We have identified IFNβ-1a as the most promising drug to be repurposed for COVID-19. The rationale relies on the evidence of IFNβ anti-viral activity in vitro against SARS-CoV-2 and animal models resembling SARS-CoV-2 infection and on a recent clinical trial where IFNβ was indicated as the key component of a successful therapeutic combination.

Methods

This is a randomized, controlled, open-label, monocentric, phase II trial (INTERCOP trial). One hundred twenty-six patients with positive swab detection of SARS-CoV-2, radiological signs of pneumonia, and mild-to-moderate disease will be randomized 2:1 to IFNβ-1a in addition to standard of care vs standard of care alone. No other anti-viral drugs will be used as part of the regimens, both in the control and the intervention arms. IFNβ-1a will be administered subcutaneously at the dose of 44 mcg (equivalent to 12 million international units) three times per week, at least 48 h apart, for a total of 2 weeks. The primary outcome is the time to negative conversion of SARS-CoV-2 nasopharyngeal swabs. Secondary outcomes include improvement or worsening in a clinical severity score measured on a 7-point ordinal scale (including transfer to intensive care unit and death), oxygen- and ventilator-free days, mortality, changes in pulmonary computed tomography severity score, hospital stay duration, reduction of viral load measured on nasopharyngeal swabs, number of serious adverse events, and changes in biochemical markers of organ dysfunction. Exploratory outcomes include blood cell counts, cytokine and inflammatory profile, peripheral mRNA expression profiles of interferon-stimulated genes, and antibodies to SARS-CoV-2 and to IFNβ-1a. INTERCOP is the first study to specifically investigate the clinical benefits of IFNβ-1a in COVID-19 patients.

Discussion

Potential implications of this trial are multifaceted: should the primary outcome be fulfilled and the treatment be safe, one may envisage that IFNβ-1a be used to reduce the infectivity of patients with mild-to moderate disease. In case IFNβ-1a reduced the duration of hospital stay and/or ameliorated the clinical status, it may become a cornerstone of COVID-19 treatment.

Trial registration

EudraCT 2020-002458-25. Registered on May 11, 2020

ClinicalTrials.gov Identifier:NCT04449380
Comparison of continuous versus intermittent enteral nutrition in critically ill patients (COINN): study protocol for a randomized comparative effectiveness trial
Authors: Hrdy Ondrej , Vrbica Kamil , Strazevska Eva , Suk Petr , Souckova Lenka , Stepanova Radka , Sas Igor , Gal Roman
Published: November 2020

Background

Enteral nutrition is part of the treatment of critically ill patients. Administration of enteral nutrition may be associated with signs of intolerance, such as high gastric residual volumes, diarrhea, and vomiting. Clinical trials regarding the effects of the mode of administration of enteral nutrition on the occurrence of these complications have yielded conflicting results. This trial aims to investigate whether the mode of administration of enteral nutrition affects the time to reach nutritional targets, intolerance, and complications.

Methods

COINN is a randomized, monocentric study for critically ill adult patients receiving enteral nutrition. Patients will be randomly assigned to two groups receiving (1) continuous or (2) intermittent administration of enteral nutrition. Enhancement of enteral nutrition will depend on signs of tolerance, mainly the gastric residual volume. The primary outcome will be the time to reach the energetic target. Secondary outcomes will be the time to reach the protein target, tolerance, complications, hospital and ICU lengths of stay, and 28-day mortality.

Discussion

This trial aims to evaluate whether the mode of application of enteral nutrition affects the time to reach nutritional targets, signs of intolerance, and complications.

Trial registration

ClinicalTrials.gov NCT03573453. Registered on 29 June 2018
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

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.
Correction to: Respiratory support in COPD patients after acute exacerbation with monitoring the quality of support (Rescue2-monitor): an open-label, prospective randomized, controlled, superiority clinical trial comparing hospital- versus home-based acute non-invasive ventilation for patients with hypercapnic chronic obstructive pulmonary disease
Authors:   On behalf of the Rescue2-monitor group
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
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

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

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

Background

Existing 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.

Methods

Visible–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.

Results

Principal 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.

Conclusion

This 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

Background

The 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.

Methods

Six 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.

Results

IMB 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.

Conclusion

Intermetatarsal 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

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

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

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

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

Pasteurella (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.
Cannabis-derived cannabidiol and nanoselenium improve gut barrier function and affect bacterial enzyme activity in chickens subjected to C. perfringens challenge
Authors: Konieczka Paweł , Szkopek Dominika , Kinsner Misza , Fotschki Bartosz , Juśkiewicz Jerzy , Banach Joanna
Published: November 2020

Revealing the multifocal mechanisms affecting cross-talk between Clostridium perfringens pathogenesis and the host response is an urgent need in the poultry industry. Herein, the activity of Cannabis sativa-derived cannabidiol (CBD) and selenium nanoparticles (Nano-Se) in modulating the host response to Clostridium perfringens challenge was investigated in broiler chickens subjected to a mild infection model. The infected chickens exhibited no clinical manifestations, confirming the potential hazard of pathogen transmission to the food chain in the commercial sector. However, both CBD and Nano-Se affected the responses of chickens to C. perfringens challenge. The beneficial actions of both agents were manifested in the upregulated expression of genes determining gut barrier function. Both CBD and Nano-Se promoted shifts in gut bacterial enzyme activity to increased energy uptake in challenged chickens and upregulated potential collagenase activity. There was no opposite effect of CBD and Nano-Se in mediating the host response to challenge, whereas an additive effect was evidenced on the upregulation of gene determining gut integrity. Collectively, these findings indicate that understanding the action mechanisms of CBD and Nano-Se is of great interest for developing a preventive strategy for C. perfringens infection in broilers.
Lrp4 in hippocampal astrocytes serves as a negative feedback factor in seizures
Authors: Yu Zheng , Zhang Meiying , Luo Bin , Jing Hongyang , Yu Yue , Wang Shunqi , Luo Shiwen
Published: November 2020

Background

Epilepsy is characterized by the typical symptom of seizure, and anti-seizure medications are the main therapeutic method in clinical, but the effects of these therapy have not been satisfactory. To find a better treatment, it makes sense to further explore the regulatory mechanisms of seizures at genetic level. Lrp4 regionally expresses in mice hippocampus where is key to limbic epileptogenesis. It is well known that neurons release a high level of glutamate during seizures, and it has been reported that Lrp4 in astrocytes down-regulates glutamate released from neurons. However, it is still unclear whether there is a relationship between Lrp4 expression level and seizures, and whether Lrp4 plays a role in seizures.

Results

We found that seizures induced by pilocarpine decreased Lrp4 expression level and increased miR-351-5p expression level in mice hippocampus. Glutamate reduced Lrp4 expression and enhanced miR-351-5p expression in cultured hippocampal astrocytes, and these effects can be partially attenuated by AP5. Furthermore, miR-351-5p inhibitor lessened the reduction of Lrp4 expression in glutamate treated hippocampal astrocytes. Local reduction of Lrp4 in hippocampus by sh Lrp4 lentivirus injection in hippocampus increased the threshold of seizures in pilocarpine or pentylenetetrazol (PTZ) injected mice.

Conclusions

These results indicated that high released glutamate induced by seizures down-regulated astrocytic Lrp4 through increasing miR-351-5p in hippocampal astrocytes via activating astrocytic NMDA receptor, and locally reduction of Lrp4 in hippocampus increased the threshold of seizures. Lrp4 in hippocampal astrocytes appears to serve as a negative feedback factor in seizures. This provides a new potential therapeutic target for seizures regulation.
Named entity recognition for Chinese judgment documents based on BiLSTM and CRF
Authors: Huang Wenming , Hu Dengrui , Deng Zhenrong , Nie Jianyun
Published: November 2020

Chinese named entity recognition (CNER) in the judicial domain is an important and fundamental task in the analysis of judgment documents. However, only a few researches have been devoted to this task so far. For Chinese named entity recognition in judgment documents, we propose the use a bidirectional long-short-term memory (BiLSTM) model, which uses character vectors and sentence vectors trained by distributed memory model of paragraph vectors (PV-DM). The output of BiLSTM is used by conditional random field (CRF) to tag the input sequence. We also improved the Viterbi algorithm to increase the efficiency of the model by cutting the path with the lowest score. At last, a novel dataset with manual annotations is constructed. The experimental results on our corpus show that the proposed method is effective not only in reducing the computational time, but also in improving the effectiveness of named entity recognition in the judicial domain.
Dynamical analysis of a stochastic rumor-spreading model with Holling II functional response function and time delay
Authors: Huo Liang’an , Chen Xiaomin
Published: November 2020

With the rapid development of information society, rumor plays an increasingly crucial part in social communication, and its spreading has a significant impact on human life. In this paper, a stochastic rumor-spreading model with Holling II functional response function considering the existence of time delay and the disturbance of white noise is proposed. Firstly, the existence of a unique global positive solution of the model is studied. Then the asymptotic behavior of the global solution around the rumor-free and rumor-local equilibrium nodes of the deterministic system is discussed. Finally, through some numerical results, the validity and availability of theoretical analysis is verified powerfully, and it shows that some factors such as the transmission rate, the intensity of white noise, and the time delay have significant relationship with the dynamical behavior of rumor spreading.
External stability and $H_{\infty }$ control of switching systems with delay and impulse
Authors: Ren Jiaojiao , Wu Cong
Published: November 2020

In this paper, we investigate the external stability and$H_{\infty }$H∞control of switching systems with time-varying delay and impulse. First of all, a modified two-direction inequality (relation) between the switching numbers and the maximum, minimum dwell time is proposed. This new inequality is applied to proving the external stability of switching systems with delay and impulse consisting of subsystems with Hurwitz stable matrices of internal dynamics. By using this new inequality, a normal$L_{2}$L2norm constraint is derived rather than weighted$L_{2}$L2norm constraint. In addition, by a realizable switching law, the obtained result is extended to the switching systems comprised of subsystems with both Hurwitz stable and unstable matrices of internal dynamics. The results are finally applied to$H_{\infty }$H∞control and illustrated by a numerical example.
Theoretical and semi-analytical results to a biological model under Atangana–Baleanu–Caputo fractional derivative
Authors: Zeb Anwar , Nazir Ghazala , Shah Kamal , Alzahrani Ebraheem
Published: November 2020

This manuscript is related to finding a solution of the SIR model under Mittag-Leffler type derivative. For the required results, we use Laplace transform together with Adomian decomposition method (LADM). The mentioned method is a powerful tool to deal with various linear and nonlinear problems of “fractional order differential equations (FODEs)”. Also, we study some results devoted to qualitative theory for the concerned model. Computational results show the verification of the established analysis. Briefly, we state that qualitative theory for the existence of solution is important to ensure whether the considered problem has a solution or not. Further ensuring the existence of solution, we investigate approximate solution which is computed in the form of infinite series. The results are graphically displayed to analyze the adopted procedure for solving nonlinear FODEs under ABC derivative.
Genetic selection for growth drives differences in intestinal microbiota composition and parasite disease resistance in gilthead sea bream
Authors: Piazzon M. Carla , Naya-Català Fernando , Perera Erick , Palenzuela Oswaldo , Sitjà-Bobadilla Ariadna , Pérez-Sánchez Jaume
Published: November 2020

Background

The key effects of intestinal microbiota in animal health have led to an increasing interest in manipulating these bacterial populations to improve animal welfare. The aquaculture sector is no exception and in the last years, many studies have described these populations in different fish species. However, this is not an easy task, as intestinal microbiota is composed of very dynamic populations that are influenced by different factors, such as diet, environment, host age, and genetics. In the current study, we aimed to determine whether the genetic background of gilthead sea bream (Sparus aurata) influences the intestinal microbial composition, how these bacterial populations are modulated by dietary changes, and the effect of selection by growth on intestinal disease resistance. To that aim, three different groups of five families of gilthead sea bream that were selected during two generations for fast, intermediate, or slow growth (F3 generation) were kept together in the same open-flow tanks and fed a control or a well-balanced plant-based diet during 9 months. Six animals per family and dietary treatment were sacrificed and the adherent bacteria from the anterior intestinal portion were sequenced. In parallel, fish of the fast- and slow-growth groups were infected with the intestinal parasite Enteromyxum leei and the disease signs, prevalence, intensity, and parasite abundance were evaluated.

Results

No differences were detected in alpha diversity indexes among families, and the core bacterial architecture was the prototypical composition of gilthead sea bream intestinal microbiota, indicating no dysbiosis in any of the groups. The plant-based diet significantly changed the microbiota in the intermediate- and slow-growth families, with a much lower effect on the fast-growth group. Interestingly, the smaller changes detected in the fast-growth families potentially accounted for more changes at the metabolic level when compared with the other families. Upon parasitic infection, the fast-growth group showed significantly lower disease signs and parasite intensity and abundance than the slow-growth animals.

Conclusions

These results show a clear genome-metagenome interaction indicating that the fast-growth families harbor a microbiota that is more flexible upon dietary changes. These animals also showed a better ability to cope with intestinal infections.
VALENCIA: a nearest centroid classification method for vaginal microbial communities based on composition
Authors: France Michael T. , Ma Bing , Gajer Pawel , Brown Sarah , Humphrys Michael S. , Holm Johanna B. , Waetjen L. Elaine , Brotman Rebecca M. , Ravel Jacques
Published: November 2020

Background

Taxonomic profiles of vaginal microbial communities can be sorted into a discrete number of categories termed community state types (CSTs). This approach is advantageous because collapsing a hyper-dimensional taxonomic profile into a single categorical variable enables efforts such as data exploration, epidemiological studies, and statistical modeling. Vaginal communities are typically assigned to CSTs based on the results of hierarchical clustering of the pairwise distances between samples. However, this approach is problematic because it complicates between-study comparisons and because the results are entirely dependent on the particular set of samples that were analyzed. We sought to standardize and advance the assignment of samples to CSTs.

Results

We developed VALENCIA (VAginaL community state typE Nearest CentroId clAssifier), a nearest centroid-based tool which classifies samples based on their similarity to a set of reference centroids. The references were defined using a comprehensive set of 13,160 taxonomic profiles from 1975 women in the USA. This large dataset allowed us to comprehensively identify, define, and characterize vaginal CSTs common to reproductive age women and expand upon the CSTs that had been defined in previous studies. We validated the broad applicability of VALENCIA for the classification of vaginal microbial communities by using it to classify three test datasets which included reproductive age eastern and southern African women, adolescent girls, and a racially/ethnically and geographically diverse sample of postmenopausal women. VALENCIA performed well on all three datasets despite the substantial variations in sequencing strategies and bioinformatics pipelines, indicating its broad application to vaginal microbiota. We further describe the relationships between community characteristics (vaginal pH, Nugent score) and participant demographics (race, age) and the CSTs defined by VALENCIA.

Conclusion

VALENCIA provides a much-needed solution for the robust and reproducible assignment of vaginal community state types. This will allow unbiased analysis of both small and large vaginal microbiota datasets, comparisons between datasets and meta-analyses that combine multiple datasets.
Patient descriptions of loss of control and eating episode size interact to influence expert diagnosis of ICD-11 binge-eating disorder
Authors: Berner Laura A. , Sysko Robyn , Rebello Tahilia J. , Roberto Christina A. , Pike Kathleen M.
Published: November 2020

Background

Although data suggest that the sense of “loss of control” (LOC) is the most salient aspect of binge eating, the definition of LOC varies widely across eating disorder assessments. The WHO ICD-11 diagnostic guidelines for binge eating do not require an objectively large amount of food, which makes accurate LOC diagnosis even more critical. However, it can be especially challenging to assess LOC in the context of elevated weight status and in the absence of compensatory behaviors. This ICD-11 field sub-study examined how descriptions of subjective experience during distressing eating episodes, in combination with different eating episode sizes, influence diagnoses of binge-eating disorder (BED).

Method

Mental health professionals with eating disorder expertise from WHO’s Global Clinical Practice Network (N = 192) participated in English, Japanese, and Spanish. Participants were asked to select the correct diagnosis for two randomly assigned case vignettes and to rate the clinical importance and ease of use of each BED diagnostic guideline.

Results

The presence of LOC interacted with episode size to predict whether a correct diagnostic conclusion was reached. If the amount consumed during a typical distressing eating episode was only subjectively large compared to objectively large, clinicians were 23.1 times more likely to miss BED than to correctly diagnose it, and they were 9.7 times more likely to incorrectly diagnose something else than to correctly diagnose BED. In addition, clinicians were 10.8 times more likely to make a false positive diagnosis of BED when no LOC was described if the episode was objectively large. Descriptions of LOC that were reliably associated with correct diagnoses across episodes sizes included two that are similar to those already included in proposed ICD-11 guidelines and a third that is not. This third description of LOC focuses on giving up attempts to control eating because perceived overeating feels inevitable.

Conclusions

Results highlight the importance of detailed clarification of the LOC construct in future guidelines. Explicitly distinguishing LOC from distressing and mindless overeating could help promote consistent and accurate diagnosis of BED versus another or no eating disorder.
Assessment of the psychosocial and economic impact according to sex in non-small cell lung cancer patients: an exploratory longitudinal study
Authors: Viñolas N. Nuria , Garcia-Campelo Rosario , Majem Margarita , Carcereny Enric , Isla Dolores , Gonzalez-Larriba José Luis , Coves Juan , De-Castro Javier , Domine Manuel , Lianes Piar , Artal Angel , Remon Jordi , Felip Enriqueta , Garrido Pilar
Published: November 2020

Background

Little is known about the impact of sex on lung cancer patients from the psychological, economic and social perspectives. This study was designed to explore the psychosocial and economic impact according to sex of metastatic non-small cell lung cancer (mNSCLC) in patients and caregivers.

Methods

Exploratory study of two cohorts of patients starting first-line treatment for mNSCLC. The following questionnaires were administered at baseline, 4 months later and following the first and second disease progression: APGAR, relationship impact scale, DUKE-UNC scale, economic impact in patients and caregiver, and Zarit scale. It was planned to include 1250 patients to get an 80% possibility of detecting as significant (p < 0.05) effect sizes less than 0.19 between men and women. Univariate comparisons were made between the tests applied to men and women. Overall survival was estimated with Kaplan–Meier method. Cox analyses were done to estimate hazard ratios (HRs) with 95% CI.

Results

333 patients were included. Most families reported to continue being functional despite the lung cancer diagnosis. Regardless of sex, they did not perceive changes in their partner relationship. Most patients felt their social support was normal. Roughly 25% of people reported a worsening in their economic situation, without remarkable differences by sex. Statistically significant differences were found between both groups regarding the caregiver’s relationship to the patient (more parents were the caregiver in females than in males, p < 0.0001) and the caregiver’s employment situation (more employed caregivers in females) (p < 0.0001). Most caregivers of both sexes considered that taking care of their relative did not pose a significant burden.

Conclusions

This study provides a preliminary insight into sex-related characteristics in the management of advanced NSCLC and its impact on the emotional, social and economic burden of patients and their caregivers, and recall the high priority of researching in cancer from a sex perspective. Nevertheless, due to the low recruitment rate and the relevant loss of patients during the follow-up, it was difficult to find differences by sex.

Trial registration

ClinicalTrials.gov identifier: NCT02336061.

Ethics committee

Comité Ético de Investigación Clínica del Hospital Clínic de Barcelona, Spain. Reference number: HCB/2014/0705.
Adult onset pan-neuronal human tau tubulin kinase 1 expression causes severe cerebellar neurodegeneration in mice
Authors: McMillan Pamela , Wheeler Jeanna , Gatlin Rachel E. , Taylor Laura , Strovas Tim , Baum Misa , Bird Thomas D. , Latimer Caitlin , Keene C. Dirk , Kraemer Brian C. , Liachko Nicole F.
Published: November 2020

The kinase TTBK1 is predominantly expressed in the central nervous system and has been implicated in neurodegenerative diseases including Alzheimer’s disease, frontotemporal lobar degeneration, and amyotrophic lateral sclerosis through its ability to phosphorylate the proteins tau and TDP-43. Mutations in the closely related gene TTBK2 cause spinocerebellar ataxia, type 11. However, it remains unknown whether altered TTBK1 activity alone can drive neurodegeneration. In order to characterize the consequences of neuronal TTBK1 upregulation in adult brains, we have generated a transgenic mouse model with inducible pan-neuronal expression of human TTBK1. We find that these inducible TTBK1 transgenic mice (iTTBK1 Tg) exhibit motor and cognitive phenotypes, including decreased grip strength, hyperactivity, limb-clasping, and spatial memory impairment. These behavioral phenotypes occur in conjunction with progressive weight loss, neuroinflammation, and severe cerebellar degeneration with Purkinje neuron loss. Phenotype onset begins weeks after TTBK1 induction, culminating in average mortality around 7 weeks post induction. The iTTBK1 Tg animals lack any obvious accumulation of pathological tau or TDP-43, indicating that TTBK1 expression drives neurodegeneration in the absence of detectable pathological protein deposition. In exploring TTBK1 functions, we identified the autophagy related protein GABARAP to be a novel interacting partner of TTBK1 and show that GABARAP protein levels increase in the brain following induction of TTBK1. These iTTBK1 Tg mice exhibit phenotypes reminiscent of spinocerebellar ataxia, and represent a new model of cerebellar neurodegeneration.