bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant association between clinical characteristics and changes in peripheral immuno-phenotype in large vessel vasculitis
Authors: Matsumoto Kotaro , Suzuki Katsuya , Yoshimoto Keiko , Seki Noriyasu , Tsujimoto Hideto , Chiba Kenji , Takeuchi Tsutomu 
Published: December 2019

Abstract
Background
Large vessel vasculitis (LVV) is a type of vasculitis characterized by granulomatous inflammation of medium- and large-sized arteries. Clinical assessment of acute phase reactants has been conventionally used to diagnose and monitor diseases; however, accurate assessment of vascular disease activity status can be difficult. In this study, we investigated comprehensive immuno-phenotyping to explore useful biomarkers associated with clinical characteristics.

Methods
Consecutive patients with newly diagnosed LVV who visited our institution between May 2016 and May 2019 were enrolled. The number of circulating T cells, B cells, natural killer cells, dendritic cells, monocytes, and granulocytes was examined and chronologically followed. Baseline and time-course changes in immuno-phenotyping associated with disease activity were assessed.

Results
Comprehensive immuno-phenotyping data from 90 samples from each of 20 patients with LVV were compared with those from healthy controls (HCs). The number of helper T (Th), follicular helper T (Tfh), CD8+ T, CD14++ CD16+ monocytes, and neutrophils were higher in patients with giant cell arteritis (GCA) and/or Takayasu arteritis (TAK) than in HCs. Among them, the number of CD8+ T and CD8+ Tem were higher in patients with TAK than in GCA. Notably, memory CD4+ and CD8+ T cells in patients with TAK remained high even in the remission phase. Further analysis revealed that the number of Th1, Th17, and Tfh cells was associated with disease relapse in GCA and TAK and that the number of CD8+ T cells was associated with relapse in TAK. Th1, Th17, and Tfh cells decreased after treatment with biologic agents, while CD8+ T cells did not.

Conclusions
Our results from peripheral immuno-phenotyping analysis indicate that the numbers of Th and Tfh cells changed along with the disease condition in both GCA and TAK, while that of CD8+ T cells did not, especially in TAK. Treatment with biologic agents decreased the proportion of Th and Tfh cells, but not CD8+ T cells, in the patients. Chronological immuno-phenotyping data explained the difference in therapeutic response, such as reactivities against biologics, between GCA and TAK.
The effect of home-based low-volume, high-intensity interval training on cardiorespiratory fitness, body composition and cardiometabolic health in women of normal body mass and those with overweight or obesity: protocol for a randomized controlled trial
Authors: Frimpong Emmanuel , Dafkin Chloe , Donaldson Janine , Millen Aletta Maria Esterhuyse , Meiring Rebecca Mary 
Published: December 2019

Abstract
Background
There is a high prevalence of women in South Africa with overweight and obesity which is associated with an increased risk of cardiometabolic disorders. Perceived barriers such as lack of time and motivation reduce engagement in beneficial activity behaviours for health. High-intensity interval training (HIIT) is a time-efficient and effective way to improve cardiometabolic risk profile regardless of a loss in body mass or change in body composition. This randomized controlled trial aims to determine the effects on cardiorespiratory fitness, body composition and cardiometabolic health and feasibility of a home-based 14-week HIIT program in women with overweight/obesity or normal body mass.

Methods
One hundred and twenty women (18–40 years old) with a body mass index between 20 and 35 kg/m2, will be stratified according to their BMI (normal, BMI 20–24.9 kg/m2; or high BMI ≥25 kg/m2) and randomized into a HIIT exercising group (HIIT) or a non-exercising control group (CON). HIIT participants will perform exercises for 11 min/session six times per week for a period of 14 weeks. The 2 × 4 HIIT protocol will require a work phase of own-body weight exercise lasting 2 minutes (85% VO2peak), repeated four times and separated by a one-minute active rest phase (65% VO2peak). CON participants will be asked to maintain their normal habitual lifestyle. Outcomes of cardiorespiratory fitness, body composition, echocardiography, central blood pressure, arterial stiffness and biomarkers of cardiometabolic health will be measured before and after the 14-week intervention. Every 4 weeks during the intervention, an objective estimation of compliance to the study protocol will be assessed by measuring participant physical activity over 7 days using an Actigraph GT3X accelerometer.

Discussion
Supervised laboratory-based HIIT interventions are effective in improving cardiometabolic health. More pragmatic exercise protocols may however show to be successful for mitigating barriers to the engagement in physical activity and exercise resulting in positive benefits to health. Investigation into home-based HIIT regimens are important in women, where globally the rising trend of overweight and obesity overshadows that of men. The results from this study may therefore inform future research on effective exercise prescription for women’s health.

Trial registration
Pan African Clinical Trial Registry (www.pactr.org - id no: PACTR201806003434299), 6th June 2018.
Increased Ca2+ signaling in NRXN1α+/− neurons derived from ASD induced pluripotent stem cells
Authors: Avazzadeh Sahar , McDonagh Katya , Reilly Jamie , Wang Yanqin , Boomkamp Stephanie D. , McInerney Veronica , Krawczyk Janusz , Fitzgerald Jacqueline , Feerick Niamh , O’Sullivan Matthew , Jalali Amirhossein , Forman Eva B. , Lynch Sally A. , Ennis Sean , Cosemans Nele , Peeters Hilde , Dockery Peter , O’Brien Timothy , Quinlan Leo R. , Gallagher Louise , Shen Sanbing 
Published: December 2019

Abstract
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases.

Methods
Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1α+/− deletions. Seven control and six NRXN1α+/− iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca2+) imaging was performed using Fluo4-AM, and the properties of Ca2+ transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1α+/− neurons.

Results
NRXN1α+/− neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca2+ transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1α+/− neurons identified by STRING and GSEA analyses.

Conclusions
This is the first report to show that human NRXN1α+/− neurons derived from ASD patients’ iPSCs present novel phenotypes of upregulated VGCCs and increased Ca2+ transients, which may facilitate the development of drug screening assays for the treatment of ASD.
OHMI: the ontology of host-microbiome interactions
Authors: He Yongqun , Wang Haihe , Zheng Jie , Beiting Daniel P. , Masci Anna Maria , Yu Hong , Liu Kaiyong , Wu Jianmin , Curtis Jeffrey L. , Smith Barry , Alekseyenko Alexander V. , Obeid Jihad S. 
Published: December 2019

Abstract
Background
Host-microbiome interactions (HMIs) are critical for the modulation of biological processes and are associated with several diseases. Extensive HMI studies have generated large amounts of data. We propose that the logical representation of the knowledge derived from these data and the standardized representation of experimental variables and processes can foster integration of data and reproducibility of experiments and thereby further HMI knowledge discovery.

Methods
Through a multi-institutional collaboration, a community-based Ontology of Host-Microbiome Interactions (OHMI) was developed following the Open Biological/Biomedical Ontologies (OBO) Foundry principles. As an OBO library ontology, OHMI leverages established ontologies to create logically structured representations of (1) microbiomes, microbial taxonomy, host species, host anatomical entities, and HMIs under different conditions and (2) associated study protocols and types of data analysis and experimental results.

Results
Aligned with the Basic Formal Ontology, OHMI comprises over 1000 terms, including terms imported from more than 10 existing ontologies together with some 500 OHMI-specific terms. A specific OHMI design pattern was generated to represent typical host-microbiome interaction studies. As one major OHMI use case, drawing on data from over 50 peer-reviewed publications, we identified over 100 bacteria and fungi from the gut, oral cavity, skin, and airway that are associated with six rheumatic diseases including rheumatoid arthritis. Our ontological study identified new high-level microbiota taxonomical structures. Two microbiome-related competency questions were also designed and addressed. We were also able to use OHMI to represent statistically significant results identified from a large existing microbiome database data analysis.

Conclusion
OHMI represents entities and relations in the domain of HMIs. It supports shared knowledge representation, data and metadata standardization and integration, and can be used in formulation of advanced queries for purposes of data analysis.
Molecular surveillance of carbapenemase-producing Pseudomonas aeruginosa at three medical centres in Cologne, Germany
Authors: Schäfer Elena , Malecki Monika , Tellez-Castillo Carlos J. , Pfennigwerth Niels , Marlinghaus Lennart , Higgins Paul G. , Mattner Frauke , Wendel Andreas F. 
Published: December 2019

Abstract
Background
Pseudomonas aeruginosa is a common pathogen causing hospital-acquired infections. Carbapenem resistance in P. aeruginosa is either mediated via a combination of efflux pumps, AmpC overexpression, and porin loss, or through an acquired carbapenemase. Carbapenemase-producing P. aeruginosa (CPPA) strains are known to cause outbreaks and harbour a reservoir of mobile antibiotic resistance genes, however, few molecular surveillance data is available. The aim of this study was to analyse the prevalence and epidemiology of CPPA in three German medical centres from 2015 to 2017.

Methods
Identification and susceptibility testing were performed with VITEK 2 system. P. aeruginosa non-susceptible to piperacillin, ceftazidime, cefepime, imipenem, meropenem and ciprofloxacin (4MRGN according to the German classification guideline) isolated from 2015 to 2017 were analysed. A two-step algorithm to detect carbapenemases was performed: phenotypic tests (EDTA- and cloxacillin-combined disk tests) followed by PCR, Sanger sequencing, and eventually whole genome sequencing. CPPA isolates were further genotyped by RAPD and PFGE. In-hospital transmission was investigated using conventional epidemiology.

Results
Sixty two P. aeruginosa isolates were available for further analysis, of which 21 were CPPA as follows: blaVIM-1 (n = 2), blaVIM-2 (n = 17), blaNDM-1/blaGES-5 (n = 1) and the newly described blaIMP-82 (n = 1). CPPA were mostly hospital-acquired (71.4%) and isolated on intensive care units (66.7%). All (except one) were from the tertiary care centre. PFGE typing revealed one large cluster of VIM-2-producing CPPA containing 13 isolates. However, using conventional epidemiology, we were only able to confirm three patient-to-patient transmissions, and one room-to-patient transmission, on several intensive care units.

Conclusions
These data give insight into the epidemiology of CPPA in three centres in Germany over a period of 3 years. Carbapenemases are a relevant resistance mechanism in 4MRGN-P. aeruginosa, illustrated by genetically related VIM-2-producing strains that seem to be endemic in this region. Our data suggest that infection control measures should especially focus on controlling transmission on the ICU and support the need for a local molecular surveillance system.
Investigating Various Factors Affecting the Long-Term Compressive Strength of Heat-Cured Fly Ash Geopolymer Concrete and the Use of Orthogonal Experimental Design Method
Authors: Zhang Hongen , Li Lang , Sarker Prabir Kumar , Long Tao , Shi Xiaoshuang , Wang Qingyuan , Cai Gaochuang 
Published: December 2019

AbstractThis work quantified the hierarchy of the influence of three common mixture design parameters on the compressive strength and the rate of strength increase over the long term of low-calcium fly ash geopolymer concrete (FAGC) through designing 16 mixtures by the orthogonal experimental design (OED) method. The parameters used in the study were liquid to fly ash (L/FA) ratio, sodium hydroxide concentration (SHC) and sodium silicate solution to sodium hydroxide solution (SS/SH) ratio. The L/FA ratio showed little effect on compressive strength when it was varied from 0.40 to 0.52. SHC showed the greatest influence on compressive strength with little impact on the rate of strength increase after the initial heat curing. Even though the SS/SH ratio showed a small effect on the initial compressive strength, it had a considerable influence on the rate of strength increase over the long term. It was found that the compressive strength at 480 days was positively related to the Na2O/SiO2 molar ratio when it was varied from 0.49 to 0.80 and the Si/Al molar ratio was increased up to 1.87. Analysis of the failure types of specimens demonstrated that compressive strength of FAGC was associated with the strength of the mortar–aggregate interface zone (MAIZ).
A clinical trial of group-based body psychotherapy to improve bodily disturbances in post-treatment cancer patients in combination with randomized controlled smartphone-triggered bodily interventions (KPTK): study protocol
Authors: Grossert Astrid , Meffert Cornelia , Hess Viviane , Rochlitz Christoph , Pless Miklos , Hunziker Sabina , Wössmer Brigitta , Geuter Ulfried , Meinlschmidt Gunther , Schaefert Rainer 
Published: December 2019

Abstract
Background
Disturbances in bodily well-being represent one key source of suffering and impairment related to cancer. There is growing evidence that body psychotherapy (BPT) is efficacious for the treatment of various mental disorders. However, with regard to cancer patients, evidence is scarce. The aims of this project are to evaluate whether bodily disturbances in post-treatment cancer patients can be improved by group BPT, and to estimate the efficacy of intermittent smartphone-triggered bodily interventions.

Methods
The project is a bi-center study with two participating centers in Switzerland, applying a pre-post convergent parallel design of a weekly group BPT using a waiting-period comparator, including a nested RCT during the group BPT phase. During the BPT phase, either a smartphone-triggered bodily intervention or a smartphone-triggered control intervention is provided at random over 5 consecutive weeks, on 6 days weekly. Patients who had received curatively intended treatment for any malignant neoplasm (treatment being completed ≥3 months) and are suffering from bodily disturbances are screened to assess eligibility. Sample size estimation is based on an a priori power analysis. We plan to include a total of N = 88 subjects, aiming at at least 52 completers.
Patients are surveyed three times (baseline assessment (T0), pre- (T1) and post-intervention assessment (T2)), and on a daily basis along BPT during five consecutive weeks. The primary outcome, bodily disturbances, is assessed using the ‘Body Image Scale‘(BIS). For the secondary outcomes standardized questionnaires are used to assess changes in experience of presence and vitality, mood, body mindfulness, somatic symptoms and somatic symptom disorder, quality of life, anxiety, and depression including suicidal tendency, vitality and mental health, as well as group cohesion. Using semi standardized interviews (at T0 and T2), we aim to explore the relation of BPT with bodily disturbances and body image in post-treatment cancer patients, as well as the acceptance and burden of the intervention.

Discussion
The proposed study has strong potential benefits for cancer patients, as it may pave the way for new therapeutic approaches to treat bodily disturbances, which persist despite curative tumor therapy. These may considerably improve patients’ biopsychosocial well-being and quality of life.

Trial registration
ClinicalTrials.govNCT03707548 (registered 9 October 2018; retrospectively registered).
A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects
Authors: Bush Jim , Kawakami Kazuki , Muniz Rafael 
Published: December 2019

Abstract
Background/objective
FKB327 is a biosimilar of the adalimumab reference product (RP). The primary objective was to assess the relative bioavailability of FKB327 after a single subcutaneous (SC) dose via prefilled syringe (PFS), auto-injector (AI), or vial with a disposable syringe (vial), in healthy subjects.

Methods
This randomized, open-label, parallel-group, single SC-dose study was conducted in 195 healthy male and female subjects who were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI, or vial. The primary pharmacokinetic (PK) parameters, areas under the serum concentration-time curve to the last detectable value (AUC0-t) and extrapolated to infinity (AUC0-∞), and maximum concentration (Cmax), were compared. Relative bioavailability was established if the ratio of geometric least squares (LS) means of the test product was within the predefined bioequivalence (BE) range of 0.80 to 1.25 of the RP for each comparison. Safety and immunogenicity were assessed.

Results
The mean serum FKB327 concentration-time profiles appeared similar across all 3 presentations. AUC0-t, AUC0-∞, and Cmax were within the predefined BE range for PFS compared with vial, suggesting comparable bioavailability. AUC0-∞ and Cmax of AI compared with vial and PFS were fully contained within BE range, although the upper limit of 90% confidence intervals of the geometric LS means ratios for AUC0-t was slightly high. Treatment-emergent adverse events in all 3 groups were mild, with no new safety concern with FKB327 identified. Similar immunogenicity was observed among administrations.

Conclusion
Among all 3 delivery methods, PK characteristics, safety profiles, and immunogenicity were similar.

Trial registration
EU Clinical Trials Registry EudraCTN2014–004469-26, registered October 14, 2014.
Time and energy costs of different foraging choices in an avian generalist species
Authors: Sotillo Alejandro , Baert Jan M. , Müller Wendt , Stienen Eric W. M. , Soares Amadeu M. V. M. , Lens Luc 
Published: December 2019

Abstract
Background
Animals can obtain a higher foraging yield by optimizing energy expenditure or minimizing time costs. In this study, we assessed how individual variation in the relative use of marine and terrestrial foraging habitats relates to differences in the energy and time investments of an avian generalistic feeder (the Lesser Black-backed Gull, Larus fuscus), and how this changes during the course of the chick-rearing period.

Methods
We analyzed 5 years of GPS tracking data collected at the colony of Zeebrugge (Belgium). Cost proxies for energy expenditure (overall dynamic body acceleration) and time costs (trip durations and time spent away from the colony), together with trip frequency, were analyzed against the relative use of the marine and terrestrial habitats.

Results
The marine habitat was most often used by males and outside weekends, when fisheries are active. Marine trips implied higher energetic costs and lower time investments. As chicks became older, terrestrial trips became more prevalent, and trip frequency reached a peak towards 20 days after hatching of the first egg. Over a full chick rearing period, energy costs varied widely between individuals, but no trends were found across the marine foraging gradient. Conversely, a higher use of marine foraging implied lower overall amounts of time spent away from the colony.

Conclusions
Foraging habitat choice was related to overall time costs incurred by gulls, but not to energy costs. The effect of chick age on foraging habitat choice and effort may be driven by energy expenditure constraints on the amount of marine foraging that can be performed. If time is less constraining to them, Lesser Black-backed Gulls may meet the increasing chick demand for food by switching from high to low energy demanding foraging strategies.
Examining seasonal variation in epistaxis in a maritime climate
Authors: McMullin Ben , Atkinson Paul , Larivée Natasha , Chin Christopher J. 
Published: December 2019

Background Epistaxis is a common reason patients present to the emergency department. There is significant variation in climate across Canada. Our study aimed to determine if epistaxis is related to season, temperature and humidity in a Maritime climate. Methods Ethics approval was obtained. A retrospective chart review was performed. Patients who presented to the Saint John Regional Hospital Emergency Room between July 2015 and December 2017 with a diagnosis of epistaxis were identified. Weather data was collected from Environment Canada. We performed multiple univariate analyses examining confounding variables. Results In total, 476 cases of epistaxis were identified. There was a significant seasonal variation; the highest number of epistaxis cases occurred in the winter ( p < 0.001). A negative correlation was seen between mean daily humidity and epistaxis ( R2 = 0.7794). Conclusion The highest number of cases presented in the winter and a negative correlation was found between epistaxis and mean daily humidity.