bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and clinical implications of bronchiectasis in patients with overlapping asthma and chronic rhinosinusitis: a single-center prospective study
Authors: Sheng Haiyan , Yao Xiujuan , Wang Xiangdong , Wang Yuhong , Liu Xiaofang , Zhang Luo 
Published: July 2021

Abstract
Background
As a typical “united airway” disease, asthma-chronic rhinosinusitis (CRS) overlap has recently drawn more attention. Bronchiectasis is a heterogeneous disease related to a variety of diseases. Whether bronchiectasis exists and correlates with asthma-CRS patients has not been fully elucidated. The purpose of the study was to explore the presence and characteristics of bronchiectasis in patients with overlapping asthma and CRS.

Methods
This report describes a prospective study with consecutive asthma-CRS patients. The diagnosis and severity of bronchiectasis were obtained by thorax high-resolution computed tomography (HRCT), the Smith radiology scale and the Bhalla scoring system. CRS severity was evaluated by paranasal sinus CT and the Lund-Mackay (LM) scoring system. The correlations between bronchiectasis and clinical data, fraction of exhaled nitric oxide, peripheral blood eosinophil counts and lung function were analyzed.

Results
Seventy-two (40.91%) of 176 asthma-CRS patients were diagnosed with bronchiectasis. Asthma-CRS patients with overlapping bronchiectasis had a higher incidence rate of nasal polyps (NPs) (P = 0.004), higher LM scores (P = 0.044), higher proportion of ≥ 1 severe exacerbation of asthma in the last 12 months (P = 0.003), lower postbronchodilator forced expiratory volume in one second (FEV1) % predicted (P = 0.006), and elevated peripheral blood eosinophil counts (P = 0.022). Smith and Bhalla scores were shown to correlate positively with NPs and negatively with FEV1% predicted and body mass index. Cutoff values of FEV1% predicted ≤ 71.40%, peripheral blood eosinophil counts > 0.60 × 109/L, presence of NPs, and ≥ 1 severe exacerbation of asthma in the last 12 months were shown to differentiate bronchiectasis in asthma-CRS patients.

Conclusions
Bronchiectasis commonly overlaps in asthma-CRS patients. The coexistence of bronchiectasis predicts a more severe disease subset in terms of asthma and CRS. We suggest that asthma-CRS patients with NPs, severe airflow obstruction, eosinophilic inflammation, and poor asthma control should receive HRCT for the early diagnosis of bronchiectasis.
Designing a stakeholder-inclusive service model for an eHealth service to support older adults in an active and social life
Authors: Broekhuis Marijke , Weering Marit Dekker-van , Schuit Cheyenne , Schürz Stefan , van Velsen Lex 
Published: July 2021

AbstractBackgroundService model design is slowly being recognized among eHealth developers as a valuable method for creating durable implementation strategies. Nonetheless, practical guidelines and case-studies that inform the community on how to design a service model for an eHealth innovation are lacking. This study describes the development of a service model for an eHealth service, titled ‘SALSA’, which intends to support older adults with a physically active and socially inclusive lifestyle.MethodsThe service model for the SALSA service was developed in eight consecutive rounds, using a mixed-methods approach. First, a stakeholder salience analysis was conducted to identify the most relevant stakeholders. In rounds 2–4, in-depth insights about implementation barriers, facilitators and workflow processes of these stakeholders were gathered. Rounds 5 and 6 were set up to optimize the service model and receive feedback from stakeholders. In rounds 7 and 8, we focused on future implementation and integrating the service model with the technical components of the eHealth service.ResultsWhile the initial goal was to create one digital platform for the eHealth service, the results of the service modelling showed how the needs of two important stakeholders, physiotherapists and sports trainers, were too different for integrating them in one platform. Therefore, the decision was made to create two platforms, one for preventive (senior sports activities) and one for curative (physical rehabilitation) purposes.ConclusionsA service model shows the interplay between service model design, technical development and business modelling. The process of service modelling helps to align the interests of the different stakeholders to create support for future implementation of an eHealth service. This study provides clear documentation on how to conduct service model design processes which can enable future learning and kickstart new research. Our results show the potential that service model design has for service development and innovation in health care.
Research article expression of surfactant protein-A and D, and CD9 in lungs of 1 and 30 day old foals
Authors: Bocking Tara , Johnson Laura , Singh Amitoj , Desai Atul , Aulakh Gurpreet Kaur , Singh Baljit 
Published: July 2021

AbstractBackgroundRespiratory diseases are a major cause of morbidity and mortality in the horses of all ages including foals. There is limited understanding of the expression of immune molecules such as tetraspanins and surfactant proteins (SP) and the regulation of the immune responses in the lungs of the foals. Therefore, the expression of CD9, SP-A and SP-D in foal lungs was examined.ResultsLungs from one day old (n = 6) and 30 days old (n = 5) foals were examined for the expression of CD9, SP-A, and SP-D with immunohistology and Western blots. Western blot data showed significant increase in the amount of CD9 protein (p = 0.0397)but not of SP-A and SP-D at 30 days of age compared to one day. Immunohistology detected CD9 in the alveolar septa and vascular endothelium but not the bronchiolar epithelium in the lungs of the foals in both age groups. SP-A and SP-D expression was localized throughout the alveolar septa including type II alveolar epithelial cells and the vascular endothelium of the lungs in all the foals. Compared to one day old foals, the expression of SP-A and SP-D appeared to be increased in the bronchiolar epithelium of 30 day old foals. Pulmonary intravascular macrophages were also positive for SP-A and SP-D in 30 days old foals and these cells are not developed in the day old foals.ConclusionsThis is the first data on the expression of CD9, SP-A and SP-D in the lungs of foals.
The effects of Vitamin D3 supplementation on Spermatogram and endocrine factors in asthenozoospermia infertile men: a randomized, triple blind, placebo-controlled clinical trial
Authors: Maghsoumi-Norouzabad Leila , Zare Javid Ahmad , Mansoori Anahita , Dadfar Mohammadreza , Serajian Amirarsalan 
Published: July 2021

AbstractObjectiveEvaluate the effects of vitamin D3 (VD3) on sperm parameters and endocrine markers in infertile men with asthenozoospermia.Materials and methodsThis randomized, triple-masking, placebo-controlled clinical trial conducted on 86 asthenozoospermia infertile men with serum 25 hydroxy vitamin D3 (25(OH)VD3)< 30 ng/ml in the infertility clinic of Ahvaz Jahad daneshgahi, Iran.Patients were randomly allocated to groups A and B, who received daily 4000 IU VD3 and matching placebo respectively for 3 months. Demographic data, dietary intake, physical activity, sun exposure, anthropometric indices, serum 25(OH)VD3, luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (T), estradiol (E2),, sex hormone-binding globulin (SHBG), free androgen index (FAI = T/SHBG. 100), T/LH and T/E2 ratios, prolactin (PRO), parathyroid hormone (PTH), osteocalcin (OCN), phosphorus and sperm parameters were assessed.ResultsThree months VD3 supplementation with 4000 IU/day had no significant effects body weight, body mass index (BMI), waist circumference (WC), body fat (BF), serum, OCN, LH, FSH, T, E2, SHBG, PRO, T/E2 ratio, FAI, semen volume, sperm count and normal sperm morphology.It increases serum 25(OH)VD3, PTH and phosphorus and seminal and serum calcium, T/LH ratio and total and progressive sperm motility and decreased significantly compared to the baseline and placebo group.ConclusionVD3 supplementation may affect sperm motility in men with asthenozoospermia and serum 25(OH)VD3 < 30 ng/ml.Trial registrationIran Clinical Trials Registry, ID: IRCT20151128025274N4, registered on 28 March 2018, URL of trial registry record:https://www.irct.ir/trial/29983
Bioinformatics integrated analysis to investigate candidate biomarkers and associated metabolites in osteosarcoma
Authors: Wang Jun , Gong Mingzhi , Xiong Zhenggang , Zhao Yangyang , Xing Deguo 
Published: July 2021

Abstract
Background
This study hoped to explore the potential biomarkers and associated metabolites during osteosarcoma (OS) progression based on bioinformatics integrated analysis.

Methods
Gene expression profiles of GSE28424, including 19 human OS cell lines (OS group) and 4 human normal long bone tissue samples (control group), were downloaded. The differentially expressed genes (DEGs) in OS vs. control were investigated. The enrichment investigation was performed based on DEGs, followed by protein–protein interaction network analysis. Then, the feature genes associated with OS were explored, followed by survival analysis to reveal prognostic genes. The qRT-PCR assay was performed to test the expression of these genes. Finally, the OS-associated metabolites and disease-metabolic network were further investigated.

Results
Totally, 357 DEGs were revealed between the OS vs. control groups. These DEGs, such as CXCL12, were mainly involved in functions like leukocyte migration. Then, totally, 38 feature genes were explored, of which 8 genes showed significant associations with the survival of patients. High expression of CXCL12, CEBPA, SPARCL1, CAT, TUBA1A, and ALDH1A1 was associated with longer survival time, while high expression of CFLAR and STC2 was associated with poor survival. Finally, a disease-metabolic network was constructed with 25 nodes including two disease-associated metabolites cyclophosphamide and bisphenol A (BPA). BPA showed interactions with multiple prognosis-related genes, such as CXCL12 and STC2.

Conclusion
We identified 8 prognosis-related genes in OS. CXCL12 might participate in OS progression via leukocyte migration function. BPA might be an important metabolite interacting with multiple prognosis-related genes.
A 5′-tRNA halve, tiRNA-Gly promotes cell proliferation and migration via binding to RBM17 and inducing alternative splicing in papillary thyroid cancer
Authors: Han Litao , Lai Hejing , Yang Yichen , Hu Jiaqian , Li Zhe , Ma Ben , Xu Weibo , Liu Wanlin , Wei Wenjun , Li Duanshu , Wang Yu , Zhai Qiwei , Ji Qinghai , Liao Tian 
Published: July 2021

Abstract
Background
tRNA-derived small noncoding RNAs (sncRNAs) are mainly categorized into tRNA halves (tiRNAs) and fragments (tRFs). Biological functions of tiRNAs in human solid tumor are attracting more and more attention, but researches concerning the mechanisms in tiRNAs-mediated tumorigenesis are rarely. The direct regulatory relationship between tiRNAs and splicing-related proteins remain elusive.

Methods
Papillary thyroid carcinoma (PTC) associated tRNA fragments were screened by tRNA fragments deep sequencing and validated by qRT-PCR and Northern Blot in PTC tissues. The biological function of tRNA fragments were assessed by cell counting kit, transwells and subcutaneous transplantation tumor of nude mice. For mechanistic study, tRNA fragments pull-down, RNA immunoprecipitation, Western Blot, Immunofluorescence, Immunohistochemical staining were performed.

Results
Herein, we have identified a 33 nt tiRNA-Gly significantly increases in papillary thyroid cancer (PTC) based on tRFs & tiRNAs sequencing. The ectopic expression of tiRNA-Gly promotes cell proliferation and migration, whereas down-regulation of tiRNA-Gly exhibits reverse effects. Mechanistic investigations reveal tiRNA-Gly directly bind the UHM domain of a splicing-related RNA-binding protein RBM17. The interaction with tiRNA-Gly could translocate RBM17 from cytoplasm into nucleus. In addition, tiRNA-Gly increases RBM17 protein expression via inhibiting its degradation in a ubiquitin/proteasome-dependent way. Moreover, RBM17 level in tiRNA-Gly high-expressing human PTC tissues is upregulated. In vivo mouse model shows that suppression of tiRNA-Gly decreases RBM17 expression. Importantly, tiRNA-Gly can induce exon 16 splicing of MAP4K4 mRNA leading to phosphorylation of downstream signaling pathway, which is RBM17 dependent.

Conclusions
Our study firstly illustrates tiRNA-Gly can directly bind to RBM17 and display oncogenic effect via RBM17-mediated alternative splicing. This fully novel model broadens our understanding of molecular mechanism in which tRNA fragment in tumor cells directly bind RNA binding protein and play a role in alternative splicing.
SAVER: sodium valproate for the epigenetic reprogramming of high-risk oral epithelial dysplasia—a phase II randomised control trial study protocol
Authors: McCarthy Caroline , Sacco Joseph , Fedele Stefano , Ho Michael , Porter Stephen , Liloglou Triantafillos , Greenhalf Bill , Robinson Max , Young Bridget , Cicconi Silvia , Chauhan Seema , Tesfaye Binyam , Jackson Richard , Sherratt Frances , Shaw Richard 
Published: July 2021

Abstract
Background
Sodium valproate (VPA) has been associated with a reduced risk of head and neck cancer development. The potential protective mechanism of action is believed to be via inhibition of histone deacetylase and subsequent epigenetic reprogramming. SAVER is a phase IIb open-label, randomised control trial of VPA as a chemopreventive agent in patients with high-risk oral epithelial dysplasia (OED). The aim of the trial is to gather preliminary evidence of the clinical and biological effects of VPA upon OED and assess the feasibility and acceptability of such a trial, with a view to inform a future definitive phase III study.

Methods
One hundred and ten patients with high-risk OED will be recruited from up to 10 secondary care sites in the UK and randomised into either VPA or observation only for 4 months. Women of childbearing potential will be excluded due to the teratogenic properties of VPA. Tissue and blood samples will be collected prior to randomisation and on the last day of the intervention/observation-only period (end of 4 months). Clinical measurement and additional safety bloods will be taken at multiple time points during the trial. The primary outcome will be a composite, surrogate endpoint of change in lesion size, change in grade of dysplasia and change in LOH profile at 8 key microsatellite regions. Feasibility outcomes will include recruitment targets, compliance with the study protocol and adverse effects. A qualitative sub-study will explore patient experience and perception of the trial.

Discussion
The current management options for patients with high-risk OED are limited and mostly include surgical resection and clinical surveillance. However, there remains little evidence whether surgery can effectively lead to a notable reduction in the risk of oral cancer development. Similarly, surveillance is associated with concerns regarding delayed diagnosis of OED progressing to malignancy. The SAVER trial provides an opportunity to investigate the effects of a repurposed, inexpensive and well-tolerated medication as a potential chemopreventive strategy for patients with high-risk OED. The clinical and biological findings of SAVER will inform the appropriateness, design and feasibility of a definitive phase III trial.

Trial registration
The trial is registered with the European Clinical Trials Database (Eudra-CT 2018-000197-30). (http://www.isrctn.com/ISRCTN12448611). The trial was prospectively registered on 24/04/2018.
Soil-transmitted helminth infections in free-ranging non-human primates from Cameroon and Gabon
Authors: Sirima C. , Bizet C. , Hamou H. , Červená B. , Lemarcis T. , Esteban A. , Peeters M. , Mpoudi Ngole E. , Mombo I. M. , Liégeois F. , Petrželková K. J. , Boussinesq M. , Locatelli S. 
Published: July 2021

Abstract
Background
Zoonotic diseases are a serious threat to both public health and animal conservation. Most non-human primates (NHP) are facing the threat of forest loss and fragmentation and are increasingly living in closer spatial proximity to humans. Humans are infected with soil-transmitted helminths (STH) at a high prevalence, and bidirectional infection with NHP has been observed. The aim of this study was to determine the prevalence, genetic diversity, distribution and presence of co-infections of STH in free-ranging gorillas, chimpanzees and other NHP species, and to determine the potential role of these NHP as reservoir hosts contributing to the environmental sustenance of zoonotic nematode infections in forested areas of Cameroon and Gabon.

Methods
A total of 315 faecal samples from six species of NHPs were analysed. We performed PCR amplification, sequencing and maximum likelihood analysis of DNA fragments of the internal transcribed spacer 2 (ITS2) nuclear ribosomal DNA to detect the presence and determine the genetic diversity of Oesophagostomum spp., Necator spp. and Trichuris spp., and of targeted DNA fragments of the internal transcribed spacer 1 (ITS1) to detect the presence of Ascaris spp.

Results
Necator spp. infections were most common in gorillas (35 of 65 individuals), but also present in chimpanzees (100 of 222 individuals) and in one of four samples from greater spot-nosed monkeys. These clustered with previously described type II and III Necator spp. Gorillas were also the most infected NHP with Oesophagostomum (51/65 individuals), followed by chimpanzees (157/222 individuals), mandrills (8/12 samples) and mangabeys (7/12 samples), with O. stephanostomum being the most prevalent species. Oesophagostomum bifurcum was detected in chimpanzees and a red-capped mangabey, and a non-classified Oesophagostomum species was detected in a mandrill and a red-capped mangabey. In addition, Ternidens deminutus was detected in samples from one chimpanzee and three greater spot-nosed monkeys. A significant relative overabundance of co-infections with Necator and Oesophagostomum was observed in chimpanzees and gorillas. Trichuris sp. was detected at low prevalence in a gorilla, a chimpanzee and a greater spot-nosed monkey. No Ascaris was observed in any of the samples analysed.

Conclusions
Our results on STH prevalence and genetic diversity in NHP from Cameroon and Gabon corroborate those obtained from other wild NHP populations in other African countries. Future research should focus on better identifying, at a molecular level, the species of Necator and Oesophagostomum infecting NHP and determining how human populations may be affected by increased proximity resulting from encroachment into sylvatic STH reservoir habitats.

Graphical Abstract
Characterization and protective activity of monoclonal antibodies directed against Fe (3+) ABC transporter substrate-binding protein of Glaesserella parasuis
Authors: Zhu Kexin , Yu Dong , An Jiahui , Li Yufeng 
Published: July 2021

AbstractGlässer’s disease is caused by the agent Glaesserella parasuis and is difficult to prevent and control. Candidate screening for subunit vaccines contributes to the prevention of this disease. Therefore, in this study, the inactivated G. parasuis reference serovar 5 strain (G. parasuis-5) was used to generate specific monoclonal antibodies (mAbs) to screen subunit vaccine candidates. Six mAbs (1A12, 3E3, 4C6, 2D1, 3E6, and 4B2) were screened, and they all reacted with the G. parasuis serovar 5 strain according to laser confocal microscopy and flow cytometry (FCM). Indirect enzyme-linked immunosorbent assay (ELISA) showed that one mAb 2D1, can react with all 15 reference serovars of G. parasuis. Protein mass spectrometry and Western blot analysis demonstrated that mAb 2D1 specifically reacts with Fe (3+) ABC transporter substrate-binding protein. A complement killing assay found that the colony numbers of bacteria were significantly reduced in the G. parasuis-5 group incubated with mAb 2D1 (p < 0.01) in comparison with the control group. Opsonophagocytic assays demonstrated that mAb 2D1 significantly enhanced the phagocytosis of 3D4/21 cells by G. parasuis (p < 0.05). RAW264.7 cells with stronger phagocytic ability were also used for the opsonophagocytic assay, and the difference was highly significant (p < 0.01). Passive immunization of mice revealed that mAb 2D1 can eliminate the bacteria in the blood and provide protection against G. parasuis-5. Our study found one mAb that can be used to prevent and control G. parasuis infection in vivo and in vitro, which may suggest that Fe (3+) ABC transporter substrate-binding protein is an immunodominant antigen and a promising candidate for subunit vaccine development.
Elevated NTCP expression by an iPSC-derived human hepatocyte maintenance medium enhances HBV infection in NTCP-reconstituted HepG2 cells
Authors: Li Xinlei , Xu Zhaohui , Mitra Bidisha , Wang Minghang , Guo Haitao , Feng Zongdi 
Published: July 2021

Abstract
Background
The sodium taurocholate cotransporting polypeptide (NTCP) is a functional receptor for hepatitis B virus (HBV). NTCP-reconstituted human hepatoma cells support HBV infection, but the infection is suboptimal and no apparent HBV spread has been observed in this system.

Results
We found that NTCP-reconstituted HepG2 cells were highly susceptible to HBV infection after cells were cultured in a commercial human inducible pluripotent stem cell (iPSC)-derived hepatocyte maintenance medium (HMM). The enhanced HBV infection coincided with increased NTCP expression, and was observed in six different clones of HepG2-NTCP cells. Promoter assays indicated that HMM activated the cytomegalovirus immediate-early (IE) promoter that drives the NTCP expression in the HepG2-NTCP cells. RNA-Seq analysis revealed that HMM upregulated multiple metabolic pathways. Despite highly upregulated NTCP expression by HMM, no obvious HBV spread was observed even in the presence of PEG 8000.

Conclusions
Our data suggest that this particular medium could be used to enhance HBV infection in NTCP-reconstituted hepatocytes in vitro.
Safety of SARS-CoV-2 vaccines: a systematic review and meta-analysis of randomized controlled trials
Authors: Chen Musha , Yuan Yue , Zhou Yiguo , Deng Zhaomin , Zhao Jin , Feng Fengling , Zou Huachun , Sun Caijun 
Published: July 2021

AbstractBackgroundVarious modalities of vaccines against coronavirus disease 2019 (COVID-19), based on different platforms and immunization procedures, have been successively approved for marketing worldwide. A comprehensive review for clinical trials assessing the safety of COVID-19 vaccines is urgently needed to make an accurate judgment for mass vaccination.Main textA systematic review and meta-analysis was conducted to determine the safety of COVID-19 vaccine candidates in randomized controlled trials (RCTs). Data search was performed in PubMed, Embase, Cochrane library, Scopus, Web of Science, and MedRxiv. Included articles were limited to RCTs on COVID-19 vaccines. A total of 73,633 subjects from 14 articles were included to compare the risks of adverse events following immunization (AEFI) after vaccinating different COVID-19 vaccines. Pooled risk ratios (RR) of total AEFI for inactivated vaccine, viral-vectored vaccine, and mRNA vaccine were 1.34 [95% confidence interval (CI) 1.11–1.61,P < 0.001], 1.65 (95%CI1.31–2.07,P < 0.001), and 2.01 (95%CI1.78–2.26,P < 0.001), respectively. No significant differences on local and systemic AEFI were found between the first dose and second dose. In addition, people aged ≤ 55 years were at significantly higher risk of AEFI than people aged ≥ 56 years, with a pooledRRof 1.25 (95%CI1.15–1.35,P < 0.001).ConclusionsThe safety and tolerance of current COVID-19 vaccine candidates are acceptable for mass vaccination, with inactivated COVID-19 vaccines candidates having the lowest reported AEFI. Long-term surveillance of vaccine safety is required, especially among elderly people with underlying medical conditions.Graphic Abstract