bluuebunny/crossref_metadata_2025 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

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

Background

Service 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.

Methods

The 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.

Results

While 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.

Conclusions

A 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

Background

Respiratory 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.

Results

Lungs 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.

Conclusions

This 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

Objective

Evaluate the effects of vitamin D3 (VD3) on sperm parameters and endocrine markers in infertile men with asthenozoospermia.

Materials and methods

This 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.

Results

Three 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.

Conclusion

VD3 supplementation may affect sperm motility in men with asthenozoospermia and serum 25(OH)VD3 < 30 ng/ml.

Trial registration

Iran 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

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

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

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

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

Glässer’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

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

Background

Various 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 text

A 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).

Conclusions

The 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
RBM5-AS1 promotes radioresistance in medulloblastoma through stabilization of SIRT6 protein
Authors: Zhu Chuanying , Li Keke , Jiang Mawei , Chen Siyu
Published: July 2021

Cancer stem cells (CSCs) contribute to radioresistance in medulloblastoma. Thus, identification of key regulators of medulloblastoma stemness is critical for improving radiotherapy for medulloblastoma. In the present study, we profiled CSC-related long non-coding RNAs (lncRNAs) between radioresistant and parental medulloblastoma cells. The roles of the lncRNA RBM5-AS1 in the stemness and radiosensitivity of medulloblastoma cells were investigated. We found that RBM5-AS1, a novel inducer of medulloblastoma stemness, was significantly upregulated in radioresistant medulloblastoma cells compared to parental cells. Knockdown of RBM5-AS1 diminished the viability and clonogenic survival of both radioresistant and parental medulloblastoma cells after radiation. Silencing of RBM5-AS1 significantly enhanced radiation-induced apoptosis and DNA damage. In vivo studies confirmed that depletion of RBM5-AS1 inhibited tumor growth and increased radiosensitivity in a medulloblastoma xenograft model. In contrast, overexpression of RBM5-AS1 reduced radiation-induced apoptosis and DNA damage in medulloblastoma cells. Mechanistically, RBM5-AS1 interacted with and stabilized sirtuin 6 (SIRT6) protein. Silencing of SIRT6 reduced the stemness and reinforced radiation-induced DNA damage in medulloblastoma cells. Overexpression of SIRT6 rescued medulloblastoma cells from RBM5-AS1 depletion-induced radiosensitization and DNA damage. Overall, we identify RBM5-AS1 as an inducer of stemness and radioresistance in medulloblastoma. Targeting RBM5-AS1 may represent a potential strategy to overcome the resistance to radiotherapy in this malignancy.
Strategies to improve pharmaceutical supply chain resilience under politico-economic sanctions: the case of Iran
Authors: Bastani Peivand , Dehghan Zahra , Kashfi Seyyed Mansoor , Dorosti Hesam , Mohammadpour Mohammadtaghi , Mehralian Gholamhossein , Ravangard Ramin
Published: July 2021

Background

Given the impact of politico-economic sanctions on the pharmaceutical supply chain, this study aims to identify practical strategies to improve the resilience of the Iranian supply chain in pharmaceutical procurement under politico-economic sanctions.

Methods

This is a qualitative content analysis study conducted in 2018. Semi-structured interviews were conducted using snowball sampling, and saturation was achieved after 18 interviews. Guba and Lincoln's criteria, namely credibility, confirmability, transferability, and dependability, were considered to ensure the validity and transparency of the study. A five-step framework analysis was applied to analyze the data using MAX QDA10.

Results

The results led to the identification of nine main themes and 26 subthemes as strategies to improve the resilience of the pharmaceutical chain. According to the thematic map, some of these strategies have an extra-sectoral character: ‘insurance organizations’, ‘strengthening relations with other countries’, ‘mechanization of the distribution system’, and ‘suppliers and manufacturers’. At the same time, some inter-sectoral strategies can help the pharmaceutical chain maintain its resilience: ‘healthcare management and policy’, ‘exploiting local potential’, ‘pricing’, and ‘integrated health information systems.’ As a strategy, ‘Medical community and consumers’ also plays a crucial role in this regard. According to the subthemes, revisions of health management, more supervision, privatization, clinical policies, strategic purchasing, improvement of the referral system, inter-sectoral cooperation, support of indigenous medicines, rational pricing, insurance system, improvement of medical coverage, and development of electronic prescription should be considered by health systems. Sufficient support for indigenous medication and supervision of the distribution system should be considered by the pharmaceutical industry, taking into account the cooperation between consumers and patients.

Conclusions

Integration of the pharmaceutical supply chain and modern technologies, more attention to business complexity, economic development, intense competition, rapid changes in customer needs, and appropriate relationship between manufacturers, distributors, prescribers, and insurance organizations as purchasers should be considered by policymakers to improve supply chain resilience.
Dynamic earthquake sequence simulation with a SBIEM without periodic boundaries
Authors: Noda Hiroyuki
Published: July 2021

Dynamic earthquake sequence simulation is an important tool for investigating the behavior of a fault that hosts a series of earthquakes because it solves all interrelated stages in the earthquake cycle consistently, including nucleation, propagation and arrest of dynamic rupture, afterslip, locking, and interseismic stress accumulation. Numerically simulating and resolving these phenomena, which have different time and length scales, in a single framework is challenging. A spectral boundary integral equation method (SBIEM) that makes use of a fast Fourier transform is widely used because it reduces required computational costs, even though it can only be used for a planar fault. The conventional SBIEM has a periodic boundary condition as a result of the discretization of the wavenumber domain with a regular mesh; thus, to obtain an approximate solution for a fault in an infinite medium, it has been necessary to simulate a region much longer than the source distribution. Here, I propose a new SBIEM that is free from this artificial periodic boundary condition. In the proposed method, the periodic boundaries are removed by using a previously proposed method for the simulation of dynamic rupture. The integration kernel for the elastostatic effect, which reaches infinitely far from the source, is expressed analytically and replaces the one in the conventional SBIEM. The new method requires simulation of a region only twice as long as the source distribution, so the computational costs are significantly less than those required by the conventional SBIEM to simulate a fault in an infinite medium. The effect of the distance λ between the artificial periodic boundaries was investigated by comparing solutions for a typical problem setting between the conventional and proposed SBIEM. The result showed that the artificial periodic boundaries cause overestimation of the recurrence interval that is proportional to λ−2. If λ is four times the fault length, the interval is overestimated by less than 1%. Thus, the artificial periodic boundaries have only a modest effect on the conclusions of previous studies.
Nutritional status and quality of life in diabetic patients on hemodialysis: a cross-sectional study from Palestine
Authors: Hafi Eba’a , Soradi Ro’ya , Diab Sarah , Samara Ahmad M. , Shakhshir Marah , Alqub Malik , Zyoud Sa’ed H.
Published: July 2021

Background

End-stage renal disease (ESRD) is a leading cause of death and morbidity worldwide. Malnutrition is a common problem among hemodialysis (HD) patients that negatively impacts their prognosis and is linked to an increase in morbidity and mortality in these patients, as well as a decrease in their quality of life (QOL). In this study, we aimed to evaluate the QOL and to investigate factors that can influence it, including nutritional status, as well as socio-demographic factors, among Palestinian diabetic patients on HD therapy.

Methods

This was a cross-sectional study that occurred at a large hemodialysis center in Palestine. Malnutrition was assessed by the malnutrition-inflammation scale (MIS), and the quality of life was evaluated by using the EuroQoL five-dimensional instrument (EQ-5D). Multivariable linear regression analysis was carried out to look at the effect of multiple variables on QOL.

Results

A total of 118 diabetic patients on HD were included. Of these, 66.9% were male, and 60.2% were aged 60 years or higher. Having multiple comorbid diseases (p=0.004) and having been on HD for >4 years (p=0.003) were significantly associated with a higher MIS score, whereas living alone (p=0.037) and having been on HD for >4 years (p=0.002) was significantly associated with lower EQ-5D score. We also observed a significant association between the MIS score and the EQ-5D score(r=−0.616, p<0.001). Multiple linear regression analysis demonstrated that diabetic hemodialysis patients who lived within a family household were positively correlated with the QOL score (standardized coefficient, 0.178; 95% confidence interval (CI), 0.042 to 0.372; p = 0.015), and MIS score was significantly and negatively correlated with QOL scores (standardized coefficient, −0.587; 95% CI, −0.047 to −0.028; p < 0.001).

Conclusions

We found that malnutrition was associated with a lower QOL score among diabetic patients on HD. We recommend general practitioners, dietitians, nephrologists, and nurses to make plans that pay more attention to this group of patients who show evidence of malnutrition. Patients on dialysis for ≥ 4 years, patients who live alone, and those suffering from multiple co-morbid diseases should receive special care due to their higher risk of being impacted by this problem.
Molecular characterization and pathogenicity of an infectious cDNA clone of tomato brown rugose fruit virus
Authors: Ma Ziyue , Zhang Hui , Ding Ming , Zhang Zhongkai , Yang Xiuling , Zhou Xueping
Published: July 2021

Tomato brown rugose fruit virus (ToBRFV) is a new member of the genus Tobamovirus, and has the potential to affect the production and marketability of tomatoes and peppers. In this study, we sequenced and analyzed the complete genome of ToBRFV isolates from tomato plants showing mosaic and mottling symptoms in Yunnan Province of China. We constructed a full-length infectious cDNA clone of ToBRFV, which could induce systemic infection with typical symptoms in tomato, Nicotiana benthamiana, and N. tabacum cv. Samsun nn plants through Agrobacterium-mediated inoculation. Further experimental evidence demonstrated that the rod-shaped virions accumulating in agroinfiltrated plants are sap-transmissible. This is the first report on the construction of a biologically active, full-length infectious cDNA clone of ToBRFV. The system developed herein will facilitate further research on functions of ToBRFV-encoded proteins and plant-ToBRFV interactions through reverse genetic approaches.
Development and optimization of an in vivo electrocardiogram recording method and analysis program for adult zebrafish
Authors: Duong ThuyVy , Rose Rebecca , Blazeski Adriana , Fine Noah , Woods Courtney E. , Thole Joseph F. , Sotoodehnia Nona , Soliman Elsayed Z. , Tung Leslie , McCallion Andrew S. , Arking Dan E.
Published: July 2021

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiological abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zebrafish ECG reading GUI (zERG), a program to acquire measurements from traces that commercial software cannot examine owing to erroneous peak calling. We evaluate normal ECG trait variation, revealing highly reproducible intervals and wave amplitude variation largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS and QT intervals. With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiological phenotypes.
Advancing lung organoids for COVID-19 research
Authors: van der Vaart Jelte , Lamers Mart M. , Haagmans Bart L. , Clevers Hans
Published: July 2021

The COVID-19 pandemic has emphasised the need to develop effective treatments to combat emerging viruses. Model systems that poorly represent a virus' cellular environment, however, may impede research and waste resources. Collaborations between cell biologists and virologists have led to the rapid development of representative organoid model systems to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that lung organoids, in particular, have advanced our understanding of SARS-CoV-2 pathogenesis, and have laid a foundation to study future pandemic viruses and develop effective treatments.
Cold acclimation induces life stage-specific responses in the cardiac proteome of western painted turtles (Chrysemys picta bellii): implications for anoxia tolerance
Authors: Alderman Sarah L. , Riggs Claire L. , Bullingham Oliver M. N. , Gillis Todd E. , Warren Daniel E.
Published: July 2021

Western painted turtles (Chrysemys picta bellii) are the most anoxia-tolerant tetrapod. Survival time improves at low temperature and during ontogeny, such that adults acclimated to 3°C survive far longer without oxygen than either warm-acclimated adults or cold-acclimated hatchlings. As protein synthesis is rapidly suppressed to save energy at the onset of anoxia exposure, this study tested the hypothesis that cold acclimation would evoke preparatory changes in protein expression to support enhanced anoxia survival in adult but not hatchling turtles. To test this, adult and hatchling turtles were acclimated to either 20°C (warm) or 3°C (cold) for 5 weeks, and then the heart ventricles were collected for quantitative proteomic analysis. The relative abundance of 1316 identified proteins was compared between temperatures and developmental stages. The effect of cold acclimation on the cardiac proteome was only evident in the context of an interaction with life stage, suggesting that ontogenic differences in anoxia tolerance may be predicated on successful maturation of the heart. The main differences between the hatchling and adult cardiac proteomes reflect an increase in metabolic scope with age that included more myoglobin and increased investment in both aerobic and anaerobic energy pathways. Mitochondrial structure and function were key targets of the life stage- and temperature-induced changes to the cardiac proteome, including reduced Complex II proteins in cold-acclimated adults that may help down-regulate the electron transport system and avoid succinate accumulation during anoxia. Therefore, targeted cold-induced changes to the cardiac proteome may be a contributing mechanism for stage-specific anoxia tolerance in turtles.
An Atypical Manifestation of Mycobacterium tuberculosis Infection
Authors: Fernández Castro Iván , Isorno-Porto María Jesús , Novo-Veleiro Ignacio , Casar-Cocheteux Clara , Barrera-López Lucía , Andrade-Piña Ariadna Helena , López-Rodríguez María , Pose Reino Antonio
Published: July 2021

Introduction: Aortitis is seen in a wide variety of diseases. It was rarely found in the past but this is changing because of new imaging techniques. Case description: We present the case of a 45-year-old man who was found on thyroid ultrasound to have infrarenal aortitis and pathological lymphadenopathies in different locations. After an exhaustive diagnostic process, tuberculous aortitis, an infrequent manifestation of extrapulmonary tuberculosis, was diagnosed. The condition resolved after a 6-month course of antibiotics and a 6-week course of corticosteroids. Conclusion: Tuberculous aortitis is an atypical manifestation of Mycobacterium tuberculosis infection. The absence of typical symptoms and the difficulty of isolating the microorganism makes its diagnosis difficult. Therefore, clinical suspicion, microbiological tests and imaging are key for reaching the diagnosis and starting treatment for a serious disease that can cause aortic aneurysm and dissection.
Smoking prevention and cessation in young people
Authors: Croghan Emma
Published: July 2021

Smoking is started primarily in adolescence and is responsible for nearly 80 000 preventable deaths in England per year. Children and young people are reported to become addicted to tobacco and smoking within 4 weeks of starting the habit, In this article, Emma Croghan considers how school nurses can aid in preventing children and young people from taking up smoking, focusing on effective interventions such as mass media campaigns and school or peer-based programmes. How to help young people stop once they have developed a smoking habit is also discussed, based on the Ask, Advise, Act steps for advice sessions with young people who smoke.
Epilepsy: recognition and management of seizures in children and young people
Authors: Pickering Christopher
Published: July 2021

A seizure describes the signs and symptoms associated with a sudden surge in brain activity. It is a symptom of either acute brain disturbance, or may indicate a diagnosis of epilepsy, which describes an underlying tendency to have seizures. There are many different seizure types, which account for the wide variation in seizure symptoms. The principles of management remain constant for all seizure types: maintain child safety, ABC support, and arrange emergency assistance and hospital transfer for prolonged episodes. In addition to this, tonic-clonic seizures lasting for more than 5 minutes require treatment with benzodiazepines. Buccal midazolam or rectal diazepam are first-line options when intravenous or intraosseous access is not available. Children and young people with epilepsy should have individualised treatment plans which, if available, further simplify emergency treatment decisions.
Considerations for humane euthanasia in exotic pet species
Authors: Brown Sarah
Published: July 2021

Most veterinary professionals in companion animal practice will be familiar with and experienced in performing euthanasia in cats and dogs, but often less so with exotic pet species. This article aims to equip the clinician with an approach to performing humane, compassionate euthanasia in such species, keeping animal welfare paramount.
Self-consistent analysis of photonic-crystal surface-emitting lasers under continuous-wave operation
Authors: Katsuno Shumpei , Inoue Takuya , Yoshida Masahiro , Zoysa Menaka De , Ishizaki Kenji , Noda Susumu
Published: July 2021

We develop a self-consistent theoretical model for simulating the lasing characteristics of photonic-crystal surface-emitting lasers (PCSELs) under continuous-wave (CW) operation that takes into account thermal effects caused by current injection. Our model enables us to analyze the lasing characteristics of PCSELs under CW operation by solving self-consistently the changes in the in-plane optical gain and refractive index distribution, which is associated with heat generation and temperature rise, and the change in the oscillation modes. We reveal that the lasing band-edge selectivity and beam quality of the PCSELs are affected by the spatial distribution of the band-edge frequency of the photonic crystal formed by the refractive index distribution, which depends on the temperature distribution in the resonator. Furthermore, we show that single-mode lasing with narrow beam divergence can be realized even at high current injection under CW operation by introducing a photonic-crystal structure with an artificially formed lattice constant distribution, which compensates such band-edge frequency distribution.
Analysis of potential distortions corresponding to the hologram printed by a holographic wave-front printer
Authors: Choi Heemin , Kang Hoonjong , Kim Nam
Published: July 2021

In this paper, potential distortions corresponding to the hologram printed by a holographic wave-front printer are analyzed. Potential distortions are classified as the magnification(demagnification) distortion, barrel distortion, pincushion distortion, SLM mounting distortion, and translation distortion, respectively. These distortions are grouped as the optics distortion, SLM mounting distortion and the translation distortion depending on the process of recording the hologram in the holographic wave-front printer. In order to evaluate each distortion, a distortion analysis method based on a local spatial frequency is proposed. Through the proposed method, a diffracted wavefield reconstructed from a quantitatively distorted hologram is theoretically analyzed, and the validity of this analysis is verified by applying the numerical reconstruction method. In the numerical reconstruction, a propagation of a distorted wavefield reconstructed from the quantitatively distorted hologram is confirmed and contributed to generate the distorted reconstruction plane, such as a focal cloud plane and a convergence plane, depending on the types of distortion.
4.7 THz asymmetric beam multiplexer for GUSTO
Authors: Mirzaei Behnam , Gan Yuner , Finkel Matvey , Groppi Christopher , Young Abram , Walker Christopher , Hu Qing , Gao Jian-Rong
Published: July 2021

A full demonstration of the Fourier phase grating used as 4.7 THz local oscillator (LO) multiplexer for Galactic/Extragalactic ULDB Spectroscopic Terahertz Observatory (GUSTO) is presented in this paper, including its design, modeling, tolerance analysis, and experimental characterizations of the angular and intensity distributions among 2 × 4 output beams and the power efficiency. A quantum cascade laser (QCL) is used to generate the input beam for evaluation of the grating performance in its all relevant aspects with an accuracy level never reported before, where good agreements with modeling results are found. This is the first asymmetric-profile grating fully modelled and characterized at a THz frequency, that further confirms the versatility of this technology for providing an intermediate optical element for feeding multiple array detectors with a single radiation source at such a scientifically interesting frequency regime.
Ultranarrow spectral line of the radiation in double qubit-cavity ultrastrong coupling system
Authors: Zhao Teng , Wu Shao-ping , Yang Guo-qing , Huang Guang-ming , Li Gao-xiang
Published: July 2021

The ultrastrongly coupling (USC) system has very important research significance in quantum simulation and quantum computing. In this paper, the ultranarrow spectrum of a circuit QED system with two qubits ultrastrongly coupled to a single-mode cavity is studied. In the regime of USC, the JC model breaks down and the counter-rotating terms in the quantum Rabi Hamiltonian leads to the level anti-crossing in the energy spectrum. Choosing a single-photon driving field at the point of avoided-level crossing, we can get an equivalent four-level dressed state model, in which the dissipation of the two intermediate states is only related to the qubits decay. Due to the electron shelving of these two metastable states, a narrow peak appears in the cavity emission spectrum. Furthermore, we find that the physical origin for the spectral narrowing is the vacuum-induced quantum interference between two transition pathways. And this interference effect couples the slowly decaying incoherent components of the density matrix into the equations of the sidebands. This result provides a possibility for the study of quantum interference effect in the USC system.