bluuebunny/crossref_metadata_2025 huggingface dataset:
Tandem repeats ubiquitously flank and contribute to translation initiation sites
Authors: Maddi Ali M. A. , Kavousi Kaveh , Arabfard Masoud , Ohadi Hamid , Ohadi Mina
Published: July 2022

Background

While the evolutionary divergence ofcis-regulatory sequences impacts translation initiation sites (TISs), the implication of tandem repeats (TRs) in TIS selection remains largely elusive. Here, we employed the TIS homology concept to study a possible link between TRs of all core lengths and repeats with TISs.

Methods

Human, as reference sequence, and 83 other species were selected, and data was extracted on the entire protein-coding genes (n = 1,611,368) and transcripts (n = 2,730,515) annotated for those species from Ensembl 102. Following TIS identification, two different weighing vectors were employed to assign TIS homology, and the co-occurrence pattern of TISs with the upstream flanking TRs was studied in the selected species. The results were assessed in 10-fold cross-validation.

Results

On average, every TIS was flanked by 1.19 TRs of various categories within its 120 bp upstream sequence, per species. We detected statistically significant enrichment of non-homologous human TISs co-occurring with human-specific TRs. On the contrary, homologous human TISs co-occurred significantly with non-human-specific TRs. 2991 human genes had at least one transcript, TIS of which was flanked by a human-specific TR. Text mining of a number of the identified genes, such asCACNA1A, EIF5AL1, FOXK1, GABRB2, MYH2, SLC6A8,andTTN, yielded predominant expression and functions in the human brain and/or skeletal muscle.

Conclusion

We conclude that TRs ubiquitously flank and contribute to TIS selection at the trans-species level. Future functional analyses, such as a combination of genome editing strategies and in vitro protein synthesis may be employed to further investigate the impact of TRs on TIS selection.
Interleukin 20 receptor subunit beta (IL20RB) predicts poor prognosis and regulates immune cell infiltration in clear cell renal cell carcinoma
Authors: Zhang Haoxun , Liu Yiwen , Wang Bowen , Wang Chunyang
Published: July 2022

Background and objective

Emerging evidence has proven the robust role of tumor mutation burden (TMB) and immune cell infiltration (ICI) in cancer immunotherapy. However, the precise effect of TMB and ICI on clear cell renal cell carcinoma (ccRCC) remains elusive and merits further investigation. Therefore, we aim to identify the TMB-related genes in predicting prognosis and to explore the potential mechanisms of the identified Interleukin 20 receptor subunit beta (IL20RB) in ICI in ccRCC.

Method

The relative information of patients with ccRCC was obtained from The Cancer Genome Atlas database (TCGA). Immune-related genes were downloaded from the Immunology Database and Analysis Portal database. Cox regression analysis was used to identify prognosis-related immune genes for ccRCC. The relationship ofIL20RBexpression levels with clinicopathological parameters was analyzed using the “limma” and “survival” packages. Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) databases were used as external validation. Quantitative Real-time PCR (qRT-PCR) and western blots were used to validate the expression levels ofIL20RBin tumor cells. Cell counting kit-8 (CCK-8) assay and colony formation assay were used to examine the effect ofIL20RBon the viability of ccRCC cells. Gene set enrichment analysis (GSEA) was introduced for the analysis ofIL20RB-related signaling pathways. Tumor Immune Estimation Resource (TIMER) and Tumor and Immune System Interaction Database (TISIDB) were utilized to determine the correlation ofIL20RBexpression levels with tumor-infiltrating immune cells (TIICs).

Results

IL20RBwas significantly overexpressed in different ccRCC tissues and cells. HighIL20RBexpression in ccRCC patients was associated with short overall survival, high tumor grade, and advanced TNM stage. After knockdown ofIL20RBwith small interfering RNA (siRNA) technology, ccRCC cells’ proliferation was significantly attenuated. Moreover, overexpression ofIL20RBcould increase the infiltration level of several immune cells, especially T follicular helper cells (Tfh), and overexpressed Tfh cells were correlated with poor prognosis in ccRCC.

Conclusions

IL20RBmay function as an immune-associated therapeutic target for it determines cancer progression and regulates immune cell infiltration in ccRCC.
In silico discovery of blood cell macromolecular associations
Authors: Gautvik Kaare M. , Sachse Daniel , Hinton Alexandra C. , Olstad Ole K. , Kiel Douglas P. , Hsu Yi-Hsiang , Utheim Tor P. , Lary Christine W. , Reppe Sjur
Published: July 2022

Background

Physical molecular interactions are the basis of intracellular signalling and gene regulatory networks, and comprehensive, accessible databases are needed for their discovery. Highly correlated transcripts may reflect important functional associations, but identification of such associations from primary data are cumbersome. We have constructed and adapted a user-friendly web application to discover and identify putative macromolecular associations in human peripheral blood based on significant correlations at the transcriptional level.

Methods

The blood transcriptome was characterized by quantification of 17,328 RNA species, including 341 mature microRNAs in 105 clinically well-characterized postmenopausal women. Intercorrelation of detected transcripts signal levels generated a matrix with > 150 million correlations recognizing the human blood RNA interactome. The correlations with calculated adjustedp-values were made easily accessible by a novel web application.

Results

We found that significant transcript correlations within the giant matrix reflect experimentally documented interactions involving select ubiquitous blood relevant transcription factors (CREB1, GATA1, and the glucocorticoid receptor (GR, NR3C1)). Their responsive genes recapitulated up to 91% of these as significant correlations, and were replicated in an independent cohort of 1204 individual blood samples from the Framingham Heart Study. Furthermore, experimentally documented mRNAs/miRNA associations were also reproduced in the matrix, and their predicted functional co-expression described. The blood transcript web application is available athttp://app.uio.no/med/klinmed/correlation-browser/blood/index.phpand works on all commonly used internet browsers.

Conclusions

Using in silico analyses and a novel web application, we found that correlated blood transcripts across 105 postmenopausal women reflected experimentally proven molecular associations. Furthermore, the associations were reproduced in a much larger and more heterogeneous cohort and should therefore be generally representative. The web application lends itself to be a useful hypothesis generating tool for identification of regulatory mechanisms in complex biological data sets.
Is cell regeneration and infiltration a double edged sword for porcine aortic valve deterioration? A large cohort of histopathological analysis
Authors: Li Li , Duan Xuejing , Wang Hongyue , Sun Yang , Zhao Wei , Lu Yang , Xu Hongyu , You Yiwei , Wang Qingzhi
Published: July 2022

Background and objective

Bioprostheses are the most common prostheses used for valve replacement in the Western medicine. The major flaw of bioprostheses is the occurrence of structural valve deterioration (SVD). This study aimed to assess the pathological features of porcine aortic valve (PAV)-SVD based on histomorphological and immunopathological characteristics of a large cohort of patients.

Methods

Histopathological data of 109 cases with resected PAV were collected. The type and amount of infiltrated cells were evaluated in the different types of bioprosthetic SVD by immunohistochemical staining.

Results

The most common cause of SVD was calcification, leaflet tear, and dehiscence (23.9%, 19.3%, and 18.3%, respectively). Immunohistochemical staining demonstrated that macrophages were infiltrated in the calcified, lacerated and dehiscence PAV, in which both M1 and M2 macrophages were existed in the calcified PAV. Importantly, the higher content of M1 macrophages and less content of M2 macrophages were found in the lacerated and dehiscence PAV, and MMP-1 expression was mainly found in the lacerated PAV. The endothelialization rate of leaflet dehiscence was higher than that of calcified and lacerated leaflets. A large number of CD31+/CD11b+ cells was aggregated in the spongy layer in the lacerated and dehiscence PAV.

Conclusion

Cell regeneration and infiltration is a double edged sword for the PAV deterioration. Macrophage infiltration is involved in the different types of SVD, while only MMP-1 expression is involved in lacerated leaflets. The macrophage subtype of circulating angiogenic cells in dehiscence and tear PAV could be identified, which could reserve macrophages in the PAV-SVD.
Platelet-hemoglobin ratio predicts amputation in patients with below-knee peripheral arterial disease
Authors: Ozbeyaz Nail Burak , Gokalp Gokhan , Algul Engin , Sahan Haluk Furkan , Aydinyilmaz Faruk , Guliyev Ilkin , Kalkan Kamuran , Erken Pamukcu Hilal
Published: July 2022

Background

Peripheral arterial disease (PAD) causes significant morbidity today. Atherosclerosis is evident in the pathophysiological process in most patients, so PAD has similar risk factors as coronary artery disease. Platelet-Hemoglobin ratio (PHR) has been proven to predict mortality in atherosclerotic heart disease. We aimed to determine the relationship between PHR and below-knee amputation.

Methods

The study is a single-center retrospective study. Platelet count/hemoglobin amount formula was used for PHR. Only PAD patients with below-knee critical extremity ischemia and unsuitable for revascularization were included in the study.

Results

235 patients were included in the study retrospectively. The mean age was 65.7 ± 9.9 years and 175(74.5%) of them were male. In the amputated group, white blood cell, neutrophil, platelet, creatinine, glucose, and PHR were higher (p = .031, p = .045, p = .011, p = .048 p = .018, p = .004, respectively). Only hemoglobin values were lower (p = .003). Multivariable regression analysis showed; age, albumin and PHR were determined as independent risk factors for amputation (Age; OR (95%CI): (1.094(1.040–1.152), p = .001) (Albumin; OR (95% CI): 1.950(1.623–1.799), p = .001) (PHR; OR (95% CI): 1.872(1.246–2.812), p = .003). Receiver operating characteristics analysis performed to determine the optimal cut-off value of PHR for amputation, the optimal value was found 2.08 (65.8% sensitivity, 67.5% specificity, p < .001).

Conclusions

PHR was a good predictor for BKA. Using the PHR, it may be possible to identify high-risk patients for amputation.
Effect of multicomponent exercise in cognitive impairment: a systematic review and meta-analysis
Authors: Venegas-Sanabria Luis Carlos , Cavero-Redondo Iván , Martínez-Vizcaino Vicente , Cano-Gutierrez Carlos Alberto , Álvarez-Bueno Celia
Published: July 2022

Background

Multicomponent physical exercise is the most recommended type of physical intervention in older adults. Experimental data suggest the relevance of the muscle-brain axis and the relationship between muscle contraction and release of brain-derived neurotrophic factor, however, the impact of this relationship on cognition remains unclear, especially in people with diagnosis of cognitive impairment. This study assesses the effect of multicomponent physical exercise on global cognition in people with mild cognitive impairment or dementia.

Methods

Randomized controlled trials published until January 2021 were searched across three electronic databases (PubMed, Scopus, and Cochrane Database). Data about exercises included in the multicomponent intervention (endurance, strength, balance, or flexibility), the inclusion of aerobic exercise, and the change in global cognition were extracted. The effect size was represented as a standardized mean difference. Risk of bias was assessed by the RoB2 tool.

Results

A total of 8 studies were included. The overall effect size suggested an effect of multicomponent exercise on global cognition. However, the subgroup analysis showed an effect only when aerobic exercise was included in the intervention. No effect when mild cognitive impairment and dementia were assessed separately was found.

Conclusion

This study suggests that multicomponent physical exercise could have an effect on global cognition in people with mild cognitive impairment or dementia only when aerobic exercise is included in the intervention. Our results support the inclusion of structured physical exercise programs in the management of people with cognitive impairment.
Benchmarking the nutrition-related commitments and practices of major French food companies
Authors: Van Dam Iris , Vandevijvere Stefanie
Published: July 2022

Background

This study benchmarked and quantitatively assessed the transparency, specificity and comprehensiveness of nutrition-related commitments and related practices of the major companies within the French food industry.

Methods

To evaluate the nutrition-related commitments and practices across policy domains such as product reformulation, labelling, marketing, and accessibility, the ‘Business Impact Assessment on Obesity and population-level nutrition’ (BIA-Obesity) was applied. A total of 33 French food companies were selected using Euromonitor 2018 market share data, including major packaged food and non-alcoholic beverage manufacturers (N = 20), quick-service restaurants (N = 7), and supermarkets (N = 6). During 2019-2020 the publicly available commitments were collected for each company, scored according to the BIA-Obesity, and company representatives were provided with the opportunity to complete and verify the collected data. The following performance metrics were included to assess company practices: the median Nutri-Score of product portfolios, the proportion of products with Nutri-Score A or B, the percentage of products (not-)permitted to be marketed to children according to the World Health Organisation Europe nutrient profile model and the proportion of ultra-processed food products as determined by the NOVA-classification. In addition supermarket flyers were collected over a 6-months period to assess the healthiness of product promotions. Correlations between commitments and performance metrics were assessed applying the Spearman’s rank correlation coefficient.

Results

Among the selected food companies, 13 companies verified and completed the publicly available data (response rate = 39%). Overall BIA-Obesity scores for company commitments varied between 2 and 74% with a median score of 28%. Scores for packaged food and non-alcoholic beverage manufacturers were higher than those for supermarkets and quick-service restaurants. The median proportion of foods with Nutri-Score A or B within product portfolios was 38% (range = 1-95%), while the median proportion of non-permitted products was 84% (range = 7-100%) and the median proportion of ultra-processed food products 63% (range = 5-100%). Stronger company commitments did not translate into better performance metrics.

Conclusions

There is room for significant improvement of both company commitments and performance. Current food industry action does not meet recommended best practices. The French government is urged to regulate food industry practices to create healthier food environments.
Implementation of a model of awareness-raising for taxi motorcyclists in Benin in relation to helmet use: a quasi-experimental study
Authors: Hounkpe Dos Santos Bella , Kpozehouen Alphonse , Glele Ahanhanzo Yolaine , Daddah Donatien , Lagarde Emmanuel , Coppieters Yves
Published: July 2022

Background

This study aims to test the effectiveness of an awareness-raising model designed based on the theory of planned behaviour regarding helmet use for motorcycle taxi drivers.

Methods

This quasi-experimental study took place in the cities of Parakou (intervention group) and Porto Novo (control group). Over a three-month period, a package of awareness-raising activities, based on the theory of planned behaviour, have been implemented in the intervention area. Data relate to knowledge, attitudes and practices regarding helmet use was collected prospectively before the intervention, at the end, and 6 months later. Stata 15 was used for data analysis. Chi-square or Fisher, Student’s or Kruskal-Wallis tests was carried out. The difference-in-difference method was used to determine the specific effect of the awareness activities.

Results

After the intervention, there was an improvement in the total score in both groups compared to baseline. The total score increased by 0.2 (0.06–0.3) in the experimental group when the number of sessions attended increased by one (p = 0.005). The difference-in-difference estimator measured among subjects who attended at least one awareness session, controlling for socio-demographic variables, showed a significantly higher difference in the total score of subjects in the experimental group compared to those in the control group both at the end of the interactive sessions and 6 months later.

Conclusion

This model improves the helmet-wearing behaviour of motorbike taxi drivers in the experimental area. It could be adapted and applied to other socio-professional groups and other types of users.
Trends in prevalence, mortality, and disability-adjusted life-years relating to chronic obstructive pulmonary disease in Europe: an observational study of the global burden of disease database, 2001–2019
Authors: Marshall Dominic C. , Al Omari Omar , Goodall Richard , Shalhoub Joseph , Adcock Ian M. , Chung Kian Fan , Salciccioli Justin D.
Published: July 2022

Introduction

Chronic Obstructive Pulmonary Disease (COPD) is associated with significant mortality and well-defined aetiological factors. Previous reports indicate that mortality from COPD is falling worldwide. This study aims to assess the burden of COPD using prevalence, mortality, and disability-adjusted life years (DALYs) between 2001 and 2019 in 28 European countries (the European Union and the United Kingdom).

Methods

We extracted COPD data from the Global Burden of Disease database based on the International Classification of Diseases versions 10 (J41, 42, 43, 44 and 47). Age-standardised prevalence rates (ASPRs), age-standardised mortality rates (ASMRs), and DALYs were analysed for European countries by sex for each year (2001–2019) and reported per 100,000 population. We used Joinpoint regression analysis to quantify changing trends in the burden of COPD.

Results

In 2019, the median ASPR across Europe was 3230/100,000 for males and 2202/100,000 for females. Between 2001 and 2019, the median percentage change in ASPR was − 9.7% for males and 4.3% for females. 23/28 countries demonstrated a decrease in ASPRs in males, and 11/28 demonstrated a decrease in females. The median percentage change in ASMR between 2001 and 2019 was − 27.5% for males and − 10.4% for females. 25/28 and 19/28 countries demonstrated a decrease in ASMR in males and females, respectively.

Conclusion

In the EU between 2001 and 2019 COPD prevalence has overall increased in females but continues to decrease in males and in some countries, female prevalence now exceeds that of males. COPD mortality in the EU has decreased overall between 2001 and 2019; however, this decrease is not universal, particularly in females, and therefore remains a substantial source of amenable mortality.
Gut Bifidobacteria enrichment following oral Lactobacillus-supplementation is associated with clinical improvements in children with cystic fibrosis
Authors: Ray Kathryn J. , Santee Clark , McCauley Kathryn , Panzer Ariane R. , Lynch Susan V.
Published: July 2022

Background

Relationships between gut microbiomes and airway immunity have been established in murine and human studies of allergy and asthma. Early life Lactobacillus supplementation alters the composition and metabolic productivity of the gut microbiome. However, little is known of how Lactobacillus supplementation impacts the gut microbiota in children with cystic fibrosis (CF) and whether specific microbiota states that arise following gut microbiome manipulation relate to pulmonary outcomes.

Methods

Stool samples were collected from CF patients enrolled in a multi-center, double-blind, randomized placebo-controlled trial of daily Lactobacillus rhamnosus strain GG (LGG) probiotic supplementation over a 12-month period. Fecal 16S rRNA biomarker sequencing was used to profile fecal bacterial microbiota and analyses were performed in QiiME.

Results

Bifidobacteria-dominated fecal microbiota were more likely to arise in LGG-treated children with CF (P = 0.04). Children with Bifidobacteria-dominated gut microbiota had a reduced rate of pulmonary exacerbations (IRR = 0.55; 95% CI 0.25 to 0.82; P = 0.01), improved pulmonary function (+ 20.00% of predicted value FEV1; 95% CI 8.05 to 31.92; P = 0.001), lower intestinal inflammation (Calprotectin; Coef =  − 16.53 μg g−1 feces; 95% CI − 26.80 to − 6.26; P = 0.002) and required fewer antibiotics (IRR = 0.43; 95% CI 0.22 to 0.69; P = 0.04) compared to children with Bacteroides-dominated microbiota who were less likely to have received LGG.

Conclusions

The majority of pediatric CF patients in this study possessed a Bacteroides- or Bifidobacteria-dominated gut microbiota. Bifidobacteria-dominated gut microbiota were more likely to be associated with LGG-supplementation and with better clinical outcomes.
Stress distribution patterns during the gait cycle in patients with anterior femoral notching following total knee replacement
Authors: Zhang Jin-Cheng , Zhang Le-Shu , Zhou Hang , Chen Wang , Hu Zheng-Hao , Chen Xiang-Yang , Feng Shuo
Published: July 2022

Background

Anterior femoral notching (AFN) is a severe complication of total knee replacement (TKR), which in a percentage of patients may lead to fractures after surgery. The purpose of this study was to investigate the stress distribution in patients with AFN and the safety depth of AFN during the gait cycle.

Methods

We performed a finite element (FE) analysis to analyse the mechanics around the femur during the gait cycle in patients with AFN. An adult volunteer was selected as the basis of the model. The TKR models were established in the 3D reconstruction software to simulate the AFN model during the TKR process, and the 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm AFN models were established, after which the prosthesis was assembled. Three key points of the gait cycle (0°, 22°, and 48°) were selected for the analysis.

Results

The stress on each osteotomy surface was stable in the 0° phase. In the 22° phase, the maximum equivalent stress at 3 mm was observed. In the 48° phase, with the increase in notch depth, each osteotomy surface showed an overall increasing trend, the stress range was more extended, and the stress was more concentrated. Moreover, the maximum equivalent force value (158.3 MPa) exceeded the yield strength (115.1 MPa) of the femur when the depth of the notch was ≥ 3 mm.

Conclusions

During the gait cycle, if there is an anterior femoral cortical notch ≥ 3 mm, the stress will be significantly increased, especially at 22° and 48°. The maximum equivalent stress exceeded the femoral yield strength and may increase the risk of periprosthetic fractures.
The effect of bariatric surgery in comparison with the control group on the prevention of comorbidities in people with severe obesity: a prospective cohort study
Authors: Ebadinejad Amir , Barzin Maryam , Abiri Behnaz , Mahdavi Maryam , Khalaj Alireza , Ebrahimi Danial , Hosseinpanah Farhad , Valizadeh Majid
Published: July 2022

Background

Obesity is a global health priority, particularly in developing countries. The preventive effect of bariatric surgery against obesity-related diseases in the developing countries of the Middle East and North Africa region, where type 2 diabetes mellitus (T2DM), hypertension (HTN), and dyslipidemia prevail, has not been examined.

Method

Severely obese participants who underwent bariatric surgery were compared with their counterparts who underwent no intervention. These patients had been followed up in two prospective cohort studies for three years. We here determined the incidence of new-onset T2DM, HTN, and dyslipidemia and reported absolute and relative risks for the incidence of these comorbidities in the two groups.

Results

In this study, 612 participants in the bariatric surgery group were compared with 593 participants in the control group. During the follow-up period, T2DM developed in eight (2.9%) people in the surgery group and 66 (15.0%) people in the control group (P < 0.001). New-onset HTN and dyslipidemia showed significantly lower frequencies in the surgery group compared to the control group (4 (1.8%) vs. 70 (20.4%) and 33 (14.3%) vs. 93 (31.5%), respectively). Regarding a less favorable metabolic profile in the surgery group at the baseline, the relative risk reductions associated with bariatric surgery were 94, 93, and 55% for the development of T2DM, HTN, and dyslipidemia, respectively.

Conclusion

The risk reduction of obesity-related comorbidities after bariatric surgery should be considered in the decision-making process for public health in the region, which bariatric surgery could result in the prevention of comorbidities.
Patient safety culture in Palestine: university hospital nurses’ perspectives
Authors: Zabin Loai M. , Zaitoun Rasha S. Abu , Abdullah Abdullah A.
Published: July 2022

Background

Understanding the perspectives of healthcare workers toward patient safety-related activities is critical in maintaining a healthy safety climate. The objectives of this research are 1) to examine the perception of Patient Safety Culture (PSC) at a university hospital in Palestine, and to highlight areas in need of improvement, and 2) to assess the relationship between the outcome dimensions (frequency of events reported, and overall perceptions of safety) and the other dimensions of PSC, and 3) to determine the relationship among selected demographic variables (gender, age, hospital tenure, work tenure, profession tenure, and hours worked per week) and nurses’ perceptions of PSC.

Methods

A cross-sectional study design was used with a convenience sample of 107 nurses. Nurses were asked by email to complete the Arabic version of the Hospital Survey of Patients’ Safety Culture (HSOPSC) using the SurveyMonkey® online account form within two weeks. The survey data were analyzed using descriptive and inferential statistics. Univariate and multiple regression were used to examine the relationships.

Results

The dimensions of patient safety with the highest positive response were organizational learning and continuous improvement (87%) and teamwork within units (86%). The dimension with the lowest positive score was the nonpunitive response to error (22%). Multiple regression revealed that the dimension of communication openness was a predictor of the overall perceptions of safety (β = 0.257,p = 0.019). In addition, the dimension of feedback and communication about error was a predictor of the frequency of the reported events (β = 0.334,p = 0.005). Furthermore, age was found to be a predictor of PSC (p < 0.05).

Conclusions

This study provides a general assessment of perceived safety among nurses in a hospital. However, we found that nurses negatively perceive a nonpunitive response to error. Therefore, strenuous efforts are required by hospital management to improve the culture of incident reporting.
Reablement – relevant factors for implementation: an exploratory sequential mixed-methods study design
Authors: Wess Theres , Steiner Wolfgang , Dür Mona , Janssen Jessie
Published: July 2022

Background

Reablement is a multi-professional and internationally established home-based health care service for mainly older people with the aim to reduce the need for long-term care and to promote self-determination. However, it is unknown which factors would facilitate the implementation of reablement in health care services. Therefore, the aim of this work was to identify relevant factors for the implementation process and to elucidate their importance based on the perspectives of experts.

Methods

Within an exploratory sequential mixed-methods design, a literature search followed by framework analysis was carried out using the five domains of the Consolidated Framework of Implementation Research (CFIR) to collect potentially relevant factors for implementation of reablement. A survey was then drawn up encompassing the factors identified. Within the survey international reablement – experts were asked to rate the relevance of these factors .

Results

The literature search identified 58 publications that served as sources for the framework analysis, where 40 potentially relevant factors were clustered into the five CFIR domains. These 40 factors were rated by experts in an online-survey. Based on the analysis of survey-data, 35 factors were considered as relevant for implementation of reablement services. The CFIR-domain characteristics of individuals, including teamwork and communication skills, was seen as most relevant.

Conclusions

The implementation of reablement services is complex and requires the consideration of numerous factors, especially regarding the CFIR-domain characteristics of individuals. From the perspective of the survey´s participants one important factor of a successful implementation was the engagement of the persons involved. It requires team members with a strong, shared vision. Communication skills are highly important to promote teamwork and intensive training is needed to establish these skills. Further research on the implementation of reablement services is essential to realize its full potential.
Factors influencing UK residents’ preferences in how psychologists present themselves online: a conjoint analysis during the early months of the COVID-19 pandemic
Authors: Jørgensen Magnus , Makransky Guido
Published: July 2022

Background

The COVID-19 pandemic has led to a surge in mental health issues in the UK and worldwide, yet many UK residents have not received the help they have needed. Earlier research has indicated that accommodating client preferences leads to better therapeutic outcomes, however, little is known about preferences in how psychologists present themselves online and what might facilitate or slow help-seeking individuals’ decision about whom to seek help from. Based on literature suggesting personal branding as an effective way for clients to choose between psychologists, we sought to investigate UK residents’ preferences for specialization and self-disclosure in online presentations of psychologists based on level of fear of COVID-19 and diagnostic status.

Methods

A sample of 187 UK residents were surveyed mid-April 2020 and analyzed using a rating-based conjoint analysis with a fractional factorial design consisting of 22 profiles. Each profile consisted of six attributes (Years of experience, area of expertise, gender, self-disclosure, training institution and facial trustworthiness). Analyses of variance (ANOVA) were used to explore preferences for area of expertise and self-disclosure depending on fear of COVID-19. An independent sample t-test was done to explore preference for self-disclosure among diagnosed residents.

Results

The conjoint model yielded a good fit (Kendall’s tau = .90,p < .001). Relative importance scores (RI) were highest for years of experience (RI = 28.84) and area of expertise (RI = 22.78). Residents with a high fear of COVID-19 preferred psychologists specialized in anxiety disorders and fear (also fear of COVID-19) more than residents with a low fear of COVID-19 (MD = .92, 95% CI = [.198, 1.64],p = .013). Residents with a high fear of COVID-19 also preferred self-disclosing psychologists more than residents with a low fear of COVID-19 (MD = 1.05, 95% CI = [.184, 1.92],p = .013). Diagnostic status was not associated with preference for self-disclosure.

Conclusions

Listing de facto specialization in psychologist profiles might facilitate prospective clients’ decision-making process. Self-disclosure appears to be important for some clients, but more research is warranted.
Prognostic signature for hepatocellular carcinoma based on 4 pyroptosis-related genes
Authors: Duan Sainan , Gao Jianying , Lou Weiming , Zhang Yize , Deng Ying , Wang Cong , Huang Haiyue , Xu Hui , Guo Sixuan , Lai Shuhui , Xi Feiyang , Li Zhangwang , Deng Libin , Zhong Yuanbin
Published: July 2022

Background

Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Many recent studies have suggested that pyroptosis is important in tumour progression. However, the role of pyroptosis-related genes (PRGs) in HCC remains unclear.

Materials and methods

We identified differentially expressed PRGs in tumours versus normal tissues. Through univariate, LASSO, and multivariate Cox regression analyses, a prognostic PRG signature was established. The signature effectiveness was evaluated by time-dependent receiver operating characteristic (t-ROC) curve and Kaplan–Meier (KM) survival analysis. The signature was validated in the ICGC (LIRI-JP) cohort. In addition, single-sample gene enrichment analysis (ssGSEA) showed the infiltration of major immune cell types and the activity of common immune pathways in different subgroups.

Results

Twenty-nine pyroptosis-related DEGs from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset were detected, and four genes (CTSV, CXCL8, MKI67 and PRF1) among them were selected to construct a prognostic signature. Then, the patients were divided into high- and low-risk groups. The pyroptosis-related signature was significantly associated with overall survival (OS). In addition, the patients in the high-risk group had lower levels of immune infiltration.

Conclusion

The prognostic signature for HCC based on 4 pyroptosis-related genes has reliable prognostic and predictive value for HCC patients.
Behavioural side effects of inhaled corticosteroids among children and adolescents with asthma
Authors: Bodum Karoline S. , Hjerrild Britta E. , Dalsgaard Søren , Rubak Sune L. M.
Published: July 2022

Background

Inhalation corticosteroids (ICS) are prescribed for treatment of asthma in approximately 3% of all children in Denmark. Despite limited evidence, case reports suggest that ICS-related behavioural adverse drug events (ADEs) may be frequent. In general, underreporting of ADEs to official databases is common, and little is known about doctor’s clinical experiences with behavioural ADEs when prescribing ICS for children with asthma. The objective was to investigate the extent of behavioural ADEs in children with asthma treated with ICS by comparing database findings to experiences of specialist doctors.

Methods

First, databases of the European Medicines Agency (EMA) and the Danish Medicines Agency (DKMA) were searched for reports made by healthcare professionals about behavioural ADEs in children from 2009 to 2018. Second, questionnaire data on behavioural ADEs were collected from eight of the 11 specialist doctors responsible for treating children with asthma at the six paediatric departments in Central Denmark Region and North Denmark Region.

Results

EMA and DKMA had registered 104 and 3 reports, respectively, on behavioural ADEs during the 10-year study period. In contrast, five of the eight specialist doctors (45.5%) had experienced patients who had developed behavioural changes during ICS treatment. However, none of the five specialist doctors had filed reports on these events to DKMA.

Conclusion

Behaviour-related ADEs to ICS in children with asthma are likely to be highly underreported in official databases and doctors treating children with ICS should be aware of potential ADEs and consider submitting ADE reports whenever appropriate.
CEBPD modulates the airway smooth muscle transcriptomic response to glucocorticoids
Authors: Kan Mengyuan , Sun Maoyun , Jiang Xiaofeng , Diwadkar Avantika R. , Parikh Vishal , Cao Gaoyuan , Gebski Eric , Jester William , Lan Bo , Panettieri Reynold A. , Koziol-White Cynthia , Lu Quan , Himes Blanca E.
Published: July 2022

Background

CCAAT/Enhancer Binding Protein D (CEBPD), a pleiotropic glucocorticoid-responsive transcription factor, modulates inflammatory responses. Of relevance to asthma, expression of CEBPD in airway smooth muscle (ASM) increases with glucocorticoid exposure. We sought to characterize CEBPD-mediated transcriptomic responses to glucocorticoid exposure in ASM by measuring changes observed after knockdown of CEBPD and its impact on asthma-related ASM function.

Methods

Primary ASM cells derived from four donors were transfected with CEBPD or non-targeting (NT) siRNA and exposed to vehicle control, budesonide (100 nM, 18 h), TNFα (10 ng/ml, 18 h), or both budesonide and TNFα. Subsequently, RNA-Seq was used to measure gene expression levels, and pairwise differential expression results were obtained for exposures versus vehicle and knockdown versus control conditions. Weighted gene co-expression analysis was performed to identify groups of genes with similar expression patterns across the various experimental conditions (i.e., CEBPD knockdown status, exposures).

Results

CEBPD knockdown altered expression of 3037 genes under at least one exposure (q-value < 0.05). Co-expression analysis identified sets of 197, 152 and 290 genes that were correlated with CEBPD knockdown status, TNFα exposure status, and both, respectively. JAK-STAT signaling pathway genes, including IL6R and SOCS3, were among those influenced by both TNFα and CEBPD knockdown. Immunoblot assays revealed that budesonide-induced IL-6R protein expression and augmented IL-6-induced STAT3 phosphorylation levels were attenuated by CEBPD knockdown in ASM.

Conclusions

CEBPD modulates glucocorticoid responses in ASM, in part via modulation of IL-6 receptor signaling.
Prognostic biomarker IL17A correlated with immune infiltrates in head and neck cancer
Authors: Yu Meng , Qian Xing Xing , Li Guang , Cheng Zexing , Lin Zhijie
Published: July 2022

Background

The underlying functions and mechanisms of the Th17 pathway in Head and neck squamous cell carcinoma (HNSCC) progression and tumor immunology are still unclear. We investigated the correlation between IL17A expression and certain clinical parameters, tumor-infiltrating immune cells (TIICs) in TCGA HNSCC samples.

Methods

HNSCC files from the TCGA database were analyzed to obtain data on immune system infiltrates, gene expression, and related clinical information. R (Version 3.6.3) software, GEPIA, and TIMER online analysis tools were used to profile the relationship between the expression of IL17A and the prognosis, clinical stages, survival status and immune cell tumor-infiltrating levels of HNSCC patients. GEPIA and TIMER online analysis tools were used to verify the data.

Results

The expression of IL17A was significantly decreased in tumor tissues from HNSCC. IL17A expression was associated with M, N stage, lymphovascular invasion, and patients OS event. GSEA revealed that IL17A was closely related to humoral immune response, T cells response, and cytokine signal. TCGA database and TIMER online analysis indicated that the B cells and T cells levels were correlated with IL17A. The correlation between IL17A expression and correlated genes was analyzed.

Conclusions

IL-17A plays a key role in HNSCC. The levels of IL17A are important values for the determination of the occurrence and development of the HNSCC. The IL17A and correlated genes may be potential immunotherapeutic targets for HNSCC.
Direct oral anticoagulants versus low-molecular-weight heparins for the treatment of acute venous thromboembolism in patients with gastrointestinal cancer: a systematic review and meta-analysis
Authors: Rungjirajittranon Tarinee , Owattanapanich Weerapat , Chinthammitr Yingyong , Ruchutrakool Theera , Suwanawiboon Bundarika
Published: July 2022

Background

The association between gastrointestinal (GI) cancer and a high incidence of venous thromboembolism (VTE) is well known. Previous randomized controlled studies demonstrated that direct oral anticoagulants (DOACs) effectively treat cancer-associated thrombosis (CAT). However, some DOACs appeared to increase the risk of bleeding, particularly in patients with GI malignancies. Therefore, the current systematic review and meta-analysis were conducted to evaluate the safety and efficacy of DOACs in GI cancer-associated thrombosis.

Methods

Two investigators individually reviewed all studies that compared DOACs and low-molecular-weight heparins (LMWHs) in GI cancer-associated thrombosis and were published in MEDLINE and EMBASE before February 2022. The effect estimates and 95% confidence intervals (CIs) from each eligible study were combined using the Mantel–Haenszel method.

Results

A total of 2226 patients were included in the meta-analysis. The rates of major bleeding in the DOAC and LMWH groups were not significantly different (relative risk [RR]: 1.31; 95% CI: 0.84–2.04; P = 0.23; I2 = 41%). However, the rate of clinically relevant nonmajor bleeding (CRNMB) was significantly higher in the DOAC group (RR: 1.76; 95% CI: 1.24–2.52; P = 0.002; I2 = 8%). The risks of recurrent VTE in the groups did not significantly differ (RR: 0.72; 95% CI: 0.49–1.04; P = 0.08; I2 = 0%).

Conclusions

The current data suggest that treatment of GI cancer-associated thrombosis with DOACs significantly increases the risk of CRNMB. However, the risk of major bleeding was not significantly different. The efficacy of DOACs for preventing recurrent VTE in GI cancer was comparable to that of LMWHs.

Trial registration

INPLASY202180113.
Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders
Authors: Winstone Joanna K. , Pathak Khyatiben V. , Winslow Wendy , Piras Ignazio S. , White Jennifer , Sharma Ritin , Huentelman Matthew J. , Pirrotte Patrick , Velazquez Ramon
Published: July 2022

Background

Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer’s disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood–brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα.

Methods

Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC–MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome.

Results

Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development.

Conclusions

Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
Mapping Colombians’ positions on sentencing for substance offenses
Authors: del Rio Forero Daniel , Marín Claudia Pineda , Sastre María Teresa Muñoz , Kpanake Lonzozou , Mullet Etienne
Published: July 2022

Background

In Colombia, a person caught in possession of an illicit substance is not judicially sanctioned as long as the quantity does not exceed the maximum allowable amounts. Given that the public is divided on the appropriateness of this policy, an examination of the various public positions was undertaken.

Method

A convenience sample of 302 adults were presented with 48 vignettes depicting a situation of everyday life easily recognizable by all in Colombia; that of a male person who is apprehended in the street by the police because he is suspected of illicit trafficking. These vignettes were created by orthogonal variation of four factors: Type of substance, amount of substance, type of charge against the offender, and offender’s age.

Results

Through cluster analysis, six qualitatively different positions were found. These positions corresponded to three distinct, classical philosophies (a) a libertarian, free-market philosophy – punishment should never be extremely severe because the trade in psychotropic substances is a trade like any other (6%), (b) a moralistic, conservative philosophy – punishment should always be extremely severe except perhaps in certain cases (52%), and (c) a progressive, human rights-inspired philosophy – punishment should always be proportional to the seriousness of the facts (42%).

Conclusion

Half of Colombian people supported a control policy according to which the use of psychotropic substances is considered profoundly immoral. Most of the other segment of the population express views similar to those of international organizations. It is therefore desirable that legislators rely on progressive international legislation to support domestic policies that are not strictly moralistic and conservative.
NBAS, a gene involved in cytotoxic degranulation, is recurrently mutated in pediatric hemophagocytic lymphohistiocytosis
Authors: Bi Xiaoman , Zhang Qing , Chen Lei , Liu Dan , Li Yueying , Zhao Xiaoxi , Zhang Ya , Zhang Liping , Liu Jingkun , Wu Chaoyi , Li Zhigang , Zhao Yunze , Ma Honghao , Huang Gang , Liu Xin , Wang Qian-fei , Zhang Rui
Published: July 2022

Hemophagocytic lymphohistiocytosis (HLH), particularly primary HLH (pHLH), is a rare, life-threatening disease. Germline genetic deficiency of 12 known HLH genes impairs cytotoxic degranulation in natural killer (NK) cells or cytotoxic T lymphocytes (CTLs) and contributes to pHLH development. However, no pathogenic mutations in these HLH genes are found in nearly 10% of HLH patients, despite a strong suspicion of pHLH, suggesting that the underlying genetic basis of HLH is still unclear. To discover novel susceptibility genes, we first selected 13 children with ppHLH (presumed primary HLH patients in the absence of detectable known HLH gene variants) and their parents for initial screening. Whole-genome sequencing (WGS) in one trio and whole-exome sequencing (WES) in twelve trios revealed that two ppHLH patients carried biallelic NBAS variants, a gene that is involved in Golgi-to-endoplasmic reticulum (ER) retrograde transport upstream of the degranulation pathway. Additionally, two candidate genes, RAB9B and KLC3, showed a direct relationship with known HLH genes in protein-protein interaction (PPI) network analysis. We analyzed NBAS, RAB9B, KLC3 and known HLH genes in an independent validation cohort of 224 pediatric HLH patients. Only biallelic NBAS variants were identified in three patients who harbored no pathogenic variants in any of the known HLH genes. Functionally, impaired NK-cell cytotoxicity and degranulation were revealed in both NBAS biallelic variant patients and in an NBAS-deficient NK-cell line. Knockdown of NBAS in an NK-cell line (IMC-1) using short hairpin RNA (shRNA) resulted in loss of lytic granule polarization and a decreased number of cytotoxic vesicles near the Golgi apparatus. According to our findings, NBAS is the second most frequently mutated gene (2.11%) in our HLH cohort after PRF1. NBAS deficiency may contribute to the development of HLH via a dysregulated lytic vesicle transport pathway.