bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the use of digital technologies to provide disability services remotely during the COVID-19 pandemic; a multiple case study design
Authors: Fortune Jennifer , Manikandan Manjula , Harrington Sarah , Hensey Owen , Kerr Claire , Koppe Sebastian , Kroll Thilo , Lavelle Grace , Long Siobhán , MacLachlan Malcolm , Nolan Denis , Norris Meriel , O’Reilly Jason , Owens Mary , Walsh Aisling , Walsh Michael , Ryan Jennifer M. 
Published: March 2024

Abstract
Background
Using digital technologies to provide services and supports remotely may improve efficiency and accessibility of healthcare, and support people with disabilities to live independently. This study aimed to explore the experience of using digital technologies to access and provide disability services and supports during the Covid-19 pandemic, from the perspective of people with disabilities, families and service providers.

Methods
Using a multiple case study design, we purposively sampled three cases based on service user characteristics and geographical reach of the service. We conducted semi-structured interviews with 40 service users and service providers. Topic guides and analysis were informed by the Consolidated Framework for Implementation Research (CFIR). Analysis followed a largely deductive approach, using the CFIR constructs as a coding framework. A summary memo was developed for each case. Influence and strength of each construct was rated to identify constructs that influenced implementation of digital technologies. Ratings were compared across services to identify facilitators and barriers to implementation.

Results
Service users and providers were positive about using digital technologies to access and provide disability services and supports remotely. Advantages over in-person delivery included reduced travel time, increased opportunity for peer support and peer learning, more choice and opportunity to participate in activities, and an enhanced sense of self while accessing services from the secure environment of their home. The urgency to identify new modes of service delivery to meet the needs of service users during Covid-19 was a strong facilitator but did not necessarily result in successful implementation. Other factors that were strong facilitators were the use of adaptations to enable service users to access the online service, service users’ willingness to try the online service, service users’ persistence when they encountered challenges, and the significant time and effort that service providers made to support service users to participate in the online service. Barriers to implementation included the complexity of accessing online platforms, poor design quality of online platforms, and organisations prioritising in-person delivery over online services.

Conclusions
These findings may allow service providers to leverage facilitators that support implementation of online disability services and supports.
COVID-19-associated costs and mortality in Germany: an incidence-based analysis from a payer’s perspective
Authors: Brandt Florian , Simone Giancarlo , Loth Jörg , Schilling Daniel 
Published: March 2024

Abstract
Background
This study aims to estimate average COVID-19-associated healthcare costs per capita in Germany from a payer perspective. In addition, insights into COVID-19-associated mortality should be gained.

Methods
For this purpose, a retrospective longitudinal analysis using health insurance claims data was performed. Patients affected by COVID-19 in Q1/2021 (investigation group (IG)) were compared to a matched non-COVID-19 control group (CG) (1:1 propensity score matching (PSM)). Mean values of healthcare costs in 2020 and 2021 were computed for both groups and then separated by age and by development of Post-COVID-19 Syndrome (PCS). Group differences were examined using Mann–Whitney U test (α = 0.05). Difference-in-Differences approach (DiD) was used to estimate average cost effects of COVID-19 in 2021. Concerning mortality, the number of deaths in 2021 was compared between IG and CG using χ2 test of independence.

Results
A total of 8,014 insurants were included (n = 4,007 per group; n = 536 per group examining PCS patients only). Total healthcare costs varied a lot in the sample, were comparable between IG and CG in 2020, but were significantly higher in the IG in 2021 (DiD estimate = € 1,063 (in total); € 3,242 (PCS group)). This was more pronounced in the older age groups. High hospital costs of a minority of patients were the most influential driver of COVID-19-associated healthcare costs. Mortality was more than doubled in the IG (tripled in patients aged ≥ 60).

Conclusions
COVID-19 is associated with significantly increased healthcare costs and mortality, especially in older age groups. The additional development of PCS further increases the costs of COVID-19.
CheV enhances the virulence of Salmonella Enteritidis, and the Chev-deleted Salmonella vaccine provides immunity in mice
Authors: Zhang Lu , Wu Tonglei , Wang Fengjie , Liu Wan , Zhao Guixin , Zhang Yanying , Zhang Zhiqiang , Shi Qiumei 
Published: March 2024

Abstract
Background
Salmonella enteritidis (SE) is a major zoonotic pathogen and causes infections in a variety of hosts. The development of novel vaccines for SE is necessary to eradicate this pathogen. Genetically engineered attenuated live vaccines are more immunogenic and safer. Thus, to develop a live attenuated Salmonella vaccine, we constructed a cheV gene deletion strain of SE (named ΔcheV) and investigated the role of cheV in the virulence of SE. First, the ability to resist environmental stress in vitro, biofilm formation capacity, drug resistance and motility of ΔcheV were analyzed. Secondly, the bacterial adhesion, invasion, intracellular survival assays were performed by cell model. Using a mouse infection model, an in vivo virulence assessment was conducted. To further evaluate the mechanisms implicated by the reduced virulence, qPCR analysis was utilized to examine the expression of the strain’s major virulence genes. Finally, the immune protection rate of ΔcheV was evaluated using a mouse model.

Results
Compared to C50336, the ΔcheV had significantly reduced survival ability under acidic, alkaline and thermal stress conditions, but there was no significant difference in survival under oxidative stress conditions. There was also no significant change in biofilm formation ability, drug resistance and motility. It was found that the adhesion ability of ΔcheV to Caco-2 cells remained unchanged, but the invasion ability and survival rate in RAW264.7 cells were significantly reduced. The challenge assay results showed that the LD50 values of C50336 and ΔcheV were 6.3 × 105 CFU and 1.25 × 107 CFU, respectively. After the deletion of the cheV gene, the expression levels of fimD, flgG, csgA, csgD, hflK, lrp, sipA, sipB, pipB, invH, mgtC, sodC, rfbH, xthA and mrr1 genes were significantly reduced. The live attenuated ΔcheV provided 100% protection in mice against SE infection.

Conclusion
All the results confirmed that the deletion of the cheV gene reduces the virulence of SE and provides significant immune protection in mice, indicating that ΔcheV could be potential candidates to be explored as live-attenuated vaccines.
Associations of a plant-centered diet and lung function across early to mid-adulthood: The CARDIA Lung Study
Authors: Wharton Robert C. , Wang Jing Gennie , Choi Yuni , Eisenberg Elliot , Jackson Mariah K. , Hanson Corrine , Liu Bian , Washko George R. , Kalhan Ravi , Jacobs David R. , Bose Sonali 
Published: March 2024

Abstract
Background
Lung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Methods
Diet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates.

Results
The study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment.

Conclusions
In this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.
Quercetin improves epithelial regeneration from airway basal cells of COPD patients
Authors: McCluskey Elizabeth S. , Liu Nathan , Pandey Abhimaneu , Marchetti Nathaniel , Kelsen Steven G. , Sajjan Umadevi S. 
Published: March 2024

Abstract
Background
Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression.

Methods
COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression.

Results
Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment.

Conclusions
These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD.

Trial registration
This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.
Cardiopulmonary exercise test to detect cardiac dysfunction from pulmonary vascular disease
Authors: Alotaibi Mona , Yang Jenny Z. , Papamatheakis Demosthenes G. , McGuire W. Cameron , Fernandes Timothy M. , Morris Timothy A. 
Published: March 2024

Abstract
Background
Cardiac dysfunction from pulmonary vascular disease causes characteristic findings on cardiopulmonary exercise testing (CPET). We tested the accuracy of CPET for detecting inadequate stroke volume (SV) augmentation during exercise, a pivotal manifestation of cardiac limitation in patients with pulmonary vascular disease.

Methods
We reviewed patients with suspected pulmonary vascular disease in whom CPET and right heart catheterization (RHC) measurements were taken at rest and at anaerobic threshold (AT). We correlated CPET-determined O2·pulseAT/O2·pulserest with RHC-determined SVAT/SVrest. We evaluated the sensitivity and specificity of O2·pulseAT/O2·pulserest to detect SVAT/SVrest below the lower limit of normal (LLN). For comparison, we performed similar analyses comparing echocardiographically-measured peak tricuspid regurgitant velocity (TRVpeak) with SVAT/SVrest.

Results
From July 2018 through February 2023, 83 simultaneous RHC and CPET were performed. Thirty-six studies measured O2·pulse and SV at rest and at AT. O2·pulseAT/O2·pulserest correlated highly with SVAT/SVrest (r = 0.72, 95% CI 0.52, 0.85; p < 0.0001), whereas TRVpeak did not (r = -0.09, 95% CI -0.47, 0.33; p = 0.69). The AUROC to detect SVAT/SVrest below the LLN was significantly higher for O2·pulseAT/O2·pulserest (0.92, SE 0.04; p = 0.0002) than for TRVpeak (0.69, SE 0.10; p = 0.12). O2·pulseAT/O2·pulserest of less than 2.6 was 92.6% sensitive (95% CI 76.6%, 98.7%) and 66.7% specific (95% CI 35.2%, 87.9%) for deficient SVAT/SVrest.

Conclusions
CPET detected deficient SV augmentation more accurately than echocardiography. CPET-determined O2·pulseAT/O2·pulserest may have a prominent role for noninvasive screening of patients at risk for pulmonary vascular disease, such as patients with persistent dyspnea after pulmonary embolism.
Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial
Authors: Liu Shuang , Lin Xiaojing , Tao Minghao , Chen Qi , Sun Hang , Han Yali , Yang Shaoling , Gao Yining , Qu Shen , Chen Haibing 
Published: March 2024

Abstract
Background
Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA.

Methods
A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population.

Results
Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11–0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P < 0.05).

Conclusions
This study is the first to demonstrate that orlistat has no significant effect on SUA levels in patients with overweight/obesity and HUA. The utility of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized.

Trial registration
Clinicaltrials.gov NCT05496075.
Remnant cholesterol is correlated with retinal vascular morphology and diabetic retinopathy in type 2 diabetes mellitus: a cross-sectional study
Authors: Chen Shuli , Xu Yi , Chen Bo , Lin Senlin , Lu Lina , Cheng Minna , Wang Yuheng , Yang Qinping , Ling Saiguang , Zhou Dengji , Shi Yan , Zou Haidong , Ma Yingyan 
Published: March 2024

Abstract
Background
The association between remnant cholesterol (RC) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) remains unclear. Morphological changes in retinal vessels have been reported to predict vascular complications of diabetes, including DR.

Methods
This cross-sectional study included 6535 individuals with T2DM. The RC value was calculated using the recognized formula. The retinal vascular parameters were measured using fundus photography. The independent relationship between RC and DR was analyzed using binary logistic regression models. Multiple linear regression and subgroup analyses were employed to investigate the link between RC and vascular parameters, including the retinal arteriolar diameter (CRAE), venular diameter (CRVE), and fractal dimension (Df). Mediation analysis was performed to assess whether the vascular morphology could explain the association between RC and DR.

Results
RC was independently associated with DR in patients with a longer duration of T2DM (> 7 years). Patients with the highest quartile RC levels had larger CRAE (5.559 [4.093, 7.025] μm), CRVE (7.620 [5.298, 9.941] μm) and Df (0.013 [0.009, 0.017]) compared with patients with the lowest quartile RC levels. Results were robust across different subgroups. The association between RC and DR was mediated by CRVE (0.020 ± 0.005; 95% confidence interval: 0.012–0.032).

Conclusions
RC may be a risk factor for DR among those who have had T2DM for a longer period of time. Higher RC levels were correlated with wider retinal arterioles and venules as well as higher Df, and it may contribute to DR through the dilation of retinal venules.
Microneedles loaded with cerium-manganese oxide nanoparticles for targeting macrophages in the treatment of rheumatoid arthritis
Authors: Xia Tian , Zhu Yuting , Li Kaiqiang , Hao Ke , Chai Yingqian , Jiang Hongyi , Lou Chao , Yu Jiachen , Yang Wei , Wang Jilong , Deng Junjie , Wang Zhen 
Published: March 2024

Abstract
Background
Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery.

Result
This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype.

Conclusion
This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.
The intracellular interplay between galectin-1 and FGF12 in the assembly of ribosome biogenesis complex
Authors: Gędaj Aleksandra , Chorążewska Aleksandra , Ciura Krzysztof , Karelus Radosław , Żukowska Dominika , Biaduń Martyna , Kalka Marta , Zakrzewska Małgorzata , Porębska Natalia , Opaliński Łukasz 
Published: March 2024

AbstractGalectins constitute a class of lectins that specifically interact with β-galactoside sugars in glycoconjugates and are implicated in diverse cellular processes, including transport, autophagy or signaling. Since most of the activity of galectins depends on their ability to bind sugar chains, galectins exert their functions mainly in the extracellular space or at the cell surface, which are microenvironments highly enriched in glycoconjugates. Galectins are also abundant inside cells, but their specific intracellular functions are largely unknown. Here we report that galectin-1, -3, -7 and -8 directly interact with the proteinaceous core of fibroblast growth factor 12 (FGF12) in the cytosol and in nucleus. We demonstrate that binding of galectin-1 to FGF12 in the cytosol blocks FGF12 secretion. Furthermore, we show that intracellular galectin-1 affects the assembly of FGF12-containing nuclear/nucleolar ribosome biogenesis complexes consisting of NOLC1 and TCOF1. Our data provide a new link between galectins and FGF proteins, revealing an unexpected glycosylation-independent intracellular interplay between these groups of proteins.