bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study
Authors: Tu Junhao , Wen Jinyang , Luo Qing , Li Xin , Wang Deyun , Ye Jing 
Published: February 2024

Abstract
Background
Allergic diseases exert a considerable impact on global health, thus necessitating investigations into their etiology and pathophysiology for devising effective prevention and treatment strategies. This study employs a Mendelian randomization (MR) analysis and meta-analysis to identify metabolite targets potentially associated with allergic diseases.

Methods
A two-sample MR analysis was conducted to explore potential causal relationships between circulating and urinary metabolites and allergic diseases. Exposures were derived from a genome-wide association study (GWAS) of 486 circulating metabolites and a GWAS of 55 targeted urinary metabolites. Outcome data for allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, were obtained from the FinnGen biobank in Europe (cohort 1) and the Biobank Japan in Asia (cohort 2). MR results from both cohorts were combined using a meta-analysis.

Results
MR analysis identified 50 circulating metabolites and 6 urinary metabolites in cohort 1 and 54 circulating metabolites and 2 urinary metabolites in cohort 2 as potentially causally related to allergic diseases. A meta-analysis of the MR results revealed stearoylcarnitine (OR 8.654; 95% CI 4.399−17.025; P = 4.06E-10) and 1-arachidonoylglycerophosphoinositol (OR 2.178; 95% CI 1.388−3.419; P = 7.15E-04) as the most reliable causal circulating metabolites for asthma and AR, respectively. Further, histidine (OR 0.734; 95% CI: 0.594−0.907; P = 0.004), tyrosine (OR 0.601; 95% CI: 0.380−0.952; P = 0.030), and alanine (OR 0.280; 95% CI: 0.125−0.628; P = 0.002) emerged as urinary metabolites with the greatest protective effects against asthma, AD, and AR, respectively.

Conclusions
Imbalances in numerous circulating and urinary metabolites may be implicated in the development and progression of allergic diseases. These findings have significant implications for the development of targeted strategies for the prevention and treatment of allergic diseases.
Assessing the acceptability and feasibility of remote spirometric monitoring for rural patients with interstitial lung disease: a multimethod approach
Authors: Boente Ryan D. , Schacht Sydney , Borton Rebecca , Vincent Joseph , Golzarri-Arroyo Lilian , Rattray Nicholas 
Published: February 2024

Abstract
Introduction
Interstitial lung disease encompasses a group of rare lung conditions causing inflammation and scarring of lung tissue. The typical method of monitoring disease activity is through pulmonary function tests performed in a hospital setting. However, accessing care can be difficult for rural patients due to numerous barriers. This study assesses the feasibility and acceptability of home spirometry telemonitoring using MIR-Spirometers and the patientMpower home-monitoring platform for rural patients with interstitial lung disease.

Methods
Unblinded, uncontrolled, prospective, multiple-methods study of the feasibility and utility of remote monitoring of 20 rural subjects with interstitial lung disease. Study assessments include adherence to twice weekly spirometry for 3 months in addition to mMRC dyspnea and EQ-5D-5L health-related quality of life questionnaires with each spirometry maneuver. Upon completion, subjects were encouraged to complete an 11-question satisfaction survey and participate in semi-structured qualitative interviews to further explore expectations and perceptions of rural patients to telehealth and remote patient monitoring.

Results
19 subjects completed the 3-month study period. Adherence to twice weekly spirometry was mean 53% ± 38%, with participants on average performing 2.26 ± 1.69 maneuvers per week. The median (Range) number of maneuvers per week was 2.0 (0.0, 7.0). The majority of participants responded favorably to the patient satisfaction survey questions. Themes regarding barriers to access included: lack of local specialty care, distance to center with expertise, and time, distance, and high cost associated with travel. Remote monitoring was well perceived amongst subjects as a way to improve access and overcome barriers.

Conclusions
Remote spirometry monitoring through web-based telehealth is acceptable and feasible for rural patients. Perceived benefits include overcoming access barriers like time, distance, and travel costs. However, cost, reimbursement, and internet access must be addressed before implementing it widely. Future studies are needed to ensure long-term feasibility and to compare outcomes with usual care.
Association of dietary inflammatory index and the SARS-CoV-2 infection incidence, severity and mortality of COVID-19: a systematic review and dose-response meta-analysis
Authors: Hao Xuanyu , Li Shiwen , Yang Yanmin , Dai Huixu , Yan Yumeng , Li Dongyang 
Published: February 2024

AbstractBackgroundSeveral studies have reported the association between dietary inflammatory index (DII) and the SARS-CoV-2 infection risk, severity or mortality of COVID-19, however, the outcomes remain controversial.ObjectiveWe sought to examine whether a dose-response association of DII and SARS-CoV-2 infection exists.DesignA dose-response meta-analysis was performed to investigate the association of DII and SARS-CoV-2 infection. We conducted a systematic search of PubMed, Embase and Web of Science up to March 15th, 2023. The odds ratios (OR) of DII and COVID-19 risk and severity were computed.ResultsTotally, 5 studies were included (1 from UK and 4 from Iran), consisting of 197,929 participants with 12,081 COVID-19 cases. Although there was heterogeneity among studies, the results indicated that higher DII was independently related to higher SARS-CoV-2 infection incidence (OR = 1.57, 95% CI: 1.14, 2.17) and COVID-19 severity (OR = 1.11, 95% CI: 1.07, 1.15) but not COVID-19 mortality (risk ratio = 1.13, 95% CI: 1.00, 1.27). The incidence of SARS-CoV-2 infection increased by 31% for each 1-point increase in the E-DII (OR = 1.31, 95% CI: 1.20, 1.43).ConclusionsThis meta-analysis suggests that an elevated DII score is associated with increased SARS-CoV-2 infectious risk and severity of COVID-19. There were not enough studies on COVID-19 mortality. Further large prospective studies in different countries are warranted to validate our results.
Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide
Authors: Toulmonde Maud , Guegan Jean-Philippe , Spalato-Ceruso Mariella , Peyraud Florent , Kind Michèle , Vanhersecke Lucile , Le Loarer François , Perret Raul , Cantarel Coralie , Bellera Carine , Bessede Alban , Italiano Antoine 
Published: February 2024

AbstractMost soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, ‘cold’ STS, characterized by an absence of tertiary lymphoid structures. The trial employed a two-stage Simon design. JX-594 was administered intratumorally at a dose of 1.109 pfu every 2 weeks for up to 4 intra-tumoral administrations. Cyclophosphamide was given orally at 50 mg twice daily in a week-on, week-off schedule, and avelumab was administered at 10 mg/kg biweekly. The primary endpoint was the 6-month non-progression rate.Fifteen patients were enrolled, with the most frequent toxicities being grade 1 fatigue and fever. Fourteen patients were assessable for efficacy analysis. At 6 months, only one patient remained progression-free, indicating that the trial did not meet the first stage endpoint of Simon’s design. Analysis of sequential tissue biopsies and plasma samples revealed an increase in CD8 density and upregulation of immune-related protein biomarkers, including CXCL10.Intra-tumoral administration of JX-594 in combination with cyclophosphamide and avelumab is safe and capable of modulating the TME in cold STS. However, the limited efficacy observed warrants further research to define the therapeutic potential of oncolytic viruses, particularly in relation to specific histological subtypes of STS.
Feeling safer: effectiveness, feasibility, and acceptability of continuous pulse oximetry for people who smoke opioids at overdose prevention services in British Columbia, Canada
Authors: Moe Jessica , Chavez Tamara , Marr Charotte , Cameron Fred , Feldman-Kiss Damian , Wang Yueqiao Elle , Xavier Jessica C. , Mamdani Zahra , Purssell Roy A. , Salmon Amy , Buxton Jane A. 
Published: February 2024

Abstract
Background
Smoking is the most common mode of unregulated opioid consumption overall and implicated in fatal overdoses in British Columbia (BC). In part, perception of decreased risk (e.g., fewer who smoke carry naloxone kits) and limited smoking-specific harm reduction services contribute to overdose deaths. Overdose prevention services (OPS) offer supervised settings for drug use. Continuous pulse oximetry, common in acute care, allows real-time, remote oxygen monitoring. We evaluated the effectiveness of a novel continuous pulse oximetry protocol aimed at allowing physical distancing (as required by COVID-19, secluded spaces, and to avoid staff exposure to vaporized opioids), its feasibility, and acceptability at OPS for people who smoke opioids.

Methods
This was a mixed methods survey study. We developed a continuous pulse oximetry protocol in collaboration with clinical experts and people with lived/living experience of substance use. We implemented our protocol from March to August 2021 at four OPS in BC permitting smoking. We included adults (≥ 18 years) presenting to OPS to smoke opioids. Peer researchers collected demographic, health, and substance use information, and conducted structured observations. OPS clients participating in our study, OPS staff, and peer researchers completed post-monitoring surveys. We analyzed responses using a thematic inductive approach and validated themes with peer researchers.

Results
We included 599 smoking events. OPS clients participating in our study had a mean age of 38.5 years; 73% were male. Most (98%) reported using “down”, heroin, or fentanyl; 48% concurrently used other substances (32% of whom reported stimulants); 76% reported smoking alone in the last 3 days; and 36% reported an overdose while smoking. Respondents reported that the protocol facilitated physical distancing, was easy to use, high satisfaction, improved confidence, improved sense of safety, and that they would use it again.

Conclusions
Continuous pulse oximetry allowed safe physical distancing, was feasible, and acceptable in monitoring people who smoke opioids at OPS.
Psychometric evaluation of the respiratory syncytial virus infection, intensity and impact questionnaire (RSV-iiiQ) in adults
Authors: Williams Valerie , DeMuro Romano Carla , Finelli Lyn , Qin Shanshan , Saretsky Todd L. , Ma Jia , Lewis Sandy , Phillips Matthew , Osborne Richard H. , Norquist Josephine M. 
Published: February 2024

Abstract
Background
Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ.

Methods
Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed.

Results
111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory.

Conclusions
RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.
The role of provincial health administration in supporting district health management teams in the Democratic Republic of Congo: eliciting an initial programme theory of a realist evaluation
Authors: Bosongo Samuel , Belrhiti Zakaria , Chenge Faustin , Criel Bart , Coppieters Yves , Marchal Bruno 
Published: February 2024

Abstract
Background
In 2006, the Ministry of Health in the Democratic Republic of Congo designed a strategy to strengthen the health system by developing health districts. This strategy included a reform of the provincial health administration to provide effective technical support to district health management teams in terms of leadership and management. The provincial health teams were set up in 2014, but few studies have been done on how, for whom, and under what circumstances their support to the districts works. We report on the development of an initial programme theory that is the first step of a realist evaluation seeking to address this knowledge gap.

Methods
To inform the initial programme theory, we collected data through a scoping review of primary studies on leadership or management capacity building of district health managers in sub-Saharan Africa, a review of policy documents and interviews with the programme designers. We then conducted a two-step data analysis: first, identification of intervention features, context, actors, mechanisms and outcomes through thematic content analysis, and second, formulation of intervention–context–actor–mechanism–outcome (ICAMO) configurations using a retroductive approach.

Results
We identified six ICAMO configurations explaining how effective technical support (i.e. personalised, problem-solving centred and reflection-stimulating) may improve the competencies of the members of district health management teams by activating a series of mechanisms (including positive perceived relevance of the support, positive perceived credibility of provincial health administration staff, trust in provincial health administration staff, psychological safety, reflexivity, self-efficacy and perceived autonomy) under specific contextual conditions (including enabling learning environment, integration of vertical programmes, competent public health administration staff, optimal decision space, supportive work conditions, availability of resources and absence of negative political influences).

Conclusions
We identified initial ICAMO configurations that explain how provincial health administration technical support for district health management teams is expected to work, for whom and under what conditions. These ICAMO configurations will be tested in subsequent empirical studies.
Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis
Authors: Gao Peng , Wang Jianyou , Tang Huan , Pang Huanhuan , Liu Jiemei , Wang Chen , Xia Fei , Chen Honglin , Xu Liting , Zhang Junzhe , Yuan Lixia , Han Guang , Wang Jigang , Liu Gang 
Published: February 2024

Abstract
Background
Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive.

Methods
We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays.

Results
The results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects.

Conclusions
In conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel.
Arthroscopic wafer procedure versus ulnar shortening osteotomy for ulnar impaction syndrome: a systematic review and meta-analysis
Authors: Shi Haifeng , Huang Yongjing , Shen Yong , Wu Ke , Zhang Zhihai , Li Qian 
Published: February 2024

Abstract
Purpose
This study aimed to systematically compare the efficacy and safety of arthroscopic wafer procedure (AWP) versus ulnar shortening osteotomy (USO) for ulnar impaction syndrome (UIS) treatment.

Methods
All the studies included in this meta-analysis compared the efficacy of AWP to USO for UIS and were acquired through a comprehensive search across multiple databases. The meta-analysis was performed by calculating the effect sizes with the Cochrane Collaboration’s RevMan 5.4 software.

Results
A total of 8 articles were included in this analysis, comprising 148 cases in the AWP group and 163 cases in the USO group. The pooled estimates indicated no significant differences in combined Darrow’s Criteria or Modified Mayo Wrist Score, Modified Mayo Wrist Score, DASH scores, grip strength, VAS score, and postoperative ulnar variation. On the other hand, the patients in the AWP group exhibited fewer complications (OR = 0.17, 95%CI 0.05–0.54, P = 0.003) and a lower reoperation rate (OR = 0.12, 95%CI 0.05–0.28, P < 0.00001) than those in the USO group.

Conclusions
The two surgical techniques were both effective in treating UIS but the AWP group showed fewer complications and a lower reoperation rate. Therefore, AWP may present a superior alternative for UIS treatment.
Phenylketonuria from the perspectives of patients in Türkiye
Authors: Esgi Merve , Ergun Hakan , Kaya Nazmi Yalcin , Atakay Deniz Yilmaz , Erucar Ege , Celik Fatma 
Published: February 2024

Abstract
Background
The present study aimed to determine the problems, unmet needs and expectations of phenylketonuria (PKU) patients in Türkiye regarding follow-up and treatment in order to provide data for future planning and implementations on PKU.

Methods
The study included patients diagnosed with PKU and/or their parents. They were informed about the study via phone calls and their verbal consents were obtained. Questions in the data collection forms, which were established separately for pediatric, adolescent, and adult age groups, were applied during the interviews and the answers were recorded.

Results
Among 182 classical PKU patients, 66 (36.3%) were in the pediatric group (0–12 years old), 44 (24.2%) were in the adolescent group (13–19 years old), and 72 (39.5%) were in the adult group (≥ 20 years old). In all patient groups, phenylalanine-restricted diet and medical nutrition products were the main options for treatment. The median of the last measured blood phenylalanine concentration (patient-reported) was 290 µmol/L, 425 µmol/L, and 750 µmol/L in the pediatric, adolescent, and adult groups, respectively. The frequency of blood testing for serum phenylalanine level according to the age groups was appropriate in nearly half of the patients. While the majority of the patients have been visiting the metabolism center they have been diagnosed with PKU for control, considerable proportion of the patients would like to change the center or the doctor they visit for control if they could. It was determined that nearly half of the patients had trouble in accessing the metabolism center. Treatment options’ being limited and expensive were the major problems. The main requests of the patients and patient relatives included easier access to the metabolism centers and more options for treatment and diet.

Conclusions
Access to the services should be easier to improve the patients’ follow-up and treatment. There is need for low-cost, easily applicable, and accessible nutrition products and effective novel pharmacological agents. Focusing on these issues in health policies by providing pedagogic/psychological support, establishing support programs also comprising the families, and increasing the awareness activities were the key outcomes.