bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plurilateral Agreements, Multilateralism and Economic Development
Authors: Hoekman Bernard M. , Mavroidis Petros C. 
Published: January 2025

Abstract
Plurilateral agreements among sub-sets of economies have a long history within the multilateral trading system. Plurilaterals may appear superficially less attractive than a set of non-discriminatory multilateral rules that apply to all WTO members but may, both in theory and in practice, be better suited to accommodate diversity across countries in the desire and ability to regulate certain aspects of economic activity. As long as such differences between countries do not lead to discrimination or encroachment on other countries’ rights under WTO rules, it is potentially beneficial for the trading system to permit groups of countries to pursue regulatory cooperation, even if other countries do not wish to follow suit. The alternatives to greater accommodation of plurilateral cooperation in the WTO are more preferential (discriminatory) trade agreements and club-based initiatives outside the WTO. Both options are arguably worse for non-participating developing countries than incorporating open, transparent plurilateral agreements into the WTO. Opponents of plurilateral initiatives operating under WTO auspices run the risk of inducing further erosion of the multilateral trading system.
Pervasive horizontal transmission of Wolbachia in natural populations of closely related and widespread tropical skipper butterflies
Authors: Ribeiro Pedro , Butenko Anzhelika , Linke Daniel , Ghanavi Hamid Reza , Meier Joana Isabel , Wahlberg Niklas , Matos-Maraví Pável 
Published: January 2025

Abstract
Background
The endosymbiotic relationship between Wolbachia bacteria and insects has been of interest for many years due to their diverse types of host reproductive phenotypic manipulation and potential role in the host’s evolutionary history and population dynamics. Even though infection rates are high in Lepidoptera and specifically in butterflies, and reproductive manipulation is present in these taxa, less attention has been given to understanding how Wolbachia is acquired and maintained in their natural populations, across and within species having continental geographical distributions.

Results
We used whole genome sequencing data to investigate the phylogenetics, demographic history, and infection rate dynamics of Wolbachia in four species of the Spicauda genus of skipper butterflies (Lepidoptera: Hesperiidae), a taxon that presents sympatric and often syntopic distribution, with drastic variability in species abundance in the Neotropical region. We show that infection is maintained by high turnover rates driven mainly by pervasive horizontal transmissions, while also presenting novel cases of double infection by distantly related supergroups of Wolbachia in S. simplicius.

Conclusions
Our results suggest that Wolbachia population dynamics is host species-specific, with genetic cohesiveness across wide geographical distributions. We demonstrate that low coverage whole genome sequencing data can be used for an exhaustive assessment of Wolbachia infection in natural populations of butterflies, as well as its dynamics in closely related host species. This ultimately leads to a better understanding of the endosymbiotic population dynamics of Wolbachia and its effects on the host’s biology and evolution.
Analysis of the MYB gene family in tartary buckwheat and functional investigation of FtPinG0005108900.01 in response to drought
Authors: Li Jinbo , Yang Xin , Tian Bianling , Tian Tian , Meng Yu , Liu Fei 
Published: January 2025

AbstractTartary buckwheat (Fagopyrum tataricum) is an important crop used for edible food and medicinal usage. Drought annually brings reduction in crop yield and quality, causing enormous economic losses. Transcription factors are often involved in the regulation of plant responses to environmental stresses. In this study, we identified 233 MYB transcription factors in tartary buckwheat and classified them into 13 groups, including 1R, R2R3, 3R, 4R types. Gene structure and conserved motifs of these 233 FtMYBs suggested the relative conservation of these FtMYBs within each group. There is strong collinearity within the genomes of F. tataricum, with identifying syntenic gene pairs of FtMYB. Further, the expansion of FtMYB genes was attributed to whole genome duplication. The enrichment analysis of cis-acting elements in the FtMYB genes indicated that FtMYBs may participate in abiotic stress responses. The transcriptional changes of FtMYB genes in tartary buckwheat were then investigated using public data and qPCR. A number of FtMYB genes exhibited apparent transcript levels in the detected tissues and most of them disturbed their expression after the treatment of PEG6000 or natural treatment of tartary buckwheat seedlings. Some of the FtMYB genes showed a similar expression trend with qPCR validation. FtMYB gene FtPinG0005108900.01 were shown to activated by PEG6000 and natural drought treatment, and its encoded protein localizes to nucleus, revealing it as a typical transcription factor. Overexpression of FtPinG0005108900.01 increase the drought tolerance, and transcriptome analysis indicated that lignin synthesis other than flavonoid biosynthesis pathway was activated in the overexpressing plants following drought treatment. Our results provided detailed evolution and comparative genomic information of FtMYBs in tartary buckwheat and dissected the function of a FtMYB gene FtPinG0005108900.01 in response to drought.
A thematic analysis of UK COVID-19 vaccine hesitancy discussions on Twitter
Authors: Jameel Reeshma , Greenfield Sheila , Lavis Anna 
Published: January 2025

Abstract
Background
Following UK approval of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on 2/12/20 and 30/12/20 respectively, discussions about them emerged on the social media platform Twitter, (now ‘X’). Previous research has shown that Twitter/ X is used by the UK public to engage with public health announcements and that social media influences public opinions of vaccines, including COVID-19 vaccines, globally. This study explored discussions on Twitter posted in response to the UK government’s posts introducing the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. The aim was to investigate vaccine hesitant views, and thereby identify barriers and facilitators to COVID-19 vaccine uptake in the UK.

Methods
Online ethnography was used to collect responses (‘tweet replies’) to 14 Twitter posts published by officials or departments of the UK government on the dates the Pfizer-BioNTech and Oxford-AstraZeneca vaccines received approval from the Medicines and Healthcare products Regulatory Agency (2/12/20 and 30/12/20, respectively). 16,508 responses were collected and those expressing vaccine hesitancy were analysed using reflexive thematic analysis.

Results
Three themes that underpinned Twitter posters’ vaccine hesitancy were identified: (1) Concerns about vaccine development and safety, (2) Information, misinformation and disinformation, (3) Distrust: Politics and ‘Big Pharma’. From these themes, eight barriers and eight facilitators to UK COVID-19 vaccine uptake were identified.

Conclusion
This paper highlights key obstacles to COVID-19 vaccine acceptance in the UK based on views from Twitter and contributes to the emerging literature on the relationship between social media and the public response to COVID-19 vaccines. In so doing, this analysis offers insights that are useful for the development of vaccine communication strategies more broadly, both in and beyond future pandemics, to ensure that public concerns are addressed, and misinformation and disinformation are appropriately countered.
Occupational physical activity and cardiovascular disease mortality in the United States, 1988–2019
Authors: Xia Tong , Chen Liwei , Li Jian 
Published: January 2025

Abstract
Background
Although leisure time physical activity (LTPA) is a beneficial factor for cardiovascular disease (CVD) mortality, relationships between occupational physical activity (OPA) and CVD mortality are inconclusive. We aimed to examine prospective associations of OPA with CVD mortality using a large representative sample of adult workers in the United States (US), and explore how socioeconomic status (SES) may influence these associations.

Methods
This cohort study included US workers (≥ 18 years) participating in the 1988 National Health Interview Survey (NHIS) and passively followed until December 31, 2019. Time (minutes/week) on strenuous OPA (e.g., lifting, pushing, or pulling heavy objects) was assessed at baseline by a questionnaire and categorized into 4 groups [i.e., none, low, medium, and high]. CVD mortality was identified by International Classification of Diseases, Tenth Version (ICD–10) and collected by the National Death Index database. We examined the association of OPA with CVD mortality using multivariable Cox proportional hazard regressions, controlling for age, sex, race/ethnicity, marital status, education, annual household income, occupation type, and pre-existing cardiometabolic disorders.

Results
In 28,604 participants (46.2% women; mean age 37.86 years), adjusted hazard ratios (95% CIs) of none, low, medium, and high OPA groups were 1.39 (1.01–1.91), 1.00 (reference), 1.18 (0.83–1.66) and 1.58 (1.12–2.22) for CVD mortality. The associations were stronger in workers with low education level (i.e., high school or less) [estimates of none, low, medium, and high OPA groups were 1.74 (1.09–2.78, P = 0.02), 1.00, 1.49 (0.92–2.42), and 1.87 (1.16–3.00)] or annual household income <$30,000 [estimates of OPA groups were 1.73 (1.16–2.56), 1.00, 1.29 (0.83–2.01), and 1.73 (1.14–2.65)].

Conclusions
We observed that workers with either high or no strenuous OPA had higher CVD mortality compared to those with low strenuous OPA, demonstrating a U-shaped association in the US. This association was particularly pronounced among workers with lower SES.
Progression and mortality of patients with cystic fibrosis in China
Authors: Zhou Wangji , Wang Yaqi , Yang Yanli , Sun Yanyan , Cheng Chongsheng , Dai Jinrong , Meng Shuzhen , Chen Keqi , Zhao Yang , Liu Xueqi , Zhang Dingding , Liu Song , Zhu Weiguo , Liu Yaping , Xu Kai-Feng , Tian Xinlun 
Published: January 2025

Abstract
Background
Patients with cystic fibrosis (CF) are rare in China and differ significantly from the Caucasian populations in terms of clinical and genetic characteristics. However, the progression and mortality of Chinese patients with CF have not been well described.

Results
This study included all 67 patients from the Peking Union Medical College Hospital CF cohort, with a median followed up time of 5.2 years. Compared to patients diagnosed with CF in childhood, adult-diagnosed patients exhibit a lower proportion of pancreatic exocrine insufficiency (25.0% vs. 77.8%, P = 0.001) and a higher body mass index (19.6 vs. 17.7 kg/m2, P = 0.045). According to the mixed-effects model, for patients ≤ 30 years of age at diagnosis, FEV1% predicted decreased 1.17% per year. The generalized linear regression model showed that higher baseline FEV1% predicted and occurrence of pulmonary exacerbations were associated with the progression of patients with CF. The survival rates at 5 years and 10 years after the diagnosis were 96.7% and 80.6%, respectively. The log-rank test showed baseline FEV1% predicted < 50%, and high CF-ABLE and 3-year prognostic scores were associated with mortality in patients with CF in China.

Conclusions
We reported the progression and mortality of patients with CF in China, which was a rare and relatively unknown population in the past. Baseline FEV1% predicted is associated with progression and mortality. Pulmonary exacerbations can accelerate the decline in lung function. The CF-ABLE and 3-year prognostic scores are applicable for predicting poor prognosis in patients with CF in China.
Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice
Authors: Carbone Carmine , De Luca Roberto , Puca Emanuele , Agostini Antonio , Caggiano Alessia , Priori Lorenzo , Esposito Annachiara , Ascrizzi Serena , Piro Geny , Salvatore Lisa , De Sanctis Francesco , Ugel Stefano , Corbo Vincenzo , Neri Dario , Tortora Giampaolo 
Published: January 2025

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type of cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective and are associated with substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting an urgent need for novel therapeutic strategies. This study investigates the preclinical efficacy of an innovative targeted therapy based on antibody-cytokine fusion proteins, specifically interleukin-2 (IL-2), a pivotal driver of cell-mediated immunity, fused to L19 antibody, which selectively binds to extra domain B of fibronectin (EDB-FN1) expressed in the tumor microenvironment.

Methods
We tested the effectiveness of different immunocytokines through in vivo characterization in syngeneic C57BL/6J orthotopic mouse models of PDAC. Based on these results, we decided to focus on L19-IL2. To assess the efficacy of this immunocytokine we developed an ex-vivo immune-spheroid interaction platform derived from murine 3D pancreatic cultures, and telomerase reverse transcriptase (TERT) specific T-lymphocytes. Moreover, we evaluated the anti-cancer effect of L19-IL2 in combination with standard therapy in vivo experiments in PDAC mouse models. Tumor samples collected after the treatments were characterized for tumor infiltrating immune cell components by bulk RNA sequencing (RNA-seq) and spatial transcriptomics (Stereo-seq) analysis.

Results
The tumor-targeted L19-IL2 fusion protein demonstrated potent, dose-dependent anti-tumor activity in mice with pancreatic tumors resistant to standard chemotherapy. Spatial Transcriptomics (ST) and RNA-seq analyses indicated that L19-IL2 treatment induced a significant influx of immune cells into the tumor microenvironment, with these cells expressing activation markers like granzymes, perforins, and the IL-2 receptors.

Conclusions
Our results demonstrated that L19-IL2 enhances immune infiltration and cytotoxicity, remodeling the “cold” tumor microenvironment (TME) in PDAC. This innovative antibody-cytokine fusion protein improves therapeutic outcomes, paving the way for novel targeted treatment strategies in PDAC.
Immunoglobulin replacement therapy in patients with primary and secondary immunodeficiencies: impact of infusion method on immunoglobulin-specific perceptions of quality of life and treatment satisfaction
Authors: Mallick Rajiv , Hahn Noemi , Scalchunes Christopher 
Published: January 2025

Abstract
Background
Immunoglobulin replacement therapy (IgRT) is the current standard of care for primary antibody deficiency patients (majority of all primary immunodeficiency (PID) diseases), with growing real-world evidence supporting use for secondary immunodeficiency (SID) patients. Infusion methods and practices can affect patients’ satisfaction with their treatment and perception of their health-related quality of life.

Methods
An online survey of US patients with PID and SID was conducted. This research investigates primarily the impact of two IgRT infusion methods, intravenous immunoglobulin therapy (IVIG) and subcutaneous immunoglobulin (SCIG), on the patient reported outcome (PRO) Life Quality Index (LQI) tool. Patient reported infusion time efficiency, physical and mental health (PROMIS GPH-2 and PROMIS GMH-2 respectively), patient acceptability of their symptom state (PASS), upper extremity disability (Quick DASH) and general health perception (via the GHP) are also investigated.

Results
Responses of 990 patients (391 IVIG and 598 SCIG) were analyzed. The median total LQI score amongst SCIG patients (84.7) was higher than IVIG patients (81.9) (p < 0.001), and was significantly higher on 3 out of 4 sub-domains of the LQI. SCIG patients scored higher on items that are related to convenience and reported less interference with everyday life: “Are convenient”, “Are scheduled according to my convenience”, “Do not interfere with my work/school” and “Require very little time and cost”. However, there was no significant difference between the two patient cohorts on other, non-IG specific PROs (PASS, PROMIS GPH-2 and GMH-2 and Quick DASH). Patient reported time per infusion was lower for SCIG infusions than IVIG infusions (pre-infusion time; 22 min vs. 63 min, p < 0.001, infusion time; 120 min vs. 240 min, p < 0.001, post-infusion time; 9 min vs. 31 min, p < 0.001). IVIG patients also reported more interference with everyday life than SCIG patients (82 vs. 86, p < 0.001).

Conclusions
The significantly higher LQI scores for patients receiving SCIG than those receiving IVIG confirms existing evidence that substitution of SCIG for IVIG may favorably impact immunoglobulin specific perceptions of quality of life and treatment satisfaction for appropriately selected patients. Our evidence on infusion times indicates similar improvement may be possible on infusion time efficiency.
The technical expert/clinical user/patient panel (TECUPP): centering patient and family perspectives in patient-reported measure development
Authors: Marsolais Elizabeth , Anhang Price Rebecca , Berdahl Carl T. , Shenk Anton , Schulson Lucy , O’Hanlon Claire E. 
Published: January 2025

AbstractPatient and caregiver perspectives are increasingly incorporated into health care research and policymaking, but their inclusion in the quality measure development process often is not robust. We describe a stakeholder panel model for incorporating patient/caregiver voices in the development of patient-reported measures, the Technical Expert/Clinical User/Patient Panel (TECUPP) model. This model is characterized by significant or equal representation of people with lived experience of the disease or condition (as patients or caregivers) to the clinicians and others with technical expertise who typically comprise technical expert panels. We report key design features of the TECUPP model and how we used this model to develop survey-based patient experience measures of timeliness of cancer diagnosis. We describe benefits and challenges of using the TECUPP model and considerations to guide others who might use it as part of developing patient-centered quality measures, based on our experience convening a TECUPP to inform development of a patient-reported measure on timeliness of cancer diagnosis. Benefits include creating space for significant contributions from patients/caregivers and development of a shared understanding of patient experiences and observability of measure domains between clinicians and patients/caregivers. Challenges include time management and managing conversations outside the project scope. Measure development efforts implementing this model should consider recruiting diverse individuals, scheduling short and frequent meetings, enabling participation from all TECUPP members, developing accessible pre-read materials, anchoring meetings with patient stories, and encouraging multiple communication modes. The TECUPP model promotes discussion and understanding by patients/caregivers and clinicians/measure experts helpful for development of survey-based patient-reported measures.
Evaluating the reliability of a microperimetry-based method for assessing visual function in the junctional zone of geographic atrophy lesions
Authors: Alibhai A. Yasin , Moult Eric M. , Jamil Muhammad Usman , Raza Khadija , Morales Marco U. , Ribeiro Ramiro , Baumal Caroline R. , Fujimoto James G. , Waheed Nadia K. 
Published: January 2025

Abstract
Purpose
To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods
A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10 − 2 fovea centered grid was performed at baseline and follow-up visits. GA regions were traced on fundus autofluorescence (FAF) images. Two graders independently registered baseline microperimetry images with baseline FAF images in a sampling of 30 eyes from the OAKS study. Agreement between the two graders’ assessments of mean sensitivity and the number of scotomatous points within a ± 250 𝜇m GA junctional zone was assessed.

Results
The intraclass correlation (ICC) and coefficient of repeatability (CoR) for the mean junctional zone sensitivity were 0.987 and 0.214 dB, respectively. The ICC and CoR for the total number of scotomatous points within the junctional zone were 0.991 and 1.42, respectively.

Conclusions
The repeatability of the methodology and its compatibility with standard MP acquisitions appear to make it well-suited for identifying and analyzing retinal sensitivity within high-risk areas of the retina.

Summary
We present a microperimetry-based methodology for assessing visual function changes in the junctional zone of geographic atrophy lesions using a standard 10 − 2 fovea centered grid in a clinical trial context. The approach’s repeatability and compatibility with standard microperimetry grids may make it useful for assessing the effects of GA therapeutics.
Application of Mendelian randomization analysis to explore causal associations of aspirin use with bone mineral density and risk of fracture
Authors: Liu Qi-Pei 
Published: January 2025

Abstract
Objective
Previous observational studies on the association between aspirin use, bone mineral density (BMD), and fracture risk have yielded controversial results. This study explored the causal relationship between aspirin use, BMD, and fracture risk using Mendelian randomization (MR).

Methods
Summary data for aspirin use and BMD of five different body parts (femoral neck, lumbar spine, forearm, heel, and ultra distal forearm) and fractures were obtained from the integrative epidemiology unit open genome-wide association studies database for bidirectional MR analysis. An appropriate model was chosen based on Cochran's Q test, with inverse variance-weighted as the primary method for MR analysis, supplemented by the weighted-median and MR-Egger methods. MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy and exclude significant outliers that could bias the results. Various sensitivity analyses, including leave-one-out analysis, were conducted to ensure the robustness of the findings.

Results
Aspirin use significantly increased lumbar spine BMD (odds ratio [OR] = 4.660; 95% confidence interval [CI]: 1.365–15.906; P = 0.014). No significant causal association was found between aspirin use and fracture risk (beta = 59.951; 95% CI: -265.189–385.091; P = 0.718). No significant reverse causality was observed.

Conclusion
This study indicates that aspirin use does not significantly affect fracture risk but has a significant protective effect on lumbar spine BMD, revealing a potential benefit of aspirin against osteoporosis.