bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adapting Participatory Workshops to a Virtual Setting: Co-Design With Muslim Women of a Faith-Based Intervention to Encourage Cancer Screening Uptake
Authors: Kotzur Marie , Amiri Rana , Gatting Lauren , Robb Kathryn A. , Ling Jonathan , Mooney John D. , Christie-de Jong Floor 
Published: October 2023

Early diagnosis of cancer through screening can reduce deaths and treatment burden if the people invited participate. Yet inequalities in screening participation remain: ethnic minority groups in particular experience barriers to cancer screening that need to be addressed in order to contribute to improving equality in health outcomes. Community-centred, participatory approaches can ensure that cancer screening interventions are culturally appropriate to the communities they are intended to serve. Virtual participatory research faces unique challenges in building the rapport required for successful collaboration between participants and researchers. This article describes the successful adaption of face-to-face participatory methods to co-designing, online, an intervention using faith-based messages to reduce cancer screening barriers. Based on the World Café method, we conducted four two-hour workshops by video call with a group of 10 Muslim women (29–65 years) from Glasgow, UK. Activities included (i) plenary and small-group discussions, (ii) graphic recording, and (iii) expert presentations. The workshops covered four topics: Islam and health, screening barriers, faith-based messages for screening barriers, and delivering a faith-based intervention. Anonymous feedback questionnaires evaluating each workshop showed the women found the workshops interesting, informative, and helpful. They reported being glad they had participated. Our findings highlight the importance of interactive discussion and low participant burden to optimise online co-design. The workshops created a faith-based cancer screening intervention engaging and accessible to Muslim women.
Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study
Authors: Leavitt Andrew D. , Konkle Barbara A. , Stine Kimo C. , Visweshwar Nathan , Harrington Thomas J. , Giermasz Adam , Arkin Steven , Fang Annie , Plonski Frank , Yver Anne , Ganne Florence , Agathon Delphine , Resa Maria de los Angeles , Tseng Li-Jung , Di Russo Gregory , Cockroft Bettina M. , Cao Liching , Rupon Jeremy 
Published: October 2023

Abstract
Patients with hemophilia A require exogenous factor VIII (FVIII) or nonfactor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector–based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain–deleted human F8 gene. In the ongoing phase 1/2, dose-ranging Alta study, 4 sequential cohorts of male participants with severe hemophilia A received a single IV dose of giroctocogene fitelparvovec. The primary end points are safety and changes in circulating FVIII activity. Interim results up to 214 weeks after treatment for all participants are presented. Eleven participants were dosed. Increases in alanine and aspartate aminotransferases were the most common treatment-related adverse events (AEs), which resolved with corticosteroid administration. Two treatment-related serious AEs (hypotension and pyrexia) were reported in 1 participant within 6 hours of infusion and resolved within 24 hours after infusion. At the highest dose level (3 × 1013 vg/kg; n = 5), the mean circulating FVIII activity level at week 52 was 42.6% (range, 7.8%-122.3%), and at week 104 it was 25.4% (range, 0.9%-71.6%) based on a chromogenic assay. No liver masses, thrombotic events, or confirmed inhibitors were detected in any participant. These interim 104-week data suggest that giroctocogene fitelparvovec is generally well tolerated with appropriate clinical management and has the potential to provide clinically meaningful FVIII activity levels, as indicated by the low rate of bleeding events in the highest dose cohort. This trial was registered at www.clinicaltrials.gov as #NCT03061201.
Tissue-infiltrating alloreactive T cells require Id3 to deflect PD-1–mediated immune suppression during GVHD
Authors: Wang Ying , He Shan , Calendo Gennaro , Bui Tien , Tian Yuanyuan , Lee Che Young , Zhou Yan , Zhao Xin , Abraham Ciril , Mo Wenbin , Chen Mimi , Sanders-Braggs Ruqayyah , Madzo Jozef , Issa Jean-Pierre , Hexner Elizabeth O. , Wiest David L. , Reshef Ran , Xue Hai-Hui , Zhang Yi 
Published: October 2023

Abstract
Persisting alloreactive donor T cells in target tissues are a determinant of graft-versus-host disease (GVHD), but the transcriptional regulators that control the persistence and function of tissue-infiltrating T cells remain elusive. We demonstrate here that Id3, a DNA-binding inhibitor, is critical for sustaining T-cell responses in GVHD target tissues in mice, including the liver and intestine. Id3 loss results in aberrantly expressed PD-1 in polyfunctional T helper 1 (Th1) cells, decreased tissue-infiltrating PD-1+ polyfunctional Th1 cell numbers, impaired maintenance of liver TCF-1+ progenitor-like T cells, and inhibition of GVHD. PD-1 blockade restores the capacity of Id3-ablated donor T cells to mediate GVHD. Single-cell RNA-sequencing analysis revealed that Id3 loss leads to significantly decreased CD28- and PI3K/AKT-signaling activity in tissue-infiltrating polyfunctional Th1 cells, an indicator of active PD-1/PD-L1 effects. Id3 is also required for protecting CD8+ T cells from the PD-1 pathway–mediated suppression during GVHD. Genome-wide RNA-sequencing analysis reveals that Id3 represses transcription factors (e.g., Nfatc2, Fos, Jun, Ets1, and Prdm1) that are critical for PD-1 transcription, exuberant effector differentiation, and interferon responses and dysfunction of activated T cells. Id3 achieves these effects by restraining the chromatin accessibility for these transcription factors. Id3 ablation in donor T cells preserved their graft vs tumor effects in mice undergoing allogeneic hematopoietic stem cell transplantation. Furthermore, CRISPR/Cas9 knockout of ID3 in human CD19–directed chimeric antigen receptor T cells retained their antitumor activity in NOD/SCID/IL2Rg−/− mice early after administration. These findings identify that ID3 is an important target to reduce GVHD, and the gene-editing program of ID3 may have broad implications in T-cell–based immunotherapy.
Comparative analyses of dynamic transcriptome profiles highlight key response genes and dominant isoforms for muscle development and growth in chicken
Authors: Wang Zhang , Tian Weihua , Wang Dandan , Guo Yulong , Cheng Zhimin , Zhang Yanyan , Li Xinyan , Zhi Yihao , Li Donghua , Li Zhuanjian , Jiang Ruirui , Li Guoxi , Tian Yadong , Kang Xiangtao , Li Hong , Dunn Ian C. , Liu Xiaojun 
Published: October 2023

Abstract
Background
Modern breeding strategies have resulted in significant differences in muscle mass between indigenous chicken and specialized broiler. However, the molecular regulatory mechanisms that underlie these differences remain elusive. The aim of this study was to identify key genes and regulatory mechanisms underlying differences in breast muscle development between indigenous chicken and specialized broiler.

Results
Two time-series RNA-sequencing profiles of breast muscles were generated from commercial Arbor Acres (AA) broiler (fast-growing) and Chinese indigenous Lushi blue-shelled-egg (LS) chicken (slow-growing) at embryonic days 10, 14, and 18, and post-hatching day 1 and weeks 1, 3, and 5. Principal component analysis of the transcriptome profiles showed that the top four principal components accounted for more than 80% of the total variance in each breed. The developmental axes between the AA and LS chicken overlapped at the embryonic stages but gradually separated at the adult stages. Integrative investigation of differentially-expressed transcripts contained in the top four principal components identified 44 genes that formed a molecular network associated with differences in breast muscle mass between the two breeds. In addition, alternative splicing analysis revealed that genes with multiple isoforms always had one dominant transcript that exhibited a significantly higher expression level than the others. Among the 44 genes, the TNFRSF6B gene, a mediator of signal transduction pathways and cell proliferation, harbored two alternative splicing isoforms, TNFRSF6B-X1 and TNFRSF6B-X2. TNFRSF6B-X1 was the dominant isoform in both breeds before the age of one week. A switching event of the dominant isoform occurred at one week of age, resulting in TNFRSF6B-X2 being the dominant isoform in AA broiler, whereas TNFRSF6B-X1 remained the dominant isoform in LS chicken. Gain-of-function assays demonstrated that both isoforms promoted the proliferation of chicken primary myoblasts, but only TNFRSF6B-X2 augmented the differentiation and intracellular protein content of chicken primary myoblasts.

Conclusions
For the first time, we identified several key genes and dominant isoforms that may be responsible for differences in muscle mass between slow-growing indigenous chicken and fast-growing commercial broiler. These findings provide new insights into the regulatory mechanisms underlying breast muscle development in chicken.
Antimicrobial resistance pattern of anaerobic bacteria causing lower respiratory tract infections
Authors: Shariff Malini , Ramengmawi Elizabeth 
Published: October 2023

Abstract
Background
Anaerobes are normal flora of the human body. However, they can cause serious infections in humans. Anaerobic bacteria are known to cause respiratory infections like pneumonia and acute exacerbation of chronic lower airway infections. These are often missed due to the complexity of their isolation and identification. Hence, this study aimed to study anaerobes causing respiratory tract infections and determine their antibiotic susceptibility.

Materials & methods
Clinical specimens such as bronchial aspirates and pleural aspirates collected from patients with respiratory diseases attending Vallabhbhai Patel Chest Institute were processed, the anaerobes isolated were identified, and their susceptibilities to various groups of antimicrobials were studied using standard microbiological methods.

Results
Three hundred and fourteen patients were included in the study, 154 males and 160 females. Of these 314 patients, 148 (47%) yielded anaerobes in their clinical samples. Seventy patients had more than one type of anaerobic organism. Hence, 235 isolates were recovered belonging to as many as 17 genera. The MIC of seven antibiotics on 154 isolates was tested. The isolates belonged mostly to the genera Bacteroides, Prevotella, Veillonella, and Actinomyces. Variable resistance was observed to most classes of antibiotics by many genera.

Conclusions
Metronidazole is commonly used against anaerobes, but the study showed that the isolates were 20–30% resistant to the antibiotic. Starting this as an empirical therapy might lead to treatment failure.
Multiply robust estimator for the difference in survival functions using pseudo-observations
Authors: Wang Ce , Wei Kecheng , Huang Chen , Yu Yongfu , Qin Guoyou 
Published: October 2023

Abstract
Background
When estimating the causal effect on survival outcomes in observational studies, it is necessary to adjust confounding factors due to unbalanced covariates between treatment and control groups. There is no study on multiple robust method for estimating the difference in survival functions. In this study, we propose a multiply robust (MR) estimator, allowing multiple propensity score models and outcome regression models, to provide multiple protection.

Method
Based on the previous MR estimator (Han 2014) and pseudo-observation approach, we proposed a new MR estimator for estimating the difference in survival functions. The proposed MR estimator based on the pseudo-observation approach has several advantages. First, the proposed estimator has a small bias when any PS and OR models were correctly specified. Second, the proposed estimator considers the advantage pf the pseudo-observation approach, which avoids proportional hazards assumption. A Monte Carlo simulation study was performed to evaluate the performance of the proposed estimator. And the proposed estimator was used to estimate the effect of chemotherapy on triple-negative breast cancer (TNBC) in real data.

Results
The simulation studies showed that the bias of the proposed estimator was small, and the coverage rate was close to 95% when any model for propensity score or outcome regression is correctly specified regardless of whether the proportional hazard assumption holds, finite sample size and censoring rate. And the simulation results also showed that even though the propensity score models are misspecified, the bias of the proposed estimator was still small when there is a correct model in candidate outcome regression models. And we applied the proposed estimator in real data, finding that chemotherapy could improve the prognosis of TNBC.

Conclusions
The proposed estimator, allowing multiple propensity score and outcome regression models, provides multiple protection for estimating the difference in survival functions.
The proposed estimator provided a new choice when researchers have a "difficult time" choosing only one model for their studies.
Federated causal inference based on real-world observational data sources: application to a SARS-CoV-2 vaccine effectiveness assessment
Authors: Meurisse Marjan , Estupiñán-Romero Francisco , González-Galindo Javier , Martínez-Lizaga Natalia , Royo-Sierra Santiago , Saldner Simon , Dolanski-Aghamanoukjan Lorenz , Degelsegger-Marquez Alexander , Soiland-Reyes Stian , Van Goethem Nina , Bernal-Delgado Enrique ,   for the BeYond-COVID project
Published: October 2023

Abstract
Introduction
Causal inference helps researchers and policy-makers to evaluate public health interventions. When comparing interventions or public health programs by leveraging observational sensitive individual-level data from populations crossing jurisdictional borders, a federated approach (as opposed to a pooling data approach) can be used. Approaching causal inference by re-using routinely collected observational data across different regions in a federated manner, is challenging and guidance is currently lacking. With the aim of filling this gap and allowing a rapid response in the case of a next pandemic, a methodological framework to develop studies attempting causal inference using federated cross-national sensitive observational data, is described and showcased within the European BeYond-COVID project.

Methods
A framework for approaching federated causal inference by re-using routinely collected observational data across different regions, based on principles of legal, organizational, semantic and technical interoperability, is proposed. The framework includes step-by-step guidance, from defining a research question, to establishing a causal model, identifying and specifying data requirements in a common data model, generating synthetic data, and developing an interoperable and reproducible analytical pipeline for distributed deployment. The conceptual and instrumental phase of the framework was demonstrated and an analytical pipeline implementing federated causal inference was prototyped using open-source software in preparation for the assessment of real-world effectiveness of SARS-CoV-2 primary vaccination in preventing infection in populations spanning different countries, integrating a data quality assessment, imputation of missing values, matching of exposed to unexposed individuals based on confounders identified in the causal model and a survival analysis within the matched population.

Results
The conceptual and instrumental phase of the proposed methodological framework was successfully demonstrated within the BY-COVID project. Different Findable, Accessible, Interoperable and Reusable (FAIR) research objects were produced, such as a study protocol, a data management plan, a common data model, a synthetic dataset and an interoperable analytical pipeline.

Conclusions
The framework provides a systematic approach to address federated cross-national policy-relevant causal research questions based on sensitive population, health and care data in a privacy-preserving and interoperable way. The methodology and derived research objects can be re-used and contribute to pandemic preparedness.
Colonic distribution of FMT by different enema procedures compared to colonoscopy – proof of concept study using contrast fluid
Authors: Skjevling Linn Kallbekken , Hanssen Hege Marie , Valle Per Christian , Goll Rasmus , Juul Frederik Emil , Arlov Øystein , Johnsen Peter Holger 
Published: October 2023

Abstract
Background
Fecal microbiota transplantation (FMT) has become an important treatment method in recurrent Clostridioides difficile infections and is under investigation as a treatment for several other diseases. FMT’s mechanism of action is assumed to be through alterations of the colon microbiota. FMT can be delivered by several methods, but few studies have directly compared how FMT is distributed in the colon by different methods. Specifically, the proximal distribution of FMT delivered by enema is unknown.

Methods
In eight participants, we administered contrast fluid (CF) with viscosity similar to an FMT in a crossover study design. First, CF was administered by colonoscopy, followed by an abdominal X-ray to visualize the CF distribution. Next, after four to eight weeks, participants were given CF, but as an enema, followed by a positioning procedure. X-rays were obtained before (enema ÷) and after (enema +) the positioning procedure.

Conclusion
Proportion of participants with CF in cecum were 100% after colonoscopy, 50% after enema + and 38% after enema ÷. In the transverse colon, proportions were 100% (colonoscopy), 88% (enema +) and 63% (enema ÷). There were no adverse events.

Interpretation
This study shows proof of concept for the distribution of FMT to proximal colon when delivered by enema. A positioning procedure after the enema slightly improves the proximal distribution. However, colonoscopy is the only method that ensures delivery to the cecum. Studies are needed to see if FMT colon distribution correlates with treatment effectiveness.

Trial registration
The study was retrospectively registered at ClinicalTrials.gov (NCT05121285) (16/11/2021).
Background malaria incidence and parasitemia during the three-dose RTS,S/AS01 vaccination series do not reduce magnitude of antibody response nor efficacy against the first case of malaria
Authors: Bell Griffin J , Gyaase Stephaney , Goel Varun , Adu Bright , Mensah Benedicta , Essone Paulin , Dosoo David , Osei Musah , Niare Karamoko , Wiru Kenneth , Brandt Katerina , Emch Michael , Ghansah Anita , Asante Kwaku Poku , Mvalo Tisungane , Agnandji Selidji Todagbe , Juliano Jonathan J , Bailey Jeffrey A 
Published: October 2023

Abstract
Background
RTS,S/AS01 has been recommended by WHO for widespread implementation in medium to high malaria transmission settings. Previous analyses have noted lower vaccine efficacies in higher transmission settings, possibly due to the more rapid development of naturally acquired immunity in the control group.

Methods
To investigate a reduced immune response to vaccination as a potential mechanism behind lower efficacy in high transmission areas, we examine initial vaccine antibody (anti-CSP IgG) response and vaccine efficacy against the first case of malaria (to exclude the effect of naturally acquired immunity) using data from three study areas (Kintampo, Ghana; Lilongwe, Malawi; Lambaréné, Gabon) from the 2009–2014 phase III trial (NCT00866619). Our key exposures are parasitemia during the vaccination series and background malaria incidence. We calculate vaccine efficacy (one minus hazard ratio) using a cox-proportional hazards model and allowing for the time-varying effect of RTS,S/AS01.

Results
We find that antibody responses to the primary three-dose vaccination series were higher in Ghana than in Malawi and Gabon, but that neither antibody levels nor vaccine efficacy against the first case of malaria varied by background incidence or parasitemia during the primary vaccination series.

Conclusions
We find that vaccine efficacy is unrelated to infections during vaccination. Contributing to a conflicting literature, our results suggest that vaccine efficacy is also unrelated to infections before vaccination, meaning that control-group immunity is likely a major reason for lower efficacy in high transmission settings, not reduced immune responses to RTS,S/AS01. This may be reassuring for implementation in high transmission settings, though further studies are needed.
Acceptability of a digital health application to empower persons with multiple sclerosis with moderate to severe disability: single-arm prospective pilot study
Authors: Kutzinski Max , Krause Nicole , Riemann-Lorenz Karin , Meyer Björn , Heesen Christoph 
Published: October 2023

Abstract
Background
Many persons with multiple sclerosis (pwMS) desire to learn how health behaviour changes (e.g., dietary adjustments, physical activity, improvements in stress management) might help them manage their disease. Previous research has shown that certain health behaviour changes can improve quality of life (QoL), fatigue and other MS outcomes. Digital health applications may be well suited to deliver relevant health behavioural interventions because of their accessibility and flexibility. The digital health application “levidex” was designed to facilitate health behaviour change by offering evidence-based patient information and cognitive-behavioural therapy techniques to pwMS. By doing so, levidex aims to improve QoL and MS symptoms such as fatigue and mental health.

Objectives
A previous study reported on the development of levidex; this non-randomised pilot study examined the feasibility (practicability and acceptability) of levidex in pwMS with moderate to severe disability. Furthermore, the intervention’s impact on empowerment, stress management, and relevant health behaviours (e.g., dietary behaviour, physical activity) was explored.

Methods
levidex was originally developed for newly diagnosed pwMS in the first year after diagnosis and eventually modified to offer access to pwMS with moderate to severe disability. Participants (n = 43) with an Expanded Disability Status Scale between 3.5 and 7.5 and a disease duration of more than one year were eligible to participate. The intervention was used over a period of six months with measurement time points at baseline, month 3 and month 6.

Results
Out of 38 participants who completed the six-month intervention period, 18 (47.4%) completed all 16 modules and 9 (23.7%) reached modules 13–16, the long-term maintenance part of levidex. Participants rated levidex positively in terms of practicability and acceptability and had only few points of criticism such as to include more physical exercise routine suggestions suitable for participants with severe impairment. Data on secondary endpoints showed no significant changes.

Conclusion
This pilot study provided evidence for the practicability and acceptability of levidex, a digital health application designed to facilitate health behaviour change in pwMS with moderate to severe disability. Adequately powered randomised controlled studies with longer follow-up periods are needed to clarify the benefit of levidex in pwMS with moderate to severe disability.

Trial registration
German Clinical Trials Register (DRKS) DRKS00032667 (14/09/2023); Retrospectively registered.