bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring how PRIME-Parkinson care is implemented and whether, how and why it produces change, for who and under what conditions: a protocol for an embedded process evaluation within the PRIME-UK randomised controlled trial
Authors: Lloyd Katherine , Tenison Emma , Smith Safi , Lithander Fiona , Kidger Judi , Brant Heather , Redwood Sabi , Ben-Shlomo Yoav , Henderson Emily J 
Published: February 2025

IntroductionThe PRIME-UK randomised controlled trial (RCT) aims to establish whether a model of care that seeks to be proactive, integrated and empower participants, caregivers and healthcare professionals can improve outcomes in people with parkinsonism. Given that this intervention is novel and complex, understanding whether and how the intervention will be acceptable, implementable, cost-effective and scalable across contexts are key questions beyond that of whether ‘it works’. We describe an embedded process evaluation to answer these questions, which aims to support interpretation of the trial results, refinement of the intervention and support future scaling of the PRIME-Parkinson model of care.Methods and analysisA mixed-methods approach will be used to collect data across four process evaluation domains: implementation, mechanism of change, acceptability and context. Quantitative data will be collected prospectively from all participants and analysed descriptively with exploratory tests of relationships as power allows. Qualitative data will be collected through semistructured interviews with a purposively sampled subpopulation of participants, caregivers and staff members as well as case studies where relevant. Interview transcripts will be analysed thematically using interpretive qualitative analysis. Synthesis of quantitative and qualitative data will also be performed to draw conclusions.Ethics and disseminationThe quantitative data will be collected as part of the main PRIME-UK RCT which was been granted NHS REC approval (21/LO/0387) on 27 July 2021. The qualitative data will be collected as part of a substudy, ‘PRIME-Qual’, which was granted NHS REC approval (21/LO/0388) on 14 July 2021. The mixed-methods process evaluation will be published after the conclusion of the trial in addition to the main trial findings.Trial registration numberNCT05127057.
Developing a core outcome set for assessing interventions and care for parents after neonatal death in high-income countries (iCHOOSE Neonatal study): protocol for a mixed-methods study
Authors: Davies Anna , Williams Charlotte , Burden Christy , Mullin Sadie , Moy Lucy , Redshaw Maggie , Patel Mehali , Fraser Abigail , Hinton Lisa , Lynch Mary , Merriel Abi , Siasakos Dimitris , Webbe James , Odd David , Timlin Laura , Watts Leanne , Bakhbakhi Danya 
Published: February 2025

IntroductionNeonatal death exerts long-lasting impact on parents’ mental health, finances and relationships, and the wider family. There is national and international momentum to evaluate interventions to support parents after the death of a baby. Core Outcome Sets (COSs) provide a minimum set of outcomes, agreed by stakeholders to be important, which should be evaluated in all studies to support evidence syntheses and identification of the most effective interventions. We aim to develop a COS for assessing interventions and care after neonatal death in high-income countries, to support future evidence syntheses and enable the identification of effective interventions and care for parents.Methods and analysisWe will develop the COS in six phases. A parent involvement group and stakeholder steering committee have been established and have informed each planned phase: (1) systematic review of quantitative studies evaluating care and interventions provided after neonatal death, to describe interventions, outcomes and outcome measurement tools used to assess intervention effectiveness; (2) qualitative interviews with parents who have experienced neonatal death to identify outcomes important and relevant to them; (3) think-aloud interviews with stakeholders (bereaved parents, healthcare professionals and other stakeholders) to develop and refine an online survey; (4) real-time online international Delphi survey with bereaved parents, healthcare professionals and other stakeholders to shortlist outcomes for consideration in the COS; (5) adapted nominal group online consensus meetings with parents, healthcare professionals and other stakeholders to agree final COS and (6) identification of a preliminary set of measurement tools.Ethics and disseminationEthical approval has been granted for all activities to be undertaken by the University of Bristol Health Sciences Faculty Research Ethics Committee (reference: 15121). We will disseminate the findings via peer-reviewed publications and relevant academic and professional conferences.PROSPERO registration numberCRD42020151365.
Ambient air pollution and birth outcomes: a scoping review to investigate the mediating and moderating variables—protocol
Authors: Perry Lucy , Mizen Amy , Ellis-Davies Kate , Fry Richard , Isham Amy 
Published: February 2025

IntroductionPregnant women and their babies are a highly vulnerable population to health effects from air pollution. This scoping review aims to understand the extent and type of evidence concerning the mediating and moderating factors between air pollution and birth outcomes. By gathering and synthesising this evidence, this review aims to identify key concepts, themes and knowledge gaps. In turn, these findings will serve as a valuable resource for researchers and policymakers by highlighting potential pathways and gaps in evidence.Methods and analysisThis scoping review protocol is based on the Joanna Briggs Institute (JBI) methodology for scoping reviews and will be reported in full with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review (PRISMA-ScR) flow diagram. This review will search eight databases: Web of Science, Scopus, PubMed, Embase, GreenFILE, CINAHL Ultimate, APA PsycINFO and MIDIRS. Results will be limited to those written or translated into English and peer-reviewed studies with no restriction on publication date. The study selection and data extraction will be completed within the software Covidence by two or more independent reviewers, with conflicts solved by group discussion. The data extracted from this process will include publication details, study characteristics and population characteristics.Ethics and disseminationThis study will not collect primary data; therefore, no formal ethical approval is required. The findings will be disseminated to academic and non-academic audiences through conferences, publications and focus groups.Trail registration numberOpen Science Framework (https://doi.org/10.17605/OSF.IO/6Y2D9).
Spatial and temporal changes of breast-conserving surgery rates and its influential factors among Chinese patients with breast cancer from 2013 to 2019: a registry-based study
Authors: Lin Queran , Li Shunrong , Shang Tongrui , Gui Xiujuan , Zhu Liling , Yang Yuan , Zhong Ziliang , Wang Xiaoyu , Dai Lingyan , Zhao Jianli , Xu Yanjie , Chen Qianru , Yan Qing , Huang Xiaoliang , Hu Wei , Liang Zijian , Song Erwei , He Jianrong , Ye Pengpeng , Chen Kai 
Published: February 2025

ObjectiveOur study aims to evaluate the spatial and temporal changes of breast-conserving surgery (BCS) rates and influential factors of BCS in Guangdong Province, China.Design, setting and participantsThis registry-based cohort study analysed the data of patients of all age groups, from the medical record cover page, which was mandatorily collected for inpatients by the Health Administrative Department of Guangdong Province, China. Patients with non-metastatic breast cancer, who underwent breast surgery between 2013 and 2019, were included.Main outcomes and measuresWe analysed the BCS rate in Guangdong Province between 2013 and 2019. Logistic regression was applied to investigate the association between patient-level influential factors and BCS, respectively. We used restricted cubic spline regression to model the non-linear association between hospital volume rank with BCS rate. Linear regression was used to evaluate the association between city-level parameters with BCS rate of each city.ResultsA total of 93 521 patients with non-metastatic breast cancer, who underwent breast surgery, were included in the analyses. Among them, 10 949 (11.7%) had BCS, with the BCS rates increasing from 0.8% in 2013 to 19.2% in 2019. Patients who were older (vs <40 years, 40–49 years: adjusted OR 0.72, 95% CI 0.68 to 0.76; 50–59 years: 0.51, 95% CI 0.48 to 0.54; ≥60 years: 0.37, 95% CI 0.35 to 0.40) and married (vs unmarried, 0.64, 95% CI 0.59 to 0.70) were less likely to undergo BCS. Patients who were employed (vs unemployed, 1.58, 95% CI 1.49 to 1.68), received cross-city surgery (vs local surgery, 1.37, 95% CI 1.31 to 1.44), lived in a high-income city (vs low-income city, β=4.40, 95% CI 1.55 to 7.24) or in a city with a higher number of physicians per 100 000 residents (0.57, 95% CI 0.31 to 0.82) were more likely to receive BCS.Conclusions and relevanceThis study suggests a significant increase in BCS rates from 2013 to 2019 in Guangdong, China. Promotion of BCS is needed, particularly among older patients, lower-volume hospitals and economically underdeveloped areas. Healthcare system should be prepared to support the increased awareness of seeking BCS among younger patients with breast cancer by improving the availability of radiotherapy, multidisciplinary team and patients’ education programme.
Effect of intermittent theta burst stimulation combined with acoustic startle priming motor training on upper limb motor function and neural plasticity in stroke individuals: study protocol for a randomised controlled proof-of-concept trial
Authors: Chen Yu , Xia Nan , Li Jinghong , Liang Weiqiang , Yin Yangyang , Zhai Linhan , Wang Mingzhu , Wang Qiuxia , Zhang Jing 
Published: February 2025

IntroductionStroke is a major cause of acquired disability globally, yet the neural mechanisms driving motor recovery post-stroke remain elusive. Recent research has underscored the growing significance of subcortical pathways in neural plasticity and motor control. Among these, the cortico-reticulospinal tract (CRST) has gained attention in rehabilitation due to its unique ascending and descending structural features as well as its cellular properties which position it as an excellent candidate to compensate for inadequate motor control post-stroke. However, the optimal strategies to harness the CRST for motor recovery remain unknown. Non-invasive modulation of the CRST presents a promising though challenging, therapeutic opportunity. Acoustic startle priming (ASP) training and intermittent theta burst stimulation (iTBS) are emerging as potential methods to regulate CRST function. This study aims to investigate the feasibility of segmentally modulating the cortico-reticular and reticulospinal tracts through ASP and iTBS while evaluating the resulting therapeutic effects.Methods and analysisThis is a randomised, blinded interventional trial with three parallel groups. A total of 36 eligible participants will be randomly assigned to one of three groups: (1) iTBS+ASP group, (2) iTBS+non-ASP group, (3) sham iTBS+ASP group. The trial comprises four phases: baseline assessment, post-first intervention assessment, assessment after 3 weeks of intervention and a 4-week follow-up. The primary outcomes are the changes in the Fugl-Meyer Assessment-Upper Extremity and Modified Ashworth Scale after the 3-week intervention. Secondary outcomes include neurophysiological metrics and neuroimaging results from diffusion tensor imaging and resting-state functional MRI.Ethics and disseminationThe trial is registered with the Chinese Clinical Trial Registry (Registration No. ChiCTR2400085220) and Medical Ethics Committee of Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology (Registration No.TJ-IRB20231109). It will be conducted in the Departments of Rehabilitation Medicine and Radiology at Tongji Hospital in Wuhan, China. The findings will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.Trial registration numberChiCTR2400085220.
Exploring the causal paths and longitudinal impact of telework on health: the TeleHealth survey–data linkage study protocol
Authors: Bracho Montes de Oca Eduardo Antonio , Int Panis Laura , Verbrugghe Mathieu , De Waegeneer Els , Cagnie Barbara , de Geus Bas , De Pauw Robby 
Published: February 2025

BackgroundThe transition from traditional office work to telework has accelerated significantly since the late 20th century, especially in light of the COVID-19 pandemic. Despite its widespread adoption, the long-term health impacts of telework remain unclear. This study seeks to clarify the telework–health relationship by integrating longitudinal self-reported health data with health-related administrative records.Methods and analysisAn online self-reported longitudinal survey with four follow-ups of 6 months each, starting in November 2024, will be set up and linked with administrative data sources. In total, a non-probabilistic sample of 5000 non-teleworkers and teleworkers will be recruited. This survey will mainly assess the effect of teleworking on mental (eg, depression and anxiety) and physical (eg, pain) health. Administrative data (eg, healthcare consumption contacts and socioeconomic status) will be extracted from Belgian administrative data sources (Statistics Belgium and the InterMutualistic Agency) for the same period. This administrative data will be linked to the survey data using the Social Security ID. The underlying relationships between telework and health will be analysed via regression models and mediation models embedded in the natural effects framework. The analysis will aim to (1) identify the impact of telework on self-reported health and administrative data, (2) identify the moderators and mediators between the telework–health relationship, (3) understand the long-term patterns of telework and health interaction and (4) predict the health outcomes of teleworkers. To mitigate biases associated with non-probabilistic samples and attrition, standardised probability weights scoring will be derived from the data.Ethics and disseminationThis study involves human participants and has been approved by the Ethics Committee of Universitair Ziekenhuis Gent (Nr°. ONZ-2023–0630). The participants will participate in the study after signing an informed consent form. The study will be disseminated in academic journals, on (social) media and on the project website.
Socioeconomic, demographic and environmental factors of child drownings in Northern Bangladesh
Authors: Alam Edris , Al Hattawi Khawla Saeed , Akter Habiba , Alam Jahangir , Alvarez Elizabeth , Sufi Fahim , Kamrul Islam Md , Towfiqul Islam Abu Reza Md 
Published: February 2025

Background
Drowning is the leading cause of death among children aged 0–17 years in rural Bangladesh, resulting in over 14 438 deaths annually—an average of 43 deaths per day. This study aims to identify socioeconomic, demographic and environmental factors linked to child drowning deaths in Northern Bangladesh—a region of high poverty, which is behind in overall socioeconomic indicators compared with other regions in the country.

Methods
We conducted a cross-sectional survey through purposive sampling to identify child fatal and non-fatal drownings among a total of 18 004 households, comprising 71 185 people, in 2 unions in Northern Bangladesh. Interviews were conducted between January and March 2024 with the households that experienced child drownings in the region. We employed a mixed-methods approach to data collection, using quantitative analysis to examine socioeconomic, demographic and environmental factors, alongside qualitative analysis to explore situational factors associated with drownings in the region.

Results
Through household visits, a total of 117 households were identified that faced child drowning incidents, comprising 84 fatal (71.8 %) and 33 non-fatal (28.2 %) drownings between 2018 and 2023. The households that faced drownings were comparatively of lower income groups, had lower rates of education and were mostly engaged in agriculture and other domestic work. In 2023, the number of drowning incidents was 34. Out of 117 drownings, 95% occurred between 9:00 and 15:00 hours, and more than 82% occurred between June and October. Out of 117 drowning incidents, approximately 97% of children did not know how to swim prior to the incident. Out of 117 respondents, 73.5% stated that they did not teach their child how to swim. Of those who taught their child to swim, the average age for learning to swim was 8.33 years. Out of 84 child drowning deaths, 75% were male and 25% were female, and the average age was 3.9 years. Out of the 84 fatal drowning deaths, 72.6% occurred in ponds.

Conclusion
Identification of socioeconomic, demographic and environmental factors associated with child drownings will help to develop feasible prevention strategies and interventions in the region.
The role of the muscle metaboreflex on cardiovascular responses to submaximal resistance exercise with different pressures and modes of blood flow restriction
Authors: Yamada Yujiro , Hammert William B. , Kataoka Ryo , Song Jun Seob , Kang Anna , Kassiano Witalo , Loenneke Jeremy P. 
Published: February 2025

This study investigated the role of the muscle metaboreflex on cardiovascular responses to submaximal resistance exercise using different pressures and modes of blood flow restriction. Fifty-three adults completed six visits. The first visit involved a performance test (two sets of unilateral knee extension exercise until task failure at 30% 1RM) with continuous blood flow restriction (80% arterial occlusion pressure). In subsequent visits, participants performed (1) a nonexercise control (Control), 70% of the repetitions completed in the performance test with the cuff inflated to (2) continuously 80% arterial occlusion (LL + 80%), (3) continuously 40% arterial occlusion (LL + 40%), (4) intermittently 80% arterial occlusion during exercise (LL + 80%Int), and (5) 0 mmHg (LL), in a randomized order. Three minutes of post-exercise circulatory occlusion was employed to assess the muscle metaboreflex activation. Blood pressure and heart rate were measured at various time points. The pre-post increase in systolic blood pressure was not greater with LL + 80%Int ( p = 0.987) but was greater with LL + 80% and LL + 40% (LL + 80% > LL + 40%, p = 0.005) than LL by 7 [95%CI: 4, 9] and 4 [95%CI; 2, 6] mmHg, respectively. Heart rate increased only with LL + 80% over LL and Control ( p < 0.001). The changes in systolic blood pressure ( p > 0.468) and heart rate ( p > 0.543) did not differ among exercise conditions from immediate post-exercise to the end of the circulatory occlusion. Systolic/diastolic blood pressure returned to a similar level as Control (∼120, ∼70 mmHg, respectively) immediately after the cuff deflation. Continuous blood flow restriction, especially with higher pressure, accentuates muscle metaboreflex activation, resulting in amplified cardiovascular responses to the exercise.
Ultra high energy cosmic rays versus models of high energy hadronic interactions
Authors: Bortolato Blaž , Kamenik Jernej F. , Tammaro Michele 
Published: February 2025

Abstract
We evaluate the consistency of hadronic interaction models in the CORSIKA simulation package with publicly available fluorescence telescope data from the Pierre Auger Observatory. By comparing the first few central moments of the extensive air shower depth maximum distributions, as extracted from measured events, to those predicted by the best-fit inferred compositions, we derive a statistical measure of the consistency of a given hadronic model with data. To mitigate possible systematic biases, we include all primaries up to iron, compensate for the differences between the measured and simulated energy spectra of cosmic rays and account for other known systematic effects. Additionally, we study the effects of including higher central moments in the fit and project our results to larger statistics.
Zee model in a modular $$A_4$$ symmetry
Authors: Nomura Takaaki , Okada Hiroshi , Qi Yong-hui 
Published: February 2025

Abstract
We study a Zee model applying a modular

$$A_4$$

A
4

symmetry in supersymmetry framework, where we construct our lepton model as minimum modular weight as possible. We show our predictions on phases and neutrino masses through numerical analysis. We find a model that can fit in both normal and inverted hierarchy cases of neutrino mass. The predictions of neutrino observables are shown where we obtain more constrained allowed region in the inverted hierarchy case.
Bcl-Xl Protects ASS1-Deficient Cancers From Arginine Starvation Induced Apoptosis
Authors: Panda Prashanta Kumar. , Paschoalini Mafra Ana Carolina. , Bastos Alliny C. S. , Cao Li , Serra Bonet Maria , Brashears Caitlyn B. , Chen Ethan Yang. , Benedict-Hamilton Heather M. , Ehrhardt William , Bomalaski John , Dehner Carina , Rogers Leonard C. , Oyama Toshinao , Van Tine Brian A. 
Published: February 2025

Abstract
Purpose: Argininosuccinate Synthetase 1 (ASS1) silencing in carcinomas and sarcomas leads to a dependence on extracellular arginine for survival. Arginine deprivation therapies, like PEGylated arginine deiminase (ADI-PEG20), have shown limited effectiveness, which may be due to underlying mechanisms that inhibit apoptosis. Experimental Design: The effects of ADI-PEG20 on cell cycle regulation, apoptosis, and Bcl-xL-mediated survival pathways in ASS1-deficient cancer cells were determined. The mechanism of cell death protection was determined by assessing caspase and PARP cleavage, CDK2 activity, MCL1 expression, and the interactions between Bcl-xL, Bax, and Bak. In vitro synergy was determined, and in vivo efficacy was modeled. Results: Treatment with ADI-PEG20 led to reduced CDK2 activity and inhibited cell cycle progression but did not induce significant cell death. Bcl-xL was found to bind to Bax and Bak, preventing the initiation of apoptosis despite arginine starvation. Inhibition of Bcl-xL allowed proapoptotic Bax and Bak to initiate the intrinsic apoptosis pathway, leading to increased cell death. This was found to be synergistic in vitro and efficacious in combination in vivo. Conclusions: The study identifies Bcl-xL as a key factor limiting the efficacy of arginine starvation therapies. Combining Bcl-xL inhibitors with arginine deprivation strategies may overcome this resistance and enhance therapeutic outcomes. These findings provide a strong preclinical rationale for testing this combination approach in Phase 1 clinical trials for ASS1-deficient cancers.
Tumor Microenvironment: Obstacles and Opportunities for T Cell–Based Tumor Immunotherapies
Authors: Hu Miao-Miao , Zhao Ying , Zhang Nan , Gong Fang-Yuan , Zhang Wei , Dong Chun-Sheng , Dai Jian-Feng , Wang Jun 
Published: February 2025

Abstract
The complex composition and dynamic change of the tumor microenvironment (TME), mainly consisting of tumor cells, immune cells, stromal cells, and extracellular components, significantly impede the effector function of cytotoxic T lymphocytes (CTL), thus representing a major obstacle for tumor immunotherapies. In this review, we summarize and discuss the impacts and underlying mechanisms of major elements in the TME (different cell types, extracellular matrix, nutrients and metabolites, etc.) on the infiltration, survival, and effector functions of T cells, mainly CD8+ CTLs. Moreover, we also highlight recent advances that may potentiate endogenous antitumor immunity and improve the efficacy of T cell–based immunotherapies in patients with cancer by manipulating components inside/outside of the TME. A deeper understanding of the effects and action mechanisms of TME components on the tumor-eradicating ability of CTLs may pave the way for discovering new targets to augment endogenous antitumor immunity and for designing combinational therapeutic regimens to enhance the efficacy of tumor immunotherapies in the clinic.