bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol: use of a smartphone application to support the implementation of a complex physical activity intervention (+Stay Active) in women with gestational diabetes mellitus—protocol for a non-randomised feasibility study
Authors: Smith Ralph , Kenworthy Yvonne , Astbury Nerys M , Birks Jacqueline , Bateman Paul , Dyson Pamela , Hirst Jane E , Jebb Susan A , Michalopoulou Moscho , Pulsford Richard , Roman Cristian , Santos Mauro , Tarassenko Lionel , Wango Nicola , Wire Amy , MacKillop Lucy H 
Published: November 2022

IntroductionPhysical activity (PA) interventions have a promising role in the management of gestational diabetes mellitus (GDM). Digital technologies can support PA at scale and remotely. The protocol describes a study designed to determine the feasibility and acceptability of a complex intervention; known as +Stay Active. +Stay Active combines motivational interviewing with a bespoke behaviour change informed smartphone application (Stay-Active) to augment PA levels in women with GDM.Methods and analysisThis is a non-randomised feasibility study using a mixed methods approach. Participants will be recruited from the GDM antenatal clinic at the Women Centre, John Radcliffe Hospital, Oxford. Following baseline assessments (visit 1) including self-reported and device determined PA assessment (wearing a wrist accelerometer), women will be invited to participate in an online motivational interview, then download and use the Stay-Active app (Android or iOS) (visit 2). Women will have access to Stay-Active until 36 weeks gestation, when engagement and PA levels will be reassessed (visit 3). The target sample size is 60 women. Primary outcomes are recruitment and retention rates, compliance and assessment of participant engagement and acceptability with the intervention. Secondary outcomes are assessment of blood glucose control, self-reported and device determined assessment of PA, usage and structured feedback of participant’s attitudes to +Stay Active, assessment of health costs and description of maternal and neonatal outcomes. This study will provide key insights into this complex intervention regarding engagement in smartphone technology and the wearing of accelerometers. These data will inform the development of a randomised controlled trial with refinements to intervention implementation.Ethics and disseminationThe study has received a favourable opinion from South Central—Hampshire B Research Ethics Committee; REC reference: 20/SC/0342. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, conferences and seminar presentations.Trial registration numberNCT11366562.
Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2): a multisite, randomised, 12-month trial to compare efficacy of standard versus peer-based approaches to retain rural people who use drugs in research
Authors: Young April M , Lancaster Kathryn E , Bielavitz Sarann , Elman Miriam R , Cook Ryan R , Leichtling Gillian , Freeman Edward , Estadt Angela T , Brown Morgan , Alexander Rhonda , Barrie Caiti , Conn Kandi , Elzaghal Rhody , Maybrier Lisa , McDowell Renee , Neal Cathy , Lapidus Jodi , Waddell Elizabeth N , Korthuis P Todd 
Published: November 2022

Introduction
Rural communities bear a disproportionate share of the opioid and methamphetamine use disorder epidemics. Yet, rural people who use drugs (PWUD) are rarely included in trials testing new drug use prevention and treatment strategies. Numerous barriers impede rural PWUD trial engagement and advancing research methods to better retain rural PWUD in clinical trials is needed. This paper describes the Peer-based Retention Of people who Use Drugs in Rural Research (PROUD-R2) study protocol to test the effectiveness of a peer-driven intervention to improve study retention among rural PWUD.

Methods and analysis
The PROUD-R2study is being implemented in 21 rural counties in three states (Kentucky, Ohio and Oregon). People who are 18 years or older, reside in the study area and either used opioids or injected any drug to get high in the past 30 days are eligible for study inclusion. Participants are allocated in a 1:1 ratio to two arms, stratified by site to assure balance at each geographical location. The trial compares the effectiveness of two retention strategies. Participants randomised to the control arm provide detailed contact information and receive standard retention outreach by study staff (ie, contacts for locator information updates, appointment reminders). Participants randomised to the intervention arm are asked to recruit a ‘study buddy’ in addition to receiving standard retention outreach. Study buddies are invited to participate in a video training and instructed to remind their intervention participant of follow-up appointments and encourage retention. Assessments are completed by intervention, control and study buddy participants at 6 and 12 months after enrolment.

Ethics and dissemination
The protocol was approved by a central Institutional Review Board (University of Utah). Results of the study will be disseminated in academic conferences and peer-reviewed journals, online and print media, and in meetings with community stakeholders.

Trial registration number

NCT03885024
Investigating the impact of oral health on pregnancy and offspring outcomes: protocol for the Lifetime Impact of ORal heAlth (LIORA) cohort study
Authors: Zhao Mei-Ling , Zhang Feng-Jing , Jiang Wen-Rong , xia yinyin , Chen Chang , Zhang Ting , Han Ting-Li , Yu Xin-Yang , Mei Peter , Zhang Hong-Mei , Jin Xin , Novakovic Boris , Leong Pamela , Thompson Murray , Saffery Richard , Cannon Richard D , Zhang Hua , Ji Ping 
Published: November 2022

IntroductionOral health is a fundamental component of well-being, and is closely associated with overall health and quality of life. Oral health may also affect the next generation. The children of mothers with poor oral health are likely to also have poor oral health as they go through life. We aim to investigate associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health.Methods and analysisThe Lifetime Impact of Oral Health study is a prospective, observational cohort study being done at a single centre in Chongqing, China. A total of 1000 pregnant women will be recruited in their first trimester (11–14 weeks gestation). After obtaining informed consent, general and oral health assessments will be undertaken. Maternal lifestyle, demographic data and biospecimens (blood, hair, urine, nail clippings, saliva, dental plaque, buccal, vaginal and anal swabs) will be collected. Pregnancy outcomes will be recorded at the time of delivery. Cord blood and placenta samples will be collected. The offspring will be followed up for general and oral health examinations, neurodevelopmental assessments and biospecimen (dental plaque, saliva, buccal swabs, exfoliated primary dentition, urine, hair, nail clippings) collection until they are 15 years old. Biological samples will undergo comprehensive metabolomic, microbiome and epigenome analyses. Associations between maternal oral health and general health, pregnancy outcomes, offspring oral health and offspring general health will be investigated and the underlying mechanisms explored.Ethics and disseminationThis project has been approved by the Research Ethics Committee of the Affiliated Hospital of Stomatology of Chongqing Medical University (CQHS-REC-2021 LSNo.23). Participants will be required to provide informed consent to participate in the study. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences.Trial registration numberChiCTR2100046898.
Peer Reviewed Evaluation of Registered End-Points of Randomised Trials (the PRE-REPORT study): a stepped wedge, cluster-randomised trial
Authors: Jones Christopher W , Adams Amanda , Misemer Benjamin S , Weaver Mark A , Schroter Sara , Khan Hayat , Margolis Benyamin , Schriger David L , Platts-Mills Timothy F 
Published: November 2022

Objective
To test whether providing relevant clinical trial registry information to peer reviewers evaluating trial manuscripts decreases discrepancies between registered and published trial outcomes.

Design
Stepped wedge, cluster-randomised trial, with clusters comprised of eligible manuscripts submitted to each participating journal between 1 November 2018 and 31 October 2019.

Setting
Thirteen medical journals.

Participants
Manuscripts were eligible for inclusion if they were submitted to a participating journal during the study period, presented results from the primary analysis of a clinical trial, and were peer reviewed.

Interventions
During the control phase, there were no changes to pre-existing peer review practices. After journals crossed over into the intervention phase, peer reviewers received a data sheet describing whether trials were registered, the initial registration and enrolment dates, and the registered primary outcome(s) when enrolment began.

Main outcome measure
The presence of a clearly defined, prospectively registered primary outcome consistent with the primary outcome in the published trial manuscript, as determined by two independent outcome assessors.

Results
We included 419 manuscripts (243 control and 176 intervention). Participating journals published 43% of control-phase manuscripts and 39% of intervention-phase manuscripts (model-estimated percentage difference between intervention and control trials = −10%, 95% CI −25% to 4%). Among the 173 accepted trials, published primary outcomes were consistent with clearly defined, prospectively registered primary outcomes in 40 of 105 (38%) control-phase trials and 27 of 68 (40%) intervention-phase trials. A linear mixed model did not show evidence of a statistically significant primary outcome effect from the intervention (estimated difference between intervention and control=−6% (90% CI −27% to 15%); one-sided p value=0.68).

Conclusions
These results do not support use of the tested intervention as implemented here to increase agreement between prospectively registered and published trial outcomes. Other approaches are needed to improve the quality of outcome reporting of clinical trials.

Trial registration number

NCT41225307.
Single amino acid variation in MAB21L1 is dominantly associated with congenital eye defects
Authors: Meng Fanlei , Li Xin , Zhang Jinlu , Gao Zhiyang , Yang Xue , Liu Ziqi , Liu Yajie , Guo Tong , Wang Likun , Yang Liping , Wang Zhaohui 
Published: November 2022

BackgroundDiagnosis of a genetic disease and determination of the causative molecular lesion rely on the availability of the disease-associated pedigrees. Microphthalmia is a congenital eye defect due to an insufficiently developed visual system; its prevalence is 1–3 in 10 000 live births.ObjectiveWe analysed a pedigree exhibiting autosomal dominant inheritance of microphthalmia to determine the genetic lesion; used AlphaFold2 to predict the changes in the protein’s 3-Dimensional structure; and compared wild-type and variant proteins in cultured cells or Drosophila model was used to explore the cellular or developmental function of the encoded product.ResultsWe identified a novel missense variation, F52L, in MAB21L1 that is absent in population databases and present exclusively in the individuals diagnosed with microphthalmia in this pedigree. Common structural changes were predicted for the disease-associated variants clustered at amino acids 49–52, and these variant products were also predominantly trapped in the cytoplasm of cultured human lens epithelia. To recapitulate its dominant effect in development, we expressed the Drosophila homologue corresponding to MAB21L1F52Land caused malformation of sensory organs.ConclusionMutations at the residues 49–52 of MAB21L1 compromise eye development. We recommend includingMAB21L1in the genetic testing panel for congenital eye disorders.
Musculoskeletal system injuries in the Polish Territorial Defence Forces
Authors: Gołuchowska Agnieszka , Sobieszek K 
Published: November 2022

BackgroundMusculoskeletal system injuries (MSIs) are the major health problem of soldiers. The aim of this study was to assess the types of MSIs that occurred most frequently among soldiers and which parts of the body they generally affected.MethodsThe study included 140 Territorial Army soldiers, both men and women, serving in the Polish Territorial Defence Forces (TDF). Times and frequency of MSIs were assessed using an original questionnaire available via a web-based platform, the TDF Information Portal and the Yammer network.ResultsAmong the participants, 42% reported MSIs, most often a single one (19%), incurred while doing military service. Damaged muscles and ligaments were the most common injuries in both groups (p>0.05). The knee joint was the main location of injuries for both sexes (24% in men vs 50% in women, p>0.05). Other parts of the body often affected by injuries were the shoulder joint (24%, p>0.05), head, spine, wrist, fingers, ankle and feet (19% each) in the male soldiers and the ankle (24%), spine (14%), head, chest, shoulder joint and foot (10% each) in the female soldiers. Injuries reoccurred with similar frequency in the female and male soldiers (43% vs 40%, p>0.05) and had the same location in both groups (43% vs 40%, respectively, p>0.05). Difficult terrain, too intensive military training and heavy loads were the main risk factors for MSIs in both groups (p>0.05).ConclusionsMore than half of all the participants (19% of the men and 33% of the women) reported at least one injury incurred during military service. Over 40% of all the study subjects had reinjuries. The males and females were similar in terms of the most common type and location of MSI. Occurrence of MSIs rarely required interruption in the military training/service.
Analysis of hyperbolically symmetric fluid configurations in modified Gauss–Bonnet gravity
Authors: Yousaf Z. , Bhatti M. Z. , Khan S. 
Published: November 2022

AbstractThis paper studies in detail the general physical properties inherent to the static fluid configurations possessing hyperbolic symmetry through the mechanism of modified Gauss–Bonnet gravity (GBG). The energy density of the anisotropic fluid configuration seems to be essentially negative, which indicates that any possible application of these fluid distributions needs severe physical constraints wherein quantum processes become significant. Several exact hyperbolically symmetric solutions with their corresponding generating functions are presented by imposing certain conditions (i.e., conformal flatness, vanishing complexity factor and stiff equation of state) on the fluid variables in the presence of higher-curvature GBG-corrections. Few of the provided stellar solutions exhibit the evolution of hyperbolically symmetric matter configurations whose center of symmetry is surrounded by a vacuum cavity.
Towards European standards for quantum technologies
Authors: van Deventer Oskar , Spethmann Nicolas , Loeffler Marius , Amoretti Michele , van den Brink Rob , Bruno Natalia , Comi Paolo , Farrugia Noel , Gramegna Marco , Jenet Andreas , Kassenberg Ben , Kozlowski Wojciech , Länger Thomas , Lindstrom Tobias , Martin Vicente , Neumann Niels , Papadopoulos Homer , Pascazio Saverio , Peev Momtchil , Pitwon Richard , Rol M. Adriaan , Traina Paolo , Venderbosch Pim , Wilhelm-Mauch Frank K. 
Published: November 2022

AbstractThe Second Quantum Revolution facilitates the engineering of new classes of sensors, communication technologies, and computers with unprecedented capabilities. Supply chains for quantum technologies are emerging, some focused on commercially available components for enabling technologies and/or quantum-technologies research infrastructures, others with already higher technology-readiness levels, near to the market.In 2018, the European Commission has launched its large-scale and long-term Quantum Flagship research initiative to support and foster the creation and development of a competitive European quantum technologies industry, as well as the consolidation and expansion of leadership and excellence in European quantum technology research. One of the measures to achieve an accelerated development and uptake has been identified by the Quantum Flagship in its Strategic Research Agenda: The promotion of coordinated, dedicated standardisation and certification efforts.Standardisation is indeed of paramount importance to facilitate the growth of new technologies, and the development of efficient and effective supply chains. The harmonisation of technologies, methodologies, and interfaces enables interoperable products, innovation, and competition, all leading to structuring and hence growth of markets. As quantum technologies mature, the time has come to start thinking about further standardisation needs.This article presents insights on standardisation for quantum technologies from the perspective of the CEN-CENELEC Focus Group on Quantum Technologies (FGQT), which was established in June 2020 to coordinate and support the development of standards relevant for European industry and research.
Coupled flow and transport modelling of a large-scale
in situ
migration experiment with
14
C-labelled natural organic matter colloids in Boom Clay
Authors: Govaerts Joan , Maes Norbert , Durce Delphine , Aertsens Marc , Brassinnes Stéphane 
Published: November 2022

Abstract

Twenty-five years ago, a unique long-term and large-scale
in situ
experiment with
14
C-labelled natural organic matter (NOM) was set up at the HADES underground research facility in Mol (Belgium) to study its migration behaviour. Natural organic matter plays an important role in the mobility of various safety-relevant radionuclides, which is critical in the context of Safety & Performance Assessment (SA/PA) calculations for a possible nuclear waste repository. The objective of this work is to enlarge the confidence in current NOM transport models by validating them with the
in situ
experiment, which is still continued to this day. Stepwise adding more complexity to the model resulted in a 10-parameter model with which excellent fits to the data are obtained. The model considers two different fractions that are transported by advection and diffusion and can be subject to both irreversible and reversible immobilization processes. The associated fitted parameter values compare well with values determined on small-scale migration experiments. This builds confidence in the NOM transport model, which in turn contributes to the confidence in the outcome of the radionuclide migration calculations performed in the context of SA/PA. These results again highlight the incredible value of such long-running experiments at underground research facilities like HADES.
High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer
Authors: Mizuno Sho , Ikegami Masachika , Koyama Takafumi , Sunami Kuniko , Ogata Dai , Kage Hidenori , Yanagaki Mitsuru , Ikeuchi Hiroshi , Ueno Toshihide , Tanikawa Michihiro , Oda Katsutoshi , Osuga Yutaka , Mano Hiroyuki , Kohsaka Shinji 
Published: November 2022

Abstract
Activating mutations in mitogen-activated protein kinase kinase 1 (MAP2K1) are involved in a variety of cancers and may be classified according to their RAF dependence. Sensitivity to combined BRAF and MEK treatments is associated with co-mutations of MAP2K1 and BRAF; however, the significance of less frequent MAP2K1 mutations is largely unknown. The transforming potential and drug sensitivity of 100 MAP2K1 variants were evaluated using individual assays and the mixed-all-nominated-in-one method. In addition, A375, a melanoma cell line harboring the BRAF V600E mutation, was used to evaluate the function of the MAP2K1 variants in combination with active RAF signaling. Among a total of 67 variants of unknown significance, 16 were evaluated as oncogenic or likely oncogenic. The drug sensitivity of the individual variants did not vary with respect to BRAF inhibitors, MEK inhibitors (MEKi), or their combination. Sensitivity to BRAF inhibitors was associated with the RAF dependency of the MAP2K1 variants, whereas resistance was higher in RAF-regulated or independent variants compared with RAF-dependent variants. Thus, the synergistic effect of BRAF and MEKis may be observed in RAF-regulated and RAF-dependent variants. MAP2K1 variants exhibit differential sensitivity to BRAF and MEKis, suggesting the importance of individual functional analysis for the selection of optimal treatments for each patient. This comprehensive evaluation reveals precise functional information and provides optimal combination treatment for individual MAP2K1 variants.
Loss of Dok-3 in Non-tumor Cells Induces Malignant Transformation of Benign Epithelial Tumor Cells of the Intestine
Authors: Arimura Sumimasa , Inoue-Yamauchi Akane , Katayama Kotoe , Kanno Tatsuo , Jozawa Hiroki , Imoto Seiya , Yamanashi Yuji 
Published: November 2022

The fundamental difference between benign and malignant tumors lies in their invasive ability. It is believed that malignant conversion of benign tumor cells is induced by a tumor cell–intrinsic accumulation of driver gene mutations. Here, we found that disruption of the Dok-3 tumor suppressor gene led to malignant progression in the intestinal benign tumor model ApcMin/+ mice. However, Dok-3 gene expression was undetectable in epithelial tumor cells and the transplantation of bone marrow cells lacking the Dok-3 gene–induced malignant conversion of epithelial tumor cells in ApcMin/+ mice, indicating a previously unrecognized tumor cell–extrinsic mechanism. Moreover, the Dok-3 loss–induced tumor invasion in ApcMin/+ mice required CD4+ and CD8+ T lymphocytes, but not B lymphocytes. Finally, whole-genome sequencing showed an indistinguishable pattern and level of somatic mutations in tumors irrespective of the Dok-3 gene mutation in ApcMin/+ mice. Together, these data indicate that Dok-3 deficiency is a tumor-extrinsic driving force of malignant progression in ApcMin/+ mice, providing a novel insight into microenvironments in tumor invasion.Significance:This study uncovers tumor cell–extrinsic cues that can induce malignant conversion of benign tumors without intensifying mutagenesis in tumors, a novel concept potentially providing a new therapeutic target in malignancy.