bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of adherence to a lifestyle-integrated programme on physical function and behavioural complexity in young older adults at risk of functional decline: a multicentre RCT secondary analysis
Authors: Mikolaizak A Stefanie , Taraldsen Kristin , Boulton Elisabeth , Gordt Katharina , Maier Andrea Britta , Mellone Sabato , Hawley-Hague Helen , Aminian Kamiar , Chiari Lorenzo , Paraschiv-Ionescu Anisoara , Pijnappels Mirjam , Todd Chris , Vereijken Beatrix , Helbostad Jorunn L , Becker Clemens 
Published: October 2022

ContextLong-term adherence to physical activity (PA) interventions is challenging. The Lifestyle-integrated Functional Exercise programmes were adapted Lifestyle-integrated Functional Exercise (aLiFE) to include more challenging activities and a behavioural change framework, and then enhanced Lifestyle-integrated Functional Exercise (eLiFE) to be delivered using smartphones and smartwatches.ObjectivesTo (1) compare adherence measures, (2) identify determinants of adherence and (3) assess the impact on outcome measures of a lifestyle-integrated programme.Design, setting and participantsA multicentre, feasibility randomised controlled trial including participants aged 61–70 years conducted in three European cities.InterventionsSix-month trainer-supported aLiFE or eLiFE compared with a control group, which received written PA advice.Outcome measuresSelf-reporting adherence per month using a single question and after 6-month intervention using the Exercise Adherence Rating Scale (EARS, score range 6–24). Treatment outcomes included function and disability scores (measured using the Late-Life Function and Disability Index) and sensor-derived physical behaviour complexity measure. Determinants of adherence (EARS score) were identified using linear multivariate analysis. Linear regression estimated the association of adherence on treatment outcome.ResultsWe included 120 participants randomised to the intervention groups (aLiFE/eLiFE) (66.3±2.3 years, 53% women). The 106 participants reassessed after 6 months had a mean EARS score of 16.0±5.1. Better adherence was associated with lower number of medications taken, lower depression and lower risk of functional decline. We estimated adherence to significantly increase basic lower extremity function by 1.3 points (p<0.0001), advanced lower extremity function by 1.0 point (p<0.0001) and behavioural complexity by 0.008 per 1.0 point higher EARS score (F(3,91)=3.55, p=0.017) regardless of group allocation.ConclusionPA adherence was associated with better lower extremity function and physical behavioural complexity. Barriers to adherence should be addressed preintervention to enhance intervention efficacy. Further research is needed to unravel the impact of behaviour change techniques embedded into technology-delivered activity interventions on adherence.Trial registration numberNCT03065088.
Prevalence of medically unexplained symptoms in adults who are high users of healthcare services and magnitude of associated costs: a systematic review
Authors: Jadhakhan Ferozkhan , Romeu Daniel , Lindner Oana , Blakemore Amy , Guthrie Elspeth 
Published: October 2022

IntroductionMedically unexplained symptoms (MUS) is a common clinical syndrome in primary and secondary healthcare service. Outcomes for patients with persistent MUS include increased disability, poorer quality of life and higher healthcare costs. The aim of this systematic review was to determine the prevalence of MUS in patients who are high users of healthcare or high-cost patients in comparison with routine users and the magnitude of associated costs.DesignA systematic review of the available literature.Data sources and eligibility criteriaThe following electronic databases were systematically searched without language restriction from inception to June 2018 and updated on 22 October 2021: MEDLINE, PsycINFO, EMBASE, CINAHL and PROSPERO. Inclusion criteria included studies investigating adults aged ≥18 years, who were high healthcare users or accrued high healthcare costs, in which the prevalence and/or associated costs of MUS was quantified. Two reviewers independently extracted information on study characteristics, exposure and outcomes.ResultsFrom 5622 identified publications, 25 studies from 9 countries involving 31 650 patients were selected for inclusion. Due to high risk of bias in many studies and heterogeneity between studies, results are described narratively. There were wide variations in prevalence estimates for MUS in high users of healthcare (2.9%–76%), but MUS was more prevalent in high use groups compared with low use groups in all but one of the 12 studies that included a comparator group. Only three studies investigated healthcare costs associated with MUS, and all three reported greater healthcare costs associated with MUS.ConclusionMUS has been found to be more prevalent in high use healthcare populations than comparator groups, but the magnitude of difference is difficult to estimate due to considerable heterogeneity between studies and potential for bias. Future studies should prioritise a standardised approach to this research area, with agreed definitions of MUS and high healthcare use.PROSPERO registration numberCRD42018100388.
Effectiveness of the Perceive, Recall, Plan and Perform intervention for persons with brain injury in community-based rehabilitation: protocol for a single-case experimental design with multiple baselines
Authors: Lindstad Marte Ørud , Obstfelder Aud Uhlen , Sveen Unni , Stigen Linda 
Published: October 2022

IntroductionThere is a need for standardised interventions in community-based rehabilitation to improve everyday performance for older adults with cognitive challenges due to acquired brain injury (ABI). The Perceive, Recall, Plan and Perform System (PRPP) of intervention has a growing research base. The intervention is suitable for any client with decreased performance in everyday tasks due to ineffective cognitive strategy application to enhance mastery in performance of needed or desired activities. There is no current evidence on the effectiveness of the PRPP intervention for this population.PurposeTo describe a protocol for a clinical trial that investigates the effectiveness of the PRPP intervention in the context of community-based rehabilitation for persons (65+ years) with difficulties in task performance due to cognitive challenges after ABI.Methods and analysisA non-concurrent multiple baseline design across participants with systematic replications (n=6) will be used. Nine sessions of PRPP intervention will be applied by trained occupational therapists in two community-based rehabilitation units. The participants will complete five repeated measurements of everyday tasks as target behaviours. PRPP Assessment stages 1 and 2 serve as outcome measures at baseline, in the intervention period, in the postintervention period and in the follow-up phase. Mastery percentage of the tasks and the participants’ application of cognitive strategies at baseline acts as a control and will be compared with the following phases within the participant. Delayed intervention phases act as a control between participants. Goal Attainment Scaling and the Barthel Index will serve as generalisation measures. Data will be analysed using systematic visual inspection of graphical data, descriptions of clinical significance and descriptive statistical analysis.Ethics and disseminationThis trial, including the data management plan, is approved by The Norwegian Regional Ethics Committee (215391). Results will be published in congresses and scientific journals.Trial registration numberNCT05148247.
Strategies for engaging senior citizens and their informal caregivers in health policy development: a scoping review protocol
Authors: Kolade Opeyemi , Porat-Dahlerbruch Joshua , van Achterberg Theo , Ellen Moriah 
Published: October 2022

IntroductionCare for senior citizens is a global policy issue. There has been limited focus on senior citizen and informal caregiver engagement in policy development. Encouraging senior citizen participation through active engagement in the policymaking process enhances the provision of better services and the creation of responsive policies and is critical to better healthcare. Accordingly, this review aims to map the available evidence to provide an overview of strategies for engaging senior citizens and informal caregivers in health policy development.Methods and analysisA scoping review will be conducted. This study will use the updated methodological guidance for conducting a scoping review developed by the Joanna Briggs Institute. This review aims to answer the question: ‘What is known in the literature about strategies for engaging senior citizens and informal caregivers in health policy development?’ Titles and abstracts will be screened to determine eligibility for full-text review based on already established eligibility criteria. Data will be extracted from relevant articles. A summary of extracted data will be presented. The results will be interpreted within the Multidimensional Framework for Patient and Family Engagement in Health and Healthcare.Ethics and disseminationEthical review is not required as scoping reviews are a form of secondary data analysis that synthesises data from publicly available sources. Findings from this proposed review will be disseminated in conferences and to the global scientific community through published academic papers in reputable health policy-related journals.
Situation of physical activity in the prevention of non-communicable diseases in Bhutan: challenges and the way forward
Authors: Tamang Monu , Dahal Benu Prasad , Dorji Thinley , Tamang Saran Tenzin , Lucero-Prisno Don Eliseo 
Published: October 2022

Bhutan is a lower-income–middle-income country in the Himalayas, between India and China. Non-communicable diseases (NCDs) are the leading cause of death and premature mortality in Bhutan, accounting for 69% and 71% of all deaths in 2014 and 2019, respectively. Although the World Health Organisation (WHO) identified physical activity as a key strategy to reduce the burden of NCDs, with rapid urbanisation, motorised transportation, and rural–urban migration, people are adapting to sedentary lifestyles, inflating the incidence of NCDs in the country. The increasing incidence of NCDs exerts a burden on the human and financial resource constraints in the health system in Bhutan.In this view point, we report evidence-based benefits of physical activity for health promotion, primary prevention of NCDs and health benefits for individuals living with NCDs. We also briefly assess the situation of physical activity in Bhutan. Then, shortcomings of existing NCDs prevention programmes are discussed along with opportunities and ways forward to effectively implementing physical activity to harness the benefits of physical activities.
Characteristics of enrolment in an intensive home-visiting programme among eligible first-time adolescent mothers in England: a linked administrative data cohort study
Authors: Cavallaro Francesca L , Gilbert Ruth , Wijlaars Linda PMM , Kennedy Eilis , Howarth Emma , Kendall Sally , van der Meulen Jan , Calin Maria Andreea , Reed Lynne , Harron Katie 
Published: October 2022

BackgroundIntensive home visiting for adolescent mothers may help reduce health disparities. Given limited resources, such interventions need to be effectively targeted. We evaluated which mothers were enrolled in the Family Nurse Partnership (FNP), an intensive home-visiting service for first-time young mothers commissioned in >130 local authorities in England since 2007.MethodsWe created a population-based cohort of first-time mothers aged 13–19 years giving birth in English National Health Service hospitals between 1 April 2010 and 31 March 2017, using administrative hospital data linked with FNP programme, educational and social care data. Mothers living in a local authority with an active FNP site were eligible. We described variation in enrolment rates across sites, and identified maternal and FNP site characteristics associated with enrolment.ResultsOf 110 520 eligible mothers, 25 680 (23.2% (95% CI: 23.0% to 23.5%)) were enrolled. Enrolment rates varied substantially across 122 sites (range: 11%–68%), and areas with greater numbers of first-time adolescent mothers achieved lower enrolment rates. Mothers aged 13–15 years were most likely to be enrolled (52%). However, only 26% of adolescent mothers with markers of vulnerability (including living in the most deprived areas and ever having been looked after as a child) were enrolled.ConclusionA substantial proportion of first-time adolescent mothers with vulnerability markers were not enrolled in FNP. Variation in enrolment across sites indicates insufficient commissioning of places that is not proportional to level of need, with mothers in areas with large numbers of other adolescent mothers least likely to receive support.
Bearing the burden of austerity: how do changing mortality rates in the UK compare between men and women?
Authors: Walsh David , Dundas Ruth , McCartney Gerry , Gibson Marcia , Seaman Rosie 
Published: October 2022

BackgroundMortality rates across the UK stopped improving in the early 2010s, largely attributable to UK Government’s ‘austerity’ policies. Such policies are thought to disproportionately affect women in terms of greater financial impact and loss of services. The aim here was to investigate whether the mortality impact of austerity—in terms of when rates changed and the scale of excess deaths—has also been worse for women.MethodsAll-cause mortality data by sex, age, Great Britain (GB) nation and deprivation quintile were obtained from national agencies. Trends in age-standardised mortality rates were calculated, and segmented regression analyses used to identify break points between 1981 and 2019. Excess deaths were calculated for 2012–2019 based on comparison of observed deaths with numbers predicted by the linear trend for 1981–2011.ResultsChanges in trends were observed for both men and women, especially for those living in the 20% most deprived areas. In those areas, mortality increased between 2010/2012 and 2017/2019 among women but not men. Break points in trends occurred at similar time points. Approximately 335 000 more deaths occurred between 2012 and 2019 than was expected based on previous trends, with the excess greater among men.ConclusionsIt remains unclear whether there are sex differences in UK austerity-related health effects. Nonetheless, this study provides further evidence of adverse trends in the UK and the associated scale of excess deaths. There is a clear need for such policies to be reversed, and for policies to be implemented to protect the most vulnerable in society.
Towards precise drone-based measurement of elevation change in permafrost terrain experiencing thaw and thermokarst
Authors: Fraser Robert H. , Leblanc Sylvain G. , Prevost Christian , van der Sluijs Jurjen 
Published: October 2022

Measuring ground elevation changes plays a crucial role in several environmental applications. For instance, permafrost soils undergo seasonal active layer freezing and thawing that causes cyclic elevation changes. Permafrost thaw can result in unidirectional ground subsidence, which may be gradual and uniform, or rapid and irregular in the case of thermokarst landforms such as slumps and degrading ice-wedges. Photogrammetric drone surveys have effectively characterized large (> 0.1 m) ground elevation changes resulting from thermokarst, yet many permafrost processes of interest lead to more subtle elevation changes. In this study, we assessed various drone-based surveying strategies for their precision to measure smaller (< 0.1 m) ground elevation changes to better characterize permafrost-driven surface dynamics. The strategies were compared by examining the short-term reproducibility of modeled elevation for 76 bare ground targets, derived from six repeat drone surveys captured under variable illumination. We found that the Phantom 4 RTK drone using direct georeferencing, combined with one fixed ground control point, could reproduce elevations with a mean absolute deviation of 0.6 cm, suggesting a minimum level of change detection of 1.4 cm at 95% confidence. Drone-based methods for measuring permafrost elevation changes should be complementary to in situ and satellite-based (e.g. differential interferometric Synthetic Aperture Radar) approaches.
Solute transport exponentially varies with time in an unsaturated zone using finite element and finite difference method
Authors: Rekha J. , Suma S. P. , Shilpa B. , Khan Umair , Hussain Syed M. , Zaib Aurang , Galal Ahmed M. 
Published: October 2022

Among several aspects, the one contributing towards the difficulty of groundwater quality evaluation is the large diversity of contamination sources. As contaminants comprising various compounds move from the soil to the water table, they will travel through several hydrologic zones. In constant unidirectional flow fields, a mathematical study of simultaneous adsorption and dispersion of a solute inside homogeneous and isotropic permeable media is described. The solute is adsorbed at a rate proportionate to its concentration in the dispersion systems, which are susceptible to input concentrations that fluctuate exponentially with time. The advection–dispersion equation (ADE) was solved numerically in this work to analyze the pollutants transport bearing in mind the coefficient of distribution and permeability by considering pollutant input concentrations. The solution is derived using the Laplace transform and Duhamel’s theorem with moving coordinates. For specified medium and fluid characteristics, mathematical methods are created to forecast the concentration of pollutants in adsorbing porous media.
NOTCH Signaling Limits the Response of Low-Grade Serous Ovarian Cancers to MEK Inhibition
Authors: Llaurado Fernandez Marta , Hijmans E. Marielle , Gennissen Annemiek M.C. , Wong Nelson K.Y. , Li Shang , Wisman G. Bea A. , Hamilton Aleksandra , Hoenisch Joshua , Dawson Amy , Lee Cheng-Han , Bittner Madison , Kim Hannah , DiMattia Gabriel E. , Lok Christianne A.R. , Lieftink Cor , Beijersbergen Roderick L. , de Jong Steven , Carey Mark S. , Bernards René , Berns Katrien 
Published: October 2022

Abstract
Low-grade serous ovarian cancer (LGSOC) is a rare subtype of epithelial ovarian cancer with high fatality rates in advanced stages due to its chemoresistant properties. LGSOC is characterized by activation of MAPK signaling, and recent clinical trials indicate that the MEK inhibitor (MEKi) trametinib may be a good treatment option for a subset of patients. Understanding MEKi-resistance mechanisms and subsequent identification of rational drug combinations to suppress resistance may greatly improve LGSOC treatment strategies. Both gain-of-function and loss-of-function CRISPR-Cas9 genome-wide libraries were used to screen LGSOC cell lines to identify genes that modulate the response to MEKi. Overexpression of MAML2 and loss of MAP3K1 were identified, both leading to overexpression of the NOTCH target HES1, which has a causal role in this process as its knockdown reversed MEKi resistance. Interestingly, increased HES1 expression was also observed in selected spontaneous trametinib-resistant clones, next to activating MAP2K1 (MEK1) mutations. Subsequent trametinib synthetic lethality screens identified SHOC2 downregulation as being synthetic lethal with MEKis. Targeting SHOC2 with pan-RAF inhibitors (pan-RAFis) in combination with MEKi was effective in parental LGSOC cell lines, in MEKi-resistant derivatives, in primary ascites cultures from patients with LGSOC, and in LGSOC (cell line–derived and patient-derived) xenograft mouse models. We found that the combination of pan-RAFi with MEKi downregulated HES1 levels in trametinib-resistant cells, providing an explanation for the synergy that was observed. Combining MEKis with pan-RAFis may provide a promising treatment strategy for patients with LGSOC, which warrants further clinical validation.
GOT2: An Unexpected Mediator of Immunosuppression in Pancreatic Cancer
Authors: Nwosu Zeribe C. , Pasca di Magliano Marina 
Published: October 2022

Summary:In this issue, Abrego and colleagues describe an unexpected role for the mitochondrial enzyme glutamic-oxaloacetic transaminase (GOT2) in pancreatic cancer, whereby it acts as a nuclear fatty acid transporter binding to and activating the PPARδ nuclear receptor. In turn, the GOT2–PPARδaxis drives immunosuppression by suppressing T cell–mediated antitumor immunity.See related article by Abrego et al., p. 2414 (3).
First record and a new species of Foxiphalus Barnard, 1979 (Crustacea: Amphipoda: Phoxocephalidae) from the Atlantic Ocean, with two new records of the family from northeastern Brazil
Authors: Andrade Luiz Felipe de , Senna André Resende de , Souza-Filho Jesser Fidelis de 
Published: October 2022

A new species of Foxiphalus Barnard, 1979 is described. The material examined was collected as part of the project "Avaliação da biota bentônica e planctônica da Bacia Potiguar e Ceará" (BPOT), off northeastern Brazilian continental slope on the state of Rio Grande do Norte at depths ranging from 135 to 283 meters. Foxiphalus potiguara sp. nov. is recognized among its congeners by: rostrum slightly exceeding the article 2 of antenna 1; lower lip outer lobes with strong shoulder cusps; maxilliped inner plate with two apical robust setae; gnathopod 2 carpus shortened; pereopod 5 basis tapering distally; and epimeral plate 3 posterior margin weakly crenulated. This is the first record of Foxiphalus for the Atlantic Ocean and we provide an amended diagnosis of the genus and an identification key to its world species. In addition, two new records of Phoxocephalidae are reported from northeastern Brazil: Heterophoxus shoemakeri Andrade & Senna, 2020 and Metharpinia dentiurosoma Alonso de Pina, 2003.
Functional Assays Reclassify Suspected Splice-Altering Variants of Uncertain Significance in Mendelian Channelopathies
Authors: O’Neill Matthew J. , Wada Yuko , Hall Lynn D. , Mitchell Devyn W. , Glazer Andrew M. , Roden Dan M. 
Published: October 2022

Background:

Rare protein-altering variants in
SCN5A
,
KCNQ1
, and
KCNH2
are major causes of Brugada syndrome and the congenital long QT syndrome. While splice-altering variants lying outside 2-bp canonical splice sites can cause these diseases, their role remains poorly described. We implemented 2 functional assays to assess 12 recently reported putative splice-altering variants of uncertain significance and 1 likely pathogenic variant without functional data observed in Brugada syndrome and long QT syndrome probands.

Methods:
We deployed minigene assays to assess the splicing consequences of 10 variants. Three variants incompatible with the minigene approach were introduced into control induced pluripotent stem cells by CRISPR genome editing. We differentiated cells into induced pluripotent stem cell–derived cardiomyocytes and studied splicing outcomes by reverse transcription-polymerase chain reaction. We used the American College of Medical Genetics and Genomics functional assay criteria (PS3/BS3) to reclassify variants.

Results:
We identified aberrant splicing, with presumed disruption of protein sequence, in 8/10 variants studied using the minigene assay and 1/3 studied in induced pluripotent stem cell-derived cardiomyocytes. We reclassified 8 variants of uncertain significance to likely pathogenic, 1 variant of uncertain significance to likely benign, and 1 likely pathogenic variant to pathogenic.

Conclusions:
Functional assays reclassified splice-altering variants outside canonical splice sites in Brugada Syndrome- and long QT syndrome-associated genes.