bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediating role of homebound status between depressive symptoms and cognitive impairment among community-dwelling older adults in the USA: a cross-sectional analysis of a cohort study
Authors: Peng Wenting , Miyawaki Christina E , Okoye Safiyyah M , Wang Wenru , Luo Yuqian , Mo Cen , Liu Minhui 
Published: October 2022

ObjectiveDepressive symptoms are known modifiable factors of cognitive impairment in older adults. However, the pathway through which depressive symptoms lead to cognitive impairment is not well understood. This study aimed to investigate whether homebound status (defined as usually unable to leave home unassisted) mediates the association between depressive symptoms and cognitive impairment in community-dwelling older adults in the USA.DesignA secondary analysis of cross-sectional data.Setting(s)Communities in the USA.ParticipantsCommunity-dwelling older adults (N=7537) from the 2011 National Health and Aging Trends Study, a nationally representative survey of Medicare Beneficiaries in the USA.Main outcome measuresParticipants’ cognitive impairment status was classified using a composite measure. Depressive symptoms were assessed using Patient Health Questionnaire-2. Homebound status was determined by the frequency, difficulty and needing help in getting outdoors. We used logistic regression and the Paramed command in STATA to analyse whether homebound mediated the association between depressive symptoms and cognitive impairment.ResultsParticipants were on average, 77.7 years old, female (58.3%) and non-Hispanic white (68.1%). About 26% of the participants were classified as having cognitive impairment, 16% reported depressive symptoms and 25% were homebound. Depressive symptoms (adjusted OR, 1.60; 95% CI 1.36 to 1.89) and homebound status (adjusted OR, 1.58; 95% CI 1.34 to 1.86) were independently associated with cognitive impairment. Homebound significantly mediated 12.5% of the total effect between depressive symptoms and cognitive impairment, with significant indirect effect (OR, 1.07; 95% CI 1.04 to 1.10), direct effect (OR, 1.61; 95% CI 1.36 to 1.91) and total effect (OR, 1.72; 95% CI 1.46 to 2.03).ConclusionsThis study supports a mediating role of homebound status in the relationship between depressive symptoms and cognitive impairment. Interventions to promote outdoor mobility should be studied for their ability to delay cognitive impairment for older adults with depressive symptoms.
Complex multidisciplinary intervention to improve Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care (the IMA-cRCT study): mixed-methods process evaluation protocol
Authors: Corral-Partearroyo Carmen , Sánchez-Viñas Alba , Gil-Girbau Montserrat , Peñarrubia-María Maria Teresa , Aznar-Lou Ignacio , Gallardo-González Carmen , Olmos-Palenzuela María del Carmen , Rubio-Valera Maria 
Published: October 2022

IntroductionMedication non-initiation, or primary non-adherence, is a persistent public health problem that increases the risk of adverse clinical outcomes. The initial medication adherence (IMA) intervention is a complex multidisciplinary intervention to improve adherence to cardiovascular and diabetes treatments in primary care by empowering the patient and promoting informed prescriptions based on shared decision-making. This paper presents the development and implementation strategy of the IMA intervention and the process evaluation protocol embedded in a cluster randomised controlled trial (the IMA-cRCT) to understand and interpret the outcomes of the trial and comprehend the extent of implementation and fidelity, the active mechanisms of the IMA intervention and in what context the intervention is implemented and works.Methods and analysisWe present the protocol for a mixed-methods process evaluation including quantitative and qualitative methods to measure implementation and fidelity and to explore the active mechanisms and the interactions between the intervention, participants and its context. The process evaluation will be conducted in primary care centres and community pharmacies from the IMA-cRCT, and participants include healthcare professionals (general practitioners, nurses and community pharmacists) as well as patients. Quantitative data collection methods include data extraction from the intervention operative records, patient clinical records and participant feedback questionnaires, whereas qualitative data collection involves semistructured interviews, focus groups and field diaries. Quantitative and qualitative data will be analysed separately and triangulated to produce deeper insights and robust results.Ethics and disseminationEthical approval has been obtained from the Research Ethics Comittee (CEIm) at IDIAP Jordi Gol (codeCEIm 21/051 P). Findings will be disseminated through publications and conferences, as well as presentations to healthcare professionals and stakeholders from healthcare organisations.Trial registration numberNCT05026775.
Engineered anti-PDL1 with IFNα targets both immunoinhibitory and activating signals in the liver to break HBV immune tolerance
Authors: Meng Chao-Yang , Sun Shiyu , Liang Yong , Xu Hairong , Zhang Chao , Zhang Min , Wang Fu-Sheng , Fu Yang-Xin , Peng Hua 
Published: October 2022

ObjectiveThe purpose of this study is to develop an anti-PDL1-based interferon (IFN) fusion protein to overcome the chronic hepatitis B virus (HBV)-induced immune tolerance, and combine this immunotherapy with a HBV vaccine to achieve the functional cure of chronic hepatitis B (CHB) infection.DesignWe designed an anti-PDL1-IFNα heterodimeric fusion protein, in which one arm was derived from anti-PDL1 antibody and the other arm was IFNα, to allow targeted delivery of IFNα into the liver by anti-PDL1 antibody. The effect of the anti-PDL1-IFNα heterodimer on overcoming hepatitis B surface antigen (HBsAg) vaccine resistance was evaluated in chronic HBV carrier mice.ResultsThe anti-PDL1-IFNα heterodimer preferentially targeted the liver and resulted in viral suppression, the PD1/PDL1 immune checkpoint blockade and dendritic cell activation/antigen presentation to activate HBsAg-specific T cells, thus breaking immune tolerance in chronic HBV carrier mice. When an HBsAg vaccine was administered soon after anti-PDL1-IFNα heterodimer treatment, we observed strong anti-HBsAg antibody and HBsAg-specific T cell responses for efficient HBsAg clearance in chronic HBV carrier mice that received the combination treatment but not in those that received either single treatment.ConclusionsTargeting the liver with an engineered anti-PDL1-IFNα heterodimer can break HBV-induced immune tolerance to an HBsAg vaccine, offering a promising translatable therapeutic strategy for the functional cure of CHB.
Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases
Authors: Michaudel Chloé , Danne Camille , Agus Allison , Magniez Aurélie , Aucouturier Anne , Spatz Madeleine , Lefevre Antoine , Kirchgesner Julien , Rolhion Nathalie , Wang Yazhou , Lavelle Aonghus , Galbert Chloé , Da Costa Gregory , Poirier Maxime , Lapière Alexia , Planchais Julien , Nádvorník Petr , Illes Peter , Oeuvray Cyriane , Creusot Laura , Michel Marie-Laure , Benech Nicolas , Bourrier Anne , Nion-Larmurier Isabelle , Landman Cecilia , Richard Mathias L , Emond Patrick , Seksik Philippe , Beaugerie Laurent , Arguello Rafael Rose , Moulin David , Mani Sridhar , Dvorák Zdenek , Bermúdez-Humarán Luis G , Langella Philippe , Sokol Harry 
Published: October 2022

ObjectiveThe extent to which tryptophan (Trp) metabolism alterations explain or influence the outcome of inflammatory bowel diseases (IBDs) is still unclear. However, several Trp metabolism end-products are essential to intestinal homeostasis. Here, we investigated the role of metabolites from the kynurenine pathway.DesignTargeted quantitative metabolomics was performed in two large human IBD cohorts (1069 patients with IBD). Dextran sodium sulphate-induced colitis experiments in mice were used to evaluate effects of identified metabolites. In vitro, ex vivo and in vivo experiments were used to decipher mechanisms involved. Effects on energy metabolism were evaluated by different methods including Single Cell mEtabolism by profiling Translation inHibition.ResultsIn mice and humans, intestinal inflammation severity negatively correlates with the amount of xanthurenic (XANA) and kynurenic (KYNA) acids. Supplementation with XANA or KYNA decreases colitis severity through effects on intestinal epithelial cells and T cells, involving Aryl hydrocarbon Receptor (AhR) activation and the rewiring of cellular energy metabolism. Furthermore, direct modulation of the endogenous tryptophan metabolism, using the recombinant enzyme aminoadipate aminotransferase (AADAT), responsible for the generation of XANA and KYNA, was protective in rodent colitis models.ConclusionOur study identified a new mechanism linking Trp metabolism to intestinal inflammation and IBD. Bringing back XANA and KYNA has protective effects involving AhR and the rewiring of the energy metabolism in intestinal epithelial cells and CD4+T cells. This study paves the way for new therapeutic strategies aiming at pharmacologically correcting its alterations in IBD by manipulating the endogenous metabolic pathway with AADAT.
Identifying opportunities for multisectoral action for drowning prevention: a scoping review
Authors: Scarr Justin-Paul , Jagnoor Jagnoor 
Published: October 2022

BackgroundDrowning is a complex health issue, where global agendas call for greater emphasis on multisectoral action, and engagement with sectors not yet involved in prevention efforts. Here, we explored the conceptual boundaries of drowning prevention in peer-review and grey literature, by reviewing the contexts, interventions, terminologies, concepts, planning models, and sector involvement, to identify opportunities for multisectoral action.MethodsWe applied scoping review method and have reported against Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews checklist. We searched four electronic databases for peer-reviewed articles published on 1 January 2005 and 31 December 2020 and five databases for grey literature published on 1 January 2014 and 31 December 2020. We applied the search term “drowning,” and charted data addressing our research questions.ResultsWe included 737 peer-reviewed articles and 68 grey documents. Peer-publications reported situational assessments (n=478, 64.86%) and intervention research (n=259, 35.14%). Drowning was reported in the context of injury (n=157, 21.30%), commonly in childhood injury (n=72, 9.77%), mortality studies (n=60, 8.14%) and in grey documents addressing adolescent, child, environmental, occupational and urban health, refugee and migrant safety and disaster. Intervention research was mapped to World Health Organization recommended actions. The leading sectors in interventions were health, leisure, education and emergency services.ConclusionAlthough drowning is often described as a major health issue, the sectors and stakeholders involved are multifarious. The interventions are more often initiated by non-health sectors, meaning multisectoral action is critical. Framing drowning prevention to reinforce cobenefits for other health and development agendas could strengthen multisectoral action. Greater investment in partnerships with non-health sectors, encouraging joint planning and implementation, and creating systems for increased accountability should be a priority in future years.
Germline mutations inWNK2could be associated with serrated polyposis syndrome
Authors: Soares de Lima Yasmin , Arnau-Collell Coral , Muñoz Jenifer , Herrera-Pariente Cristina , Moreira Leticia , Ocaña Teresa , Díaz-Gay Marcos , Franch-Expósito Sebastià , Cuatrecasas Miriam , Carballal Sabela , Lopez-Novo Anael , Moreno Lorena , Fernàndez Guerau , Díaz de Bustamante Aranzazu , Peters Sophia , Sommer Anna K , Spier Isabel , te Paske Iris B A W , van Herwaarden Yasmijn J , Castells Antoni , Bujanda Luis , Capellà Gabriel , Steinke-Lange Verena , Mahmood Khalid , Joo JiHoon Eric , Arnold Julie , Parry Susan , Macrae Finlay A , Winship Ingrid M , Rosty Christophe , Cubiella Joaquin , Rodríguez-Alcalde Daniel , Holinski-Feder Elke , de Voer Richarda , Buchanan Daniel D , Aretz Stefan , Ruiz-Ponte Clara , Valle Laura , Balaguer Francesc , Bonjoch Laia , Castellvi-Bel Sergi 
Published: October 2022

BackgroundPatients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts.MethodsAfter a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. TheWNK2gene was disrupted in HT-29 cells by gene editing, andWNK2variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion.ResultsWe identified 2 rare germline variants in theWNK2gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2.ConclusionAfter whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in theWNK2gene. Functional studies suggested germlineWNK2variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease.
Micro-guidewire electrocoagulation for the treatment of intracranial aneurysms that are inaccessible by microcatheterization: a case series and review of the literature
Authors: Lu Guang-Dong , Zhao Lin-Bo , Jia Zhen-Yu , Liu Sheng 
Published: October 2022

BackgroundThe use of traditional endovascular techniques for aneurysms that are difficult to catheterize is challenging. We present our experience of using micro-guidewire electrocoagulation for the treatment of aneurysms that were inaccessible by a microcatheter.MethodsSeven consecutive patients who underwent endovascular electrocoagulation for the treatment of aneurysms between January 2020 and May 2022 were retrospectively included. Patient demographics, treatment procedures, and follow-up outcomes were assessed. A review of the literature was also performed.ResultsAll of the seven treated aneurysms were ruptured, and micro-guidewire electrocoagulation was only conducted if the microcatheter could not advance into the aneurysm or parent artery. After electrocoagulation for 1–4 min, all seven aneurysms disappeared on contrast angiography. Parent artery occlusion was observed in six cases, and post-procedure infarctions of the operating region were identified in three patients. The 3-month follow-up modified Rankin Scale score was 0 in all except one patient. Follow-up angiography was available in six patients, and complete obliteration of the aneurysm was observed in all of them. With a mean follow-up time of 13.6 months, there was no rebleeding in any of the cases. To date, there are only eight published cases of aneurysms treated using micro-guidewire electrocoagulation, and seven of them achieved total occlusion of the aneurysm without neurological deficits.ConclusionsEndovascular electrocoagulation is practicable and effective for the treatment of aneurysms that are inaccessible by a microcatheter during short-term observation. Studies on larger populations are needed to further confirm the safety and long-term outcomes for this technique.
Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study
Authors: Verburgt Esmée , Janssen Esther , Jacob Mina A , Cai Mengfei , ter Telgte Annemieke , Wiegertjes Kim , Kessels Roy P C , Norris David G , Marques Jose , Duering Marco , Tuladhar Anil M , De Leeuw Frank-Erik 
Published: October 2022

BackgroundSmall hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes.MethodsParticipants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI−).ResultsDWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (β=0.36, 95% CI=0.05 to 0.68, p=0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (β=−0.03, 95% CI=−0.05 to −0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8–13.8) years compared with DWI− participants. No differences were found in risk of all-cause mortality, stroke or dementia.ConclusionPresence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.
Identification of the ideal recruitment situation in pandemic research: learning from the RECOVERY trial in Northern England: a qualitative study
Authors: Coe Dorothy , Dorgan Sharon , Smith Justine , Wroe Caroline 
Published: October 2022

BackgroundIn early 2020, little was known about treatments for COVID-19. The UK responded by initiating a call for research, leading to the formation of the National Institute for Health Research (NIHR) Urgent Public Health (UPH) group. Fast-track approvals were initiated and support was offered to research sites via the NIHR. The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial was designated UPH. High recruitment rates were required for timely results. Recruitment rates were inconsistent across different hospitals and places.PurposeThe Factors Affecting Recruitment to the RECOVERY trial study was designed to seek out the facilitators and barriers to recruitment across a population of 3 million served by eight different hospitals and suggest recommendations for recruitment to UPH research during a pandemic situation.MethodsA qualitative grounded theory study using situational analysis was used. This included a contextualisation of each recruitment site containing prepandemic operational status, prior research activity, COVID-19 admission rates and UPH activity. Additionally, one-to-one interviews using topic guides were completed with NHS staff involved in the RECOVERY trial. Analysis sought out the narratives that shaped recruitment activity.ResultsAn ideal recruitment situation was identified. The closer sites were able to move towards that ideal situation, the easier they found it to implement the most significant factor on recruitment: embedding research recruitment into standard care. The ability to move to the ideal recruitment situation was mediated by five significant elements: uncertainty, prioritisation, leadership, engagement and communication.ConclusionEmbedding recruitment into routine clinical care was the most influential factor on recruitment to the RECOVERY trial. To enable this, sites needed to attain the ideal recruitment situation. Prior research activity, size of site and regulator grading did not correlate with high recruitment rates. Research should be at the forefront of prioritisation during future pandemics.
Factors associated with sexually transmitted shigella in men who have sex with men: a systematic review
Authors: Siddiq Mohammed , O'Flanagan Holly , Richardson Daniel , Llewellyn Carrie D 
Published: October 2022

BackgroundOutbreaks of sexually transmitted shigella have been reported in men who have sex with men (MSM) since the 1970s and present a major public health issue. Understanding the factors associated with the sexual transmission of shigella may inform future control strategies.MethodsWe systematically searched four bibliographical databases (January 2000–February 2022) for manuscripts in English. We used a two-stage process to assess eligibility: the primary author conducted an initial screen and then three authors conducted independent full-text reviews to determine the final eligible manuscripts. We only included manuscripts that included MSM diagnosed with sexually transmitted shigella where specific factors associated with transmission were identified.ResultsThirteen manuscripts met the inclusion criteria that included 547 individuals. Sexually transmitted shigella in MSM was associated with: residing in a capital city/urban region, living with HIV (including engaging in seroadaptive sexual behaviour, having a low CD4 count, having a HIV viral load >100 000 and not engaging with HIV care), using HIV pre-exposure prophylaxis, use of geospatial mobile phone applications to meet sexual partners, visiting sex on premises venues, chemsex and recreational drug use, sexual behaviour (including multiple non-regular sexual partners and oral-anal sexual contact) and concomitant STIs.ConclusionWe have highlighted some important risk behaviours and factors that are associated with sexually transmitted shigella in MSM that can be used to target future shigella control interventions.
How do New Zealand youth perceive the smoke-free generation policy? A qualitative analysis
Authors: Hoek Janet , Lee Ell , Teddy Lani , Fenton Elizabeth , Ball Jude , Edwards Richard 
Published: October 2022

IntroductionAotearoa New Zealand (NZ) plans to introduce a smoke-free generation (SFG) policy, alongside denicotinisation and reducing the availability of tobacco products. The SFG has a clear rationale, yet we know little about how young people, those the policy targets, perceive it. To inform policy design, communication and implementation, we explored how NZ youth perceived the SFG.MethodsWe undertook in-depth interviews with a sample of 20 youth aged 17 or 18 and explored their knowledge of the SFG, and how they perceived its individual and societal implications. We interpreted the data using a reflexive thematic analysis approach.ResultsWe identified two overarching themes. The first theme, ‘societal good and protection from harm’, reflected benefits participants associated with the SFG, which outweighed perceptions of lost freedoms. The second theme, ‘privileging personal choice’, corresponded to two small groups within the sample. The first preferred measures they considered less restrictive, such as increasing the purchase age, and some came to support the SFG as they rationalised their views. The second subgroup expressed more entrenched opposition and felt the SFG deprived them of a choice.ConclusionsYoung people’s deep reflection on the SFG led most to view it as liberating rather than restrictive. Communications that avoid prompting heuristic-based responses could encourage youth to reflect on the policy and elicit strong support from the group the SFG aims to benefit.