bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the efficiency and person-centredness of occupational therapy input into care-plans in a forensic mental health and rehabilitation service
Authors: Ige Joshua Jesudunsin Ige , Alston Amanda , Boreland Velmer , Caudwell Megan , Ashbourne Rhiannon , Ford Bronwen , Katsere Fortunate , Banham Georgia 
Published: October 2024

Care-planning is vital to the delivery of timely, person-centred, safe and effective care. Despite the understanding of the benefits of person-centred care-plan in both services, occupational therapists (OTs) within our forensic and rehabilitation services had difficulties in inputting into patient care-plan an efficient and person-centred manner.The OT team developed a Quality Improvement (QI) project to improve the efficiency of the OT process to create more time for care-planning and improve person-centredness of OT input into care-plans to 82% in the forensic services and rehabilitation services by December 2023.The results indicated an increase in the person-centredness of care-plans from 63.64% to 84.34% within the rehabilitation service and an increase from 65.15% to 95.45% in the forensic service. This project used feedback from patients to develop our input into care-plans. The project also increased the efficiency of the admission process and released time to be spent on care-planning and treatment.We improved the quality of our input to care-plans in a sustainable way by using the Royal Academy of Improvement sustainability measure and taking actions which included training our band 6 and 7 OTs to complete their monthly audit and reporting this as part of the head of nursing report for assurance in our monthly Clinical and Operational Assurance Team meetings. These actions ensured that our project fitted with the organisation’s strategic aims and values. We also used low carbon alternatives by holding most of our improvement meetings online and eliminating the use of paper.Lastly, we improved the generalisability of this project by using the Goal Directed Care Plan audit tool, which is a well-researched, evidence-based tool created by service-users, carers and members of staff. This was used to train members of staff and develop an example of a person-centred input into care-plans to improve their practice.
Prevalence of unplanned first pregnancy and socioeconomic factors in Benin: a cross-sectional and analytical study
Authors: Mintogbe Mahouli Mireille-Marie , Adje Elihou , Dougnon Victorien Tamègnon , Ahoussinou Clément , Sanni Mouftaou Amadou 
Published: October 2024

BackgroundEarly or unplanned pregnancy is an obstacle to the well-being of adolescent girls, especially as early motherhood has health and social consequences on the young mother and the newborn. This also negatively impacts maternal and infant morbidity and mortality. The aim of this study is to determine the prevalence of unplanned first pregnancies and the explanatory factors among adolescent girls.MethodsData were collected from a sample of 738 adolescent girls aged 15–19 years in the 12 departments of Benin. Analyses focused on teenagers who were pregnant for the first time or had at least one child at the time of the survey (337 individuals). Descriptive and bivariate analyses and logistic regression were used.ResultsThe prevalence of unplanned first pregnancies was 80.1% (n=270). The frequency of unplanned first pregnancies was higher among adolescents who had reached secondary school or higher (85.7%, p=0.027), those who had spent their socialisation period in big cities (88.5%, p=0.018) and those whose financial needs were not met (84.8%, p=0.014). The main explanatory factor identified was unmet financial needs. Indeed, adolescents with unmet financial needs were 1.7 times (p=0.041) more likely to have an unplanned first pregnancy than those whose needs were met.ConclusionMultisectoral interventions are needed to reduce the prevalence of unplanned first pregnancies, which can compromise adolescent girls’ academic and career plans. These interventions could focus on sexual and reproductive health education, girl empowerment, improvement of households’ socioeconomic conditions, etc.
Variation in the use of primary care-led investigations prior to a cancer diagnosis: analysis of the National Cancer Diagnosis Audit
Authors: Akter Nurunnahar , Lyratzopoulos Georgios , Swann Ruth , Rubin Greg , McPhail Sean , Rafiq Meena , Aminu Abodunrin , Zakkak Nadine , Abel Gary 
Published: October 2024

IntroductionUse of investigations can help support the diagnostic process of patients with cancer in primary care, but the size of variation between patient group and between practices is unclear.MethodsWe analysed data on 53 252 patients from 1868 general practices included in the National Cancer Diagnosis Audit 2018 using a sequence of logistic regression models to quantify and explain practice-level variation in investigation use, accounting for patient-level case-mix and practice characteristics. Four types of investigations were considered: any investigation, blood tests, imaging and endoscopy.ResultsLarge variation in practice use was observed (OR for 97.5th to 2.5th centile being 4.02, 4.33 and 3.12, respectively for any investigation, blood test and imaging). After accounting for patient case-mix, the spread of practice variation increased further to 5.61, 6.30 and 3.60 denoting that patients with characteristics associated with higher use (ie, certain cancer sites) are over-represented among practices with lower than the national average use of such investigation. Practice characteristics explained very little of observed variation, except for rurality (rural practices having lower use of any investigation) and concentration of older age patients (practices with older patients being more likely to use all types of investigations).ConclusionThere is very large variation between practices in use of investigation in patients with cancer as part of the diagnostic process. It is conceivable that the diagnostic process can be improved if investigation use was to be increased in lower use practices, although it is also possible that there is overtesting in practices with very high use of investigations, and in fact both undertesting and overtesting may co-exist.
Identification of research gaps to improve care for healthy ageing:a scoping review
Authors: Cesari Matteo , Canevelli Marco , Amuthavalli Thiyagarajan Jotheeswaran , Choi Soung-Eun , Grushevska Polina , Kumar Saloni , Chen Muyan , Jang Hyobum , Sumi Yuka , Banerjee Anshu 
Published: October 2024

ObjectiveSeveral research gaps affect the improvement of care for healthy ageing. Their identification is crucial to developing a specific research prioritisation agenda supporting progress at the micro (clinical), meso (service delivery) and macro (system) levels. To achieve this, a scoping review was carried out to describe the most significant gaps impeding the improvement of care for healthy ageing.DesignA scoping review of the literature was conducted according to the Joanna Briggs Institute methodology. The selected articles were analysed to identify topics or areas essential for improving care for healthy ageing but requiring further support from research.Eligibility criteriaEvery type of scientific article, except for randomised controlled trials, was considered of potential interest without restrictions on publication date, type of publication and methodology.Information sourcesA systematic search (last search: 6 December 2023) was conducted using PubMed, MEDLINE and Scopus.ResultsOverall, 1558 articles were retrieved from the literature. Of these, 310 were finally retained for this work. A total of 1195 research gaps were identified (average: 3.85 per article) and clustered into the 13 primary areas: ageing, care approach, caregivers, health economics, health, interventions, policies, research, settings, training, technology, specific populations and understanding the older person. In particular, research for improving the person-centred approach (n=38), better considering cultural diversities (n=27), implementing integrated care (n=25) and ensuring access to care (n=25) were the most prevalent priorities reported in the literature.ConclusionsA wide range of factors spanning multiple disciplines, from clinical to policy levels, require special consideration, exploration and resolution. The findings of this scoping review represent an essential step in identifying gaps for developing a research prioritisation agenda to improve care for healthy ageing.
Consensus on drivers of maintenance treatment choice and patterns of care in advanced ovarian cancer
Authors: Perez-Fidalgo Alejandro , Schmalfeldt Barbara , George Angela , Gourley Charlie , Pignata Sandro , Lorusso Domenica , Barretina-Ginesta Maria Pilar , Romero Ignacio , Grimm Christoph , Van Gorp Toon , Rossing Maria , Collins Dearbhaile C , Fernebro Josefin , Bjørge Line , Leary Alexandra , de la Motte Rouge Thibault , Harter Philipp , Kurzeder Christian , Savva-Bordalo Joana , You Benoit 
Published: October 2024

ObjectivesMaintenance therapies, including poly (ADP-ribose) polymerase (PARP) inhibitors and/or bevacizumab, have substantially improved the prognosis of patients with advanced ovarian cancer. Owing to the variability in treatment strategies across Europe, a Delphi study was conducted among European experts to understand the heterogeneity of clinical practice and identify key factors driving maintenance treatment decisions for advanced ovarian cancer.MethodsA pragmatic literature review was conducted to identify key questions regarding maintenance treatment strategies in patients with advanced ovarian cancer. Utilizing a Delphi methodology, consensus was assessed among a panel of 16 experts using a questionnaire based on results of the pragmatic literature review.ResultsPanelists agreed thatBRCAmutation and homologous recombination status should be assessed in parallel at diagnosis, and that first-line platinum chemotherapy may be initiated concurrently. There was a consensus that alternative homologous recombination deficiency tests are acceptable provided they are clinically validated. Panelists agreed that Response Evaluation Criteria in Solid Tumors (RECIST) and CA-125 elimination rate constant K (KELIM) scores can help assess tumor chemosensitivity and guide treatment-related decisions. Panelists defined high-risk disease as International Federation of Gynecology and Obstetrics (FIGO) stage IV disease or stage III with residual disease after initial/interval cytoreduction. Risk of disease progression was a key determinant of choice between PARP inhibitor, bevacizumab, or both in combination, as maintenance therapy in advanced ovarian cancer.ConclusionsKey drivers for selecting advanced ovarian cancer maintenance treatments include tumor mutational status as a key biomarker and clinician perception of the risk for early disease progression.
Comparison of survival outcomes and safety between early and late initiation of niraparib maintenance in newly diagnosed advanced epithelial ovarian cancer
Authors: Kim Se Ik , Kim Ji Hyun , Park Eun Young , Kim Eun Taeg , Choi Eunjin , Kim Jae-Weon , Park Sang-Yoon , Lim Myong Cheol 
Published: October 2024

ObjectiveThis multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between early and late initiation of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer.MethodsWe included patients with stage III–IV ovarian cancer who showed a complete or partial response to frontline platinum-based chemotherapy and received niraparib maintenance therapy between October 2019 and December 2022. The primary endpoint was the HR for progression-free survival based on the median initiation interval, which was defined as the duration between the completion of chemotherapy and commencement of maintenance therapy. The secondary endpoint was the comparison of progression-free survival at another time point that determined the interval that maximized the difference between the survival curves of the two groups using the Contal and O’Quigley method.ResultsThis analysis included 146 patients who received niraparib maintenance therapy. The median age was 58 years (IQR 50–63.3). The median initiation interval was 8.4 (IQR 5.7–8.9) weeks. After adjusting for prognostic factors for progression-free survival identified through multivariable analysis, early initiation (≤8 weeks) of niraparib was associated with significantly better progression-free survival (HR=0.57; 95% CI 0.33 to 0.99; p=0.047). Furthermore, the initiation interval that maximized the difference in progression-free survival was 6 weeks. Multivariable analysis revealed that early initiation (≤6 weeks) of niraparib significantly increased progression-free survival (HR=0.37; 95% CI 0.18 to 0.76; p=0.007). The rate of treatment discontinuation due to treatment-emergent adverse events was higher (12.5% versus. 2.8%; p=0.036) in patients receiving niraparib within 6 weeks than those treated later, with no significant effect in those initiating treatment within 8 weeks.ConclusionEarly initiation of niraparib maintenance therapy within 8 weeks of chemotherapy completion improved progression-free survival, with further benefits observed with treatment within 6 weeks in patients with newly diagnosed advanced ovarian cancer.
Alum-anchored IL-12 combined with cytotoxic chemotherapy and immune checkpoint blockade enhanced antitumor immune responses in head and neck cancer models
Authors: Fabian Kellsye P , Santiago-Sanchez Ginette , Padget Michelle R , Lassoued Wiem , Allen Clint Tanner , Battula Sailaja , Kaufman Howard , Hodge James W 
Published: October 2024

BackgroundFirst-line treatment with pembrolizumab plus chemotherapy in recurrent and metastatic head and neck squamous cell carcinomas (HNSCC) has improved survival. However, the overall response rate with this standard of care regimen (SOC) remains limited. Interleukin (IL)-12 is a potent cytokine that facilitates the crosstalk between innate and adaptive immunity, making it crucial in the antitumor response. Alum-anchored murine IL-12 (mANK-101) has been demonstrated to elicit robust antitumor responses in diverse syngeneic models, which were correlated with increased immune effector functions and prolonged local retention of IL-12. This study investigates the therapeutic benefit of combining mANK-101 with SOC in the MOC1 and MOC2 murine HNSCC tumor models.MethodsMOC1 and MOC2 tumor-bearing C57BL/6 mice were administered with a single intratumoral injection of mANK-101 and weekly intraperitoneal injections of cisplatin and α-programmed death 1 (PD-1) for 3 weeks. For MOC1, flow cytometry and cytokine array were performed to assess the immune effector functions associated with the combinational treatment. Multiplex immunofluorescence was employed to characterize the influence of the treatment on the immune architecture in the tumors. RNA analysis was implemented for in-depth examination of the macrophage and effector populations.ResultsIn the MOC1 and MOC2 models, combination therapy with mANK-101, cisplatin, and α-PD-1 resulted in superior tumor growth inhibition and resulted in the highest rate of tumor-free survival when compared with treatment cohorts that received mANK-101 monotherapy or SOC treatment with α-PD-1 plus cisplatin. Furthermore, the combination therapy protected against tumor re-growth on rechallenge and controlled the growth of distal tumors. The improved therapeutic effect was associated with increased CD8+T-cell recruitment, increased CD8+and CD4+activity, and repolarization of the macrophage population from M2 to M1 at the tumor site. Elevated and prolonged interferon-γ expression is central to the antitumor activity mediated by the combination therapy. In addition, the combination therapy with mANK-101+cisplatin+α-PD-1 induced the formation of tertiary lymphoid structure-like immune aggregates in the peritumoral space.ConclusionThe current findings provide a rationale for the combination of alum-tethered IL-12 with cisplatin and α-PD-1 for HNSCC.
AKAP12 positive fibroblast determines immunosuppressive contexture and immunotherapy response in patients with TNBC by promoting macrophage M2 polarization
Authors: Liu Zhenkun , Hu Siyuan , Zhao Xinlei , Xu Wenxin , Ju Feng , Gu Meiying , Weng Jialei , Du Yabing 
Published: October 2024

BackgroundTriple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with high aggressiveness and poor prognosis. Cancer-associated fibroblasts (CAFs) are major components of the TNBC microenvironment and play an important role in tumor progression and treatment responses. Our goal is to identify specific CAFs subpopulations contributing to TNBC development.MethodsMultiomics analyses were applied to identify the CAFs-specific genes related to immunotherapy response. The clinical significance of a CAFs subset with A-kinase anchoring protein 12 (AKAP12) positive was explored in 80 patients with TNBC through double-labeling immunofluorescence assay. Cytometry by time-of-flight and RNA sequencing were performed to elucidate the immune landscape of TNBC microenvironment and functional mechanism of AKAP12+CAFs.ResultsMultiomics analyses identified an AKAP12+CAFs subset associated with the immunotherapy response of TNBC, and a high population of these cells is correlated with poor prognosis in patients with TNBC. Intratumoral AKAP12+CAFs promote formation of an immunosuppressive tumor microenvironment by spatially mediating macrophage M2 polarization via interleukin-34 (IL-34)/macrophage-colony stimulating factor receptor (CSF1R) signaling in TNBC. Single-cell RNA sequencing analyses revealed that AKAP12+fibroblasts interact with macrophages through the PI3K/AKT/IL-34 axis. In addition, pharmacological blockade of the IL-34/CSF1R signaling enhances the efficacy of anti-programmed cell death protein-1 antibody in TNBC rodent models.ConclusionsAKAP12 is mainly expressed in fibroblasts in TNBC. AKAP12+CAFs population is negatively associated with the prognosis of patients with TNBC. AKAP12+CAFs shape the immunosuppressive TNBC microenvironment by releasing IL-34 to promote macrophage M2 polarization. Targeting IL-34 may boost the immunotherapeutic efficacy for TNBC.
Targeting CD93 on monocytes revitalizes antitumor immunity by enhancing the function and infiltration of CD8+T cells
Authors: Jiang Da , Huang Aiqi , Zhu Bai-Xi , Gong Jiangling , Ruan Yong-Hao , Liu Xing-Chen , Zheng Limin , Wu Yan 
Published: October 2024

BackgroundLimited activation and infiltration of CD8+T cells are major challenges facing T cell-based immunotherapy for most solid tumors, of which the mechanism is multilayered and not yet fully understood.MethodsLevels of CD93 expression on monocytes from paired non-tumor, peritumor and tumor tissues of human hepatocellular carcinoma (HCC) were evaluated. The underlying mechanisms mediating effects of CD93+monocytes on the inhibition and tumor exclusion of CD8+T cells were studied through both in vitro and in vivo experiments.ResultsIn this study, we found that monocytes in the peritumoral tissues of HCC significantly increased levels of CD93 expression, and these CD93+monocytes collocated with CD8+T cells, whose density was much higher in peritumor than intratumor areas. In vitro experiments showed that glycolytic switch mediated tumor-induced CD93 upregulation in monocytes via the Erk signaling pathway. CD93 on the one hand could enhance PD-L1 expression through the AKT-GSK3β axis, while on the other hand inducing monocytes to produce versican, a type of matrix component which interacted with hyaluronan and collagens to inhibit CD8+T cell migration. Consistently, levels of CD93+monocytes positively correlated with the density of peritumoral CD8+T cells while negatively correlated with that of intratumoral CD8+T cells. Targeting CD93 on monocytes not only increased the infiltration and activation of CD8+T cells but also enhanced tumor sensitivity to anti-PD-1 treatment in mice in vivo.ConclusionThis study identified an important mechanism contributing to the activation and limited infiltration of CD8+T cells in solid tumors, and CD93+monocytes might represent a plausible immunotherapeutic target for the treatment of HCC.
MYH7-related myopathies: clinical, myopathological and genotypic spectrum in a multicentre French cohort
Authors: Bahout Marie , Severa Gianmarco , Kamoun Emna , Bouhour Françoise , Pegat Antoine , Toutain Annick , Lagrange Emmeline , Duval Fanny , Tard Celine , De la Cruz Elisa , Féasson Léonard , Jacquin-Piques Agnès , Richard Pascale , Métay Corinne , Cavalli Michele , Romero Norma Beatriz , Evangelista Teresinha , Sole Guilhem , Carlier Robert Yves , Laforêt Pascal , Acket Blandine , Behin Anthony , Fernández-Eulate Gorka , Léonard-Louis Sarah , Quijano-Roy Susana , Pereon Yann , Salort-Campana Emmanuelle , Nadaj-Pakleza Aleksandra , Masingue Marion , Malfatti Edoardo , Stojkovic Tanya , Villar-Quiles Rocío Nur 
Published: October 2024

BackgroundMyosin heavy chain 7 (MYH7)-related myopathies (MYH7-RMs) are a group of muscle disorders linked to pathogenic variants in theMYH7gene, encoding the slow/beta-cardiac myosin heavy chain, which is highly expressed in skeletal muscle and heart. The phenotype is heterogeneous including distal, predominantly axial or scapuloperoneal myopathies with variable cardiac involvement.MethodsWe retrospectively analysed the clinical, muscle MRI, genetic and myopathological features of 57MYH7patients. Patients received a thorough neurological (n=57, 100%), cardiac (n=51, 89%) and respiratory (n=45, 79%) assessment. Muscle imaging findings and muscle biopsies were reappraised in 19 (33%) and 27 (47%) patients, respectively.ResultsWe identified three phenotypes with varying degrees of overlap: distal myopathy (70%), scapuloperoneal (23%) and axial with peculiar cervical spine rigidity called the ‘sphinx’ phenotype (7%). 14% of patients had either dilated cardiomyopathy, hypertrophic cardiomyopathy or left ventricular non-compaction cardiomyopathy. 31% of patients had prominent respiratory involvement, including all patients with the ‘sphinx’ phenotype. Muscle MRI showed involvement of tibialis anterior, followed by quadriceps, and erector spinae in patients with axial phenotype. Cores represented the most common myopathological lesion. We report 26 pathogenic variants ofMYH7gene, 9 of which are novel.ConclusionsMYH7-RMs have a large phenotypic spectrum, including distal, scapuloperoneal or axial weakness, and variable cardiac and respiratory involvement. Tibialis anterior is constantly and precociously affected both clinically and on muscle imaging. Cores represent the most common myopathological lesion. Our detailed description ofMYH7-RMs should improve their recognition and management.