bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synesis as a framework to enable safety interventions in complex healthcare environments
Authors: Bavare Aarti , Wrenn Tiffany , Lam Anne , Cargill Jamie , Salinas Lauren , Idowu Itode , Razavi Asma , Pinto Venessa Lynn , Williams Eric 
Published: January 2025

BackgroundDespite wide adoption in the healthcare of safety event report (SER) systems, there is a paucity of unified structures for prompt analysis and action while retaining reporter confidentiality. We used a synesis framework to change siloed reviews of safety reports to a comprehensive appraisal of quality, safety, productivity and reliability to facilitate interventions.MethodsAfter a needs assessment survey, we launched serial plan-do-study-act cycles to (1) enhance teams’ ability to access SERs, (2) facilitate regular multidisciplinary review of SERs to identify actionable opportunities, (3) allocate action priority using failure mode and effects analysis, and (4) launch actions and summarise data. Team of Teams model allowed for empowered execution. Measures included process—completion of review, team engagement, proportion of ‘open’ (those without action plan) reports within 1 month of filing; outcome—number of actions launched and completed, dissemination of actions and postintervention survey results; and balancing—resources invested.Results26 multidisciplinary leaders reviewed 3175 of the 3406 total reported SERs across four clinical units over 18 months. The proportion of reviewed to total SERs increased significantly from the first 6 months (75%) to the second 12 months (99%) (p<0.001), and the proportion of ‘open’ to reviewed SERs decreased significantly from 43% to 5.3% (p<0.001). Many local- and organisational-level actions were launched efficiently by the engaged and aligned team. Action impact was assessed by reviewing trends in SER themes and findings, and actions and impact were disseminated at unit, divisional and organisational levels. Postintervention survey showed improvement in leaders’ perceptions about SER reviews.SummaryWe successfully implemented a sustainable process to comprehensively review, prioritise and act on SERs in our large institution and facilitated safety interventions using a synesis framework.
Universal health coverage for women of reproductive ages: a survey-based comprehensive assessment of service utilisation and health expenditure in Tanzania
Authors: Kagoye Sophia Adam , Urassa Mark , Mangya Charles , Kishamawe Coleman , Todd Jim , Marston Milly , Binyaruka Peter , Boerma Ties 
Published: January 2025

IntroductionUniversal health coverage (UHC) for women of reproductive ages is a critical component of country and global health strategies but most evidence in high-fertility settings is limited to maternity care. Our study aimed to comprehensively assess women’s health service utilisation and expenditure, including an equity dimension.MethodsWe conducted a household survey among 15–49 years as a nested study within the Magu health and demographic surveillance study, northwest Tanzania, during 2020–2021. Data were collected on self-reported health, fertility, utilisation of health services, health expenditure and health insurance. We analysed key indicators by household wealth quintiles, place of residence and health insurance, using logistic regression models controlling for age and other confounders.ResultsAmong 8665 women aged 15–49 years (response rate 81%), 3.0% reported poor or very poor health, 13% gave birth in the preceding year, and health insurance coverage was 5.1%. Coverage of antenatal (99.5%) and institutional delivery care (88%) were high; 7.3% of women reported at least one outpatient visit in the last 4 weeks, of which 81% were for their own non-maternal healthcare; 9.3% had been admitted to a hospital during the last year, and 74% of these admissions were for deliveries. The total average annual health expenditure per woman was about TZS 16 860 (US$7.50), of which 82% was for her own healthcare and 18% for maternity care. Additionally, women spent about TZS 23 172 (US$10.00) per year on self-treatment. The poorest women had poorer self-reported health, lower coverage of maternity care, lower utilisation of services for their own healthcare and lower health insurance coverage, and limited their expenditure by making greater use of nearby public services than richer women.ConclusionWomen spent more financial resources on their own non-maternal healthcare than maternity care with poorer women still facing disadvantages for their own healthcare. Health insurance programmes were hardly but were associated with an increase in service use. Comprehensive assessments of women’s health needs, service use and expenditures with an equity focus are crucial for shaping UHC strategies tailored to women of reproductive ages.
Applying a diffusion of innovations framework to characterise diffusion groups and more effectively reach late adopters: a cross-sectional study on COVID-19 vaccinations in Canada in late 2021
Authors: Memedovich Ally , Steele Brian , Orr Taylor , Hollis Aidan , Salmon Charleen , Hu Jia , Zinszer Kate , Williamson Tyler , Beall Reed 
Published: January 2025

BackgroundRogers’ diffusion of innovation theory suggests innovations are adopted in stages by different groups (innovators/early adopters, early majority, late majority and late adopters). In healthcare, this could mean that there is the potential to worsen health disparities as later groups tend to also face more social and structural barriers. Determining the unique sociodemographic characteristics, beliefs and attitudes of those in each diffusion category could be useful for theorising how to reach later groups more effectively.MethodsUsing a cross-sectional survey among Canadian adults in late 2021, we assigned respondents to diffusion groups based on when they received their first dose, relative to others within their age group in accordance with Rogers’ model (ie, cut points: 16%, 50%, 84% with 100% being all those vaccinated within the age group). Participants answered questions about their COVID-19 vaccinations and questions related to their motivations, beliefs, values and attitudes towards COVID-19. A multinomial logistic regression model assessed the likelihood of participants being associated with each diffusion category (with the significance level set at p<0.05).ResultsThe final sample included 2131 respondents. Late adopters were significantly more likely to identify as non-white, live in rural locations and receive vaccinations at pharmacies. Innovators and early adopters were significantly more likely to get vaccinated in settings other than pharmacies or community centres.ConclusionA diffusion group-based analysis brought insight into how vaccination strategies could be tailored to reach each diffusion group sooner, particularly late adopters who encounter more barriers.
‘It was just the given thing to do’: exploring enablers for high childhood vaccination uptake in East London’s Bangladeshi community—a qualitative study
Authors: Ali Ifra , Bell Sadie , Mounier-Jack Sandra 
Published: January 2025

BackgroundDespite being an underserved ethnic minority group, characteristics which have been associated with low vaccine uptake, the Bangladeshi community in the UK exhibits high childhood vaccination uptake for several vaccines, including measles, mumps and rubella compared with several ethnic groups. This study explored key enablers for early childhood vaccination uptake among the Bangladeshi community in East London, UK.MethodsA qualitative study using semi-structured interviews was conducted with 23 Bangladeshi parents 11 primary healthcare professionals (HCPs) and 5 community service providers (CSPs) involved in delivering childhood vaccination services, predominantly in the East London borough of Tower Hamlets. Parents were recruited purposively from the community while HCPs and CSPs were recruited from relevant organisations. The Social Ecological Model (SEM) was used as a theoretical framework for data collection and analysis. Data were analysed thematically.ResultsMultilevel vaccination enablers identified by parents, HCPs and CSPs across the different levels of the SEM included: parental trust in the immunisation programme and HCPs; a rigorous call and recall service; the normalisation of receiving childhood vaccinations within the Bangladeshi community and the availability of culturally tailored and accessible vaccination services.ConclusionsThis study highlights how multi-level trust in a vaccination programme can propel positive vaccine uptake in an underserved, ethnic minority population. Our findings suggest culturally sensitive, person-centred delivery of vaccination services, alongside leveraging community dynamics and trusted social networks, are imperative to meeting the informational, linguistic and cultural needs that facilitate vaccine uptake within the Bangaldeshi community. We recommend using existing trusted community networks to disseminate tailored vaccine information and actively reminding parents about due vaccinations to promote uptake amongst other underserved, ethnic minority communities with low uptake in high-income settings. Further research involving non-immunising parents is recommended to gain more comprehensive insight into vaccine decision-making within this community.
Unveiling the pathways: identifying the multifaceted determinants of low birth weight among neonates in low-income countries: a case-control study
Authors: Ayele Angefa , Boneya Dukele , Jara Dube , Beka Jitu , Gelchu Miesa , Edin Alo 
Published: January 2025

BackgroundLow birth weight, as defined by the WHO, refers to the weight of a neonate below 2500 g at birth and is a significant public health concern globally, with both short- and long-term consequences. Despite the significance of low birth weight as a public health indicator, information gaps persist. Identifying at-risk mothers requires an understanding of the risk factors associated with low birth weight. Therefore, this study aimed to determine the common determinants of low birth weight among neonates born at public hospitals in Southern Ethiopia.MethodsAn unmatched case–control study was conducted among 258 neonates (86 cases and 172 controls) born at public hospitals between 15 April and 25 May 2022. The study participants were selected using a consecutive and systematic sampling technique. Data were analysed using Stata V.14, and a multivariable logistic regression model was performed. Statistical significance was declared at a p value<0.05.ResultsA total of 86 birth records of neonates with low birth weight and 172 birth records of neonates with normal birth weight were reviewed. The results revealed that lack of iron and folic acid supplementation (adjusted odds ratio (AOR) 2.47; 95% CI 1.16 to 5.25), lack of additional meal intake (AOR 2.66; 95% CI 1.16 to 6.00), anaemia (AOR 3.45; 95% CI 1.63 to 7.28), pregnancy-induced hypertension (AOR 2.49; 95% CI 1.04 to 5.97), mid-upper arm circumference (MUAC) (AOR 6.74; 95% CI 2.87 to 7.00), gestational age at first antenatal care (ANC) of ≥24 (AOR 7.31; 95% CI 3.43 to 15.58) and minimum food diversity (AOR 4.2; 95% CI 1.94 to 9.20) were common determinants of low birth weight.ConclusionLack of iron and folic acid supplementation, additional meal intake, being anaemic, pregnancy-induced hypertension, gestational age at first ANC visit, MUAC ≤23 and minimum food diversity were common determinants of low birth weight. Initiating ANC services for all mothers and evaluating different risk factors may help to reduce low birth weight.
Nutritional status and risk factors for malnutrition among children aged 1–6 years in tribal communities of Malappuram district, Kerala: a cross-sectional study
Authors: Perayil Anjaly , K Sreelakshmi Mohandas 
Published: January 2025

IntroductionMalnutrition has critical consequences for physical and cognitive growth, as well as for development. In Kerala, Malappuram district has the highest burden of malnutrition and is home to nearly half of the Paniya tribal population of the state.ObjectiveTo estimate the prevalence of undernutrition and the factors associated with the nutritional status of tribal children 1–6 years of age in Malappuram district of Kerala, India.MethodsA community-based cross-sectional study was carried out between April to September 2022 among the tribal settlements in Nilamboor, Perinthalmanna and Edavanna, divisions of Malappuram district. A multistage cluster sampling was done and the minimum calculated sample size was 142. Parents of each child were interviewed using a semi-structured questionnaire along with anthropometric measurements for estimating height and weight. Data were analysed using ENA software and SPSS V.20.ResultsThe prevalence of underweight, stunting and wasting were found to be 43%, 41.4% and 34.7%, respectively. Among them, 14%, 21.3% and 8.5% were severely underweight, severely stunted and severely wasted in this study population. Socio-demographic characteristics like maternal and paternal unemployment, maternal illiteracy, maternal habits like alcohol consumption, chewing tobacco and acute morbidities among children like diarrhoea and cough were found to be independent predictors for underweight among the tribal children of Malappuram district. Maternal unemployment and alcohol consumption were found to be independent predictors for stunting. For wasting, paternal unemployment, weaning practices and episodes of diarrhoea were found to be independent predictors.ConclusionSocio-demographic factors like parental unemployment, illiteracy and habits like alcohol consumption and tobacco use strongly influence the nutritional status of tribal children. An appropriately planned educational campaign and targeted interventions for improving nutritional status have to be deployed in these tribal communities.
Evaluating strategies for global respiratory pandemic control at ports: a modelling study
Authors: Guan Tong , Duoduwa Sharon Esi , Balakumar S , A Janhavi , Gan Gregory , Lim Jue Tao , Dickens Borame L 
Published: January 2025

BackgroundHeavy reliance on container shipping during the COVID-19 pandemic with lockdown implementation and air travel bans placed substantial pressure on shipping crews and ports. Long waiting times at ports, substantial economic losses and massive supply chain disruption of essential and medical goods were observed. To minimise this for future pandemic preparedness, we explore the use of quarantining and testing of crews preboarding instead of quarantining at port calls or during voyages.MethodsUsing a microsimulation model of 10 000 vessels and 300 000 crew, we examine the effectiveness of nine predeparture control strategies in reducing COVID-19 outbreak sizes, from no control to the use of 7-day and 14-day quarantining, and addition of polymerase chain reaction (PCR) or antigen rapid test (ART) testing. To assess different infection parameters, we explored three variants (Alpha, Delta and Omicron), four prevalences (0.1%, 0.5%, 1% and 2%) and three quarantine compliances (50%, 90% and 100%).ResultsAcross the prevalences with no intervention, our modelled simulations estimate that approximately 3%, 15%, 28% and 47% of crews are infected, totalling around 9400, 44 900, 82 600 and 141 300 infections. At 2% prevalence, averaged across variants and compliances, when 7-day predeparture quarantining (7DQ) is introduced, 23 900 (range: 21 500–25 200) estimated cases are averted, rising up to 40 900 (40 200–41 600) for 14DQ. With additional predeparture PCR testing, this increases further to 102 100 (100 100–104 500) and 106 800 (106 100–108 100) respectively. Should ART testing be used instead, 92 600 (92 200–93 200) and 100 000 (98 900–101 100) estimated cases are averted. The use of predeparture PCR testing and PCR testing 1 week before departure has the greatest reduction at 108 200 (106 400–110 600) and 111 600 (110 500–113 000).ConclusionIn our simulation model, we show that preboarding control measures can be effective in limiting outbreaks, reducing the number of active cases on marine vessels without access to adequate medical care while simultaneously reducing port congestion and facilitating for the greater global transport of essential goods.
Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria
Authors: Li Lixing , Xu Xin , Wang Wentao , Huang Peiran , Yu Lei , Ren Zhenggang , Fan Jia , Zhou Jian , Zhang Lan , Wang Zheng 
Published: January 2025

BackgroundNumerous studies have demonstrated limited survival benefits of transarterial chemoembolization (TACE) alone in the treatment of intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. The advent of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has opened new avenues for HCC treatment. However, TACE combined with ICIs has not been investigated for patients with intermediate-stage HCC beyond the up-to-seven criteria. The study aims to evaluate the efficacy and safety of this treatment strategy for such patients.MethodsIn this single-arm, prospective, phase II study, we enrolled eligible patients with HCC who were treated with TACE plus programmed cell death protein 1 (PD-1) inhibitors (sintilimab) from April 2021 to February 2023. The study’s primary objectives were to assess progression-free survival (PFS) and safety. Secondary objectives included measuring the objective response rate (ORR) and disease control rate (DCR) as per both Response Evaluation Criteria in Solid Tumors (RECIST) V.1.1 and modified RECIST (mRECIST) criteria, as well as overall survival (OS). Additionally, we conducted correlation analyses to identify predictors influencing the efficacy of tumor treatment.Result20 patients participated in this study, with a median follow-up duration of 22.0 months. Median PFS was 8.4 months (95% CI: 4.7 to 19.7) according to both RECIST V.1.1 and mRECIST. The ORR was 30.0% (95% CI: 14.6% to 51.9%) per RECIST 1.1% and 60% (95% CI: 38.7% to 78.1%) per mRECIST. DCR was 95.0% (95% CI: 76.4% to 99.1%) according to both RECIST V.1.1 and mRECIST. Median OS was not yet reached. Notably, 20% (4/20) of patients underwent successful conversion to curative surgical resection. Treatment-related adverse events (TRAEs) mainly included elevated aspartate aminotransferase levels (19/20, 95.0%), elevated alanine aminotransferase levels (18/20, 90.0%), hypothyroidism (18/20, 90.0%), and reduced appetite (10/20, 50.0%). Among all participants, only one experienced grade 3 TRAE (myocarditis). We employed the Elastic Net regression model to analyze radiomic features from tumor and peritumoral areas to predict the efficacy of this treatment strategy.ConclusionTACE plus PD-1 inhibitors demonstrated promising efficacy and an acceptable safety profile, suggesting it as a potential treatment option for patients with intermediate-stage HCC beyond up-to-seven criteria. Furthermore, our study indicates that specific image-based features may serve as predictors for patients likely to benefit from this treatment approach.Trial registration numberNCT04842565.
Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines
Authors: Lahusen Anton , Minhöfer Nora , Lohse Kim-André , Blechner Christine , Lindenmayer Jessica , Eiseler Tim , Wellstein Anton , Kleger Alexander , Seufferlein Thomas , Windhorst Sabine , Lin Yuan-Na 
Published: January 2025

BackgroundPancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a “cold” tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.MethodsWe used an unbiased screening approach of T cell resistant and sensitive murine KPC (KrasLSL-G12D/+; Trp53fl/fl; Ptf1aCre/+) PDAC cells in a three-dimensional co-culture platform with syngeneic antigen-educated T cells to identify potential cell-intrinsic drivers of T cell suppression in PDAC. Comparative transcriptomic analysis was performed to reveal promising candidates that mediate resistance to T cells. We investigated their contribution by shRNA-mediated knockdown and pharmacological inhibition in murine in vitro and in vivo studies, as well as in patient-derived organoids (PDOs). A combination of transcriptomic analyses, cytometric and immunohistochemistry techniques allowed us to validate the underlying T cell response phenotypes of PDAC cells. The action of TGM2 via interaction with tubulin and the impact of microtubule dynamics and vesicle trafficking were evaluated by protein analyses and live-cell imaging. Correlation analyses via TCGA data complemented the functional studies.ResultsWe identified transglutaminase 2 (TGM2) as a mediator of T cell suppression in PDAC. We report that high levels of TGM2 expression in patients’ tumors correlate with immunosuppressive signatures and poor overall survival. We found that TGM2 regulates vesicle trafficking by modulating microtubule network density and dynamics in pancreatic cancer cells, thus facilitating the secretion of immunosuppressive cytokines, which impair effector T cell functionality. In TGM2-expressing PDOs, pharmacological TGM2 inhibition or treatment with nocodazole increased T cell-mediated apoptosis. Also, pretreatment of TGM2highPDOs with sublethal doses of the spindle poisons paclitaxel or vincristine increased CD8+T cell activation and sensitized PDOs toward T cell-mediated cytotoxicity.ConclusionsThese findings indicate that targeting microtubular function therapeutically may enhance antitumor T cell responses by impacting activity of immunosuppressive cytokines in the PDAC microenvironment.
Angiographic signs during mechanical thrombectomy as predictors of post-stroke epilepsy: a multicenter retrospective study
Authors: Jiang Zongzhi , Sun Yining , Zheng Zhaoshi , Han Kai , Mo Zhanhao , Liu Songyan 
Published: January 2025

BackgroundPost-stroke epilepsy (PSE) is a major complication of stroke. However, data about the predictors of PSE in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy are limited.ObjectiveTo evaluate the relationship between intraoperative angiographic signs and PSE risk in patients with anterior circulation AIS who underwent mechanical thrombectomy.MethodsWe conducted a retrospective study. A total of 800 patients with AIS who underwent mechanical thrombectomy were classified into case and control groups based on the occurrence of PSE. Propensity score matching (PSM) (1:4) was applied using covariates such as age, sex, National Institutes of Health Stroke Scale score at admission, and baseline modified Rankin Scale score. Conditional logistic regression and mediation analysis were performed. Subgroup analyses were conducted to assess the effect of modification. A diagnostic model based on the angiographic signs and clinical characteristics was developed.ResultsAfter PSM, 67 and 234 patients with and without PSE, respectively, were selected. The PSE group had significantly higher incidences of hemorrhagic transformation, early seizures, early venous filling (EVF) sign, inferior frontal gyrus (IFG), hippocampus, basal ganglia blush sign, and larger infarct size. After adjusting for hypertension, diabetes, hemorrhagic transformation, infarct size, early seizure, IFG, and hippocampus involvement, EVF remained independently associated with PSE. Hemorrhagic transformation mediated 14.87% of the EVF–PSE associations. Comparison of the evaluation metrics of each model showed that model 3 exhibited the best overall performance.ConclusionHemorrhagic transformation mediates the EVF–PSE association. EVF signs are key predictors of PSE following mechanical thrombectomy.