bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing apples and oranges in youth depression treatments? A quantitative critique of the evidence base and guidelines
Authors: Stringaris Argyris , Burman Charlotte , Delpech Raphaelle , Uher Rudolph , Bhudia Dayna , Miliou Despoina , Rokas Ioannis-Marios , Kyriakopoulos Marinos , Foulkes Lucy , Moreno Carmen , Cortese Samuele , Lewis Glyn , Krebs Georgina 
Published: January 2025

ObjectivesShould a young person receive psychotherapy or medication for their depression and on what evidence do we base this decision? In this paper, we test the factors across modalities that may influence comparability between medication and psychotherapy trials.MethodsWe included 92 randomised controlled trials (RCTs) of psychotherapy and medication for child and adolescent depression (mean age 4–18 years). Using meta-analyses, we compared (a) participant characteristics and (b) trial characteristics in medication and psychotherapy trials. Lastly, we examined whether psychotherapy controls are well-matched to active conditions.ResultsParticipants in medication RCTs had higher depression severity and were more frequently male compared with psychotherapy RCTs. There was a dramatic difference in the within-subject improvement due to placebo (SMD=−1.9 (95% CI: −2.1 to −1.7)) vs. psychotherapy controls (SMD=−0.6 (95% CI: −0.9 to −0.3)). Within psychotherapy RCTs, control conditions were less intensive on average than active conditions.ConclusionsMedication and psychotherapy RCTs differ on fundamental participant and methodological characteristics, thereby raising questions about their comparability. Psychotherapy controls often involve little therapist contact and are easy-to-beat comparators. These findings cast doubt on the confidence with which psychotherapy is recommended for youth depression and highlight the pressing need to improve the evidence base.
Evaluation of the implementation of personalised outcomes forecasts to optimise supervised exercise therapy in patients with intermittent claudication: a multimethods process evaluation
Authors: Marcellis Laura H M , Sinnige Anneroos , van Bergen Anne G E , Spruijt Steffie , Kittelson Andrew , Teijink Joep A W , van der Wees Philip J , Hoogeboom Thomas J 
Published: January 2025

BackgroundPersonalised outcomes forecasts (POFs) were introduced among physical and exercise therapists in the Netherlands to optimise supervised exercise therapy for patients with intermittent claudication. Yet, therapists’ initial adoption and sustainable implementation of POFs can be influenced by various factors.ObjectivesThe purpose of this study was to examine therapists’ adoption of the POFs, their fidelity to the measurement protocol for supervised exercise therapy, and their perceived barriers and facilitators for using POFs in practice.MethodsA multimethod process evaluation was conducted, including quantitative descriptive and pre–post approaches, as well as a qualitative framework approach. To examine adoption, we evaluated the proportion of therapists who expressed interest in POFs by completing one of three provided e-learnings and the proportion of therapists who started using POFs in practice. To examine fidelity to the measurement protocol, we compared the per-episode proportion of follow-up measurements documented by therapists preimplementation and postimplementation. Qualitative data on barriers and facilitators were identified through semistructured interviews with therapists.ResultsOne year after the implementation, 89% of therapists eligible to use POFs (n=1727) completed at least one e-learning and 51% of therapists started using POFs. The per-episode proportion of documented follow-up measurements per therapist increased, from a mean rate of 37% (3 months) and 22% (6 months) during the preimplementation period to a mean rate of 53% (3 months) and 32% (6 months) during the postimplementation period (p<0.001). Among interviewed therapists (n=12), identified barriers included competing demands and a lack of skills or confidence. Identified facilitators included the potential to improve the quality of care and a positive user attitude.ConclusionsOur findings suggest that although there is initial interest in and adoption of POFs, addressing barriers and leveraging facilitators through tailored implementation strategies could further increase their utilisation in practice.
Challenges with achieving and maintaining oral cholera vaccine coverage: insights from serial cross-sectional representative surveys in a cholera-endemic community in the Democratic Republic of the Congo
Authors: Koyuncu Aybüke , Bugeme Patrick Musole , Dent Juan , Hutchins Chloe , Xu Hanmeng , Gallandat Karin , Cumming Oliver , Matundanya Joseph , Cikomola Aimé , Rukakiza Delphin , Nkombo Merveille , Mufitini Jaime Saidi , Bashige Rumedeka Baron , Akilimali Laurent , Lee Elizabeth C , Welo Placide Okitayemba , Knee Jackie , Azman Andrew S , Malembaka Espoir Bwenge 
Published: January 2025

BackgroundWe conducted three serial cross-sectional representative surveys after a mass cholera vaccination campaign in Uvira, Democratic Republic of the Congo to (1) estimate the vaccination coverage and explore heterogeneity by geographic and demographic factors; (2) examine barriers and facilitators of vaccine uptake and (3) describe the changes in coverage over time and predict future coverage.MethodsWe collected data on sociodemographics, self-reported vaccination status, population movement and knowledge, attitudes and behaviours related to killed oral cholera vaccines (kOCVs) in August 2021, April 2022 and April 2023, approximately 11, 19 and 30 months postvaccination. We compared the characteristics of participants by vaccination status and explored the potential role of population movement as a cause for low coverage. We used an exponential decay model to predict the proportion of the population vaccinated with ≥1 dose of kOCV over time based on age-specific coverage.ResultsWe enrolled 8735 participants from 1433 households across all surveys. Coverage in survey 1 (August 2021) was 55% for ≥1 dose of kOCV (95% CI 51 to 60) and 23% for ≥2 doses (95% CI 20 to 27). Vaccine refusal was associated with a lack of confidence in the vaccine’s safety, and 29% of unvaccinated adults reported it was unlikely they would accept kOCVs if an additional mass vaccination campaign was conducted in their area. Coverage of ≥1 one dose of kOCV declined on average by 18% per year (95% credible interval 14 to 23) and was 39% (95% CI 36 to 43) by survey 3 (approx. 30 months after second dose campaign).ConclusionsOur findings suggest that in settings like Uvira, efforts to strengthen vaccine confidence are needed to achieve higher campaign coverage, and vaccine coverage dilution may be reduced by more frequent and coordinated geographic vaccination efforts.
A retrospective study to understand the differences in maternal mortality among women admitted in critical and stable conditions in Malawi
Authors: Munthali Laura , Chirombo James , Makhaza Lumbani , Riches Jennifer , Mbewe Malangizo , Bilesi Rosemary , Tagiyeva-Milne Nara , Lissauer David 
Published: January 2025

IntroductionAddressing the burden of preventable maternal deaths remains a critical focus of global health efforts in countries like Malawi which still has a high maternal mortality ratio of 381 deaths per 100 000 live births. We investigated the differences in case characteristics, survival and causes of death between pregnant and recently pregnant women who died, following their admission in stable or critical conditions to healthcare facilities in Malawi.MethodsWe conducted a retrospective analysis of maternal deaths of women from all district and central hospitals of Malawi between August 2020 and August 2022. Data were sourced from the national maternal and newborn health surveillance platform. We performed descriptive analyses, stratified by condition on admission, to identify differences in case characteristics between the two groups, and an exploratory survival analysis, to understand the differences in time to death since admission. Lastly, we performed a principal component analysis to reduce dimensionality to identify the main factors leading to deaths.ResultsObstetric haemorrhage was the predominant cause of death among women admitted in stable condition, while those admitted in critical condition primarily died of hypertensive disorders. Most deaths in both categories occurred on the day of admission, corresponding to their primary causes of death. The key factors leading to deaths were mostly healthcare worker factors followed by administrative factors.ConclusionUnderstanding and responding to the different underlying causes of maternal mortality and contributing factors in the stable and critical cohorts are vital to designing well-targeted and impactful interventions to prevent maternal deaths.
Role of IPF genetic risk loci in post-COVID-19 lung abnormalities: a cohort study
Authors: Marinescu Daniel-Costin , Wong Alyson W , Shah Aditi , Hague Cameron J , Murphy Darra , Yang Julia , Johnston James , Leung Janice , Carlsten Christopher , Ryerson Christopher J 
Published: January 2025

IntroductionPersistent lung abnormalities following COVID-19 infection are common. Similar parenchymal changes are observed in idiopathic pulmonary fibrosis (IPF). We investigated whether common genetic risk factors in IPF are associated with developing lung parenchymal abnormalities following severe COVID-19 disease.MethodsConsecutive adults hospitalised for laboratory-confirmed COVID-19 infection were prospectively recruited from March to May 2020. Three single-nucleotide polymorphisms (SNPs) conferring risk for IPF were genotyped (MUC5Brs35705950, ATP11Ars1278769 andDPP9rs12610495). High-resolution CT and pulmonary function tests were performed at 3 months postdischarge from hospital. Ground glass opacities and reticulation on imaging were visually quantified by two expert thoracic radiologists. Linear regression was used to evaluate the association between risk alleles at each of the three SNPs and (a) lung parenchymal abnormalities as well as (b) pulmonary function, adjusted for age, sex, smoking history and days spent on supplemental oxygen during acute illness.Results71 patients were included. Mean age was 63±16 years, 62% were male, 31% were ever-smokers and median hospital length of stay was 9±11 days, with 23% requiring mechanical ventilation. TheMUC5Brisk allele was associated with a significant decrease in ground glass (β=−0.8, 95% CI −1.5 to –0.1, p=0.02) at 3 months, and this finding was paralleled by a concurrent but non-significant trend towards increased diffusion capacity for carbon monoxide (DLCO) (β=8.8, 95% CI −1.2 to 18.8, p=0.08) compared with patients without this risk allele. None of the risk alleles were significantly associated with reticulation at 3 months.ConclusionIn an adjusted analysis controlling for severity of infection,MUC5Bwas associated with reduced ground glass and a trend towards concordant higher DLCO at 3 months after severe COVID-19 illness. This hypothesis-generating result suggests a possible protective effect ofMUC5Bin postinfectious lung abnormalities as compared with fibrosis in IPF, highlighting a plausible trade-off between its role in immune defence and epithelial cell function.
Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation
Authors: Maravelia Panagiota , Yao Haidong , Cai Curtis , Nascimento Silva Daniela , Fransson Jennifer , Nilsson Ola B , Lu Yong-Chen William , Micke Patrick , Botling Johan , Gatto Francesca , Rovesti Giulia , Carlsten Mattias , Sallberg Matti , Stål Per , Jorns Carl , Buggert Marcus , Pasetto Anna 
Published: January 2025

BackgroundTumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy.ObjectiveWe evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment.DesignT cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing.ResultsBioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes.ConclusionThese findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC.
Can a novel computer vision-based framework detect head-on-head impacts during a rugby league tackle?
Authors: Mohan Manish , Weaving Dan , Gardner Andrew J , Hendricks Sharief , Stokes Keith A , Phillips Gemma , Cross Matt , Owen Cameron , Jones Ben 
Published: January 2025

BackgroundHead-on-head impacts are a risk factor for concussion, which is a concern for sports. Computer vision frameworks may provide an automated process to identify head-on-head impacts, although this has not been applied or evaluated in rugby.MethodsThis study developed and evaluated a novel computer vision framework to automatically classify head-on-head and non-head-on-head impacts. Tackle events from professional rugby league matches were coded as either head-on-head or non-head-on-head impacts. These included non-televised standard-definition and televised high-definition video clips to train (n=341) and test (n=670) the framework. A computer vision framework consisting of two deep learning networks, an object detection algorithm and three-dimensional Convolutional Neural Networks, was employed and compared with the analyst-coded criterion. Sensitivity, specificity and positive predictive value were reported.ResultsThe overall performance evaluation of the framework to classify head-on-head impacts against manual coding had a sensitivity, specificity and positive predictive value (95% CIs) of 68% (58% to 78%), 84% (78% to 88%) and 0.61 (0.54 to 0.69) in standard-definition clips, and 65% (55% to 75%), 84% (79% to 89%) and 0.61 (0.53 to 0.68) in high-definition clips.ConclusionThe study introduces a novel computer vision framework for head-on-head impact detection. Governing bodies may also use the framework in real time, or for retrospective analysis of historical videos, to establish head-on-head rates and evaluate prevention strategies. Future work should explore the application of the framework to other head-contact mechanisms and also the utility in real time to identify potential events for clinical assessment.
Genetic features and pharmacological rescue of novel Kv7.2 variants in patients with epilepsy
Authors: Song Yue , Xia Yang , Peng Ziyue , Meng Yuhuan , Jing Wenwen , Xie Li , Cao Tianhua , Zhang Jiahui , Song Huilin , Meng Lingdi , Zhang Yi , Sui Shengbin , Mao Di , Jia Ying , Qiao Shupei , Yu Shihui , Zhang Xue 
Published: January 2025

BackgroundIncreasing evidence indicates a robust correlation between epilepsy and variants of the Kv7.2 (KCNQ2) channel, which is critically involved in directing M-currents and regulating neuronal excitability within the nervous system. With the advancement of next-generation sequencing, the identification ofKCNQ2variants has surged. Nonetheless, their functional impacts are still being determined, introducing uncertainty into the diagnostic process for affected families and potentially hindering their ability to participate in targeted precision medicine trials. This study aims to elucidate the pathogenicity of these novel variants and explore potential therapeutic interventions.MethodsWhole-cell patch-clamp recordings, western blotting, and immunofluorescent staining were performed to elucidate the functional consequences of the identified variants. Moreover, coimmunoprecipitation techniques were conducted to explore protein interactions, thus facilitating a deeper understanding of the underlying pathogenetic mechanisms contributing to the disease. Ultimately, the effects of pharmacological interventions were evaluated in vitro using the patch-clamp technique.ResultsHerein, we identified 12 novelKCNQ2variants, further expanding the mutational spectrum ofKCNQ2. Our investigation revealed that one gain-of-function variant (p.L102V (c.304C>G)) and three loss-of-function variants (p.H328Q (c.984C>G), p.A336V (c.1007C>T) and p.D563Efs*22 (c.1688_1689insACTT)) had different impacts on the binding of calmodulin and phosphati-dylinositol-4,5-bisphosphate, potentially altering their localisation and protein stability. Furthermore, the application of ML213, unlike Retigabine and ICA-069673, led to a significant increase in the current of p.H328Q.ConclusionThis study expanded the mutational spectrum ofKCNQ2and analysed the genetic and functional consequences, as well as the pharmacological rescue, of fourde novo KCNQ2variants. These findings offer valuable insights into the precise medicine ofKCNQ2-related epilepsy.
Cross-sectional and longitudinal association of sleep patterns and aneurysmal vulnerability biomarkers on high-resolution magnetic resonance vessel wall imaging
Authors: Duan Chuan-Zhi , Huang Chi , Wen Zhuohua , Li Yu-Xin , Huang Mengshi , Ma Gengwu , Li Cai-Hong , Yuan Hao , Xu Anqi , Shi HongYu , Lin Jiancheng , Li Can , Huang Jiwan , Ge Runze , Bi Yiming , Qian Yi , Su Shixing , Zhang Xin , Li Xifeng , Wen Zhibo , Feng Xin 
Published: January 2025

BackgroundAneurysm wall enhancement (AWE) on vessel wall imaging (VWI) scans is a robust biomarker for aneurysmal vulnerability. This study aimed to explore the association of different sleep patterns with AWE and other vulnerability features.MethodsPatients with unruptured intracranial aneurysms were prospectively recruited. Sleep characteristics were collected through a standard questionnaire. Poor sleep quality was defined using the Pittsburgh Sleep Quality Index (PSQI)>5. Cross-sectional multistate predictive models were used to identify various sleep patterns related to aneurysmal vulnerability. In longitudinal observation, core covariates were adjusted with each sleep characteristic to verify cross-sectional results.ResultsA total of 344 aneurysms were enrolled for cross-sectional analyses, while 74 cases (21.5%) that did not receive preventive treatment participated in longitudinal follow-up. In cross-sectional analysis, U-shaped relationships were evident between AWE and nocturnal sleep duration and siesta habit. Improper nocturnal sleep duration, inappropriate siesta habits, insomnia, and snoring were significantly associated with multiple VWI markers of aneurysmal vulnerability (all P<0.05). Notably, all vulnerability indicators were related to poor sleep quality. In longitudinal analysis, short nocturnal sleep duration, snoring, and poor sleep quality were independently associated with aneurysmal progression (all P<0.05).ConclusionsUnhealthy sleep patterns were significantly associated with multiple features related to aneurysmal vulnerability. Interventional studies are needed to evaluate the role of improving sleep burden and individual sleep symptoms as potential targets for reducing the risk of aneurysm rupture.
Residual sleepiness and impaired alertness in treated obstructive sleep apnoea: role of hypoxic burden and sleep fragmentation
Authors: Tankéré Pierre , Taillard Jacques , PetitJean Thierry , Le-Cam Pierre , Ricordeau François , Blanchard Margaux , Vanbuis Jade , Nofal Anice , Tamisier Renaud , Peter-Derex Laure , Stauffer Emeric 
Published: January 2025

The pathophysiology of residual sleepiness in treated obstructive sleep apnoea (OSA) remains poorly understood. Animal models suggest that it may involve neuronal damage due to intermittent hypoxia and sleep fragmentation. In a cohort of 122 continuous positive airway pressure (CPAP) treated OSA patients referred for maintenance of wakefulness test, we explored the determinants of (objective) alertness and those of (subjective) sleepiness assessed by Epworth Sleepiness Scale.We found that in logistic models, residual hypoxic burden was significatively associated with objective impaired alertness (OR=1.005, 95% CI 1.002 to 1.008), p=0.003), whereas arousal index >25/h was significatively associated with subjective residual sleepiness (OR=1.23, 95% CI 1.05to 1.43, p=0.02). This suggests that hypoxia and sleep fragmentation may be involved in different dimensions of residual hypersomnolence in treated OSA.
Stressors contributing to burnout among acute care and trauma surgery care teams: a systems-analysis approach
Authors: Kwong Elizabeth , Adapa Karthik , Goodacre Viola , Vizer Lisa , Ra Jin , Greenberg Caprice , Ivester Thomas , Charguia Nadia , Marks Lawrence B , Mazur Lukasz 
Published: January 2025

BackgroundBurnout negatively impacts healthcare professionals’ well-being, leading to an increased risk of human errors and patient harm. There are limited assessments of burnout and associated stressors among acute care and trauma surgery teams.MethodsAcute care and trauma surgery team members at a US academic medical center were administered a survey that included a 2-item Maslach Burnout Inventory and 21 workplace stressors based on the National Academy of Medicine’s systems model of clinician burnout and professional well-being. Stressors were summarized and presented to participants in focus groups. Contextual inquiries (CIs) were conducted to gather additional information about key stressors. Qualitative data were used to generate an affinity model, which participants then validated and used to prioritize top stressors. Participants rated stressors by level of impact and level of effort, and improvement recommendations were made based on these results.Results74% (n=14/19) acute care and trauma surgery team members reported high burnout. Key stressors included inadequate staffing, organizational culture, excessive workload, and inefficient workflows. Attending faculty (surgeons) classified the following key priorities for improvement: (i) improve throughput and patient flow, (ii) provide better information technology support, and (iii) improve rewards and support. Non-faculty (advanced practice providers (APPs), nurses, staff) classified the following for improvement: (i) align APP job responsibilities, (ii) improve lack of recognition from leadership, and (iii) robust and consistent APP training.ConclusionsA contextual design approach to studying burnout using surveys, focus groups, CIs, modeling, and validation and prioritization is a feasible method for identifying key stressors and improvements that may enable more impactful and appropriately targeted interventions. Results indicate high levels of burnout among acute care and trauma surgery team members, requiring prioritized attention to operational and relationship issues necessary to care for patients. Efforts to improve surgery teams’ workflows, auxiliary support, compensation, and relationships with leadership may address burnout.Level of evidenceLevel V.