bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fuzzy system ensembles entomological, epidemiological, demographic and environmental data to unravel the dengue transmission risk in an endemic city
Authors: de Souza Leandro André , de Oliveira Felipe , Lopes Renata Defante , Rivas Açucena Veleh , Martins Caroline Amaral , Silva Isaac , Villela Daniel A. M. , Teixeira Marcello Goulart , Xavier Samanta Cristina das Chagas , Maciel-de-Freitas Rafael 
Published: September 2024

Abstract
Background
The effectiveness of dengue control interventions depends on an effective integrated surveillance system that involves analysis of multiple variables associated with the natural history and transmission dynamics of this arbovirus. Entomological indicators associated with other biotic and abiotic parameters can assertively characterize the spatiotemporal trends related to dengue transmission risk. However, the unpredictability of the non-linear nature of the data, as well as the uncertainty and subjectivity inherent in biological data are often neglected in conventional models.

Methods
As an alternative for analyzing dengue-related data, we devised a fuzzy-logic approach to test ensembles of these indicators across categories, which align with the concept of degrees of truth to characterize the success of dengue transmission by Aedes aegypti mosquitoes in an endemic city in Brazil. We used locally gathered entomological, demographic, environmental and epidemiological data as input sources using freely available data on digital platforms. The outcome variable, risk of transmission, was aggregated into three categories: low, medium, and high. Spatial data was georeferenced and the defuzzified values were interpolated to create a map, translating our findings to local public health managers and decision-makers to direct further vector control interventions.

Results
The classification of low, medium, and high transmission risk areas followed a seasonal trend expected for dengue occurrence in the region. The fuzzy approach captured the 2020 outbreak, when only 14.06% of the areas were classified as low risk. The classification of transmission risk based on the fuzzy system revealed effective in predicting an increase in dengue transmission, since more than 75% of high-risk areas had an increase in dengue incidence within the following 15 days.

Conclusions
Our study demonstrated the ability of fuzzy logic to characterize the city’s spatiotemporal heterogeneity in relation to areas at high risk of dengue transmission, suggesting it can be considered as part of an integrated surveillance system to support timely decision-making.
The effect of parental pain, disability benefits and education on risk of long-term sick leave due to musculoskeletal disorders and the modifying effect of sleep and physical activity: the HUNT study
Authors: Moe Karoline , Skarpsno Eivind Schjelderup , Nilsen Tom Ivar Lund , Mork Paul Jarle , Aasdahl Lene 
Published: September 2024

Abstract
Background
Family factors, sleep, and physical activity have previously been associated with risk of sick leave and disability benefits due to musculoskeletal disorders. However, how these factors act during adolescence and young adulthood is unclear. The aim of this study was to (i) examine if chronic pain, disability benefits and education in parents influence the risk of long-term sick leave due to musculoskeletal disorders in young adulthood, and (ii) to explore if offspring sleep problems and physical activity modify these effects.

Methods
A population-based prospective study of 18,552 adolescents and young adults (≤ 30 years) in the Norwegian HUNT Study. Survey data was linked to national registry data on sick leave, disability benefits, family relations and educational attainment. We used Cox regression to estimate hazard ratio (HR) with 95% confidence interval (CI) for long-term (≥ 31 days) sick leave due to a musculoskeletal disorder in offspring associated with parental factors and the joint effect of parental factors and offspring lifestyle factors.

Results
Parental chronic pain (HR 1.36, 95% CI 1.27–1.45), disability benefits (HR 1.41, 95% CI 1.33–1.48) and low educational attainment (HR 1.78, 95% CI 1.67–1.90) increased the risk of long-term sick leave due to musculoskeletal disorders among offspring. There was no strong evidence that sleep and physical activity modified these effects.

Conclusion
Chronic pain, disability benefit and low education in parents increased the risk of long-term sick leave due to musculoskeletal disorders among offspring, but these effects were not modified by offspring sleep problems or physical activity level. The findings suggest that efforts beyond individual lifestyle factors might be important as preventive measures.
Analytical validation of the LungLB test: a 4-color fluorescence in-situ hybridization assay for the evaluation of indeterminate pulmonary nodules
Authors: Lutman Michelle L. , Gramajo-Leventon Daniel , Tahvilian Shahram , Baden Lara , Gilbert Courtney L. , Trejo Michael , Vail Eric , Donovan Michael J. , Katchman Benjamin A. , Pagano Paul C. 
Published: September 2024

Abstract
Background
Evaluation of indeterminate pulmonary nodules (IPNs) often creates a diagnostic conundrum which may delay the early detection of lung cancer. Rare circulating genetically abnormal cells (CGAC) have previously demonstrated utility as a biomarker for discriminating benign from malignant small IPNs in the LungLB assay. CGAC are identified using a unique 4-color fluorescence in-situ hybridization (FISH) assay and are thought to reflect early cell-based events in lung cancer pathogenesis and the anti-tumor immune response. LungLB is a prognostic tool that combines the CGAC biomarker and clinical features to aid in IPN evaluation by improving the stratification of patient risk of malignancy.

Methods
Herein we describe the analytical performance of the LungLB blood test. Analytical validation was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines with adaptations for rare cell-based assays. Multiple operators, reagent lots, and assay runs were tested to examine accuracy, precision, reproducibility, and interfering factors.

Results
The FISH probes used in the LungLB assay demonstrate 100% sensitivity and specificity for their intended chromosomal loci (3q29, 3p22.1, 10q22.3 and 10cen). LungLB demonstrates analytical sensitivity of 10 CGAC per 10,000 lymphocytes analyzed, 100% analytical specificity, and high linearity (R2 = 0.9971). Within run measurements across 100 samples demonstrated 96% reproducibility. Interfering factors normally found in blood (lipemia, biotin) and exposure to adverse temperatures (-20ºC or 37ºC) did not interfere with results. Sample stability was validated to 96 hours.

Conclusion
The analytical performance of LungLB in this validation study successfully demonstrates it is robust and suitable for everyday clinical use.
Augmented reality visualization for ultrasound-guided interventions: a pilot randomized crossover trial to assess trainee performance and cognitive load
Authors: Liao Shu-Chen , Shao Shih-Chieh , Gao Shi-Ying , Lai Edward Chia-Cheng 
Published: September 2024

Abstract
Background
Augmented reality (AR) technology involving head-mounted displays (HMD) represents a significant innovation in medical education, particularly for training in guided invasive procedures. Novice physicians often face challenges in simultaneously identifying anatomical landmarks and performing procedures when learning point-of-care ultrasound (POCUS). Our primary objective was to determine the effectiveness of AR in enhancing physician training for ultrasound-guided interventions using AR visual overlays. The secondary objective was to compare cognitive load between traditional ultrasound training settings and AR-assisted training settings.

Methods
This randomized crossover study, conducted from 2021 to 2022, compared performance and cognitive load of trainees attempting accurate central venous catheter (CVC) placement using an AR-HMD to display ultrasound images (AR-US), compared with standard ultrasound without visual overlay (S-US). We enrolled 47 trainees, including 22 final-year undergraduate medical students and 25 postgraduate physicians (years 1–4) from three hospitals in Taiwan. All participants had basic training in US-guided CVC placement but lacked AR-US experience. Performance and cognitive load were assessed using time measurements and NASA Task Load Index (NASA-TLX), covering the dimensions of Mental-, Physical- and Temporal Demand, and Performance, Effort and Frustration.

Results
We found AR technology reduced the time required for critical steps in CVC placement, while minimizing users’ neck strain. Female and junior trainees using AR-US identified anatomy and localized veins faster than those using S-US. Using AR-US, female trainees significantly outperformed males in anatomical identification [mean difference (MD): -10.79 s (95% CI: -2.37 to -19.21)]. The NASA-TLX cognitive load assessment showed mental workload trending lower in all dimensions except performance while using AR-US, compared to S-US. Similarly, junior trainees’ effort- and frustration scores were lower [MD: -2.73 (95% CI: -5.04 to -0.41) and -2.41 (95% CI: -4.51 to -0.31), respectively], as were female trainees’ effort scores [MD: -3.07 (95% CI: -6.10 to -0.03)] when using AR-US, compared to S-US, whereby these differences were statistically significant.

Conclusions
AR technology helped improve trainee performance and reduced cognitive load during ultrasound-guided CVC placement. These findings support the application of AR technology to enhance physician training in ultrasound-guided interventional procedures, suggesting that AR-HMDs could be a valuable tool in medical education.

Trial registration
The trial was registered with Clinicaltrials.gov on 20/09/2023 as a clinical trial, under the identifier NCT 06055400.
Workplace learning: the bidirectional relationship between stress and self-regulated learning in undergraduates
Authors: Marsch Stephan , Yanagida Takuya , Steinberg Evelyn 
Published: September 2024

AbstractThe present study focused on the relationships between various aspects of self-regulated learning (SRL) and stress among undergraduate health science students in workplace settings. Although both constructs are associated with academic achievement it is still unclear how they influence each other. Employing a longitudinal diary design, the aim of the present study was to examine whether perceived stress in the previous week impacts SRL-aspects in the current week and, conversely, whether SRL-aspects in the previous week impacts stress in the current week. Subjects were 192 undergraduate health sciences students in their workplace placements. SRL-aspects and stress were assessed using scales and previously tested single-item measures. The 21 SRL-aspects used in this study included cognition (learning strategies), motivation, emotion, perception of the learning environment, and regulation of these areas on a metalevel (monitoring and control). Data collected over 15 weeks were analyzed using multilevel vector autoregressive models, with the data nested within weeks and one model dedicated to each SRL-aspect and its relationship with stress. Among the 21 path estimates assessing the impact of prior stress on individual SRL-aspects, 10 were statistically significant. For individual SRL-aspects impacting stress, 7 out of 21 paths were statistically significant (p < .05). Notably, no model showed statistical significance of effects in both directions. Except for two results, cross-lagged relationships were negative, indicating that better SRL-aspects from the previous week resulted in reduced stress in the current week and vice versa. The effects for the cross-lagged paths from SRL-aspects to stress were predominantly of medium size, whereas the influence of stress on individual SRL-aspects was predominantly small. The present study highlights a potentially causal and mostly negative relationship between stress and various aspects of SRL, but also that the individual relationships require differentiated consideration. The results can be used to develop targeted interventions in the practical part of the training of health science students to reduce stress and improve specific aspects of SRL. Furthermore, these findings underscore assumptions regarding connections between anxiety and increased stress, negative relationships between stress and motivation, and the importance of effective time management strategies for stress reduction.
Development and evaluation of an emergency department serious game for undergraduate medical students
Authors: Aster Alexandra , Hütt Christopher , Morton Caroline , Flitton Maxwell , Laupichler Matthias Carl , Raupach Tobias 
Published: September 2024

Abstract
Background
Serious games are risk-free environments training various medical competencies, such as clinical reasoning, without endangering patients’ safety. Furthermore, serious games provide a context for training situations with unpredictable outcomes. Training these competencies is particularly important for healthcare professionals in emergency medicine.

Methods
Based on these considerations, we designed, implemented, and evaluated a serious game in form of an emergency department, containing the features of a virtual patient generator, a chatbot for medical history taking with self-formulated questions, artificially generated faces based on an artificial intelligence algorithm, and feedback for students. The development process was based on an already existing framework resulting in an iterative procedure between development and evaluation. The serious game was evaluated using the System Usability Scale and the User Experience Questionnaire.

Results
The System Usability Scale provided a substantial result for the usability. In terms of the user experience, four scales yielded positive results, whereas two scales yielded neutral results.

Conclusion
The evaluation of both usability and user experience yielded overall positive results, while simultaneously identifying potential areas for improvement. Further studies will address the implementation of additional game design elements, and testing student learning outcome.
Unleashing the full potential of digital outcome measures in clinical trials: eight questions that need attention
Authors: Tackney Mia S. , Carpenter James R. , Villar Sofía S. 
Published: September 2024

AbstractThe use of digital health technologies to measure outcomes in clinical trials opens new opportunities as well as methodological challenges. Digital outcome measures may provide more sensitive and higher-frequency measurements but pose vital statistical challenges around how such outcomes should be defined and validated and how trials incorporating digital outcome measures should be designed and analysed. This article presents eight methodological questions, exploring issues such as the length of measurement period, choice of summary statistic and definition and handling of missing data as well as the potential for new estimands and new analyses to leverage the time series data from digital devices. The impact of key issues highlighted by the eight questions on a primary analysis of a trial are illustrated through a simulation study based on the 2019 Bellerophon INOPulse trial which had time spent in MVPA as a digital outcome measure. These eight questions present broad areas where methodological guidance is needed to enable wider uptake of digital outcome measures in trials.
Estimating pneumococcal carriage dynamics in adults living with HIV in a mature infant pneumococcal conjugate vaccine programme in Malawi, a modelling study
Authors: Phiri Joseph , Sibale Lusako , Mlongoti Lukerensia , Mitole Ndaona , Kusakala Alice , Khwiya Mercy , Kayembe Thokozani , Lisimba Edwin , Kapwata Prosperina , Malisita Ken , Chaguza Chrispin , Ferreira Daniela M. , Thindwa Deus , Jambo Kondwani 
Published: September 2024

Abstract
Background
Adults living with human immunodeficiency virus (ALWHIV) receiving antiretroviral therapy (ART) exhibit higher pneumococcal carriage prevalence than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting at least 10 years after introducing infant PCV13 in routine immunisation.

Methods
We collected longitudinal nasopharyngeal swabs from individuals aged 18–45 in Blantyre, Malawi. The study group included both HIV- individuals and those living with HIV, categorised based on ART duration as either exceeding 1 year (ART > 1y) or less than 3 months (ART < 3 m). Samples were collected at baseline and then weekly for 16 visits. To detect pneumococcal carriage, we used classical culture microbiology, and to determine pneumococcal serotypes, we used latex agglutination. We modelled trajectories of serotype colonisation using multi-state Markov models to capture pneumococcal carriage dynamics, adjusting for age, sex, number of under 5 year old (< 5y) children, social economic status (SES), and seasonality.

Results
We enrolled 195 adults, 65 adults in each of the study groups. 51.8% were females, 25.6% lived with more than one child under 5 years old, and 41.6% lived in low socioeconomic areas. The median age was 33 years (IQR 25–37 years). The baseline pneumococcal carriage prevalence of all serotypes was 31.3%, with non-PCV13 serotypes (NVT) at 26.2% and PCV13 serotypes (VT) at 5.1%. In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (hazard ratio [HR], NVT [1.53]; VT [1.96]). It was also higher in low than high SES (NVT [1.38]; VT [2.06]), in adults living with 2 + than 1 child < 5y (VT [1.78]), and in ALWHIV on ART > 1y than HIV- adults (NVT [1.43]). Moreover, ALWHIV on ART > 1y cleared pneumococci slower than HIV- adults ([0.65]). Residual VT 19F and 3 were highly acquired, although NVT remained dominant.

Conclusions
The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART > 1y is likely due to impaired nasopharyngeal clearance, which results in prolonged carriage. Our findings provide baseline estimates for comparing pneumococcal carriage dynamics after implementing new PCV strategies in ALWHIV.
Deoxyhypusine synthase deficiency syndrome zebrafish model: aberrant morphology, epileptiform activity, and reduced arborization of inhibitory interneurons
Authors: Shojaeinia Elham , Mastracci Teresa L. , Soliman Remon , Devinsky Orrin , Esguerra Camila V. , Crawford Alexander D. 
Published: September 2024

AbstractDHPS deficiency syndrome is an ultra-rare neurodevelopmental disorder (NDD) which results from biallelic mutations in the gene encoding the enzyme deoxyhypusine synthase (DHPS). DHPS is essential to synthesize hypusine, a rare amino acid formed by post-translational modification of a conserved lysine in eukaryotic initiation factor 5 A (eIF5A). DHPS deficiency syndrome causes epilepsy, cognitive and motor impairments, and mild facial dysmorphology. In mice, a brain-specific genetic deletion of Dhps at birth impairs eIF5AHYP-dependent mRNA translation. This alters expression of proteins required for neuronal development and function, and phenotypically models features of human DHPS deficiency. We studied the role of DHPS in early brain development using a zebrafish loss-of-function model generated by knockdown of dhps expression with an antisense morpholino oligomer (MO) targeting the exon 2/intron 2 (E2I2) splice site of the dhps pre-mRNA. dhps knockdown embryos exhibited dose-dependent developmental delay and dysmorphology, including microcephaly, axis truncation, and body curvature. In dhps knockdown larvae, electrophysiological analysis showed increased epileptiform activity, and confocal microscopy analysis revealed reduced arborisation of GABAergic neurons. Our findings confirm that hypusination of eIF5A by DHPS is needed for early brain development, and zebrafish with an antisense knockdown of dhps model features of DHPS deficiency syndrome.
Impact of a transformative health literacy model for Thai older adults with hypertension
Authors: Sukcharoen Pilaiporn , Sakunpong Nanchatsan , Polruk Jidapa , Chumdaeng Sureeporn 
Published: September 2024

Abstract
Background
Hypertension is the important risk factor for cause disability and death, particularly if there is a loss of self-care knowledge. Health literacy encompasses the comprehension and awareness of health-related information, which is beneficial for managing the health of older adults with hypertension. Therefore, the objective of this study was to examine the impact of a transformative health literacy model to develop the health literacy levels among Thai senior citizen with hypertension.

Method
This research employed an experiment. Thirty-six participants engaged in the transformative health literacy model. The instrument is the health literacy in hypertension scale, which had acceptable reliability and validity.

Results
The study revealed that the level of health literacy in the post-test and follow-up phases of the experimental group who received the health literacy promotion model was significantly higher than the pre-test level of health literacy at a significance level of 0.05.

Conclusion
The study outcomes create a new pathway to enhancements of health literacy in Thai older adults with hypertension.
A multi-view feature representation for predicting drugs combination synergy based on ensemble and multi-task attention models
Authors: Monem Samar , Hassanien Aboul Ella , Abdel-Hamid Alaa H. 
Published: September 2024

AbstractThis paper proposes a novel multi-view ensemble predictor model that is designed to address the challenge of determining synergistic drug combinations by predicting both the synergy score value values and synergy class label of drug combinations with cancer cell lines. The proposed methodology involves representing drug features through four distinct views: Simplified Molecular-Input Line-Entry System (SMILES) features, molecular graph features, fingerprint features, and drug-target features. On the other hand, cell line features are captured through four views: gene expression features, copy number features, mutation features, and proteomics features. To prevent overfitting of the model, two techniques are employed. First, each view feature of a drug is paired with each corresponding cell line view and input into a multi-task attention deep learning model. This multi-task model is trained to simultaneously predict both the synergy score value and synergy class label. This process results in sixteen input view features being fed into the multi-task model, producing sixteen prediction values. Subsequently, these prediction values are utilized as inputs for an ensemble model, which outputs the final prediction value. The ‘MVME’ model is assessed using the O’Neil dataset, which includes 38 distinct drugs combined across 39 distinct cancer cell lines to output 22,737 drug combination pairs. For the synergy score value, the proposed model scores a mean square error (MSE) of 206.57, a root mean square error (RMSE) of 14.30, and a Pearson score of 0.76. For the synergy class label, the model scores 0.90 for accuracy, 0.96 for precision, 0.57 for kappa, 0.96 for the area under the ROC curve (ROC-AUC), and 0.88 for the area under the precision-recall curve (PR-AUC).