bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Prompt Engineering for Multimodal LLM Glaucoma Diagnosis
Authors: Agbareia Reem , Omar Mahmud , Zloto Ofira , Chandala Nisha , Tai Tania , Glicksberg Benjamin S , Nadkarni Girish N , Klang Eyal 
Published: November 2024

AbstractBackground and AimThis study evaluates the diagnostic performance of multimodal large language models (LLMs), GPT-4o and Claude Sonnet 3.5, in detecting glaucoma from fundus images. We specifically assess the impact of prompt engineering and the use of reference images on model performance.MethodsWe utilized the ACRIMA public dataset, comprising 705 labeled fundus images, and designed four prompt types, ranging from simple instructions to more refined prompts with reference images. The two model were tested across 5640 API runs, with accuracy, sensitivity, specificity, PPV, and NPV assessed through non-parametric statistical tests.ResultsClaude Sonnet 3.5 achieved a highest sensitivity of 94.92%, a specificity of 73.46%, and F1 score of 0.726. GPT-4o reached a highest sensitivity of 81.47%, a specificity of 50.49%, and F1 score of 0.645. The incorporation of prompt engineering and reference images improved GPT-4o’s accuracy by 39.8% and Claude Sonnet 3.5’s by 64.2%, significantly enhancing both models’ performance.ConclusionMultimodal LLMs demonstrated potential in diagnosing glaucoma, with Claude Sonnet 3.5 achieving a sensitivity of 94.92%, far exceeding the 22% sensitivity reported for primary care physicians in the literature. Prompt engineering, especially with reference images, significantly improved diagnostic performance. As LLMs become more integrated into medical practice, efficient prompt design may be key, and training doctors to use these tools effectively could enhance clinical outcomes.
Cholinergic neurotransmission in the anterior cingulate cortex is associated with cognitive performance in healthy older adults: Baseline characteristics of the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) trial
Authors: de Figueiredo Pelegrino Ana , Attarha Mouna , Toussaint Paule-Joanne , Ouellet Lydia , Grant Sarah-Jane , Van Vleet Thomas , de Villers-Sidani Etienne 
Published: November 2024

ABSTRACTAging is associated with dysfunction in the cholinergic system, including degeneration of basal forebrain cholinergic terminals that innervate the cortex, which directly contributes to age- and disease-related cognitive decline. In this study, we used [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) imaging to assess the effect of age on cholinergic terminal integrity in predefined regions of interest and its relationship to cognitive performance in healthy older adults who underwent neuropsychological assessment and FEOBV PET brain imaging. Our results showed age-related reductions in FEOBV binding, particularly in the anterior cingulate cortex-our primary region of interest-as well as in the striatum, posterior cingulate cortex, and primary auditory cortex. Notably, FEOBV binding in the anterior cingulate cortex was positively correlated with cognitive performance on the NIH EXAMINER Executive Composite Score. These findings suggest that [18F]FEOBV PET imaging can be used as a reliable biomarker to assess cholinergic changes in the human brain and indicate that preserving the cholinergic integrity of the basal forebrain may help maintain cognitive function and protect against age-related cognitive decline.
Bilingualism measures in children: A critical review of content overlap, development, and pragmatic quality
Authors: Leung Kai Ian , Molnar Monika 
Published: November 2024

AbstractPurposeA variety of assessment tools (e.g., questionnaires) measure the type and degree of bilingualism in children in both research and clinical settings. Although these tools are often assumed to evaluate the same constructs and be interchangeable, this may not be the case, as indicated by other recent reviews. This review critically evaluated existing measures of child bilingualism, focusing on item-content overlap, measure development, and pragmatic quality.MethodA database and manual search identified studies on child bilingualism measure development, which were then appraised using the Psychometric and Pragmatic Evidence Rating Scale and the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN).ResultAnalysis across the six identified measures showed weak between-measure content overlap, with less than one quarter of items shared on average, suggesting they assess different constructs.Ratings indicated varied pragmatic quality, especially in assessor burden (training, interpretation). COSMIN evaluations also highlighted shortcomings in measure design and development.ConclusionThe findings underscore the need for improved content validity and better pragmatic criteria for the clinical use of these tools. We offer recommendations for measure selection dependent on use case (e.g., setting-specific needs) and suggestions for future bilingualism measure development, prioritizing a pragmatic approach.
Applications of Synthetic Data Integration for Deep Learning for Volumetric Analysis and Segmentation in Thoracic CT Imaging
Authors: Zeyrek Ali , Navarro Sergio M 
Published: November 2024

AbstractThis study presents a framework for processing Digital Imaging and Communications in Medicine (DICOM) medical imaging data by integrating synthetic objects for volumetric analysis and simulation for applications in assessment of computed tomography (CT) imaging used in thoracic surgery. Functions are designed to generate synthetic objects including geometric shapes such as spheres, cubes, rectangular prisms, cylinders, and blobs with known volumes. Validation is performed through test functions to ensure accuracy and consistency. Additionally, the use of UNet models for segmenting various chest pathologies, such as hemothorax and pneumothorax, as well as organs, is demonstrated. The created framework is used to generate synthetic data to address the scarcity of publicly available hemothorax CT imaging data. Models achieved high performance, assessed by various metrics. The framework and models provide a robust tool for data augmentation and analysis in medical imaging, potentially enhancing clinical decision-making and supporting research in thoracic surgery and related fields.
RGFSAMNet: An interpretable COVID-19 detection and classification by using the deep residual network with global feature fusion and attention mechanism
Authors: Ul Karim S M Rakib , Bala Diponkor , Rasul Rownak Ara , Goggins Sean 
Published: November 2024

AbstractArtificial intelligence has shown considerable promise in fields like medical imaging. Existing testing limitations necessitate reliable approaches for screening COVID-19 and measuring its adverse effects on the lungs. CT scans and chest X-ray images are vital in quantifying and accurately classifying COVID-19 infections. One significant advantage of deep learning models in medical image analysis for detection and classification is that they are a top-notch way to diagnose diseases. For this purpose, we have utilized the power of a deep residual learning network with a global feature fusion technique and attention mechanism to develop our proposed model named “RGFSAMNet” in this study to diagnose the COVID-19 infected patient accurately from a CT scan and chest X-ray images. We have used two publicly available datasets named “SARS-COV-2,” which consists of 2482 CT scan images with two classes, and another chest X-ray dataset that contains 12,576 images with three classes. To check the effectiveness of our model, we have trained and tested the model on two different types of datasets. We also generated the Grad-CAM, LIME, and SHAP visualization based on our proposed model, which can represent the identification of the affected area’s regions in images and describe the model’s interpretability level. These experimental results show that the proposed model architecture can achieve accurate classification of COVID-19 affected CT scans and X-ray images despite a lack of data, with the highest accuracy of 99.60% on test data for CT scans and 99.48% on X-ray image detection and classification. We also developed a web-based User Interface (UI) for the model validation to detect and classify COVID-19 images. Our proposed model exceeds some previous state-of-the-art performance levels. We think our contributions will help clinicians detect and classify COVID-19 images effectively and save human lives.
Healthcare Expenditure on Atrial Fibrillation in the United States: The Medical Expenditure Panel Survey 2016-2021
Authors: See Claudia , Grubman Scott , Shah Nisarg , Hu Jiun-Ruey , Nanna Michael , Freeman James V. , Murugiah Karthik 
Published: November 2024

ABSTRACTObjectivesTo provide a contemporary nationally representative assessment of atrial fibrillation (AF) and atrial flutter (AFL) expenditures in the United States.BackgroundAF prevalence is rising over time and management is evolving. However, there has been no contemporary national assessment of expenditures of AF.MethodsUsing Medical Expenditure Panel Survey (MEPS) 2016-2021 data, we identified individuals with AF or AFL using International Classification of Disease (ICD)-10 codes and reported total and categorized expenditures. Using two-part and gamma regression models, respectively, we estimated the incremental expenditures with AF for the entire population and for individuals with common coexisting comorbidities. Among individuals with AF, we identified characteristics associated with higher expenditures.ResultsOf a weighted surveyed population of 248,067,064 adults, 3,564,763 (1.4%) had AF. Mean age was 71.9 ± 10.6 years and 45.7% were female. Mean unadjusted annual total healthcare expenditure for individuals with AF was $25,451 ± $1,100 compared with $9,254 ± $82 for individuals without AF. The highest spending categories were inpatient visits ($7,975 ± $733) and prescriptions ($6,505 ± $372). AF expenditures increased over the study period by 11.1%. After adjustment, the incremental annual expenditure attributable to AF was $6,188 per person. Incremental expenditures with AF were highest for those with cancer ($11,967, 95% CI $4,410 - $19,525), while AF did not significantly increase expenditures in HF (-$2,756, 95% CI -$10,048 - $4,535). Modified Charlson Comorbidity Index of 1 or ≥2, uninsured status, cancer, poor income level, ASCVD, COPD, and later survey year were associated with higher expenditures.ConclusionAF is associated with substantial healthcare expenditures which are increasing over time. With changes in screening and management, expenditures need periodic reassessments.CONDENSED ABSTRACTIntroductionAF prevalence is rising, but contemporary national expenditure assessments are lacking.MethodsTwo-part and gamma regression models of MEPS 2016-2021 data (all-payer cross-sectional US survey) estimated AF effect on healthcare expenditures.ResultsOf 248,067,064 adults, 1.4% had AF, with mean age 72.1 years and 45.7% female. Mean unadjusted annual expenditure was $25,451 ± $1,100 ($9,254 ± $82 without AF). Incremental adjusted annual expenditure attributable to AF was $6,188. Modified CCI of 1 or ≥2, uninsured status, cancer, poor income level, ASCVD, COPD, and later survey year were associated with higher expenditure.DiscussionAF expenditures are substantial and increasing.
Integrating post-validation surveillance of lymphatic filariasis with the WHO STEPwise approach to non-communicable disease risk factor surveillance in Niue, a study protocol
Authors: Craig Adam T , Lawford Harriet , Mokoia Grizelda , Ikimau Minerva , Fetaui Peter , Marqardt Tonia , Lau Colleen L 
Published: November 2024

AbstractBackgroundLymphatic filariasis (LF),a mosquito-borne parasitic disease caused by three species of filarial worms, was first detected in Niue, a small Pacific Island nation of approximately 1,600 people, in 1954. After extensive efforts involving multiple rounds of Mass Drug Administration, Niue was validated by the World Health Organization (WHO) as having eliminated LF as a public health problem in 2016. However, no surveillance has been conducted since validation to confirm infection rates have remained below WHO’s elimination threshold. WHO has encouraged an integrated approach to disease surveillance; integrating LF post-validation surveillance (PVS) with existing surveys is an anticipated recommendation of the upcoming WHO LF-PVS guidelines. This paper describes a protocol for the implementation of an integrated approach to LF-PVS in Niue. We hypothesise that the approach describe here will offer a cost-efficient and operationally feasible means of monitoring the disease in the population.MethodsThe LF-PVS will be implemented as part of a planned national population-based WHO STEPwise approach to non-communicable disease (NCD) risk factor surveillance (STEPS) in Niue. Integration between the LF-PVS and STEPS will occur at multiple points, including during pre-survey community awareness raising and engagement, when obtaining informed consent, during the collection of demographics, risk factor, and location data, and when collecting finger-prick blood samples (for glucose as part of the STEPS survey and LF as part of the LF-PVS). The primary outcome measure for LF transmission will be antigen positivity. Microfilaria slides will be prepared for any antigen-positive cases. Dried blood spots will be prepared for all participants for Multiplex Bead Assays-based analysis to detect anti-filarial antibodies. We estimate a total sample size of 1,062 participants aged 15-69, representing approximately 66% of the population.ConclusionsThe results of this study will provide insight into the status of LF in Niue and evaluate the advantages, challenges, and opportunities offered by integrated approaches to disease surveillance.
Revolutionizing large-scale DNA synthesis with microchip-based massive in parallel synthesis system
Authors: Zhang Xiandi , Jiang Xianger , Wang Yun , Chen Qinzhen , Zhang Ruihong , Jiang Hao , Zhang Hu , Beltran Antoni , Yang Weiya , Liang Chenglong , Chen Ning , Huang Yun , Ding Guqiao , Xie Chengwang , Gao Nanfeng , Zheng Kaijing , Liu Juntao , Xu Wei , Huang Jinlei , Cai Dong , Zhu Lihao , Mo Songjin , Shen Mengzhe , Zhang Wenwei , Lehner Ben , Ni Ming , Wang Jian , Xu Xun , Shen Yue 
Published: November 2024

AbstractDNA synthesis serves as the fundamental enabling technology of engineering biology, aiming to provide DNA molecules of designed composition, length, and complexity at scale and low cost. Current high-throughput DNA synthesis technologies rely on intricate chip manufacturing and microfluidic systems to provide large-scale synthetic oligonucleotides, at the expense of low concentration and limited compatibility in the processing of longer DNA constructs assembly. Here, we report a microchip-based massive in parallel synthesis (mMPS), pioneering an “identification-sorting-synthesis-recycling” iteration mechanism to microchips for high throughput DNA synthesis. In comparison to microarray-based methods, we demonstrate that our method can increase the DNA product concentration by 4 magnitudes (to picomole-scale per sequence) and greatly simplifies the downstream processes for large-scale gene synthesis construction. By the construction of 1.97 million-diversity variant libraries that cover 1,254 human protein domains, we demonstrated the uniformity of the constructed variant libraries using mMPS-derived oligos is greatly improved, with amino acid distribution highly consistent as designed. In addition, by synthesizing 285 1kb-to-3kb genes with varying degrees of sequence complexity from previously reported strains A501 and 3DAC, potential ancestor of early archaea and bacteria, our result shows that the overall gene assembly success rate using mMPS-derived oligos is increased by 10-fold in comparison to other methods. Our mMPS technology holds the potential to close the gap between the quality and cost of writing DNA in increasing demand across many sectors of research and industrial activities.
The mitochondrial-targeted peptide therapeutic elamipretide improves cardiac and skeletal muscle function during aging without detectable changes in tissue epigenetic or transcriptomic age
Authors: Mitchell Wayne , Pharaoh Gavin , Tyshkovskiy Alexander , Campbell Matthew , Marcinek David J. , Gladyshev Vadim N. 
Published: November 2024

ABSTRACTAging-related decreases in cardiac and skeletal muscle function are strongly associated with various comorbidities. Elamipretide (ELAM), a novel mitochondrial-targeted peptide, has demonstrated broad therapeutic efficacy in ameliorating disease conditions associated with mitochondrial dysfunction across both clinical and pre-clinical models. ELAM is proposed to restore mitochondrial bioenergetic function by stabilizing inner membrane structure and increasing oxidative phosphorylation coupling and efficiency. Although ELAM treatment effectively attenuates physiological declines in multiple tissues in rodent aging models, it remains unclear whether these functional improvements correlate with favorable changes in molecular biomarkers of aging. Herein, we investigated the impact of 8-week ELAM treatment on pre- and post-measures of C57BL/6J mice frailty, skeletal muscle, and cardiac muscle function, coupled with post-treatment assessments of biological age and affected molecular pathways. We found that health status, as measured by frailty index, cardiac strain, diastolic function, and skeletal muscle force are significantly diminished with age, with skeletal muscle force changing in a sex-dependent manner. Conversely, ELAM mitigated frailty accumulation and was able to partially reverse these declines, as evidenced by treatment-induced increases in cardiac strain and muscle fatigue resistance. Despite these improvements, we did not detect statistically significant changes in gene expression or DNA methylation profiles indicative of molecular reorganization or reduced biological age in most ELAM-treated groups. However, pathway analyses revealed that ELAM treatment showed pro-longevity shifts in gene expression such as upregulation of genes involved in fatty acid metabolism, mitochondrial translation and oxidative phosphorylation, and downregulation of inflammation. Together, these results indicate that ELAM treatment is effective at mitigating signs of sarcopenia and heart failure in an aging mouse model, but that these functional improvements occur independently of detectable changes in epigenetic and transcriptomic age. Thus, some age-related changes in function may be uncoupled from changes in molecular biological age.
Landmark-based estimates of genomic disparity
Authors: Mohan Ashwini V. , Goswami Anjali , Streicher Jeffrey W. 
Published: November 2024

AbstractGenomic architecture has played a key role in the evolution of biodiversity. Structural comparisons of genome sequences have informed the study of supergenes, sex chromosomes, and some of the earliest divergences in the tree of life. However, multi-species comparisons of whole genome sequences still have many computational and analytical limitations. Here we present a computationally non-intensive approach, based on geometric morphometrics, that generates disparity scores using conserved sequences as landmarks. This ‘geno-metric’ method captures structural differences in homologous chromosomal regions and can be applied at micro- and macroevolutionary scales. Using ultraconserved elements (UCEs) as landmarks, we provide empirical demonstrations with chromosome 5 from theDrosophila virilisgroup and 40 placental mammal genomes. These examples identify chromosomal rearrangements while also confirming that UCE landmark placement has strong parallels with morphometrics regarding chromosome size, landmark orientation, phylogenetic signal of landmarks, and landmark availability. Using simulations, we show that UCE-inferred disparity is correlated with overall levels of chromosome evolution which can be further studied using macroevolutionary models of continuous trait evolution. Landmark-based estimates of disparity are a valuable addition to the comparative genomic toolkit in that they offer an intuitive, rapid mechanism for detecting chromosomal expansions, contractions, and rearrangements. We also highlight the potential for this approach to identify translocations and genome duplications.Significance StatementThe increased throughput of genome sequencing has outpaced the development of analytical tools to extract information from these big data, creating an urgent need for novel methodological perspectives in genomics. We describe and validate a morphometric approach based on conserved genomic landmarks that effectively captures multi-species variation of chromosome structure. Using the principles of morphological disparity, the throughput of comparative genomics can be greatly increased, and the syntenic organization of chromosomes placed in quantitative and macroevolutionary contexts.
The influence of trait intolerance of uncertainty on behavioural flexibility
Authors: Williams Brendan , Rodriguez-Sobstel Claudia , FitzGibbon Lily , Morriss Jayne , Christakou Anastasia 
Published: November 2024

AbstractIdentifying and responding adaptively to a change in our environment is an essential skill. However, differences in our ability to detect and our disposition to react to these changes mean that some individuals are better equipped to deal with change than others. Here, we investigate whether intolerance of uncertainty, a transdiagnostic dimension of psychopathology, is associated with performance during a reversal learning task. We assessed task performance of 145 subjects using behavioural measures and computational modelling across two time points (approximately 12 days apart). Intolerance of uncertainty and its prospective and inhibitory subscales were associated with task performance, irrespective of self-reported levels of trait anxiety. Intolerance of uncertainty and its inhibitory subscale were positively associated with increased sensitivity to reinforcement from positive, but not negative, feedback. Furthermore, the inhibitory subscale was positively associated with better performance, both overall (as indexed by accuracy) and immediately following a change in reward contingencies (as indexed by perseveration). Lastly, the prospective subscale interacted with the extent to which choice was driven by expected value across time points. These findings provide novel evidence for how trait intolerance of uncertainty may modulate behavioural flexibility in changeable environments. The study points towards exciting avenues for further research into the development of IU-related behaviours across the lifespan and their implications for mental health.