1.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
2.Advanced Imaging Techniques for Assessing Fat, Iron, and Fibrosis in Chronic Liver Disease
Sabarish NARAYANASAMY ; Manuela FRANCA ; Ilkay S. IDILMAN ; Meng YIN ; Sudhakar K. VENKATESH
Gut and Liver 2025;19(1):31-42
Imaging plays a critical role in the management of chronic liver disease (CLD) because it is a safe and painless method to assess liver health. The widely used imaging techniques include ultrasound, computed tomography and magnetic resonance imaging. These techniques allow the measurement of fat deposition, iron content, and fibrosis, replacing invasive liver biopsies in many cases. Early detection and treatment of fibrosis are crucial, as the disease can be reversed in its early stages. Imaging also aids in guiding treatment decisions and monitoring disease progression. In this review, we describe the most common imaging manifestations of liver disease and the current state-of-the-art imaging techniques for the evaluation of liver fat, iron, and fibrosis.
3.Developing an Explainable Artificial Intelligence System for the Mobile-Based Diagnosis of Febrile Diseases Using Random Forest, LIME, and GPT
Kingsley F. ATTAI ; Constance AMANNAH ; Moses EKPENYONG ; Daniel E. ASUQUO ; Oryina K. AKPUTU ; Okure U. OBOT ; Peterben C. AJUGA ; Jeremiah C. OBI ; Omosivie MADUKA ; Christie AKWAOWO ; Faith-Michael UZOKA
Healthcare Informatics Research 2025;31(2):125-135
Objectives:
This study proposes a mobile-based explainable artificial intelligence (XAI) platform designed for diagnosing febrile illnesses.
Methods:
We integrated the interpretability offered by local interpretable model-agnostic explanations (LIME) and the explainability provided by generative pre-trained transformers (GPT) to bridge the gap in understanding and trust often created by machine learning models in critical healthcare decision-making. The developed system employed random forest for disease diagnosis, LIME for interpretation of the results, and GPT-3.5 for generating explanations in easy-to-understand language.
Results:
Our model demonstrated robust performance in detecting malaria, achieving precision, recall, and F1-scores of 85%, 91%, and 88%, respectively. It performed moderately well in detecting urinary tract and respiratory tract infections, with precision, recall, and F1-scores of 80%, 65%, and 72%, and 77%, 68%, and 72%, respectively, maintaining an effective balance between sensitivity and specificity. However, the model exhibited limitations in detecting typhoid fever and human immunodeficiency virus/acquired immune deficiency syndrome, achieving lower precision, recall, and F1-scores of 69%, 53%, and 60%, and 75%, 39%, and 51%, respectively. These results indicate missed true-positive cases, necessitating further model fine-tuning. LIME and GPT-3.5 were integrated to enhance transparency and provide natural language explanations, thereby aiding decision-making and improving user comprehension of the diagnoses.
Conclusions
The LIME plots revealed key symptoms influencing the diagnoses, with bitter taste in the mouth and fever showing the highest negative influence on predictions, and GPT-3.5 provided natural language explanations that increased the reliability and trustworthiness of the system, promoting improved patient outcomes and reducing the healthcare burden.
4.Interactive Engagement with Self-Paced Learning Content in a Didactic Course
Nazlee SHARMIN ; Shahram HOUSHYAR ; Thomas R. STEVENSON ; Ava K. CHOW
Healthcare Informatics Research 2025;31(1):96-106
Objectives:
A growing number of health professional institutions around the world are embracing innovative technologies to increase student engagement, primarily to improve clinical and simulated learning experiences. Didactic learning is an essential component of dental and medical curricula. However, limited research is available regarding the implementation of technology-infused teaching in classroom settings. We developed self-paced interactive learning content using the HTML5 Package (H5P) to promote student engagement in a didactic course within a dental hygiene program.
Methods:
A total of 52 interactive artifacts were created and administered to students as supplementary learning material. A descriptive study was conducted to explore student perceptions and engagement with the H5P content, as well as to evaluate the impact of these artifacts on academic performance.
Results:
Students performed significantly better on exam questions associated with interactive H5P content posted in the learning management system compared to other questions. Most students were highly engaged with the H5P content during the week leading up to each summative assessment. However, two of the three students with the highest course grades demonstrated consistent engagement with this content throughout the course.
Conclusions
Our results highlight the effectiveness of interactive content created using the H5P platform in fostering student engagement. The development of self-paced interactive materials may benefit various aspects of didactic teaching, including both synchronous and asynchronous online learning.
5.Effectiveness of a low FODMAP diet and aerobic exercise in reducing epigastric symptoms among individuals with functional dyspepsia- A randomized controlled trial
Davis PRABHAKAR ; Kini R ; Premkumar K
International Journal of Gastrointestinal Intervention 2025;14(2):57-63
Background:
Recent studies recommended that addition of dietary modifications notably the low FODMAP (Fructo-Oligosaccharides, Di-, Monosaccharides, And Polyols) diet and regular aerobic exercise can provide effective symptom control in functional dyspepsia (FD). This study assessed the combined effects of low FODMAP diet and regular aerobic exercise on dyspeptic symptoms in patients with FD.
Methods:
This prospective randomized controlled trial was conducted among patients with FD where eligible participants were assigned in a 1:1 ratio to either the intervention group (a low FODMAP diet and a regular aerobic exercise along with conventional therapy) or the control group (conventional therapy alone) for 24 weeks. The Structured Assessment of Gastrointestinal symptom (SAGIS) score for assessing the gastrointestinal symptoms and the Short Form Nepean Dyspepsia Index (SF-NDI) for analyzing health-related quality of life (HRQOL) done at baseline, 12 and 24 weeks.
Results:
Overall, 70 patients were included in this study, 35 each in both arm with the mean ± standard deviation age of the patients was 43 ± 10 years. At baseline, the mean SAGIS score for the intervention arm was 54 ± 12.5 and the control arm was 50 ± 10 where the scores were comparable between the two groups. After 12 weeks, there was a significant change in the epigastric symptoms from baseline between both arms was –3.571 ± 1.044. Further, the mean difference of SAGIS score was –3.571 ± 1.044 (90% confidence interval [CI] –5.668 to –1.475, P = 0.001) and SF-NDI of –12.086 ± 1.394 (90% CI –14.892 to –9.280, P < 0.001). Thus, there was a statistically significant reduction in the SAGIS score and SF-NDI from baseline in the intervention arm when compared to the control arm (P < 0.05).
Conclusion
The combination of a low FODMAP diet and regular aerobic exercise was effective in reducing epigastric symptoms and improved the quality of life among individuals with FD compared with conventional therapy alone.
6.Analysis of the current status of red blood cell transfusion in very preterm infants from Chinese Neonatal Network in 2022
Yan MO ; Aimin QIAN ; Ruimiao BAI ; Shujuan LI ; Xiaoqing YU ; Jin WANG ; K. Shoo LEE ; Siyuan JIANG ; Qiufen WEI ; Wenhao ZHOU
Chinese Journal of Pediatrics 2025;63(1):55-61
Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.
7.Measuring energy expenditure in Göttingen Minipigs using indirect calorimetry: validation and methodological considerations
Simon K. BREDUM ; Julie JACOBSEN ; Susanna CIRERA ; Berit Ø. CHRISTOFFERSEN
Laboratory Animal Research 2025;41(1):104-118
Background:
Obesity affects nearly a billion people globally and is associated with various health consequences.Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate.
Results:
Sub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In substudy 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted R2 : 0.73–0.85).
Conclusions
The present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.
8.The Utilization of Navigation and Emerging Technologies With Endoscopic Spine Surgery: A Narrative Review
Abhinav K. SHARMA ; Rafael Garcia DE OLIVEIRA ; Siravich SUVITHAYASIRI ; Piya CHAVALPARIT ; Chien Chun CHANG ; Yong H. KIM ; Charla R. FISCHER ; Sang LEE ; Samuel CHO ; Jin-Sung KIM ; Don Young PARK
Neurospine 2025;22(1):105-117
Endoscopic spine surgery (ESS) is growing in popularity worldwide. An expanding body of literature demonstrates rapid functional recovery with reduced morbidity compared to open techniques. Both full endoscopic spine surgery, or uniportal endoscopy, and unilateral biportal endoscopy (UBE) can be employed in conjunction with various navigation and enabling technologies for assistance with localization of anatomic orientation and assessment of the intraoperative target spinal pathology. This review article describes various navigation technologies in ESS, including 2-dimensional (2D) fluoroscopic imaging, 2D fluoroscopic navigation, 3-dimensional C-arm navigation, augmented reality, and spinal robotics. Employment of enabling navigation and emerging technology with the registration of patient-specific anatomy enables clear delineation of anatomic landmarks and facilitation of a successful procedure. Additionally, avoidance of common pitfalls during use of navigation systems in ESS is discussed in this review.
9.Open Versus Minimally Invasive Spine Surgery in the Treatment of Single-Level Degenerative Lumbar Spondylolisthesis: An AO Spine Global Cross-Sectional Study
Luca AMBROSIO ; Sathish MUTHU ; Samuel K. CHO ; Micheal S. VIRK ; Juan P. CABRERA ; Patrick C. HSIEH ; Andreas K. DEMETRIADES ; Stipe ĆORLUKA ; S. Tim YOON ; Gianluca VADALÀ ;
Neurospine 2025;22(1):40-47
Objective:
This study aims to assess global trends in the use of open surgery versus minimally invasive surgery (MIS) for the treatment of single-level L4–5 degenerative lumbar spondylolisthesis (DLS).
Methods:
A cross-sectional online survey issued by the AO Spine Knowledge Forum Degenerative was conducted among AO Spine members between July and September 2023. Participants were presented with 3 clinical cases of L4–5 grade 1 DLS, each with varying degrees of stenosis and instability. The survey captured surgeon demographics and preferences for open versus MIS approaches. Statistical analysis, including chi-square tests and logistic regression, was performed to explore associations between surgical choices and surgeon demographics.
Results:
A total of 943 surgeons responded, with 479 completing the survey. Open surgery was the preferred approach in all 3 cases (58.8%, 57.3%, and 42.4%, respectively), particularly in cases involving central and bilateral foraminal stenosis. MIS was the second most common choice, particularly for unilateral foraminal stenosis with mild instability (38.8%). Surgeons’ preferences varied significantly by region, age, and fellowship training, with younger and fellowship-trained surgeons more likely to prefer MIS.
Conclusion
The study highlights the continued predominance of open surgery for DLS, especially in complex cases, despite the growing acceptance of MIS. Significant regional and demographic variations in surgical preferences suggest the need for tailored guidelines and standardized training protocols to optimize patient outcomes. Future research should focus on the long-term efficacy of these approaches and the impact of evolving technologies on surgical decision-making.
10.Effects of Combined Exercise Training on Symptoms and Physical Fitness in Young Adults with Mild Long COVID
Tae Gu CHOI ; Jae Yeop KIM ; Ho Jeong MIN ; Hyun Jeong KIM ; Kanokwan BUNSAWAT ; Setor K KUNUTSOR ; Kevin S HEFFERNAN ; Sae Young JAE
The Korean Journal of Sports Medicine 2025;43(1):1-12
Purpose:
The aim of this study was to examine whether a combined exercise (EX), including aerobic, resistance, and inspiratory muscle training, reduces fatigue and dyspnea, improves physical fitness, and if increased physical fitness after exercise is associated with attenuating symptoms in young adults with mild long coronavirus disease (COVID) symptoms.
Methods:
Twenty-eight young adults (aged 23±4 years) with long COVID were randomly assigned to either the EX group (n=14), which underwent aerobic, resistance, and inspiratory muscle training three times per week for 8 weeks, or the control (CON) group (n=14). Symptoms of dyspnea and fatigue were assessed using self-report questionnaires.Cardiorespiratory fitness was directly measured during cardiopulmonary exercise testing, while muscle strength was measured by isokinetic muscle testing. These variables were measured before and after the exercise intervention.
Results:
Compared to the CON group, the EX group showed improvements in symptoms of fatigue and dyspnea, maximal oxygen consumption (VO2peak ), and peak torque, with significant interaction effects observed (p< 0.05). The EX group exhibited a mean difference of 2.9 mL/kg/min in VO2peak (95% confidence interval [CI], 1.8−4.0) and 13.0 Nm (95% CI, 6.1−19.8) in peak torque compared to the CON group (p<0.05). Improvements in VO2peak were negatively associated with attenuations in both fatigue and dyspnea after the exercise intervention (p<0.05).
Conclusion
These findings indicate that EX training can effectively alleviate symptoms and improve physical fitness in young adults with mild long COVID. Structured exercise training may serve as an effective intervention to improve the health of those with long COVID.

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