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12 pages, 560 KiB  
Article
Association of Dipeptidyl Peptidase-4 Inhibitor Use with COVID-19 Mortality in Diabetic Patients: A Nationwide Cohort Study in Korea
by Jung Wan Park, Mi Kyung Kwak, Samel Park, Nam Hun Heo and Eun Young Lee
J. Clin. Med. 2025, 14(16), 5815; https://doi.org/10.3390/jcm14165815 (registering DOI) - 17 Aug 2025
Abstract
Background/Objectives: Patients with diabetes mellitus face increased risk of severe outcomes and mortality from COVID-19. Dipeptidyl peptidase-4 (DPP-4) inhibitors, widely used antidiabetic agents, are hypothesized to affect COVID-19 outcomes via anti-inflammatory and immune-modulating mechanisms. However, real-world evidence, especially in Korean populations, remains limited. [...] Read more.
Background/Objectives: Patients with diabetes mellitus face increased risk of severe outcomes and mortality from COVID-19. Dipeptidyl peptidase-4 (DPP-4) inhibitors, widely used antidiabetic agents, are hypothesized to affect COVID-19 outcomes via anti-inflammatory and immune-modulating mechanisms. However, real-world evidence, especially in Korean populations, remains limited. Methods: We conducted a retrospective cohort study using Korea’s nationwide Health Insurance Review and Assessment (HIRA) database. Adults with diabetes hospitalized for confirmed COVID-19 between 1 March 2021, and 28 February 2022, were included and stratified by DPP-4 inhibitor use. The primary outcome was 30-day all-cause mortality. Cox proportional hazards models adjusted for age, sex, and comorbidities estimated hazard ratios (HRs). Subgroup analyses examined angiotensin receptor blocker (ARB) and insulin use. Results: Among 16,134 eligible patients, 7082 received DPP-4 inhibitors. The 30-day mortality rate was lower in DPP-4 inhibitor users than non-users (4.3% vs. 10.3%, p < 0.0001). Adjusted analyses showed DPP-4 inhibitor use was associated with reduced mortality risk (adjusted HR: 0.455; 95% CI: 0.414–0.499). Subgroup analyses yielded consistent results across ARB and insulin users. Kaplan-Meier curves demonstrated higher survival probability in the DPP-4 inhibitor group. Conclusions: In this nationwide Korean cohort, DPP-4 inhibitor use was associated with lower mortality among hospitalized diabetic patients with COVID-19. While these findings suggest a potential benefit, causality cannot be confirmed due to the observational design. Prospective studies are needed to verify these associations and explore underlying mechanisms. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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20 pages, 826 KiB  
Article
Relative Grip Strength as a Screening Indicator for Metabolic Syndrome in Korean Adults: A Cross-Sectional Study Using Data from KNHANES
by Jongsuk Park and Sangho Kim
Medicina 2025, 61(8), 1473; https://doi.org/10.3390/medicina61081473 (registering DOI) - 16 Aug 2025
Abstract
Background and Objectives: This study aimed to assess the association between relative grip strength (RGS) and metabolic syndrome (MetS) in Korean adults and to explore sex- and age-specific cutoff values for screening purposes. Materials and Methods: This cross-sectional study analyzed data [...] Read more.
Background and Objectives: This study aimed to assess the association between relative grip strength (RGS) and metabolic syndrome (MetS) in Korean adults and to explore sex- and age-specific cutoff values for screening purposes. Materials and Methods: This cross-sectional study analyzed data from 12,072 Korean adults (aged 19–64 years) who participated in the 2017–2019 Korea National Health and Nutrition Examination Survey. Receiver operating characteristic (ROC) curve analysis was performed stratified by sex and age group, and participants were categorized into adequate (ARG) and low (LRG) RGS groups. Multivariable logistic regression was used to examine the association between RGS (as both categorical and continuous variables) and MetS, adjusting for lifestyle and behavioral covariates. Results: The RGS demonstrated moderate discriminatory power for MetS, with area under the curve (AUC) values ranging from 0.601 to 0.742. Age- and sex-specific cutoff values for RGS progressively decreased with age. Individuals in the LRG group had significantly higher odds of MetS across all age and sex groups. The LRG group had significantly greater odds of MetS in nearly all subgroups (e.g., women aged 20–39 years: odds ratio [OR] = 6.846; men: OR = 3.502). As a continuous variable, each 0.1-unit increase in RGS was associated with a 22.1–33.4% reduction in the odds of MetS (p < 0.001). Conclusions: RGS is inversely associated with MetS, particularly in women and younger adults. Although its discriminatory ability is moderate, the RGS may serve as a simple and accessible screening indicator to help identify individuals with an increased metabolic risk. Full article
(This article belongs to the Section Epidemiology & Public Health)
16 pages, 441 KiB  
Article
Correlations Between Immuno-Inflammatory Biomarkers and Hematologic Indices Stratified by Immunologic SNP Genotypes
by Simona-Alina Abu-Awwad, Ahmed Abu-Awwad, Simona Sorina Farcas, Cristina Annemari Popa, Paul Tutac, Iuliana Maria Zaharia, Claudia Alexandrina Goina, Alexandra Mihailescu and Nicoleta Andreescu
J. Clin. Med. 2025, 14(16), 5792; https://doi.org/10.3390/jcm14165792 - 15 Aug 2025
Abstract
Background/Objectives: Chronic low-grade inflammation drives cardiometabolic risk; functional SNPs may influence individual cytokine and hematologic phenotypes. We investigated genotype-specific relationships between circulating immuno-inflammatory biomarkers and routine blood indices in apparently healthy adults. Methods: In this cross-sectional study, 155 fasting volunteers (26–72 [...] Read more.
Background/Objectives: Chronic low-grade inflammation drives cardiometabolic risk; functional SNPs may influence individual cytokine and hematologic phenotypes. We investigated genotype-specific relationships between circulating immuno-inflammatory biomarkers and routine blood indices in apparently healthy adults. Methods: In this cross-sectional study, 155 fasting volunteers (26–72 years) were genotyped for IL1RN rs1149222 and TNF-proximal rs2071645. Serum IL-1β, TNF-α, oxidized LDL (oxLDL) and C-reactive protein (CRP) were quantified by ELISA, and complete blood counts were recorded simultaneously. Genotype effects were tested with ANOVA/Kruskal–Wallis; Spearman correlations and age-, sex-, BMI-adjusted linear models explored genotype-stratified associations. Results: Among 155 adults, IL1RN rs1149222 significantly affected IL-1β (TT > TG ≈ GG; ANOVA p = 0.042) and oxLDL (overall p = 0.036), with the clearest difference between heterozygotes and major-allele homozygotes. The same variant produced a modest fall in erythrocyte count and hemoglobin restricted to heterozygotes (RBC p = 0.036; Hb p = 0.041). TNF-proximal rs2071645 strongly raised TNF-α (GG > GA > AA; p < 0.0001) and led to a moderate oxLDL increase, driven by GA versus AA carriers (pairwise p = 0.013), while leaving red-cell indices and CRP unchanged. Baseline leukocyte counts, differentials and derived ratios showed no genotype dependence, and multivariable models revealed no epistatic interaction between the two loci. Conclusions: IL1RN rs1149222 and TNF-related rs2071645 generate two independent inflammatory signatures—an IL-1β-oxidative axis linked to mild erythropoietic suppression and a TNF-lipid axis without hematologic shift. Integrating targeted genotyping with inexpensive hematologic ratios may refine early risk stratification and guide tailored preventive strategies in ostensibly healthy populations. Full article
(This article belongs to the Section Hematology)
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13 pages, 5754 KiB  
Article
Increasing Prevalence of Potential Vitamin D Toxicity and Its Risk Factors in Korea: A Large Population-Based Study
by Rihwa Choi, Gayoung Chun, Sung-Eun Cho, Sunhyun Ahn, Sang Gon Lee and Eun Hee Lee
Nutrients 2025, 17(16), 2614; https://doi.org/10.3390/nu17162614 - 12 Aug 2025
Viewed by 334
Abstract
Background/Objectives: Vitamin D plays an important role in a wide range of health outcomes, including immune regulation, bone metabolism, cardiovascular health, and cancer prevention. However, recent data on the prevalence and risk factors for elevated serum 25-hydroxyvitamin D [25(OH)D] concentrations—indicative of potential [...] Read more.
Background/Objectives: Vitamin D plays an important role in a wide range of health outcomes, including immune regulation, bone metabolism, cardiovascular health, and cancer prevention. However, recent data on the prevalence and risk factors for elevated serum 25-hydroxyvitamin D [25(OH)D] concentrations—indicative of potential vitamin D toxicity—remain limited in Korea. Methods: We conducted a retrospective analysis of laboratory data from individuals who underwent serum 25(OH)D testing between 2020 and 2022. Potential vitamin D toxicity was defined as serum 25(OH)D levels exceeding 50, 100, or 150 ng/mL. The prevalence of potential toxicity was examined by age, sex, test month, and year. Results: A total of 1,198,947 individuals (mean age, 45.7 ± 19.4 years; 31.6% male) were included in the study. The prevalence of serum 25(OH)D > 50 ng/mL increased from 4.41% in 2020 to 6.21% in 2022, and that of >100 ng/mL rose from 0.09 to 0.12% over the same period. The proportions exceeding 50 and 100 ng/mL also rose significantly (p < 0.05), while >150 ng/mL remained rare (0.01%) and stable. Elevated 25(OH)D concentrations were more frequently observed among females, children aged 0–9 years, and adults aged ≥50 years (adjusted odds ratios for multivariable logistic regression > 1.0, p < 0.05). Conclusions: Although the prevalence of potential vitamin D toxicity remains low, its continuous upward trend highlights the need for increased public awareness, clinical monitoring, and guideline-based supplementation strategies to prevent inadvertent vitamin D intoxication, particularly in the aging population. Full article
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14 pages, 233 KiB  
Article
Ten-Year Trends in Hepatocellular Carcinoma Mortality: Examining the Interaction Between Fibrosis Score and Patient Age
by Ayrton Bangolo, Hadrian Hoang-Vu Tran, Budoor Alqinai, Rishabh Goyal, Shehwar Ahmed, Aamna Qasim, Gabriela Rojas, Shubham Madan, Helena Barbosa, Zainab Mustafa, Risham Waseem, Gabriel Ingersoll, Hamza Khan, Alison Guzzetti, Jonathan Daniel, Samiya Parkar, Aakriti Tiwari, Sarah Lafleur, Rajasekhar Cingapagu, Saliha Y. Amasyali, Eric Pin-Shiuan Chen and Simcha Weissmanadd Show full author list remove Hide full author list
Diseases 2025, 13(8), 256; https://doi.org/10.3390/diseases13080256 - 12 Aug 2025
Viewed by 231
Abstract
Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only [...] Read more.
Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients. Full article
11 pages, 634 KiB  
Article
Bioelectrical Impedance Profiling to Estimate Neuropathic and Vascular Risk in Patients with Type 2 Diabetes Mellitus
by Elizabeth Quiroga-Torres, Fernanda Marizande, Cristina Arteaga, Marcelo Pilamunga, Lisbeth Josefina Reales-Chacón, Silvia Bonilla, Doménica Robayo, Sara Buenaño, Sebastián Camacho, William Galarza and Alberto Bustillos
Diagnostics 2025, 15(16), 2005; https://doi.org/10.3390/diagnostics15162005 - 11 Aug 2025
Viewed by 492
Abstract
Background/Objectives: Microvascular complications are a major source of disability in type 2 diabetes mellitus (T2DM). We investigated whether body composition indices derived from multifrequency bioelectrical impedance analysis (BIA) independently predict neuropathy, retinopathy, nephropathy, and stroke, and whether they improve risk discrimination beyond the [...] Read more.
Background/Objectives: Microvascular complications are a major source of disability in type 2 diabetes mellitus (T2DM). We investigated whether body composition indices derived from multifrequency bioelectrical impedance analysis (BIA) independently predict neuropathy, retinopathy, nephropathy, and stroke, and whether they improve risk discrimination beyond the established clinical variables. Methods: In this cross-sectional analytical study (March 2024–February 2025), 124 adults with T2DM ≥ 12 months attending the outpatient diabetes clinic of the Universidad Técnica de Ambato (Ecuador) were enrolled. After an overnight fast and 15 min supine rest, thirteen whole-body BIA metrics including skeletal muscle mass (SMM), intracellular water (ICW), phase angle (PhA), and visceral fat area (VFA) were obtained with a segmental analyzer (InBody S10). Complications were ascertained with standard clinical and laboratory protocols. Principal component analysis (PCA) summarized the correlated BIA measures; multivariable logistic regression (adjusted for age, sex, diabetes duration, HbA1c, BMI, and medication use) generated odds ratios (ORs) per standard deviation (SD). Discrimination was assessed with bootstrapped receiver-operating characteristic curves. Results: The first principal component, driven by SMM, ICW, and PhA, accounted for a median 68% (range 65–72%) of body composition variance across all complications. Each SD increase in SMM lowered the odds of neuropathy (OR 0.54, 95% CI 0.41–0.71) and nephropathy (OR 0.70, 0.53–0.92), whereas VFA raised the risk of neuropathy (OR 1.55, 1.22–1.97) and retinopathy (OR 1.47, 1.14–1.88). PhA protected most strongly against stroke (OR 0.55, 0.37–0.82). Composite models integrating SMM, PhA, and adiposity indices achieved AUCs of 0.79–0.85, outperforming clinical models alone (all ΔAUC ≥ 0.05) and maintaining good calibration (Hosmer–Lemeshow p > 0.20). Optimal probability cut-offs (0.39–0.45) balanced sensitivity (0.74–0.80) and specificity (0.68–0.72). Conclusions: A lean tissue BIA signature (higher SMM, ICW, PhA) confers independent protection against neuropathy, retinopathy, nephropathy, and stroke, whereas visceral adiposity amplifies the risk. Because the assessment is rapid, inexpensive, and operator-independent, routine multifrequency BIA can be embedded into diabetes clinics to triage patients for early specialist referral and to monitor interventions aimed at preserving muscle and reducing visceral fat, thereby enhancing microvascular risk management in T2DM. Full article
(This article belongs to the Special Issue Advances in Modern Diabetes Diagnosis and Treatment Technology)
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17 pages, 524 KiB  
Article
Associations Between Self-Perceived Psychosocial Stress and Markers of Adiposity in Ga Mashie, Urban Ghana: Evidence from a Cross-Sectional Population-Based Survey
by Emeline Rougeaux, Samuel Amon, Leonard Baatiema, Sandra Boatemaa Kushitor, Mawuli Komla Kushitor, Sedzro Kojo Mensah, Rolando Leiva-Granados, Akanksha A. Marphatia, Jonathan C. K. Wells, Carlos Salvador Grijalva-Eternod, Irene Akwo Kretchy and Edward Fottrell
Obesities 2025, 5(3), 60; https://doi.org/10.3390/obesities5030060 - 9 Aug 2025
Viewed by 176
Abstract
Prior research from Ghana suggests psychosocial stress is associated with lower body mass index (BMI) and waist circumference (WC), both markers of adiposity, contrasting with meta-analyses showing positive associations in other settings. This study aimed to explore how stress was associated with markers [...] Read more.
Prior research from Ghana suggests psychosocial stress is associated with lower body mass index (BMI) and waist circumference (WC), both markers of adiposity, contrasting with meta-analyses showing positive associations in other settings. This study aimed to explore how stress was associated with markers of adiposity in urban Ghanaian adults. Data included 854 adults from the Contextual Awareness, Response and Evaluation Diabetes in Ghana survey carried out in November–December 2022 in Ga Mashie, a deprived area of the capital Accra. Associations between self-perceived stress (Perceived Stress Scale 10, categorized into low and average–high stress) and BMI or WC-for-height ratio (WHR) were assessed using linear regression. Results were adjusted for survey design and confounders and stratified by sex. Greater stress was associated with higher BMI and WHR in females (adjusted coeff. [95% CI]: BMI: 2.3 [0.5, 4.0], WHR: 0.03 [0.00, 0.06]). No associations were found in males. These findings highlight the need to understand the complex interactions between gender, stress, and increasing burdens of obesity and other associated non-communicable diseases in urban African settings, with a view to designing context-specific interventions to reduce risk. Full article
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18 pages, 926 KiB  
Article
A Population-Based Study of Sex Differences in Cardiovascular Disease Mortality Among Adults with Ocular Cancer in the United States, 2000–2021
by Duke Appiah, Abdulkader Almosa, Eli Heath, Noah De La Cruz and Obadeh Shabaneh
Curr. Oncol. 2025, 32(8), 447; https://doi.org/10.3390/curroncol32080447 - 8 Aug 2025
Viewed by 254
Abstract
Little is known about the manifestation of cardiovascular diseases (CVD) among individuals with ocular cancer (OC), a population for whom reports on sex-based differences in survival remain inconsistent. We evaluated the occurrence of CVD mortality after the diagnosis of OC in the United [...] Read more.
Little is known about the manifestation of cardiovascular diseases (CVD) among individuals with ocular cancer (OC), a population for whom reports on sex-based differences in survival remain inconsistent. We evaluated the occurrence of CVD mortality after the diagnosis of OC in the United States. We used data from 11,460 adults diagnosed with OC from 2000 to 2021 who were ≥18 years and were enrolled in the Surveillance, Epidemiology, and End Results program. We used competing risk models to estimate hazard ratios (HR) and 95% confidence intervals (CI). About 55% of adults were male, with uveal melanoma being the most common OC (72.1%). During a median follow-up of 5.4 years, 4561 deaths occurred, with 15% attributable to CVD. In models adjusted for sociodemographic and clinico-pathophysiological factors, male adults had elevated risk for CVD mortality (HR: 1.54, 95%CI: 1.31–1.81). The sex difference in CVD mortality was more prominent for adults diagnosed with OC before 65 years of age (HR: 2.15; 95%CI: 1.48–3.11). These associations remained largely unchanged in propensity score analysis. In this study of adults with OC, CVD deaths were higher among young and middle-aged males. Implementation of optimal cardiovascular health interventions after diagnosis of OC, especially among men, holds promise in enhancing survival in this population. Full article
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21 pages, 583 KiB  
Article
Gender Differences in the Relationship Between Fatigue, Different Types of Physical Activity, Postural Changes, and Sleep Quality in University Students—Part II Analyses from a Cross-Sectional Study
by Verner Marijančić, Silvije Šegulja, Mirela Vučković, Ivana Sović, Stanislav Peharec, Tanja Grubić Kezele and Gordana Starčević-Klasan
J. Funct. Morphol. Kinesiol. 2025, 10(3), 307; https://doi.org/10.3390/jfmk10030307 - 8 Aug 2025
Viewed by 331
Abstract
Background: Fatigue can be a useful tool to understand the effects of physical activity (PA) and sedentary behavior on musculoskeletal health in university students. Methods: The aim of this cross-sectional study was to examine gender differences in the relationships between fatigue and specific [...] Read more.
Background: Fatigue can be a useful tool to understand the effects of physical activity (PA) and sedentary behavior on musculoskeletal health in university students. Methods: The aim of this cross-sectional study was to examine gender differences in the relationships between fatigue and specific types and levels of PA, posture, sleep quality (SQ), and non-specific low back pain (NS-LBP) in young adult university students aged 18–25 years. A total of 180 students completed all required tests. Results: Female students had higher total fatigue as they generally engaged in more PA in contrast to male students, who had higher total fatigue when they engaged in less moderate and less vigorous PA. With increasing sedentary behavior, overall fatigue was pronounced in both sexes, although female students spent significantly more time sitting. Poorer SQ correlated with NS-LBP and higher levels of sleep-related fatigue in female students. Males with pronounced hypekyphosis and females with pronounced lordosis were more fatigued. In addition, fatigue was more pronounced in female students with a higher extensor/flexor ratio, suggesting that trunk extensors are more fatigued due to the need to maintain lumbar spine stability. Conclusions: Our findings suggest that the choice of PA should be gender-specific to prevent chronic musculoskeletal disorders and fatigue in young adult university students. Full article
(This article belongs to the Special Issue Physical Activity for Optimal Health: 2nd Edition)
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12 pages, 856 KiB  
Article
Impact of Sex on Lung Function in Adult Langerhans Cell Histiocytosis
by Antonio Fabozzi, Gianluca Paciucci, Giulia de Rose, Roberto Romiti, Giovanna Palumbo, Gregorino Paone, Matteo Bonini and Paolo Palange
Life 2025, 15(8), 1258; https://doi.org/10.3390/life15081258 - 7 Aug 2025
Viewed by 558
Abstract
Background: Langerhans Cell Histiocytosis (LCH) is a rare histiocytic hematological disorder that frequently involves the lungs. Due to a lack of data about sex-related differences in LCH, the aim of this study is to evaluate sex-related differences in pulmonary function in a cohort [...] Read more.
Background: Langerhans Cell Histiocytosis (LCH) is a rare histiocytic hematological disorder that frequently involves the lungs. Due to a lack of data about sex-related differences in LCH, the aim of this study is to evaluate sex-related differences in pulmonary function in a cohort of patients with LCH. Methods: We retrospectively analyzed data from 79 adult patients diagnosed with LCH. Demographic, clinical, and spirometric data were collected and compared by sex. Continuous variables were analyzed using the Mann–Whitney test and categorical variables were analyzed with the Chi-square test. Results: Out of 79 patients, 47 (59.5%) were females and 32 (40.5%) were males. Women showed significantly lower diffusing capacity of the lungs for carbon monoxide (DLCO%) and lower diffusing capacity of the lungs for carbon monoxide per unit of alveolar volume (DLCO/VA%) compared to men. Females showed a trend toward lower small airway indices, including maximal expiratory flow at 25 (MEF25%) and forced expiratory flow at 25–75% (FEF25–75%), though this was not statistically significant, while the residual volume-to-total lung capacity (RV/TLC) ratio was significantly higher in women. Among the functional parameters, DLCO% showed the highest accuracy (AUC 0.70) in the identification of lung involvement after multivariate regression analysis. Conclusions: Our findings suggest that the combination of lower gas exchange efficiency and increased peripheral air trapping secondary to small airway involvement in female patients may reflect the presence of a distinct functional LCH phenotype in women characterized by early small airway involvement and altered ventilation–perfusion dynamics, which may influence the clinical management of these patients. Furthermore, the moderate predictive value of DLCO% for lung involvement at baseline in LCH women suggests that DLCO may contribute to the detection of LCH women with lung involvement, although it should not be considered a definitive diagnostic test without a prospective and independent external validation. Full article
(This article belongs to the Section Medical Research)
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23 pages, 3243 KiB  
Article
Design of Experiments Leads to Scalable Analgesic Near-Infrared Fluorescent Coconut Nanoemulsions
by Amit Chandra Das, Gayathri Aparnasai Reddy, Shekh Md. Newaj, Smith Patel, Riddhi Vichare, Lu Liu and Jelena M. Janjic
Pharmaceutics 2025, 17(8), 1010; https://doi.org/10.3390/pharmaceutics17081010 - 1 Aug 2025
Viewed by 374
Abstract
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription [...] Read more.
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article
(This article belongs to the Special Issue Quality by Design in Pharmaceutical Manufacturing)
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13 pages, 873 KiB  
Article
Integrating Clinical Parameters into Thyroid Nodule Malignancy Risk: A Retrospective Evaluation Based on ACR TI-RADS
by Nikolaos Angelopoulos, Ioannis Androulakis, Dimitrios P. Askitis, Nicolas Valvis, Rodis D. Paparodis, Valentina Petkova, Anastasios Boniakos, Dimitra Zianni, Andreas Rizoulis, Dimitra Bantouna, Juan Carlos Jaume and Sarantis Livadas
J. Clin. Med. 2025, 14(15), 5352; https://doi.org/10.3390/jcm14155352 - 29 Jul 2025
Viewed by 576
Abstract
Background/Objectives: Thyroid nodules are commonly found through sensitive imaging methods like ultrasonography. While most nodules are benign and asymptomatic, certain characteristics may indicate malignancy, prompting fine needle aspiration biopsy. Factors like age and gender affect cancer risk, complicating ultrasound-based risk systems. We [...] Read more.
Background/Objectives: Thyroid nodules are commonly found through sensitive imaging methods like ultrasonography. While most nodules are benign and asymptomatic, certain characteristics may indicate malignancy, prompting fine needle aspiration biopsy. Factors like age and gender affect cancer risk, complicating ultrasound-based risk systems. We aimed to determine whether the cytological malignancy rate of thyroid nodules could be adjusted for several clinical parameters. Methods: Data from patients aged 18 and above with thyroid nodules assessed via fine needle aspiration (FNA) were retrospectively reviewed. Malignancy classification was based on cytopathology and histopathology results. The study examined how various clinical parameters, adjusted for the ACR TI-RADS category, affected thyroid nodule malignancy rates, including age, sex, Body Mass Index (BMI), nodule size, presence of autoimmunity, and thyroxine therapy. Additionally, we analyzed the performance of ACR TI-RADS in predicting malignant cytology across different age subgroups of thyroid nodules. Results: The study included 1128 thyroid nodules from 1001 adult patients, with a median age of 48 years and predominantly female (76.68%). Malignancy rates varied across ACR TI-RADS categories, with higher rates associated with larger nodules and younger age groups. Age emerged as a significant predictor of malignancy, with a consistent decrease in the odds ratio for malignant cytology with advancing age across all ACR TI-RADS categories, indicating its potential utility in risk assessment alongside nodule size and sex. Conclusions: Raising the size threshold for recommending FNA of TR3-3 nodules and incorporating patients’ age and gender into the evaluation process could enhance the system’s accuracy in assessing thyroid nodules and guiding clinical management decisions. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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13 pages, 1017 KiB  
Article
Elevated Serum TNF-α/IL-1β Levels and Under-Nutrition Predict Early Mortality and Hospital Stay Burden in Pulmonary Tuberculosis
by Ionut-Valentin Stanciu, Ariadna-Petronela Fildan, Adrian Cosmin Ilie, Cristian Oancea, Livia Stanga, Emanuela Tudorache, Felix Bratosin, Ovidiu Rosca, Iulia Bogdan, Doina-Ecaterina Tofolean, Ionela Preotesoiu, Viorica Zamfir and Elena Dantes
J. Clin. Med. 2025, 14(15), 5327; https://doi.org/10.3390/jcm14155327 - 28 Jul 2025
Viewed by 359
Abstract
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised [...] Read more.
Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL−1 vs. 16.2 pg mL−1; p = 0.009) and IL-1β (5.34 pg mL−1 vs. 3.67 pg mL−1; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL−1) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL−1 rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m−2) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article
(This article belongs to the Section Infectious Diseases)
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20 pages, 1699 KiB  
Article
Cross-Sectional Study of Variations in Cephalometric Parameters in Arab Orthodontic Patients with Skeletal Class I and II
by Kareem Midlej, Peter Proff, Nezar Watted and Fuad A. Iraqi
J. Clin. Med. 2025, 14(15), 5292; https://doi.org/10.3390/jcm14155292 - 26 Jul 2025
Viewed by 380
Abstract
Objectives: Previous literature has already discussed the effects of age and sex on the diagnosis and treatment of malocclusion problems. However, this effect varies among different ethnic groups. These differences have not yet been investigated in many populations, such as Arab orthodontic patients [...] Read more.
Objectives: Previous literature has already discussed the effects of age and sex on the diagnosis and treatment of malocclusion problems. However, this effect varies among different ethnic groups. These differences have not yet been investigated in many populations, such as Arab orthodontic patients and residents of Israel. Therefore, it is crucial to understand such variations in specific populations for better diagnosis and treatment. The main aim of this study is to provide novel knowledge concerning skeletal classes I and II among a cohort of Arab patients who are citizens of Israel. We used parameters obtained from lateral cephalograms to understand the variations among different sex and age subgroups. We also examined the correlations and performed principal component analysis (PCA). Methods: This study was based on the coded records of 394 Arab patients diagnosed with skeletal Class I occlusion (SCIO) or skeletal Class II malocclusion (SCIIMO), according to the individualized ANB (Calculated_ANB) of Panagiotidis and Witt. Results: Among patients with SCIO, males had a significantly more horizontal growth pattern (PFH/AFH) and anterior mandible rotation (ML-NSL) than females. Regarding patients with SCIIMO, female adults had more hyperdivergent jaw bases than adolescents (ML-NL) and a more posteriorly rotated mandible (ML-NSL). Spearman’s analysis revealed many significant correlations, like Calculated_ANB, ANB angle, and Wits appraisal. The PCA results showed a remarkable ability to explain 88.6% of the sample variance using four principal components. Conclusions: This research revealed new information regarding Arab orthodontic patients diagnosed with skeletal class I or II. The results demonstrate the differences between the two classes. In addition, this study demonstrated the variation and correlation of cephalometric parameters among different sex and age subgroups in skeletal class I and II Arab patients, especially considering Calculated_ANB. Therefore, this study highlights the need to consider these differences when diagnosing patients and to distinguish the differences across different sex and age subgroups in the diagnosis and treatment process. Furthermore, the PCA results showed the importance of ML-NSL, SN-Pg, PFH/AFH ratio, and NL-ML in explaining the data variance. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
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11 pages, 833 KiB  
Article
The Association Between Serum Alpha-Carotene and Root Caries in U.S. Adults: A Cross-Sectional Study
by Michelle Zak, Yash Brahmbhatt, Abdullah Muhsain, Balqais AlShammari, Badriyah Mandani, Meshari Alenezi, Abdulrahman Salem and Hend Alqaderi
Life 2025, 15(8), 1188; https://doi.org/10.3390/life15081188 - 26 Jul 2025
Viewed by 405
Abstract
Root caries is a form of decay affecting root surfaces of teeth, often exacerbated by periodontal disease, reduced salivary flow, and compromised mucosal health, all factors strongly influenced by nutrition. Despite this connection, few studies have addressed the role of vitamins in oral [...] Read more.
Root caries is a form of decay affecting root surfaces of teeth, often exacerbated by periodontal disease, reduced salivary flow, and compromised mucosal health, all factors strongly influenced by nutrition. Despite this connection, few studies have addressed the role of vitamins in oral health. This study examines the association between serum levels of alpha-carotene (α-carotene), a potent antioxidant and proxy for vitamin A, and the experience of root caries. Using data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional analysis and applied a weighted multiple logistic regression model, adjusting for potential confounders including age, sex, education level, race, income-to-poverty ratio, and presence of gum disease. Higher serum α-carotene levels were inversely associated with root caries. Each unit increase in serum α-carotene was associated with a 9% decrease in the odds of having root caries (OR = 0.91; 95% CI: 0.86–0.97; p = 0.004). In this nationally representative sample of U.S. adults, lower serum α-carotene levels were associated with a higher prevalence of root caries. These findings highlight the potential role of nutritional assessment and integration in oral health. Longitudinal and mechanistic studies are needed to confirm and further explore α-carotene’s effects on oral health. Full article
(This article belongs to the Section Physiology and Pathology)
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