Antimicrobial resistance has intensified the search for alternatives to conventional antibiotics, particularly against multidrug-resistant bacterial pathogens that increasingly compromise treatment outcomes in hospitals and community settings. This narrative review examines bacteriophage therapy as an alternative for combating multidrug-resistant bacteria. Recent literature is discussed thematically, with emphasis on original studies, clinical datasets, translational experiments, and regulatory documents. The current evidence base consists predominantly of compassionate-use reports, small cohorts, and early-phase trials, including CRISPR-enhanced and inhaled phage platforms, which report safety observations, compartment-specific responses, and microbiome effects in individual studies. Mechanistic considerations discussed in the review include route-specific delivery, phage–host ecological interactions, resistance trade-offs, and phage–antibiotic synergy. While microbiological and clinical responses have been reported in individual studies, no confirmatory randomized trial has demonstrated clinical efficacy for any phage therapy indication. Manufacturing, standardization, and regulatory pathways for scaled deployment also remain unresolved. Regulatory developments in Europe, the United Kingdom, the United States, and Australia remain heterogeneous and predominantly access-based or compassionate-use-based rather than approval-based. Specific technical challenges include incomplete standardization of susceptibility testing and the need for robust monitoring of immune neutralization, endotoxin burden, and long-term ecological effects. Routine clinical adoption of phage therapy will ultimately depend on outcomes of adequately powered confirmatory trials, alongside resolution of manufacturing, regulatory, and standardization challenges.
Antimicrobial resistance has intensified the search for alternatives to conventional antibiotics, particularly against multidrug-resistant bacterial pathogens that increasingly compromise treatment outcomes in hospitals and community settings. This narrative review examines bacteriophage therapy as an alternative for combating multidrug-resistant bacteria. Recent literature is discussed thematically, with emphasis on original studies, clinical datasets, translational experiments, and regulatory documents. The current evidence base consists predominantly of compassionate-use reports, small cohorts, and early-phase trials, including CRISPR-enhanced and inhaled phage platforms, which report safety observations, compartment-specific responses, and microbiome effects in individual studies. Mechanistic considerations discussed in the review include route-specific delivery, phage–host ecological interactions, resistance trade-offs, and phage–antibiotic synergy. While microbiological and clinical responses have been reported in individual studies, no confirmatory randomized trial has demonstrated clinical efficacy for any phage therapy indication. Manufacturing, standardization, and regulatory pathways for scaled deployment also remain unresolved. Regulatory developments in Europe, the United Kingdom, the United States, and Australia remain heterogeneous and predominantly access-based or compassionate-use-based rather than approval-based. Specific technical challenges include incomplete standardization of susceptibility testing and the need for robust monitoring of immune neutralization, endotoxin burden, and long-term ecological effects. Routine clinical adoption of phage therapy will ultimately depend on outcomes of adequately powered confirmatory trials, alongside resolution of manufacturing, regulatory, and standardization challenges.
Hypertension and obesity frequently coexist and increase cardiovascular risk through vascular dysfunction, autonomic imbalance, and metabolic dysregulation. This study investigated the effects of an 8-week mat Pilates program on body composition, blood pressure, vascular function, autonomic nervous system activity, and health-related physical fitness in obese men with elevated or stage 1 hypertension.
Twenty-three men with elevated or stage 1 hypertension and a body mass index (BMI) ≥ 25 kg/m2 were initially recruited and randomly assigned to a control group (CON) or an experimental group (EXP). After withdrawal or loss to follow-up, 20 participants completed the study and were included in the final analysis (CON, n = 10; EXP, n = 10). The EXP performed mat Pilates three times per week for eight weeks, while CON maintained their usual lifestyle. Outcomes were assessed before and after the intervention.
Significant group × time interaction effects were observed for body weight, BMI, fat mass, hemodynamic variables, vascular indices, selected heart rate variability measures, and health-related physical fitness. Lean body mass and percent body fat improved significantly within the EXP, although the corresponding interaction effects were not significant. Overall, the EXP showed more favorable changes than the CON in several cardiometabolic and fitness-related outcomes.
An 8-week mat Pilates program was associated with favorable changes in body composition, blood pressure and vascular function, autonomic nervous system indices, and health-related physical fitness in obese men with elevated or stage 1 hypertension. However, because body weight and fat mass also decreased and the sample size was small, these findings should be interpreted cautiously. This study cannot determine whether the changes resulted from the Pilates intervention itself, concurrent body composition changes, or their combined effects. Trial registration: KCT0010502; https://cris.nih.go.kr/cris/index/index.do.
Hypertension and obesity frequently coexist and increase cardiovascular risk through vascular dysfunction, autonomic imbalance, and metabolic dysregulation. This study investigated the effects of an 8-week mat Pilates program on body composition, blood pressure, vascular function, autonomic nervous system activity, and health-related physical fitness in obese men with elevated or stage 1 hypertension.
Twenty-three men with elevated or stage 1 hypertension and a body mass index (BMI) ≥ 25 kg/m2 were initially recruited and randomly assigned to a control group (CON) or an experimental group (EXP). After withdrawal or loss to follow-up, 20 participants completed the study and were included in the final analysis (CON, n = 10; EXP, n = 10). The EXP performed mat Pilates three times per week for eight weeks, while CON maintained their usual lifestyle. Outcomes were assessed before and after the intervention.
Significant group × time interaction effects were observed for body weight, BMI, fat mass, hemodynamic variables, vascular indices, selected heart rate variability measures, and health-related physical fitness. Lean body mass and percent body fat improved significantly within the EXP, although the corresponding interaction effects were not significant. Overall, the EXP showed more favorable changes than the CON in several cardiometabolic and fitness-related outcomes.
An 8-week mat Pilates program was associated with favorable changes in body composition, blood pressure and vascular function, autonomic nervous system indices, and health-related physical fitness in obese men with elevated or stage 1 hypertension. However, because body weight and fat mass also decreased and the sample size was small, these findings should be interpreted cautiously. This study cannot determine whether the changes resulted from the Pilates intervention itself, concurrent body composition changes, or their combined effects. Trial registration: KCT0010502; https://cris.nih.go.kr/cris/index/index.do.
Oxidative stress—an imbalance between reactive oxygen/nitrogen species and antioxidant defenses—contributes not only to the developmental origins of asthma but also to poor control, airway remodeling, and corticosteroid-resistant inflammation in children. Persistent oxidant exposure, nutritional insufficiency, and mitochondrial dysfunction sustain redox imbalance in pediatric asthma, suggesting potential roles for environmental, dietary, and nutraceutical strategies—defined here as natural bioactive compounds providing health benefits beyond basic nutrition, including polyphenols such as curcumin, quercetin, and resveratrol, and essential minerals such as zinc and selenium—that complement standard therapy. To summarize evidence on preventive and therapeutic approaches that modulate oxidative stress in pediatric asthma, focusing on environmental control, antioxidant-rich dietary patterns, single and multi-component nutraceuticals, and mitochondria-targeted interventions. A structured review of PubMed, Scopus, and Embase (1995–2025) identified peer-reviewed English-language epidemiologic studies, mechanistic models, and clinical trials evaluating oxidative stress, antioxidant status, and asthma outcomes in children and, when relevant, adults. Reference lists of major reviews were screened to identify additional studies. Interventions that reduce exposure to air pollutants and tobacco smoke, combined with antioxidant-rich diets such as high fruit/vegetable intake and Mediterranean-style patterns, are consistently associated with improved lung function, fewer symptoms, and reduced inflammation. Clinical trials of single antioxidants (vitamin D, vitamin E, zinc, selenium, magnesium) show modest, context-dependent benefits, primarily in children with baseline deficiencies. Emerging research suggests that multi-component nutraceuticals—including polyphenols and coordinated micronutrient formulations—may enhance redox balance and improve pulmonary or vascular outcomes, though current evidence is limited by small sample sizes and heterogeneity. Experimental data strongly support mitochondria-targeted mechanisms, but pediatric clinical validation remains sparse. Strategies that reduce oxidative burden or strengthen antioxidant defenses appear biologically plausible adjuncts to standard asthma therapy. Further large, biomarker-guided trials are needed to clarify efficacy, identify responsive phenotypes, and determine the role of multi-component approaches relative to single-nutrient supplementation.
Oxidative stress—an imbalance between reactive oxygen/nitrogen species and antioxidant defenses—contributes not only to the developmental origins of asthma but also to poor control, airway remodeling, and corticosteroid-resistant inflammation in children. Persistent oxidant exposure, nutritional insufficiency, and mitochondrial dysfunction sustain redox imbalance in pediatric asthma, suggesting potential roles for environmental, dietary, and nutraceutical strategies—defined here as natural bioactive compounds providing health benefits beyond basic nutrition, including polyphenols such as curcumin, quercetin, and resveratrol, and essential minerals such as zinc and selenium—that complement standard therapy. To summarize evidence on preventive and therapeutic approaches that modulate oxidative stress in pediatric asthma, focusing on environmental control, antioxidant-rich dietary patterns, single and multi-component nutraceuticals, and mitochondria-targeted interventions. A structured review of PubMed, Scopus, and Embase (1995–2025) identified peer-reviewed English-language epidemiologic studies, mechanistic models, and clinical trials evaluating oxidative stress, antioxidant status, and asthma outcomes in children and, when relevant, adults. Reference lists of major reviews were screened to identify additional studies. Interventions that reduce exposure to air pollutants and tobacco smoke, combined with antioxidant-rich diets such as high fruit/vegetable intake and Mediterranean-style patterns, are consistently associated with improved lung function, fewer symptoms, and reduced inflammation. Clinical trials of single antioxidants (vitamin D, vitamin E, zinc, selenium, magnesium) show modest, context-dependent benefits, primarily in children with baseline deficiencies. Emerging research suggests that multi-component nutraceuticals—including polyphenols and coordinated micronutrient formulations—may enhance redox balance and improve pulmonary or vascular outcomes, though current evidence is limited by small sample sizes and heterogeneity. Experimental data strongly support mitochondria-targeted mechanisms, but pediatric clinical validation remains sparse. Strategies that reduce oxidative burden or strengthen antioxidant defenses appear biologically plausible adjuncts to standard asthma therapy. Further large, biomarker-guided trials are needed to clarify efficacy, identify responsive phenotypes, and determine the role of multi-component approaches relative to single-nutrient supplementation.
To determine the level of agreement between remote and in-person assessment for the Timed Up and Go test (TUG), the Lateral Step-Up test (LSU), the Five-Times-Sit-To-Stand test (FTSTS), and the Pediatric Balance Scale (PBS) in children with cerebral palsy (CP).
Fifteen children diagnosed with unilateral and bilateral spastic CP and Gross Motor Function Classification System levels I–II underwent these four tests in two distinct environments. These assessments were conducted 24 to 48 hours apart, first in person at the physiotherapy clinic and then remotely at home via the VSee platform. Before the remote assessment, all parents attended a preliminary training session that covered technical proficiency with VSee, the proper setup of home equipment, and essential safety protocols.
Children had a median age of 7 (IQR = 6–10) years old. All children successfully finished all four tests in both the home and clinic settings without any reported safety issues. The agreement was good for the time of repetitions in the FTSTS: ICC = 0.884 (95% CI: 0.654 to 0.961; MD = –1.26 seconds, 95% CI: –2.81 to 0.28, p = 0.102), and excellent for the total time of the TUG: ICC = 0.998 (95% CI: 0.990 to 0.999; MD = –0.42 seconds, 95% CI: –0.76 to –0.08, p = 0.017), the total score in the PBS: ICC = 0.998 (95% CI: 0.992 to 0.999; MD = 0.26 units, 95% CI: 0.01 to 0.52, p = 0.041), and the total number of steps in the LSU: ICC = 0.988 (95% CI: 0.965 to 0.996; MD = 0.53 steps, 95% CI: –0.68 to 1.75, p = 0.364).
Remote evaluation of the FTSTS, TUG, LSU, and PBS demonstrates good-to-excellent agreement with in-person assessment. However, wide limits of agreement indicated individual variability.
To determine the level of agreement between remote and in-person assessment for the Timed Up and Go test (TUG), the Lateral Step-Up test (LSU), the Five-Times-Sit-To-Stand test (FTSTS), and the Pediatric Balance Scale (PBS) in children with cerebral palsy (CP).
Fifteen children diagnosed with unilateral and bilateral spastic CP and Gross Motor Function Classification System levels I–II underwent these four tests in two distinct environments. These assessments were conducted 24 to 48 hours apart, first in person at the physiotherapy clinic and then remotely at home via the VSee platform. Before the remote assessment, all parents attended a preliminary training session that covered technical proficiency with VSee, the proper setup of home equipment, and essential safety protocols.
Children had a median age of 7 (IQR = 6–10) years old. All children successfully finished all four tests in both the home and clinic settings without any reported safety issues. The agreement was good for the time of repetitions in the FTSTS: ICC = 0.884 (95% CI: 0.654 to 0.961; MD = –1.26 seconds, 95% CI: –2.81 to 0.28, p = 0.102), and excellent for the total time of the TUG: ICC = 0.998 (95% CI: 0.990 to 0.999; MD = –0.42 seconds, 95% CI: –0.76 to –0.08, p = 0.017), the total score in the PBS: ICC = 0.998 (95% CI: 0.992 to 0.999; MD = 0.26 units, 95% CI: 0.01 to 0.52, p = 0.041), and the total number of steps in the LSU: ICC = 0.988 (95% CI: 0.965 to 0.996; MD = 0.53 steps, 95% CI: –0.68 to 1.75, p = 0.364).
Remote evaluation of the FTSTS, TUG, LSU, and PBS demonstrates good-to-excellent agreement with in-person assessment. However, wide limits of agreement indicated individual variability.
Acute wheeze is one of the most common paediatric presentations to emergency care. Although blood eosinophils (BEO) are an established biomarker of type 2 inflammation in stable asthma, their role in guiding acute management—particularly systemic corticosteroid use—remains unclear. The aim of this review was to map and synthesise the existing evidence on the measurement and clinical utility of BEO sampled during acute wheeze exacerbations in children. A scoping review was conducted in accordance with Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guidelines. Medline, Embase, Cochrane Library and Web of Science were searched for studies published in the last 20 years involving children under 16 years presenting acutely with wheeze and undergoing eosinophil testing. Prospective and retrospective studies were included. Data were summarised descriptively according to eosinophil measurement methods, reported values, cut-offs and associations with characteristics and treatment response. Eight heterogeneous studies (n = 855) met inclusion criteria, comprising five observational or retrospective studies and three randomised controlled trials. BEO reporting varied widely, with inconsistent units, cut-offs and poorly described sampling timing. No study utilised point-of-care testing. Across studies, eosinophil dynamics differed by age, wheeze phenotype, disease severity and viral aetiology, preventing meaningful comparison. Evidence supporting eosinophil-guided corticosteroid use was limited. Two studies demonstrated improved outcomes with systemic corticosteroids in children with rhinovirus-associated wheeze and higher BEO, while lower BEO were observed in respiratory syncytial virus (RSV)-associated wheeze. There is a paucity of high-quality data describing BEO during acute wheeze exacerbations in children. Current evidence underpinning eosinophil-guided care is largely derived from stable outpatient cohorts and may not be directly applicable to acute settings. Prospective studies with standardised sampling of BEO during acute presentations are needed to inform precision-based corticosteroid use.
Acute wheeze is one of the most common paediatric presentations to emergency care. Although blood eosinophils (BEO) are an established biomarker of type 2 inflammation in stable asthma, their role in guiding acute management—particularly systemic corticosteroid use—remains unclear. The aim of this review was to map and synthesise the existing evidence on the measurement and clinical utility of BEO sampled during acute wheeze exacerbations in children. A scoping review was conducted in accordance with Joanna Briggs Institute methodology and Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) guidelines. Medline, Embase, Cochrane Library and Web of Science were searched for studies published in the last 20 years involving children under 16 years presenting acutely with wheeze and undergoing eosinophil testing. Prospective and retrospective studies were included. Data were summarised descriptively according to eosinophil measurement methods, reported values, cut-offs and associations with characteristics and treatment response. Eight heterogeneous studies (n = 855) met inclusion criteria, comprising five observational or retrospective studies and three randomised controlled trials. BEO reporting varied widely, with inconsistent units, cut-offs and poorly described sampling timing. No study utilised point-of-care testing. Across studies, eosinophil dynamics differed by age, wheeze phenotype, disease severity and viral aetiology, preventing meaningful comparison. Evidence supporting eosinophil-guided corticosteroid use was limited. Two studies demonstrated improved outcomes with systemic corticosteroids in children with rhinovirus-associated wheeze and higher BEO, while lower BEO were observed in respiratory syncytial virus (RSV)-associated wheeze. There is a paucity of high-quality data describing BEO during acute wheeze exacerbations in children. Current evidence underpinning eosinophil-guided care is largely derived from stable outpatient cohorts and may not be directly applicable to acute settings. Prospective studies with standardised sampling of BEO during acute presentations are needed to inform precision-based corticosteroid use.
Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) have attained a manageable chronic status as more infected people experience increases in their life quality and expectancy. Health system factors affect adherence to Antiretroviral Therapy (ART) among persons living with HIV (PLHIV). Nonetheless, literature on health-system factors and ART adherence among PLHIV is sparse. This study therefore aimed to elucidate clinical and health system factors associated with ART adherence among PLHIV in Tamale Metropolis.
We conducted a facility-based cross-sectional survey of 418 PLHIV in the Tamale Metropolis, selected by convenience sampling from three major ART centres. Each factor associated with ART adherence, considered statistically significant at a p-value of < 0.05 with a 95% confidence interval, was analysed using both binary and multivariate logistic regression. Adherence was assessed by self-report of missed doses in the past 30 days, categorised as good (≥ 95% of prescribed doses taken) or poor (< 95% of prescribed doses taken).
The overall ART adherence rate was 93.1% (95% CI: 90.3%–95.2%). Clinical and health system factors significantly associated with higher adherence included the absence of post-pill fatigue (AOR = 0.09; 95% CI: 0.02–0.37), absence of complaints regarding pill size (AOR = 3.71; 95% CI: 1.23–11.18), lower cost of accessing therapy (AOR = 0.27; 95% CI: 0.10–0.73), uninterrupted ART supply (AOR = 7.76; 95% CI: 1.02–59.30), and strong social support systems (AOR = 6.62; 95% CI: 1.18–37.21).
An adherence rate of 93% was obtained which falls short of the 95% global benchmark. Clinical factors promoting adherence included the absence of fatigue and concerns related to pill size, while health system-related factors promoting adherence included reduced cost of access, consistent ART supply, and good social support. The Ghana AIDS Commission and its implementing partners are urged to strengthen community-based social support networks, expand ART distribution points, and develop targeted educational initiatives to improve therapy adherence and contribute to achieving epidemic control. Limitations of this study include the use of self-reported adherence (potential recall and social desirability bias) and the cross-sectional design, which precludes causal inference.
Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) have attained a manageable chronic status as more infected people experience increases in their life quality and expectancy. Health system factors affect adherence to Antiretroviral Therapy (ART) among persons living with HIV (PLHIV). Nonetheless, literature on health-system factors and ART adherence among PLHIV is sparse. This study therefore aimed to elucidate clinical and health system factors associated with ART adherence among PLHIV in Tamale Metropolis.
We conducted a facility-based cross-sectional survey of 418 PLHIV in the Tamale Metropolis, selected by convenience sampling from three major ART centres. Each factor associated with ART adherence, considered statistically significant at a p-value of < 0.05 with a 95% confidence interval, was analysed using both binary and multivariate logistic regression. Adherence was assessed by self-report of missed doses in the past 30 days, categorised as good (≥ 95% of prescribed doses taken) or poor (< 95% of prescribed doses taken).
The overall ART adherence rate was 93.1% (95% CI: 90.3%–95.2%). Clinical and health system factors significantly associated with higher adherence included the absence of post-pill fatigue (AOR = 0.09; 95% CI: 0.02–0.37), absence of complaints regarding pill size (AOR = 3.71; 95% CI: 1.23–11.18), lower cost of accessing therapy (AOR = 0.27; 95% CI: 0.10–0.73), uninterrupted ART supply (AOR = 7.76; 95% CI: 1.02–59.30), and strong social support systems (AOR = 6.62; 95% CI: 1.18–37.21).
An adherence rate of 93% was obtained which falls short of the 95% global benchmark. Clinical factors promoting adherence included the absence of fatigue and concerns related to pill size, while health system-related factors promoting adherence included reduced cost of access, consistent ART supply, and good social support. The Ghana AIDS Commission and its implementing partners are urged to strengthen community-based social support networks, expand ART distribution points, and develop targeted educational initiatives to improve therapy adherence and contribute to achieving epidemic control. Limitations of this study include the use of self-reported adherence (potential recall and social desirability bias) and the cross-sectional design, which precludes causal inference.
Diabetes mellitus is a growing non-communicable disease (NCD) imposing major health and economic burdens in Ethiopia. While prior national and subnational estimates have been published using Global Burden of Disease (GBD) 2019 data, this study provides novel, updated estimates reflecting newly delineated regional boundaries and recent socio-demographic shifts using GBD 2023 data. We aimed to estimate the national and subnational burden and trends of diabetes mellitus in Ethiopia from 1990 to 2023.
This analysis is part of the GBD 2023 study, a collaborative effort between the Ethiopian Public Health Institute and the Institute for Health Metrics and Evaluation. Estimates were generated using standard GBD modeling tools [DisMod-MR 2.1 and Cause of Death Ensemble modeling (CODEm)] for incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and DALYs [with 95% uncertainty intervals (UI)] across Ethiopia’s regions and city administrations.
In 2023, Ethiopia’s age-standardized prevalence of all forms of diabetes mellitus (type 1 and type 2 combined) was 2,996.4 (95% UI: 2,704.8–3,269.5) cases per 100,000 population. Type 2 diabetes accounted for nearly 99% of cases. The Somali region had the lowest prevalence (2,243.1 per 100,000), about 45% lower than in Sidama (4,066.4 per 100,000), highlighting marked regional disparities. The age-standardized DALY rate was 1,124.2 per 100,000. While high fasting plasma glucose was the leading proximal risk factor, high body mass index ranked as the top upstream modifiable risk factor (264.1 DALYs per 100,000).
This study highlights the substantial and unevenly distributed burden of diabetes mellitus in Ethiopia, driven predominantly by type 2 diabetes and modifiable metabolic risk factors. These findings call for tailored, region-specific strategies, such as targeted obesity prevention in high-prevalence urban centers and strengthened health system capacity in high-mortality pastoral regions to curb the future burden and align with global NCD targets.
Diabetes mellitus is a growing non-communicable disease (NCD) imposing major health and economic burdens in Ethiopia. While prior national and subnational estimates have been published using Global Burden of Disease (GBD) 2019 data, this study provides novel, updated estimates reflecting newly delineated regional boundaries and recent socio-demographic shifts using GBD 2023 data. We aimed to estimate the national and subnational burden and trends of diabetes mellitus in Ethiopia from 1990 to 2023.
This analysis is part of the GBD 2023 study, a collaborative effort between the Ethiopian Public Health Institute and the Institute for Health Metrics and Evaluation. Estimates were generated using standard GBD modeling tools [DisMod-MR 2.1 and Cause of Death Ensemble modeling (CODEm)] for incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and DALYs [with 95% uncertainty intervals (UI)] across Ethiopia’s regions and city administrations.
In 2023, Ethiopia’s age-standardized prevalence of all forms of diabetes mellitus (type 1 and type 2 combined) was 2,996.4 (95% UI: 2,704.8–3,269.5) cases per 100,000 population. Type 2 diabetes accounted for nearly 99% of cases. The Somali region had the lowest prevalence (2,243.1 per 100,000), about 45% lower than in Sidama (4,066.4 per 100,000), highlighting marked regional disparities. The age-standardized DALY rate was 1,124.2 per 100,000. While high fasting plasma glucose was the leading proximal risk factor, high body mass index ranked as the top upstream modifiable risk factor (264.1 DALYs per 100,000).
This study highlights the substantial and unevenly distributed burden of diabetes mellitus in Ethiopia, driven predominantly by type 2 diabetes and modifiable metabolic risk factors. These findings call for tailored, region-specific strategies, such as targeted obesity prevention in high-prevalence urban centers and strengthened health system capacity in high-mortality pastoral regions to curb the future burden and align with global NCD targets.
Early-life oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant defenses, has increasingly been proposed as an important contributor to the developmental origins of childhood asthma. Prenatal and early postnatal exposures—including pollutants, tobacco smoke, maternal distress, nutritional imbalance, and allergen-derived oxidase activity—may disrupt epithelial integrity and redox-regulated immune pathways, potentially predisposing the developing lung to allergic inflammation. To synthesize current mechanistic and epidemiologic evidence on how oxidative stress during early life may contribute to asthma development, with particular focus on environmental drivers, redox–immune interactions, and gene-environment susceptibility. A structured review of PubMed, Scopus, and Embase identified peer-reviewed English-language studies from birth cohorts, mechanistic models, and biomarker analyses evaluating oxidative stress, antioxidant capacity, and asthma-related outcomes. Environmental oxidants and nutritional deficiencies may increase ROS production, promoting epithelial injury, activation of redox-sensitive pathways such as NF-κB and MAPK, and the release of epithelial alarmins including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP). These signals can influence innate immune activation and antigen-presenting cell function, favoring Th2/Th17-biased immune responses. Genetic variants in antioxidant pathways, including GSTM1, GSTP1, and Nrf2, may further modify susceptibility to oxidant exposures. Epidemiologic studies from birth cohorts report associations between early-life oxidative exposures, reduced lung growth, wheezing, allergic sensitization, and asthma risk. Current mechanistic and epidemiologic evidence suggests that oxidative stress may represent an important biological pathway linking early-life environmental exposures with asthma susceptibility, although further studies are needed to clarify its role within the complex network of factors contributing to asthma development.
Early-life oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS) and antioxidant defenses, has increasingly been proposed as an important contributor to the developmental origins of childhood asthma. Prenatal and early postnatal exposures—including pollutants, tobacco smoke, maternal distress, nutritional imbalance, and allergen-derived oxidase activity—may disrupt epithelial integrity and redox-regulated immune pathways, potentially predisposing the developing lung to allergic inflammation. To synthesize current mechanistic and epidemiologic evidence on how oxidative stress during early life may contribute to asthma development, with particular focus on environmental drivers, redox–immune interactions, and gene-environment susceptibility. A structured review of PubMed, Scopus, and Embase identified peer-reviewed English-language studies from birth cohorts, mechanistic models, and biomarker analyses evaluating oxidative stress, antioxidant capacity, and asthma-related outcomes. Environmental oxidants and nutritional deficiencies may increase ROS production, promoting epithelial injury, activation of redox-sensitive pathways such as NF-κB and MAPK, and the release of epithelial alarmins including IL-33, IL-25, and thymic stromal lymphopoietin (TSLP). These signals can influence innate immune activation and antigen-presenting cell function, favoring Th2/Th17-biased immune responses. Genetic variants in antioxidant pathways, including GSTM1, GSTP1, and Nrf2, may further modify susceptibility to oxidant exposures. Epidemiologic studies from birth cohorts report associations between early-life oxidative exposures, reduced lung growth, wheezing, allergic sensitization, and asthma risk. Current mechanistic and epidemiologic evidence suggests that oxidative stress may represent an important biological pathway linking early-life environmental exposures with asthma susceptibility, although further studies are needed to clarify its role within the complex network of factors contributing to asthma development.
Tremor is one of the most common neurological movement disorders, arising from dysfunction in the neuromuscular system. However, comprehensive analyses of peripheral blood elements, red blood cells (RBC) and white blood cells (WBC) counts, as well as liver and kidney function in patients with tremor remain limited. This cross-sectional study investigated alterations in serum elements, complete blood counts, and liver function in patients with tremor. The study sought to identify independent risk factors and evaluate their diagnostic performance.
Blood samples from 79 patients with tremor and 82 healthy controls were analyzed. Serum elements, RBC, WBC, platelet (PLT), liver function, and renal function were measured using the QL8000 element analyzer, XN 2800 automated hematology analyzer, and Roche Cobas 8000 system.
Serum copper (Cu) and lead (Pb) levels were significantly elevated in tremor patients. These patients also showed increased monocytes, decreased eosinophils, and impaired liver function, including elevated aspartate aminotransferase and globulin with reduced albumin.
Tremor patients show distinct alterations in Cu, Pb, monocyte counts, eosinophil counts, and liver function markers. These findings suggest that these parameters may serve as potential diagnostic indicators and therapeutic targets. Cu and Pb were identified as independent risk factors, and their combination significantly improved diagnostic efficiency.
Tremor is one of the most common neurological movement disorders, arising from dysfunction in the neuromuscular system. However, comprehensive analyses of peripheral blood elements, red blood cells (RBC) and white blood cells (WBC) counts, as well as liver and kidney function in patients with tremor remain limited. This cross-sectional study investigated alterations in serum elements, complete blood counts, and liver function in patients with tremor. The study sought to identify independent risk factors and evaluate their diagnostic performance.
Blood samples from 79 patients with tremor and 82 healthy controls were analyzed. Serum elements, RBC, WBC, platelet (PLT), liver function, and renal function were measured using the QL8000 element analyzer, XN 2800 automated hematology analyzer, and Roche Cobas 8000 system.
Serum copper (Cu) and lead (Pb) levels were significantly elevated in tremor patients. These patients also showed increased monocytes, decreased eosinophils, and impaired liver function, including elevated aspartate aminotransferase and globulin with reduced albumin.
Tremor patients show distinct alterations in Cu, Pb, monocyte counts, eosinophil counts, and liver function markers. These findings suggest that these parameters may serve as potential diagnostic indicators and therapeutic targets. Cu and Pb were identified as independent risk factors, and their combination significantly improved diagnostic efficiency.
Artificial intelligence (AI) has rapidly advanced in radiology, demonstrating high performance across a wide range of diagnostic tasks. However, clinical adoption remains slower and more uneven than anticipated. This discrepancy reflects a fundamental gap between algorithm validation and clinical implementation. Current validation strategies primarily rely on controlled datasets and performance metrics such as accuracy and area under the curve, which often fail to capture the complexity of clinical environments. This article examines the nature of this “validation gap” and argues that it reflects a broader structural mismatch between how AI systems are evaluated and how clinical care operates. We propose a conceptual framework comprising three levels of validation: technical validity, workflow validity, and clinical validity. While most studies focus on technical performance, limited attention is given to integration into clinical workflows and impact on patient outcomes. Key factors contributing to this gap include limited generalizability across diverse populations and imaging protocols, poor alignment with clinical workflows, and the underrepresentation of uncertainty in model outputs. These limitations hinder effective implementation and may reduce trust in AI systems. Bridging this gap requires a shift toward more comprehensive validation strategies, including multicenter and prospective studies, improved workflow integration, and explicit incorporation of uncertainty and human–AI interaction. Ultimately, the clinical value of AI in radiology should be assessed not only by its performance in controlled settings but also by its ability to support decision-making and improve patient outcomes in real-world practice.
Artificial intelligence (AI) has rapidly advanced in radiology, demonstrating high performance across a wide range of diagnostic tasks. However, clinical adoption remains slower and more uneven than anticipated. This discrepancy reflects a fundamental gap between algorithm validation and clinical implementation. Current validation strategies primarily rely on controlled datasets and performance metrics such as accuracy and area under the curve, which often fail to capture the complexity of clinical environments. This article examines the nature of this “validation gap” and argues that it reflects a broader structural mismatch between how AI systems are evaluated and how clinical care operates. We propose a conceptual framework comprising three levels of validation: technical validity, workflow validity, and clinical validity. While most studies focus on technical performance, limited attention is given to integration into clinical workflows and impact on patient outcomes. Key factors contributing to this gap include limited generalizability across diverse populations and imaging protocols, poor alignment with clinical workflows, and the underrepresentation of uncertainty in model outputs. These limitations hinder effective implementation and may reduce trust in AI systems. Bridging this gap requires a shift toward more comprehensive validation strategies, including multicenter and prospective studies, improved workflow integration, and explicit incorporation of uncertainty and human–AI interaction. Ultimately, the clinical value of AI in radiology should be assessed not only by its performance in controlled settings but also by its ability to support decision-making and improve patient outcomes in real-world practice.
Artificial intelligence (AI) is transforming clinical decision-making across cranio-maxillofacial trauma, oral health, and systemic disease. These domains are increasingly recognised as biologically and clinically interconnected, yet they are often studied and managed independently. This perspective introduces the concept of an integrative triangle linking facial trauma, oral health, and systemic disease, with AI serving as the computational bridge that enables cross-domain modelling and coordinated care. AI applications within this framework include imaging-based fracture detection, patient-specific implant design, automated oral disease diagnosis, multimodal risk prediction, and longitudinal outcome modelling. By integrating imaging, clinical, laboratory, and behavioural data, AI can identify shared inflammatory and metabolic pathways influencing trauma recovery and chronic disease progression. This closed-loop paradigm supports continuous learning, allowing outcomes in one domain to inform prediction and intervention in the others. The integrative triangle provides a translational roadmap for precision medicine, moving from isolated prediction toward coordinated prevention and intervention. Future development will require multimodal data integration, prospective validation, and responsible governance to ensure explainable and equitable AI deployment. This framework positions facial trauma and oral health as central components of systemic precision medicine and highlights AI as a catalyst for integrated, patient-centred care.
Artificial intelligence (AI) is transforming clinical decision-making across cranio-maxillofacial trauma, oral health, and systemic disease. These domains are increasingly recognised as biologically and clinically interconnected, yet they are often studied and managed independently. This perspective introduces the concept of an integrative triangle linking facial trauma, oral health, and systemic disease, with AI serving as the computational bridge that enables cross-domain modelling and coordinated care. AI applications within this framework include imaging-based fracture detection, patient-specific implant design, automated oral disease diagnosis, multimodal risk prediction, and longitudinal outcome modelling. By integrating imaging, clinical, laboratory, and behavioural data, AI can identify shared inflammatory and metabolic pathways influencing trauma recovery and chronic disease progression. This closed-loop paradigm supports continuous learning, allowing outcomes in one domain to inform prediction and intervention in the others. The integrative triangle provides a translational roadmap for precision medicine, moving from isolated prediction toward coordinated prevention and intervention. Future development will require multimodal data integration, prospective validation, and responsible governance to ensure explainable and equitable AI deployment. This framework positions facial trauma and oral health as central components of systemic precision medicine and highlights AI as a catalyst for integrated, patient-centred care.
Recent studies argue that other physiological solutions are superior to normal saline, which is due to their physiological features, better outcomes in critical care, and lower risk of hyperchloremia and acidosis; nonetheless, it is still a mystery how normal saline has dominated the field of fluid therapy worldwide. Moreover, there is an ongoing debate on whether harm to human health may limit its spread in the future. Additionally, new evidence revealed some of the deleterious effects of normal saline, including coagulopathy, metabolic acidosis, acute kidney injury (AKI), and higher mortality in ICU. The predominant cause for these outcomes appears to be the excess chloride concentration of normal saline relative to plasma. Therefore, it appears relevant to suggest that a normal saline solution should be normalized to that of human serum to overcome these pitfalls. An ideal normal saline solution shall be similar to human serum in its pH, osmolarity, and content of sodium, chloride, and essential minerals.
Recent studies argue that other physiological solutions are superior to normal saline, which is due to their physiological features, better outcomes in critical care, and lower risk of hyperchloremia and acidosis; nonetheless, it is still a mystery how normal saline has dominated the field of fluid therapy worldwide. Moreover, there is an ongoing debate on whether harm to human health may limit its spread in the future. Additionally, new evidence revealed some of the deleterious effects of normal saline, including coagulopathy, metabolic acidosis, acute kidney injury (AKI), and higher mortality in ICU. The predominant cause for these outcomes appears to be the excess chloride concentration of normal saline relative to plasma. Therefore, it appears relevant to suggest that a normal saline solution should be normalized to that of human serum to overcome these pitfalls. An ideal normal saline solution shall be similar to human serum in its pH, osmolarity, and content of sodium, chloride, and essential minerals.
To evaluate ultrasound-derived congestion phenotypes in acute decompensated heart failure with preserved ejection fraction (HFpEF) and their association with cardiac remodeling and in-hospital outcomes.
This prospective study included 235 patients (median age 77.0 years, 75.3% women) with acute decompensated HFpEF. Within 2 hours of admission, all patients underwent echocardiography, lung ultrasound (B-lines), venous excess ultrasound score (VExUS) assessment, and bioimpedance analysis. Patients were classified into three phenotypes based on pulmonary (B-lines > 3) and systemic venous congestion (VExUS): low-low (no significant pulmonary or systemic congestion), pulmonary-dominant, and mixed severe. The primary endpoint was in-hospital mortality.
Moderate-to-severe venous congestion (VExUS grade 2–3) was present in 60.8% of patients. The mixed severe phenotype predominated (60.9%) and was associated with higher body mass index (BMI) and waist (p < 0.001). This group demonstrated more advanced cardiac dysfunction, including higher E/e’ (14.9 vs. 11.9; p < 0.001), greater left atrial remodeling (left atrial volume index 45.0 vs. 39.0 mL/m2; p < 0.001), and increased left ventricular mass index (p = 0.010). Right ventricular (RV) involvement was more pronounced, with lower TAPSE (18.0 vs. 20.0 mm; p < 0.001) and higher tricuspid regurgitation velocity (p < 0.001). Markers of congestion showed a gradient, with higher NT-proBNP (3,072.5 vs. 1,197.0 pg/mL; p < 0.001), increased extracellular water (129% vs. 101%; p < 0.001), and lower phase angle (4.9 vs. 5.5; p < 0.001). In-hospital mortality was highest in the mixed severe phenotype [11.2% vs. 3.0% and 1.7%; p = 0.039; odds ratio (OR) 5.67]. B-lines correlated with tricuspid regurgitation velocity, E/e’, and extracellular water (all r ≥ 0.50).
Ultrasound-derived congestion phenotyping in HFpEF identifies distinct profiles associated with atrial and ventricular remodeling and worse in-hospital outcomes. Future studies are required to determine whether phenotype-guided decongestive strategies can improve outcomes beyond risk stratification.
To evaluate ultrasound-derived congestion phenotypes in acute decompensated heart failure with preserved ejection fraction (HFpEF) and their association with cardiac remodeling and in-hospital outcomes.
This prospective study included 235 patients (median age 77.0 years, 75.3% women) with acute decompensated HFpEF. Within 2 hours of admission, all patients underwent echocardiography, lung ultrasound (B-lines), venous excess ultrasound score (VExUS) assessment, and bioimpedance analysis. Patients were classified into three phenotypes based on pulmonary (B-lines > 3) and systemic venous congestion (VExUS): low-low (no significant pulmonary or systemic congestion), pulmonary-dominant, and mixed severe. The primary endpoint was in-hospital mortality.
Moderate-to-severe venous congestion (VExUS grade 2–3) was present in 60.8% of patients. The mixed severe phenotype predominated (60.9%) and was associated with higher body mass index (BMI) and waist (p < 0.001). This group demonstrated more advanced cardiac dysfunction, including higher E/e’ (14.9 vs. 11.9; p < 0.001), greater left atrial remodeling (left atrial volume index 45.0 vs. 39.0 mL/m2; p < 0.001), and increased left ventricular mass index (p = 0.010). Right ventricular (RV) involvement was more pronounced, with lower TAPSE (18.0 vs. 20.0 mm; p < 0.001) and higher tricuspid regurgitation velocity (p < 0.001). Markers of congestion showed a gradient, with higher NT-proBNP (3,072.5 vs. 1,197.0 pg/mL; p < 0.001), increased extracellular water (129% vs. 101%; p < 0.001), and lower phase angle (4.9 vs. 5.5; p < 0.001). In-hospital mortality was highest in the mixed severe phenotype [11.2% vs. 3.0% and 1.7%; p = 0.039; odds ratio (OR) 5.67]. B-lines correlated with tricuspid regurgitation velocity, E/e’, and extracellular water (all r ≥ 0.50).
Ultrasound-derived congestion phenotyping in HFpEF identifies distinct profiles associated with atrial and ventricular remodeling and worse in-hospital outcomes. Future studies are required to determine whether phenotype-guided decongestive strategies can improve outcomes beyond risk stratification.
Obesity during the menopausal transition accelerates vascular aging through systemic inflammation, insulin resistance, and estrogen loss. These pathological processes impair endothelial function and arterial compliance, thereby increasing cardiovascular risk while simultaneously disrupting cerebral circulation, neurovascular regulation, and neuroendocrine stability that contribute to cognitive decline and psychological vulnerability. Regular exercise has emerged as an important non-pharmacological strategy to counteract these multidimensional impairments. Particular attention has been given to the modifying role of hormonal status and the differential adaptations observed between premenopausal and postmenopausal states. Evidence indicates that aerobic and multimodal programs enhance nitric oxide bioavailability, vascular elasticity, and cerebral perfusion, whereas resistance training contributes to musculoskeletal strength, metabolic regulation, and psychological resilience. Novel approaches such as interval-based or hypoxic exercise may provide additional benefits for postmenopausal women but require individualized supervision. Importantly, exercise-induced vascular improvements extend beyond cardiovascular protection, restoring cerebral blood flow, promoting hippocampal plasticity, and stabilizing hypothalamic–pituitary–adrenal axis function. These adaptations mediate enhancements in memory, executive performance, mood regulation, and stress resilience. This review synthesizes current findings across aerobic training, resistance training, combined training, high-intensity interval training, and hypoxic conditioning, and proposes an integrative vascular–cognitive–mental health framework that unifies these domains into a coherent model, with vascular function as a central mechanistic pathway linking exercise to cognitive and psychological outcomes, while underscoring the need for precision exercise prescriptions tailored to hormonal status, vascular risk, and functional capacity in obese women.
Obesity during the menopausal transition accelerates vascular aging through systemic inflammation, insulin resistance, and estrogen loss. These pathological processes impair endothelial function and arterial compliance, thereby increasing cardiovascular risk while simultaneously disrupting cerebral circulation, neurovascular regulation, and neuroendocrine stability that contribute to cognitive decline and psychological vulnerability. Regular exercise has emerged as an important non-pharmacological strategy to counteract these multidimensional impairments. Particular attention has been given to the modifying role of hormonal status and the differential adaptations observed between premenopausal and postmenopausal states. Evidence indicates that aerobic and multimodal programs enhance nitric oxide bioavailability, vascular elasticity, and cerebral perfusion, whereas resistance training contributes to musculoskeletal strength, metabolic regulation, and psychological resilience. Novel approaches such as interval-based or hypoxic exercise may provide additional benefits for postmenopausal women but require individualized supervision. Importantly, exercise-induced vascular improvements extend beyond cardiovascular protection, restoring cerebral blood flow, promoting hippocampal plasticity, and stabilizing hypothalamic–pituitary–adrenal axis function. These adaptations mediate enhancements in memory, executive performance, mood regulation, and stress resilience. This review synthesizes current findings across aerobic training, resistance training, combined training, high-intensity interval training, and hypoxic conditioning, and proposes an integrative vascular–cognitive–mental health framework that unifies these domains into a coherent model, with vascular function as a central mechanistic pathway linking exercise to cognitive and psychological outcomes, while underscoring the need for precision exercise prescriptions tailored to hormonal status, vascular risk, and functional capacity in obese women.
The increasing survival rates among paediatric and adolescent cancer patients has increased attention on long-term consequences of chemotherapy, particularly male fertility. This review addresses age- and dose-dependent gonadotoxicity and drug type on reproductive potential. It further investigates the damage, including disruption of the hypothalamic-pituitary-gonadal axis and epigenetic alterations that may pose transgenerational risks. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for studies from database inception to April 2025. Inclusion criteria included paediatric and adolescent male cancer patients or adult survivors of childhood cancer and reported chemotherapy-related effects on fertility. Preclinical animal models were included to elucidate epigenetic changes. Due to heterogeneity of study designs, a narrative synthesis was performed to categorize findings into hormonal, cellular, and clinical outcomes. Chemotherapy-induced infertility is highly dependent on the developmental stage and specific regimen. Alkylating agents and platinum-based therapies were consistently associated with impaired spermatogenesis, hormonal disruption, and azoospermia or oligospermia. Chemotherapy and cranial irradiation were altered hormonal system that regulates male reproduction and persists epigenetic changes in germ cells. Fertility preservation for postpubertal males is through sperm cryopreservation, while prepubertal boys relied on experimental strategies such as testicular tissue cryopreservation and in vitro spermatogenesis. Chemotherapy induces epigenetic after-effects, including altered DNA methylation patterns that persist even after spermatogenesis recovers. Chemotherapy compromises male fertility through cytotoxic damage and potential long-term genomic instability. The findings highlight that reproductive recovery does not guarantee genomic recovery (epigenetically intact sperm). Consequently, oncofertility care must adapt a reproductive health model that prioritizes early, customized counselling and use of biomarkers to better predict and preserve fertility in young survivors. Although sperm banking remains a standard approach for postpubertal, promising experimental may expand fertility options for prepubertal boys in future.
The increasing survival rates among paediatric and adolescent cancer patients has increased attention on long-term consequences of chemotherapy, particularly male fertility. This review addresses age- and dose-dependent gonadotoxicity and drug type on reproductive potential. It further investigates the damage, including disruption of the hypothalamic-pituitary-gonadal axis and epigenetic alterations that may pose transgenerational risks. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar was conducted for studies from database inception to April 2025. Inclusion criteria included paediatric and adolescent male cancer patients or adult survivors of childhood cancer and reported chemotherapy-related effects on fertility. Preclinical animal models were included to elucidate epigenetic changes. Due to heterogeneity of study designs, a narrative synthesis was performed to categorize findings into hormonal, cellular, and clinical outcomes. Chemotherapy-induced infertility is highly dependent on the developmental stage and specific regimen. Alkylating agents and platinum-based therapies were consistently associated with impaired spermatogenesis, hormonal disruption, and azoospermia or oligospermia. Chemotherapy and cranial irradiation were altered hormonal system that regulates male reproduction and persists epigenetic changes in germ cells. Fertility preservation for postpubertal males is through sperm cryopreservation, while prepubertal boys relied on experimental strategies such as testicular tissue cryopreservation and in vitro spermatogenesis. Chemotherapy induces epigenetic after-effects, including altered DNA methylation patterns that persist even after spermatogenesis recovers. Chemotherapy compromises male fertility through cytotoxic damage and potential long-term genomic instability. The findings highlight that reproductive recovery does not guarantee genomic recovery (epigenetically intact sperm). Consequently, oncofertility care must adapt a reproductive health model that prioritizes early, customized counselling and use of biomarkers to better predict and preserve fertility in young survivors. Although sperm banking remains a standard approach for postpubertal, promising experimental may expand fertility options for prepubertal boys in future.
Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder marked by fever, rash, joint pain, and hyperferritinemia. While immune dysregulation is implicated in AOSD, the exact causal mechanisms remain unclear. This study aimed to investigate the genetic causal relationship between 731 immune cell phenotypes and AOSD, and to identify protective or risk-associated profiles.
Using a two-sample Mendelian randomization (TSMR) approach, we applied inverse variance weighted (IVW) as the primary method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods for robustness. Genetic instrumental variables for immune traits were sourced from recent genome-wide association studies (GWAS), and AOSD genetic predispositions were derived from the finn-b-STILL_ADULT cohort, comprising 201,947 individuals of European ancestry (3,403 AOSD cases and 198,544 controls).
We identified 49 immune cell-related traits showing nominally significant associations with AOSD (all adjusted P > 0.05 after FDR correction). Among these, 34 traits showed nominally protective trends, while 15 showed nominally risk-associated trends. Reciprocally, AOSD showed nominally suggestive effects on 40 immune cell traits, with 25 exhibiting a trend toward decreased levels and 15 toward increased levels. Additionally, we conducted multiple sensitivity analyses to explore potential heterogeneity and pleiotropy, though the primary findings did not survive FDR correction.
These nominally significant associations between immune cell traits and AOSD, though not surviving FDR correction, may offer hypothesis-generating insights for future therapeutic research. The observed directional trends—with certain traits showing nominally protective or risk-associated patterns—suggest potential avenues for further exploration in the development of targeted treatment approaches for AOSD.
Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder marked by fever, rash, joint pain, and hyperferritinemia. While immune dysregulation is implicated in AOSD, the exact causal mechanisms remain unclear. This study aimed to investigate the genetic causal relationship between 731 immune cell phenotypes and AOSD, and to identify protective or risk-associated profiles.
Using a two-sample Mendelian randomization (TSMR) approach, we applied inverse variance weighted (IVW) as the primary method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods for robustness. Genetic instrumental variables for immune traits were sourced from recent genome-wide association studies (GWAS), and AOSD genetic predispositions were derived from the finn-b-STILL_ADULT cohort, comprising 201,947 individuals of European ancestry (3,403 AOSD cases and 198,544 controls).
We identified 49 immune cell-related traits showing nominally significant associations with AOSD (all adjusted P > 0.05 after FDR correction). Among these, 34 traits showed nominally protective trends, while 15 showed nominally risk-associated trends. Reciprocally, AOSD showed nominally suggestive effects on 40 immune cell traits, with 25 exhibiting a trend toward decreased levels and 15 toward increased levels. Additionally, we conducted multiple sensitivity analyses to explore potential heterogeneity and pleiotropy, though the primary findings did not survive FDR correction.
These nominally significant associations between immune cell traits and AOSD, though not surviving FDR correction, may offer hypothesis-generating insights for future therapeutic research. The observed directional trends—with certain traits showing nominally protective or risk-associated patterns—suggest potential avenues for further exploration in the development of targeted treatment approaches for AOSD.
Tricuspid valve endocarditis has potential associations with various conditions, but it is commonly related to intravenous drug abuse. Often, its eradication can become very challenging due to high post-operative mortality and high rate of recurrence due to persistence of drug abuse habits. The bidirectional Glenn shunt (BGS), typically employed in congenital heart surgery, combined with tricuspid valvectomy, has occasionally been used for recurrent endocarditis. Herein, we present a 31-year-old woman with drug addiction scheduled for her fourth reintervention due to the early degeneration and infection of a previous pulmonary homograft used for recurring tricuspid valve endocarditis. The final surgical strategy was valvectomy and BGS, aimed at eliminating all potential sources of infection and providing more time for the patient to overcome drug addiction, enabling further treatment if necessary.
Tricuspid valve endocarditis has potential associations with various conditions, but it is commonly related to intravenous drug abuse. Often, its eradication can become very challenging due to high post-operative mortality and high rate of recurrence due to persistence of drug abuse habits. The bidirectional Glenn shunt (BGS), typically employed in congenital heart surgery, combined with tricuspid valvectomy, has occasionally been used for recurrent endocarditis. Herein, we present a 31-year-old woman with drug addiction scheduled for her fourth reintervention due to the early degeneration and infection of a previous pulmonary homograft used for recurring tricuspid valve endocarditis. The final surgical strategy was valvectomy and BGS, aimed at eliminating all potential sources of infection and providing more time for the patient to overcome drug addiction, enabling further treatment if necessary.
The recent improvements of the ultrasounds technology and the probes have led the dental community to start to apply this technology at macrovascular and microvascular level. This scoping review aims to investigate the diagnostic and research applications of ultrasonography in periodontics. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science, to identify relevant studies in periodontology: The search strategy included the following terms: “ultrasonography”, “echography”, “ultrasound”, “dentistry”. The review was conducted in accordance with the PRISMA-ScR guidelines. In addition, a manual search was conducted through the following journals from the last 10 years: Journal of Clinical Periodontology, the Journal of Dental Research and Oral Surgery, and Oral Medicine, Oral Pathology and Oral Radiology. Ten studies were included, covering different applications of ultrasonography in periodontology. Ultrasonography was employed in peri-implant and periodontal diagnosis, assessment of soft tissue thickness and vascularization, palatal wound and bone healing. This review highlights the effectiveness of ultrasonography in diagnosis and surgical evaluation. Further research, standardized protocols, and randomized clinical trials are needed, expanding the investigation to more fields relevant to the maxillofacial district.
The recent improvements of the ultrasounds technology and the probes have led the dental community to start to apply this technology at macrovascular and microvascular level. This scoping review aims to investigate the diagnostic and research applications of ultrasonography in periodontics. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science, to identify relevant studies in periodontology: The search strategy included the following terms: “ultrasonography”, “echography”, “ultrasound”, “dentistry”. The review was conducted in accordance with the PRISMA-ScR guidelines. In addition, a manual search was conducted through the following journals from the last 10 years: Journal of Clinical Periodontology, the Journal of Dental Research and Oral Surgery, and Oral Medicine, Oral Pathology and Oral Radiology. Ten studies were included, covering different applications of ultrasonography in periodontology. Ultrasonography was employed in peri-implant and periodontal diagnosis, assessment of soft tissue thickness and vascularization, palatal wound and bone healing. This review highlights the effectiveness of ultrasonography in diagnosis and surgical evaluation. Further research, standardized protocols, and randomized clinical trials are needed, expanding the investigation to more fields relevant to the maxillofacial district.
Although emotions play a fundamental role in modulating pain perception, their objective assessment in clinical contexts remains challenging. Recent advances in artificial intelligence (AI) have opened new opportunities to measure emotional states through facial expression analysis, physiological signal modeling, natural language processing (NLP), and multimodal data integration. In affective computing, the field that focuses on technologies designed to recognize, interpret, process, and simulate human emotions, facial expression-based emotion recognition has progressed from traditional machine learning methods to advanced deep learning approaches, including convolutional neural networks (CNNs), attention-based hybrid models, and transformer architectures. Similarly, recurrent neural networks and self-supervised learning methods have been implemented for developing models from physiological signals such as electrocardiography, photoplethysmography, galvanic skin response, and related biosignals. Additionally, NLP systems can extract affective information from naturalistic text, using both lexicon-based and transformer-based models. Finally, multimodal fusion and alignment techniques allow the integration of heterogeneous data streams, providing richer and more ecologically valid emotion representations. Collectively, these strategies offer powerful tools for advancing automatic pain assessment (APA) in cancer care, with the potential to support personalized, emotion-aware therapeutic approaches. However, from an AI perspective, several open challenges remain, including multimodal representation learning under weak supervision, robustness to missing or degraded modalities, limited explainability of affective inference models, lack of standardized benchmarking protocols, and the presence of bias and domain shift in emotion datasets. Given the inherently subjective, context-dependent, and culturally mediated features of the emotional experience, further research is needed to address these technical limitations, integrating technological advances with the intrinsic complexity of emotion interpretation.
Although emotions play a fundamental role in modulating pain perception, their objective assessment in clinical contexts remains challenging. Recent advances in artificial intelligence (AI) have opened new opportunities to measure emotional states through facial expression analysis, physiological signal modeling, natural language processing (NLP), and multimodal data integration. In affective computing, the field that focuses on technologies designed to recognize, interpret, process, and simulate human emotions, facial expression-based emotion recognition has progressed from traditional machine learning methods to advanced deep learning approaches, including convolutional neural networks (CNNs), attention-based hybrid models, and transformer architectures. Similarly, recurrent neural networks and self-supervised learning methods have been implemented for developing models from physiological signals such as electrocardiography, photoplethysmography, galvanic skin response, and related biosignals. Additionally, NLP systems can extract affective information from naturalistic text, using both lexicon-based and transformer-based models. Finally, multimodal fusion and alignment techniques allow the integration of heterogeneous data streams, providing richer and more ecologically valid emotion representations. Collectively, these strategies offer powerful tools for advancing automatic pain assessment (APA) in cancer care, with the potential to support personalized, emotion-aware therapeutic approaches. However, from an AI perspective, several open challenges remain, including multimodal representation learning under weak supervision, robustness to missing or degraded modalities, limited explainability of affective inference models, lack of standardized benchmarking protocols, and the presence of bias and domain shift in emotion datasets. Given the inherently subjective, context-dependent, and culturally mediated features of the emotional experience, further research is needed to address these technical limitations, integrating technological advances with the intrinsic complexity of emotion interpretation.
Myxofibrosarcoma (MFS) is characterized by high local recurrence and complex microenvironmental interactions. Although three-dimensional (3D) culture systems better mimic in vivo tumor architecture than conventional two-dimensional (2D) monolayer cultures, the global proteomic consequences of dimensionality in MFS remain incompletely defined.
We performed quantitative mass spectrometry-based proteomic profiling of eight independently established patient-derived MFS cell lines cultured under 2D monolayer and 3D spheroid conditions. Differential protein expression and pathway enrichment analyses were conducted to delineate dimensionality-driven molecular programs.
Culture dimensionality emerged as the principal determinant of proteomic variation across all cell lines. Compared with monolayers, 3D spheroids exhibited significant enrichment of hypoxia response, autophagy-related processes, extracellular matrix organization, and PI3K-Akt signaling pathways. In contrast, 2D cultures preferentially upregulated DNA replication, RNA processing, and cell-cycle-associated pathways. These findings indicate that 3D architecture alone is sufficient to induce coordinated stress-adaptive and survival-oriented proteomic reprogramming in MFS cells.
This study provides a comprehensive proteomic atlas defining dimensionality-dependent molecular states in MFS. While functional validation was beyond the scope of this work, the pathway rewiring identified here establishes a mechanistic framework for future hypothesis-driven investigations targeting autophagy- and PI3K-Akt-associated vulnerabilities in 3D MFS models.
Myxofibrosarcoma (MFS) is characterized by high local recurrence and complex microenvironmental interactions. Although three-dimensional (3D) culture systems better mimic in vivo tumor architecture than conventional two-dimensional (2D) monolayer cultures, the global proteomic consequences of dimensionality in MFS remain incompletely defined.
We performed quantitative mass spectrometry-based proteomic profiling of eight independently established patient-derived MFS cell lines cultured under 2D monolayer and 3D spheroid conditions. Differential protein expression and pathway enrichment analyses were conducted to delineate dimensionality-driven molecular programs.
Culture dimensionality emerged as the principal determinant of proteomic variation across all cell lines. Compared with monolayers, 3D spheroids exhibited significant enrichment of hypoxia response, autophagy-related processes, extracellular matrix organization, and PI3K-Akt signaling pathways. In contrast, 2D cultures preferentially upregulated DNA replication, RNA processing, and cell-cycle-associated pathways. These findings indicate that 3D architecture alone is sufficient to induce coordinated stress-adaptive and survival-oriented proteomic reprogramming in MFS cells.
This study provides a comprehensive proteomic atlas defining dimensionality-dependent molecular states in MFS. While functional validation was beyond the scope of this work, the pathway rewiring identified here establishes a mechanistic framework for future hypothesis-driven investigations targeting autophagy- and PI3K-Akt-associated vulnerabilities in 3D MFS models.
Previous