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10 pages, 336 KiB  
Article
The Impact of Obesity on Clostridioides difficile Infection Outcomes: A Retrospective Cohort Study
by Alaa Atamna, Manar Khalaila, Tanya Babich, Anan Zriek, Haim Ben Zvi, Gida Ayada, Avishay Elis, Jihad Bishara and Amir Nutman
J. Clin. Med. 2025, 14(15), 5459; https://doi.org/10.3390/jcm14155459 (registering DOI) - 3 Aug 2025
Abstract
Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m2) and [...] Read more.
Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) hospitalized patients with CDI. Methods: This retrospective cohort study included patients with CDI hospitalized in Beilinson hospital between January 2013 and January 2020. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, colectomy, intensive care unit (ICU) admission and length of hospital stay (LOS). Multivariate analysis was performed to identify the risk factors independently associated with 90-day mortality. Results: The study included 889 patients: 131 (15%) obese and 758 (85%) non-obese. The obese group was younger (median age 65 years vs. 73 years (p < 0.01)) and with a higher rate of diabetes mellitus (57/131 (44%) vs. 180/758 (24%) (p < 0.01)). The 90-day mortality was lower in the obese group: 19/131 (15%) vs. 170/752 (23%) (p = 0.04). The 30-day mortality was 8/131 (6%) vs. 96/757 (13%) (p = 0.03). ICU admission was 9/131 (7%) vs. 23/758 (3%) (p = 0.03), and median LOS was 19 vs. 12 days (p < 0.01) in obese and non-obese groups, respectively. In the multivariable analysis, after adjustment for age, Charlson’s comorbidity index ≥3, assistance in activities of daily living, treatment with proton pump inhibitors and severity of illness, obesity was not a significant risk factor for 90-day mortality (OR = 0.65, 95% CI: 0.38–1.01; p = 0.1). Conclusions: In this study, obesity was not significantly associated with 90-day mortality after adjustment for other risk factors; however, ICU admission was higher and LOS longer in this group. Full article
17 pages, 516 KiB  
Article
Incidence and Predictive Factors of Acute Kidney Injury After Major Hepatectomy: Implications for Patient Management in Era of Enhanced Recovery After Surgery (ERAS) Protocols
by Henri Mingaud, Jean Manuel de Guibert, Jonathan Garnier, Laurent Chow-Chine, Frederic Gonzalez, Magali Bisbal, Jurgita Alisauskaite, Antoine Sannini, Marc Léone, Marie Tezier, Maxime Tourret, Sylvie Cambon, Jacques Ewald, Camille Pouliquen, Lam Nguyen Duong, Florence Ettori, Olivier Turrini, Marion Faucher and Djamel Mokart
J. Clin. Med. 2025, 14(15), 5452; https://doi.org/10.3390/jcm14155452 (registering DOI) - 2 Aug 2025
Abstract
Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop [...] Read more.
Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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9 pages, 206 KiB  
Article
Examining the Relationship Between Balance and Functional Status in the Geriatric Population
by Eleni Vermisso, Effrosyni Stamou, Garyfallia Tsichli, Ioanna Foteinou and Anna Christakou
Med. Sci. 2025, 13(3), 110; https://doi.org/10.3390/medsci13030110 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: Aging is associated with a gradual decline in physical capabilities, often leading to impaired balance and reduced functional status, which are major contributors to falls in older adults. Although many studies have assessed these variables independently, a limited amount of research has [...] Read more.
Background/Objectives: Aging is associated with a gradual decline in physical capabilities, often leading to impaired balance and reduced functional status, which are major contributors to falls in older adults. Although many studies have assessed these variables independently, a limited amount of research has explored the direct relationship between balance and functional status in a healthy geriatric population. The aim of this study was to investigate the relationship between balance and functional capacity and to assess the influence of demographic factors such as age, comorbidities, smoking status, and history of falls. Methods: A sample of community-dwelling older adults (19 women, 16 men) (n = 35), aged 60 years and above (M = 78 years; SD = 9.23) from Sparta, Greece, took part in the present study. Participants were assessed using three validated tools: (a) the Five Times Sit-to-Stand test, (b) the Timed Up-and-Go test, and (c) the Berg Balance Scale. Spearman’s rank correlation coefficient was used for statistical analysis (α = 0.05). Results: Age was positively correlated with poorer performance in the Five Times Sit-to-Stand (r = 0.40; p < 0.01) and the Timed Up-and-Go test (r = 0.47; p < 0.01) and negatively correlated with Berg Balance Scale scores (r = −0.51; p < 0.01). Comorbidities and smoking were also associated with the Berg Balance Scale. A strong negative correlation was observed between balance and the other two functional tests (Five Times Sit-to-Stand: r = −0.51; Timed Up-and-Go: r = −0.66; both p < 0.01). Conclusions: The findings highlight the importance of evaluating both balance and functional capacity in older adults as interrelated factors that can significantly influence quality of life and fall risk. Future research with larger and more diverse populations is recommended to confirm the present findings and to use exercise programs to prevent falls in the geriatric population. Full article
25 pages, 384 KiB  
Article
Perception of Corporate Governance Factors in Mitigating Financial Statement Fraud in Emerging Markets: Jordan Experience
by Mohammed Shanikat and Mai Mansour Aldabbas
J. Risk Financial Manag. 2025, 18(8), 430; https://doi.org/10.3390/jrfm18080430 (registering DOI) - 1 Aug 2025
Abstract
This study investigates the influence of corporate governance on reducing financial statement fraud (FSF) in Jordanian service and industrial companies listed on the Amman Stock Exchange from 2018 to 2022. To achieve this, the study employed the Beneish M-score model to assess the [...] Read more.
This study investigates the influence of corporate governance on reducing financial statement fraud (FSF) in Jordanian service and industrial companies listed on the Amman Stock Exchange from 2018 to 2022. To achieve this, the study employed the Beneish M-score model to assess the likelihood of FSF and logistic regression to examine the influence of corporate governance structure on fraud mitigation. The study identified 13 independent variables, including board size, board director’s independence, board director’s compensation, non-duality of CEO and chairman positions, board diversity, audit committee size, audit committee accounting background, number of annual audit committee meetings, external audit fees, board family business, the presence of women on the board of directors, firm size, and market listing on FSF. The study included 74 companies from both sectors—33 from the industrial sector and 41 from the service sector. Primary data was collected from financial statements and other information published in annual reports between 2018 and 2022. The results of the study revealed a total of 295 cases of fraud during the examined period. Out of the 59 companies analyzed, 21.4% demonstrated a low probability of fraud, while the remaining 78.6% (232 observations) showed a high probability of fraud. The results indicate that the following corporate governance factors significantly impact the mitigation of financial statement fraud (FSF): independent board directors, board diversity, audit committee accounting backgrounds, the number of audit committee meetings, family business involvement on the board, and firm characteristics. The study provides several recommendations, highlighting the importance for companies to diversify their boards of directors by incorporating different perspectives and experiences. Full article
(This article belongs to the Section Business and Entrepreneurship)
13 pages, 643 KiB  
Article
Using Artificial Intelligence for Detecting Diabetic Foot Osteomyelitis: Validation of Deep Learning Model for Plain Radiograph Interpretation
by Francisco Javier Álvaro-Afonso, Aroa Tardáguila-García, Mateo López-Moral, Irene Sanz-Corbalán, Esther García-Morales and José Luis Lázaro-Martínez
Appl. Sci. 2025, 15(15), 8583; https://doi.org/10.3390/app15158583 (registering DOI) - 1 Aug 2025
Abstract
Objective: To develop and validate a ResNet-50-based deep learning model for automatic detection of osteomyelitis (DFO) in plain radiographs of patients with diabetic foot ulcers (DFUs). Research Design and Methods: This retrospective study included 168 patients with type one or type two diabetes [...] Read more.
Objective: To develop and validate a ResNet-50-based deep learning model for automatic detection of osteomyelitis (DFO) in plain radiographs of patients with diabetic foot ulcers (DFUs). Research Design and Methods: This retrospective study included 168 patients with type one or type two diabetes and clinical suspicion of DFO confirmed via a surgical bone biopsy. An experienced clinician and a pretrained ResNet-50 model independently interpreted the radiographs. The model was developed using Python-based frameworks with ChatGPT assistance for coding. The diagnostic performance was assessed against the histopathological findings, calculating sensitivity, specificity, the positive predictive value (PPV), the negative predictive value (NPV), and the likelihood ratios. Agreement between the AI model and the clinician was evaluated using Cohen’s kappa coefficient. Results: The AI model demonstrated high sensitivity (92.8%) and PPV (0.97), but low-level specificity (4.4%). The clinician showed 90.2% sensitivity and 37.8% specificity. The Cohen’s kappa coefficient between the AI model and the clinician was −0.105 (p = 0.117), indicating weak agreement. Both the methods tended to classify many cases as DFO-positive, with 81.5% agreement in the positive cases. Conclusions: This study demonstrates the potential of IA to support the radiographic diagnosis of DFO using a ResNet-50-based deep learning model. AI-assisted radiographic interpretation could enhance early DFO detection, particularly in high-prevalence settings. However, further validation is necessary to improve its specificity and assess its utility in primary care. Full article
(This article belongs to the Special Issue Applications of Sensors in Biomechanics and Biomedicine)
14 pages, 898 KiB  
Article
Cardiovascular Risk in Rheumatic Patients Treated with JAK Inhibitors: The Role of Traditional and Emerging Biomarkers in a Pilot Study
by Diana Popescu, Minerva Codruta Badescu, Elena Rezus, Daniela Maria Tanase, Anca Ouatu, Nicoleta Dima, Oana-Nicoleta Buliga-Finis, Evelina Maria Gosav, Damiana Costin and Ciprian Rezus
J. Clin. Med. 2025, 14(15), 5433; https://doi.org/10.3390/jcm14155433 (registering DOI) - 1 Aug 2025
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Abstract
Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and [...] Read more.
Background: Despite therapeutic advances, morbidity and mortality remain high in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA), primarily due to increased cardiovascular risk. Objectives: Our study aimed to evaluate the cardiovascular risk profile and biomarker dynamics in patients with RA and PsA treated with Janus kinase inhibitors (JAKis). To our knowledge, this is the first study assessing Lp(a) levels in this context. Methods: This prospective, observational study assessed 48 adult patients. The follow-up period was 12 months. Traditional cardiovascular risk factors and biological markers, including lipid profile, lipoprotein(a) [Lp(a)], and uric acid (UA), were assessed at baseline and follow-up. Correlations between JAKi therapy, lipid profile changes, and cardiovascular risk factors were investigated. Cox regression analysis was used to identify predictors of non-major cardiovascular events. Results: A strong positive correlation was observed between baseline and 12-month Lp(a) levels (r = 0.926), despite minor statistical shifts. No major cardiovascular events occurred during follow-up; however, 47.9% of patients experienced non-major cardiovascular events (e.g., uncontrolled arterial hypertension, exertional angina, and new-onset arrhythmias). Active smoking [hazard ratio (HR) 9.853, p = 0.005], obesity (HR 3.7460, p = 0.050), and arterial hypertension (HR 1.219, p = 0.021) were independent predictors of these events. UA (HR 1.515, p = 0.040) and total cholesterol (TC) (HR 1.019, p = 0.034) were significant biochemical predictors as well. Elevated baseline Lp(a) combined with these factors was associated with an increased event rate, particularly after age 60. Conclusions: Traditional cardiovascular risk factors remain highly prevalent and predictive, underscoring the need for comprehensive cardiovascular risk management. Lp(a) remained stable and may serve as a complementary biomarker for risk stratification in JAKi-treated patients. Full article
(This article belongs to the Section Immunology)
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34 pages, 434 KiB  
Article
Mobile Banking Adoption: A Multi-Factorial Study on Social Influence, Compatibility, Digital Self-Efficacy, and Perceived Cost Among Generation Z Consumers in the United States
by Santosh Reddy Addula
J. Theor. Appl. Electron. Commer. Res. 2025, 20(3), 192; https://doi.org/10.3390/jtaer20030192 (registering DOI) - 1 Aug 2025
Viewed by 39
Abstract
The introduction of mobile banking is essential in today’s financial sector, where technological innovation plays a critical role. To remain competitive in the current market, businesses must analyze client attitudes and perspectives, as these influence long-term demand and overall profitability. While previous studies [...] Read more.
The introduction of mobile banking is essential in today’s financial sector, where technological innovation plays a critical role. To remain competitive in the current market, businesses must analyze client attitudes and perspectives, as these influence long-term demand and overall profitability. While previous studies have explored general adoption behaviors, limited research has examined how individual factors such as social influence, lifestyle compatibility, financial technology self-efficacy, and perceived usage cost affect mobile banking adoption among specific generational cohorts. This study addresses that gap by offering insights into these variables, contributing to the growing literature on mobile banking adoption, and presenting actionable recommendations for financial institutions targeting younger market segments. Using a structured questionnaire survey, data were collected from both users and non-users of mobile banking among the Gen Z population in the United States. The regression model significantly predicts mobile banking adoption, with an intercept of 0.548 (p < 0.001). Among the independent variables, perceived cost of usage has the strongest positive effect on adoption (B=0.857, β=0.722, p < 0.001), suggesting that adoption increases when mobile banking is perceived as more affordable. Social influence also has a significant positive impact (B=0.642, β=0.643, p < 0.001), indicating that peer influence is a central driver of adoption decisions. However, self-efficacy shows a significant negative relationship (B=0.343, β=0.339, p < 0.001), and lifestyle compatibility was found to be statistically insignificant (p=0.615). These findings suggest that reducing perceived costs, through lower fees, data bundling, or clearer communication about affordability, can directly enhance adoption among Gen Z consumers. Furthermore, leveraging peer influence via referral rewards, Partnerships with influencers, and in-app social features can increase user adoption. Since digital self-efficacy presents a barrier for some, banks should prioritize simplifying user interfaces and offering guided assistance, such as tutorials or chat-based support. Future research may employ longitudinal designs or analyze real-life transaction data for a more objective understanding of behavior. Additional variables like trust, perceived risk, and regulatory policies, not included in this study, should be integrated into future models to offer a more comprehensive analysis. Full article
13 pages, 724 KiB  
Article
Investigating the Diagnostic Utility of LncRNA GAS5 in NAFLD Patients
by Maysa A. Mobasher, Alaa Muqbil Alsirhani, Sahar Abdulrahman Alkhodair, Amir Abd-elhameed, Shereen A. Baioumy, Marwa M. Esawy and Marwa A. Shabana
Biomedicines 2025, 13(8), 1873; https://doi.org/10.3390/biomedicines13081873 (registering DOI) - 1 Aug 2025
Viewed by 32
Abstract
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in [...] Read more.
Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions globally. This study aimed to assess the long non-coding RNAs (lncRNAs) growth arrest-specific 5 (GAS5), miR-29a-3p, and neurogenic locus notch homolog protein 2 (NOTCH2) as biomarkers in patients with NAFLD and find out if they are related to any clinical factors. Subjects and Methods: Thirty-eight age-matched healthy persons and thirty-eight NAFLD patients were enrolled. Patients were split into the following three groups: non-alcoholic steatohepatitis (NASH) (n = 12), patients with NAFLD-related cirrhosis (n = 8), and patients with NAFLD-related simple steatosis (n = 18). Real-time PCR was utilized to examine the expression. Results: The lncRNA GAS5 and NOTCH2 were higher in NAFLD cases in comparison to controls. On the other hand, microRNA-29a-3p was underexpressed in NAFLD cases in comparison to controls. Regarding NAFLD diagnosis, lncRNA GAS5 was the best single marker with a sensitivity of 100% and a specificity of 94.7% at the cutoff values of ≥1.16-fold change. Regarding different stages of the disease, the highest level of lncRNA GAS5 was in cirrhosis. lncRNA GAS5 expression, among other studied parameters, is still a significant predictor of NAFLD (adjusted odds ratio of 162, C.I. = 5.7–4629) (p = 0.003). LncRNA GAS5 has a positive correlation with NOTCH2 and a negative correlation with miR-29a-3p. LncRNA GAS5, NOTCH2, and RNA-29a-3p were significantly different in NAFLD cases compared to controls. Conclusions: lncRNA GAS5 appears to be the most effective single marker for detecting NAFLD. LncRNA GAS5 expression is a significant independent predictor of NAFLD. LncRNA GAS5 can differentiate different NAFLD stages. Full article
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15 pages, 5769 KiB  
Article
Higher Winter Precipitation and Temperature Are Associated with Smaller Earlywood Vessel Size but Wider Latewood Width in Quercus faginea Lam.
by Ignacio García-González, Filipe Campelo, Joana Vieira and Cristina Nabais
Forests 2025, 16(8), 1252; https://doi.org/10.3390/f16081252 - 1 Aug 2025
Viewed by 45
Abstract
Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions [...] Read more.
Quercus faginea Lam., a winter-deciduous oak native to the Iberian Peninsula, typically grows under a Mediterranean climate. To identify the main drivers influencing radial wood increment, we analyzed the climatic signals in tree-ring width and wood anatomical traits using increment cores. Winter conditions influenced both latewood width and earlywood vessel size in the first row. Latewood was positively correlated with precipitation and temperature, with the long-term positive effect of winter water supply supported by SPEI. In contrast, vessel size showed negative correlations, also reflecting a long-term negative effect of winter precipitation. Consequently, conditions that enhanced latewood width and overall tree-ring growth appear to be associated with the formation of smaller earlywood vessels. Although ample winter precipitation replenishes soil water reserves and supports prolonged wood formation, it may also induce anaerobic soil conditions that promote root fermentation, depleting carbohydrates needed for cell turgor and expansion, and ultimately regulating earlywood vessel size. This physiological decoupling may help explain the lack of a significant correlation between latewood width and earlywood vessel size, underscoring their independent responses to environmental influences. Our findings highlighted the complex interplay between various climatic conditions affecting Q. faginea, with implications for understanding its adaptive capacity in changing climates. Full article
(This article belongs to the Section Forest Ecophysiology and Biology)
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12 pages, 954 KiB  
Article
Health-Related Quality of Life and Internalising Symptoms in Romanian Children with Congenital Cardiac Malformations: A Single-Centre Cross-Sectional Analysis
by Andrada Ioana Dumitru, Andreea Mihaela Kis, Mihail-Alexandru Badea, Adrian Lacatusu and Marioara Boia
Healthcare 2025, 13(15), 1882; https://doi.org/10.3390/healthcare13151882 - 1 Aug 2025
Viewed by 82
Abstract
Background and Objectives: Although survival after congenital cardiac malformations (CCM) has improved, little is known about Romanian children’s own perceptions of health-related quality of life (HRQoL) or their emotional burden. We compared HRQoL, depressive symptoms, and anxiety across lesion severity strata and [...] Read more.
Background and Objectives: Although survival after congenital cardiac malformations (CCM) has improved, little is known about Romanian children’s own perceptions of health-related quality of life (HRQoL) or their emotional burden. We compared HRQoL, depressive symptoms, and anxiety across lesion severity strata and explored clinical predictors of impaired HRQoL. Methods: In this cross-sectional study (1 May 2023–30 April 2025), 72 children (mean age 7.9 ± 3.0 years, 52.8% male) attending a tertiary cardiology clinic completed the Romanian-validated Pediatric Quality of Life Inventory (PedsQL), Children’s Depression Inventory (CDI) and the Screen for Child Anxiety-Related Emotional Disorders questionnaire (SCARED-C, child version). Lesions were classified as mild (n = 22), moderate (n = 34), or severe (n = 16). Left-ventricular ejection fraction (LVEF) and unplanned cardiac hospitalisations over the preceding 12 months were extracted from electronic records. Results: Mean PedsQL total scores declined stepwise by severity (mild 80.9 ± 7.3; moderate 71.2 ± 8.4; severe 63.1 ± 5.4; p < 0.001). CDI and SCARED-C scores rose correspondingly (CDI: 9.5 ± 3.0, 13.6 ± 4.0, 18.0 ± 2.7; anxiety: 15.2 ± 3.3, 17.2 ± 3.8, 24.0 ± 3.4; both p < 0.001). PedsQL correlated positively with LVEF (r = 0.51, p < 0.001) and negatively with hospitalisations (r = −0.39, p = 0.001), depression (r = −0.44, p < 0.001), and anxiety (r = −0.47, p < 0.001). In multivariable analysis, anatomical severity remained the sole independent predictor of lower HRQoL (β = −8.4 points per severity tier, p < 0.001; model R2 = 0.45). Children with ≥ 1 hospitalisation (n = 42) reported poorer HRQoL (69.6 ± 8.0 vs. 76.1 ± 11.1; p = 0.005) and higher depressive scores (p < 0.001). Conclusions: HRQoL and internalising symptoms in Romanian children with CCM worsen with increasing anatomical complexity and recent hospital utilisation. The severity tier outweighed functional markers as the main determinant of HRQoL, suggesting that psychosocial screening and support should be scaled to lesion complexity. Integrating the routine use of the Romanian-validated PedsQL, CDI, and SCARED-C questionnaire into cardiology follow-up may help identify vulnerable patients early and guide targeted interventions. Full article
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12 pages, 269 KiB  
Article
Exploring the Interplay Between Glycated Albumin, AGEs, and Inflammation in Old Patients with CKD
by Simone Vettoretti, Lara Caldiroli, Paolo Molinari, Amanda Villa, Massimiliano M. Corsi Romanelli, Elena Vianello, Elena Dozio and Simonetta Genovesi
Metabolites 2025, 15(8), 515; https://doi.org/10.3390/metabo15080515 (registering DOI) - 1 Aug 2025
Viewed by 114
Abstract
Introduction: Chronic kidney disease (CKD) increases cardiovascular risk through mechanisms such as oxidative stress and the accumulation of advanced glycation end products (AGEs). Glycated albumin (GA) is associated with cardiovascular risk in CKD patients, but its relationship with AGEs and systemic inflammation remains [...] Read more.
Introduction: Chronic kidney disease (CKD) increases cardiovascular risk through mechanisms such as oxidative stress and the accumulation of advanced glycation end products (AGEs). Glycated albumin (GA) is associated with cardiovascular risk in CKD patients, but its relationship with AGEs and systemic inflammation remains unclear. This study investigated these associations in old patients with severe CKD, with and without diabetes. Methods: We conducted a cross-sectional analysis in 122 patients aged ≥ 65 years with CKD stages G3a–G5, including 67 diabetics and 55 non-diabetics. Patients with confounding comorbidities were excluded. We measured GA, AGEs, various AGEs receptors (RAGE) isoforms, and inflammatory cytokines (CRP, IL-6, TNFα, and MCP-1) using standardized assays. Statistical analyses included group comparisons, correlation coefficients, and multivariate regression. Results: Of 122 patients (mean age 77.7 ± 11.3 years), diabetics had higher GA percentages than non-diabetics (22.0 ± 7.1% vs. 17.5 ± 5.4%, p = 0.0001), while AGEs (2931 ± 763 vs. 3156 ± 809 AU; p = 0.118) and inflammatory markers (CRP 0.240[0.380] vs. 0.200[0.280] mg/dL; p = 0.142; IL-6 3.4[4.0] vs. 3.0[3.8] pg/mL; p = 0.238) were similar between groups. Overall, GA was inversely correlated with estimated glomerular filtration rate (eGFR) (ρ = −0.189, p = 0.037) and positively with glycated hemoglobin (HbA1c) (ρ = 0.525, p < 0.0001), but showed no significant correlation with AGEs, RAGE isoforms, or inflammatory cytokines. In multivariate analysis, only HbA1c remained independently associated with GA (β = 0.222, p = 0.005). Conclusions: In old patients with severe CKD, GA appears to be a more useful marker of glycemic control than glycation stress, the latter of which is the result of multiple factors, including impaired kidney function and systemic inflammation. Full article
15 pages, 606 KiB  
Article
Assessment of the Physical and Emotional Health-Related Quality of Life Among Congestive Heart Failure Patients with Preserved and Reduced Ejection Fraction at a Quaternary Care Teaching Hospital in Coastal Karnataka in India
by Rajesh Kamath, Vineetha Poojary, Nishanth Shekar, Kanhai Lalani, Tarushree Bari, Prajwal Salins, Gwendolen Rodrigues, Devesh Teotia and Sanjay Kini
Healthcare 2025, 13(15), 1874; https://doi.org/10.3390/healthcare13151874 - 31 Jul 2025
Viewed by 137
Abstract
Introduction: Congestive heart failure (CHF), a complex clinical syndrome characterized by the heart’s inability to pump blood effectively due to structural or functional impairments, is a growing public health concern, with profound implications for patients’ physical and emotional well-being. In India, the burden [...] Read more.
Introduction: Congestive heart failure (CHF), a complex clinical syndrome characterized by the heart’s inability to pump blood effectively due to structural or functional impairments, is a growing public health concern, with profound implications for patients’ physical and emotional well-being. In India, the burden of CHF is rising due to aging demographics and increasing prevalence of lifestyle-related risk factors. Among the subtypes of CHF, heart failure with preserved ejection fraction (HFpEF), i.e., heart failure with left ventricular ejection fraction of ≥50% with evidence of spontaneous or provokable increased left ventricular filling pressure, and heart failure with reduced ejection fraction (HFrEF), i.e., heart failure with left ventricular ejection fraction of 40% or less and is accompanied by progressive left ventricular dilatation and adverse cardiac remodeling, may present differing impacts on health-related quality of life (HRQoL), i.e., an individual’s or a group’s perceived physical and mental health over time, yet comparative data remains limited. This study assesses HRQoL among CHF patients using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), one of the most widely used health-related quality of life questionnaires for patients with heart failure based on physical and emotional dimensions and identifies sociodemographic and clinical variables influencing these outcomes. Methods: A cross-sectional analytical study was conducted among 233 CHF patients receiving inpatient and outpatient care at the Department of Cardiology at a quaternary care teaching hospital in coastal Karnataka in India. Participants were enrolled using convenience sampling. HRQoL was evaluated through the MLHFQ, while sociodemographic and clinical characteristics were recorded via a structured proforma. Statistical analyses included descriptive measures, independent t-test, Spearman’s correlation and stepwise multivariable linear regression to identify associations and predictors. Results: The mean HRQoL score was 56.5 ± 6.05, reflecting a moderate to high symptom burden. Patients with HFpEF reported significantly worse HRQoL (mean score: 61.4 ± 3.94) than those with HFrEF (52.9 ± 4.64; p < 0.001, Cohen’s d = 1.95). A significant positive correlation was observed between HRQoL scores and age (r = 0.428; p < 0.001), indicating that older individuals experienced a higher burden of symptoms. HRQoL also varied significantly across NYHA functional classes (χ2 = 69.9, p < 0.001, ε2 = 0.301) and employment groups (χ2 = 17.0, p < 0.001), with further differences noted by education level, gender and marital status (p < 0.05). Multivariable linear regression identified age (B = 0.311, p < 0.001) and gender (B = –4.591, p < 0.001) as significant predictors of poorer HRQoL. Discussion: The findings indicate that patients with HFpEF experience significantly poorer HRQoL than those with HFrEF. Older adults and female patients reported greater symptom burden, underscoring the importance of demographic-sensitive care approaches. These results highlight the need for routine integration of HRQoL assessment into clinical practice and the development of comprehensive, personalized interventions addressing both physical and emotional health dimensions, especially for vulnerable subgroups. Conclusions: CHF patients, especially those with HFpEF, face reduced HRQoL. Key factors include age, gender, education, employment, marital status, and NYHA class, underscoring the need for patient-centered care. Full article
(This article belongs to the Special Issue Patient Experience and the Quality of Health Care)
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20 pages, 2714 KiB  
Article
Diagnosing Bias and Instability in LLM Evaluation: A Scalable Pairwise Meta-Evaluator
by Catalin Anghel, Andreea Alexandra Anghel, Emilia Pecheanu, Adina Cocu, Adrian Istrate and Constantin Adrian Andrei
Information 2025, 16(8), 652; https://doi.org/10.3390/info16080652 (registering DOI) - 31 Jul 2025
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Abstract
The evaluation of large language models (LLMs) increasingly relies on other LLMs acting as automated judges. While this approach offers scalability and efficiency, it raises serious concerns regarding evaluator reliability, positional bias, and ranking stability. This paper presents a scalable framework for diagnosing [...] Read more.
The evaluation of large language models (LLMs) increasingly relies on other LLMs acting as automated judges. While this approach offers scalability and efficiency, it raises serious concerns regarding evaluator reliability, positional bias, and ranking stability. This paper presents a scalable framework for diagnosing positional bias and instability in LLM-based evaluation by using controlled pairwise comparisons judged by multiple independent language models. The system supports mirrored comparisons with reversed response order, prompt injection, and surface-level perturbations (e.g., paraphrasing, lexical noise), enabling fine-grained analysis of evaluator consistency and verdict robustness. Over 3600 pairwise comparisons were conducted across five instruction-tuned open-weight models using ten open-ended prompts. The top-performing model (gemma:7b-instruct) achieved a 66.5% win rate. Evaluator agreement was uniformly high, with 100% consistency across judges, yet 48.4% of verdicts reversed under mirrored response order, indicating strong positional bias. Kendall’s Tau analysis further showed that local model rankings varied substantially across prompts, suggesting that semantic context influences evaluator judgment. All evaluation traces were stored in a graph database (Neo4j), enabling structured querying and longitudinal analysis. The proposed framework provides not only a diagnostic lens for benchmarking models but also a blueprint for fairer and more interpretable LLM-based evaluation. These findings underscore the need for structure-aware, perturbation-resilient evaluation pipelines when benchmarking LLMs. The proposed framework offers a reproducible path for diagnosing evaluator bias and ranking instability in open-ended language tasks. Future work will apply this methodology to educational assessment tasks, using rubric-based scoring and graph-based traceability to evaluate student responses in technical domains. Full article
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15 pages, 7649 KiB  
Article
S100A14 as a Potential Biomarker of the Colorectal Serrated Neoplasia Pathway
by Pierre Adam, Catherine Salée, Florence Quesada Calvo, Arnaud Lavergne, Angela-Maria Merli, Charlotte Massot, Noëlla Blétard, Joan Somja, Dominique Baiwir, Gabriel Mazzucchelli, Carla Coimbra Marques, Philippe Delvenne, Edouard Louis and Marie-Alice Meuwis
Int. J. Mol. Sci. 2025, 26(15), 7401; https://doi.org/10.3390/ijms26157401 (registering DOI) - 31 Jul 2025
Viewed by 174
Abstract
Accounting for 15–30% of colorectal cancer cases, the serrated pathway remains poorly characterized compared to the adenoma–carcinoma sequence. It involves sessile serrated lesions as precursors and is characterized by BRAF mutations (BRAFV600E), CpG island hypermethylation, and microsatellite instability (MSI). Using label-free [...] Read more.
Accounting for 15–30% of colorectal cancer cases, the serrated pathway remains poorly characterized compared to the adenoma–carcinoma sequence. It involves sessile serrated lesions as precursors and is characterized by BRAF mutations (BRAFV600E), CpG island hypermethylation, and microsatellite instability (MSI). Using label-free proteomics, we compared normal tissue margins from patients with diverticular disease, sessile serrated lesions, low-grade adenomas, and high-grade adenomas. We identified S100A14 as significantly overexpressed in sessile serrated lesions compared to low-grade adenomas, high-grade adenomas, and normal tissues. This overexpression was confirmed by immunohistochemical scoring in an independent cohort. Gene expression analyses of public datasets showed higher S100A14 expression in BRAFV600E-mutated and MSI-H colorectal cancers compared to microsatellite stable BRAFwt tumors. This finding was confirmed by immunohistochemical scoring in an independent colorectal cancer cohort. Furthermore, single-cell RNA sequencing analysis from the Human Colon Cancer Atlas revealed that S100A14 expression in tumor cells positively correlated with the abundance of tumoral CD8+ cytotoxic T cells, particularly the CD8+ CXCL13+ subset, known for its association with a favorable response to immunotherapy. Collectively, our results demonstrate for the first time that S100A14 is a potential biomarker of serrated neoplasia and further suggests its potential role in predicting immunotherapy responses in colorectal cancer. Full article
(This article belongs to the Special Issue Molecular Diagnosis and Treatment of Colorectal Cancer)
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20 pages, 5322 KiB  
Article
Regulation of Tetraspanin CD63 in Chronic Myeloid Leukemia (CML): Single-Cell Analysis of Asymmetric Hematopoietic Stem Cell Division Genes
by Christophe Desterke, Annelise Bennaceur-Griscelli and Ali G. Turhan
Bioengineering 2025, 12(8), 830; https://doi.org/10.3390/bioengineering12080830 (registering DOI) - 31 Jul 2025
Viewed by 170
Abstract
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity [...] Read more.
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity via asymmetric cell divisions, sustaining the stem cell pool. Quiescent LSCs are known to be resistant to tyrosine kinase inhibitors (TKIs), potentially through BCR::ABL-independent signaling pathways. We hypothesize that dysregulation of genes governing asymmetric division in LSCs contributes to disease progression, and that their expression pattern may serve as a prognostic marker during the chronic phase of CML. (2) Methods: Genes related to asymmetric cell division in the context of hematopoietic stem cells were extracted from the PubMed database with the keyword “asymmetric hematopoietic stem cell”. The collected relative gene set was tested on two independent bulk transcriptome cohorts and the results were confirmed by single-cell RNA sequencing. (3) Results: The expression of genes involved in asymmetric hematopoietic stem cell division was found to discriminate disease phases during CML progression in the two independent transcriptome cohorts. Concordance between cohorts was observed on asymmetric molecules downregulated during blast crisis (BC) as compared to the chronic phase (CP). This downregulation during the BC phase was confirmed at single-cell level for SELL, CD63, NUMB, HK2, and LAMP2 genes. Single-cell analysis during the CP found that CD63 is associated with a poor prognosis phenotype, with the opposite prediction revealed by HK2 and NUMB expression. The single-cell trajectory reconstitution analysis in CP samples showed CD63 regulation highlighting a trajectory cluster implicating HSPB1, PIM2, ANXA5, LAMTOR1, CFL1, CD52, RAD52, MEIS1, and PDIA3, known to be implicated in hematopoietic malignancies. (4) Conclusion: Regulation of CD63, a tetraspanin involved in the asymmetric division of hematopoietic stem cells, was found to be associated with poor prognosis during CML progression and could be a potential new therapeutic target. Full article
(This article belongs to the Special Issue Micro- and Nano-Technologies for Cell Analysis)
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