Medical Sciences

12 pages, 1984 KB

Open AccessArticle

Sensory Recovery After Free Muscle Flap Reconstruction—A Clinical Study of Protective and Discriminative Function of Free Gracilis and Latissimus Dorsi Muscle Flaps Without Neurotization

by Maximilian C. Stumpfe, Moritz Billner, Marc Hellweg, Maximilian Hirschmann, Rakan R. Al-Turki, Celena A. Sörgel, Vadym Burchak, Nikolaus Wachtel and Denis Ehrl

Med. Sci. 2025, 13(4), 262; https://doi.org/10.3390/medsci13040262 - 7 Nov 2025

Abstract

Background/Objectives: Free gracilis (GM) and latissimus dorsi muscle (LDM) flaps are reliable options for complex defect coverage, but long-term sensory outcomes remain underexplored. Sensory impairment, especially the loss of protective cutaneous sensation, increases the risk of injury, thermal damage, and ulceration in reconstructed [...] Read more.

Background/Objectives: Free gracilis (GM) and latissimus dorsi muscle (LDM) flaps are reliable options for complex defect coverage, but long-term sensory outcomes remain underexplored. Sensory impairment, especially the loss of protective cutaneous sensation, increases the risk of injury, thermal damage, and ulceration in reconstructed areas. This study aimed to systematically assess multidimensional sensory recovery after free muscle flap (FMF) reconstruction. Methods: In a prospective single-center study, 94 patients (49 GM, 45 LDM) underwent standardized sensory testing following FMF transfer. Five modalities were evaluated: pressure detection (Semmes-Weinstein monofilaments), vibration perception, two-point discrimination (2PD), sharp–dull differentiation, and temperature differentiation. Measurements were compared to contralateral healthy skin (CHS). Subgroup analyses were performed by anatomical region (head, trunk, extremities). Results: All sensory modalities were significantly impaired in FMF compared to CHS (p < 0.0001). Mean pressure thresholds were markedly higher in FMF (248.8 g) versus CHS (46.8 g). Vibration perception scores were reduced (FMF 3.97 vs. CHS 5.31), and 2PD was significantly poorer (11.6 cm vs. 4.7 cm). Sharp–dull and thermal discrimination were largely absent in FMF (positivity rates < 20%), with 58.5% of patients demonstrating only deep pressure sensation (≥300 g). No significant differences were found between GM and LDM in most modalities, except for worse 2PD in GM. Subgroup analyses confirmed uniform deficits across all anatomical regions. Conclusions: FMFs without neurotization result in profound, persistent sensory deficits, particularly the loss of protective sensation. Clinically, fascio-cutaneous flaps with nerve coaptation should be considered in functionally critical regions. Future strategies should focus on neurotization techniques to enhance sensory recovery. Full article

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19 pages, 31470 KB

Open AccessSystematic Review

Exit Meta-Analysis on the Effect of HIV on COVID-19 Mortality, Hospitalization, and ICU Admission

by Lubna A. Zar, Shahd Hamran, Izzaldin Alremawi, Mohamed Elahtam, Asmaa Abdelmaksoud, Rida Arif and Tawanda Chivese

Med. Sci. 2025, 13(4), 261; https://doi.org/10.3390/medsci13040261 - 7 Nov 2025

Abstract

Purpose: The COVID-19 pandemic has led to the publication of numerous primary studies and meta-analyses; however, conclusive evidence on whether HIV infection influences COVID-19 outcomes among people living with HIV (PLHIV) is still lacking. This research uses a novel technique, the exit meta-analysis [...] Read more.

Purpose: The COVID-19 pandemic has led to the publication of numerous primary studies and meta-analyses; however, conclusive evidence on whether HIV infection influences COVID-19 outcomes among people living with HIV (PLHIV) is still lacking. This research uses a novel technique, the exit meta-analysis, to conclusively update the evidence of HIV’s impact on COVID-19-related mortality, hospitalization, and need for Intensive Care Unit (ICU) admission in severe disease. Methods: A search of PubMed, EMBASE, Cochrane Reviews (CDSR), SCOPUS, CINAHL reviews and Google Scholar databases was conducted up to the 18 January 2024 for meta-analyses and observational studies that reported adjusted associations for the effect of HIV on COVID-19 related mortality, hospitalization, and ICU admission. Evidence from existing meta-analyses was summarized narratively, and an updated meta-analysis was carried out using a bias-adjusted inverse variance heterogeneity model. Subgroup analysis was carried out for age groups and geographical regions. Results: Of 3153 records identified, 20 meta-analyses and 56 primary studies, with a total of 27,936,428 participants, including 655,882 PLHIV, were included. A review of the meta-analyses showed conflicting results for all outcomes. In the updated synthesis, HIV was associated with higher odds of mortality (aOR 1.43, 95% CI: 1.01–1.86, I² = 90.7%) and ICU admission (aOR 1.49, 95% CI: 0.67–2.30, I² = 88.8%), but not hospitalization (aOR 1.11, 95% CI: 0.78–1.48, I² = 97.5%). The results for both ICU admission and hospitalization include the null value, leading to lower certainty. The exit meta-analysis suggested conclusive results for mortality (DAts score = −0.012) and hospitalization (DAts score = −0.014), but not for ICU admission. Conclusions: This exit meta-analysis provides conclusive evidence that HIV increases mortality in people with COVID-19; however, more studies may be required to address ICU admission and hospitalization. Full article

(This article belongs to the Section Immunology and Infectious Diseases)

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14 pages, 1281 KB

Open AccessSystematic Review

Data Augmentation and Synthetic Data Generation in Rare Disease Research: A Scoping Review

by Rebecca Finetti, Bianca Roncaglia, Anna Visibelli, Ottavia Spiga and Annalisa Santucci

Med. Sci. 2025, 13(4), 260; https://doi.org/10.3390/medsci13040260 - 6 Nov 2025

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Abstract

Background: Rare diseases represent a significant research challenge due to the limited availability of data, small patient cohorts, and heterogeneous phenotypes. Data augmentation and synthetic data generation are increasingly adopted to mitigate these limitations. Methods: This scoping review maps the application of data [...] Read more.

Background: Rare diseases represent a significant research challenge due to the limited availability of data, small patient cohorts, and heterogeneous phenotypes. Data augmentation and synthetic data generation are increasingly adopted to mitigate these limitations. Methods: This scoping review maps the application of data augmentation and synthetic data generation methods as strategies to address these limitations. A total of 118 studies published between 2018 and 2025 were identified through PubMed, Scopus, and Electronics Engineers (IEEE) Xplore. Results: Imaging data headed the field, followed by clinical and omics datasets. Classical augmentation, mainly geometric and photometric transformations, emerged as the most frequent approach, while deep generative models have rapidly expanded since 2021. Rule- and model-based methods were less common but demonstrated high interpretability in small datasets. Conclusions: Overall, these techniques enabled dataset expansion and improved model robustness. However, both approaches require rigorous validation to confirm biological plausibility. Together, these methods can transform data scarcity from a barrier into a driver of methodological innovation, enabling more inclusive rare disease research. Full article

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24 pages, 676 KB

Open AccessSystematic Review

Integrating Mental Health into Diabetes Care: Closing the Treatment Gap for Better Outcomes—A Systematic Review

by Shakila Jahan Shimu, Shamima Akter, Md. Majedur Rahman, Shahida Arbee, Mohammad Sarif Mohiuddin, Sadman Sazzad, Mahjabin Raiqa, Mohammad Mohabbulla Mohib, Afsana R. Munmun and Mohammad Borhan Uddin

Med. Sci. 2025, 13(4), 259; https://doi.org/10.3390/medsci13040259 - 3 Nov 2025

Viewed by 520

Abstract

Background: Diabetes and mental health conditions frequently co-occur, with depression and anxiety affecting up to 20–30% of people with diabetes. These comorbidities worsen glycemic control, adherence, and quality of life, yet mental health is often neglected in diabetes care. Integrating mental health services [...] Read more.

Background: Diabetes and mental health conditions frequently co-occur, with depression and anxiety affecting up to 20–30% of people with diabetes. These comorbidities worsen glycemic control, adherence, and quality of life, yet mental health is often neglected in diabetes care. Integrating mental health services into diabetes management is recommended by international organizations to improve patient outcomes. Objectives: To systematically review the evidence on integrated mental health interventions in diabetes care, compared to usual diabetes care, in improving patient outcomes (glycemic control, mental health, adherence, quality of life). Methods: We searched PubMed/MEDLINE, Embase, PsycINFO, and Scopus (2000 through July 2024) for studies of diabetes care integrating mental health support (e.g., collaborative care, co-location, stepped care, or digital interventions). Inclusion criteria were controlled trials or cohort studies involving individuals with type 1 or type 2 diabetes receiving an integrated mental health intervention, with outcomes on glycemic control and/or mental health. Two reviewers independently screened titles/abstracts and full texts, with disagreements resolved by consensus. Data on study design, population, intervention components, and outcomes were extracted. Risk of bias was assessed using Cochrane or appropriate tools. Results: Out of records identified, 64 studies met inclusion criteria (primarily randomized controlled trials). Integrated care models consistently improved depression and anxiety outcomes and diabetes-specific distress, and yielded modest but significant reductions in glycated hemoglobin (HbA1c) compared to usual care. Many interventions also enhanced treatment adherence and self-management behaviors. For example, collaborative care trials showed greater depression remission rates and small HbA1c improvements (~0.3–0.5% absolute reduction) relative to standard care. Co-located care in diabetes clinics was associated with reduced diabetes distress, depression scores, and HbA1c over 12 months. Digital health integrations (telepsychiatry, online cognitive-behavioral therapy) improved psychological outcomes and adherence, with some reporting slight improvements in glycemic control. Integrated approaches often increased uptake of mental health services (e.g., higher referral completion rates) and showed high patient satisfaction. A subset of studies reported fewer emergency visits and hospitalizations with integrated care, and one economic analysis found collaborative care cost-effective in primary care settings. Conclusions: Integrating mental health into diabetes care leads to better mental health outcomes and modest improvements in glycemic control, without adverse effects. Heterogeneity across studies is noted, but the overall evidence supports multidisciplinary, patient-centered care models to address the psychosocial needs of people with diabetes. Healthcare systems should prioritize implementing and scaling integrated care, accompanied by provider training and policy support, to improve outcomes and bridge the persistent treatment gap. Future research should focus on long-term effectiveness, cost-effectiveness, and strategies to reach diverse populations. Full article

(This article belongs to the Section Translational Medicine)

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21 pages, 3651 KB

Open AccessSystematic Review

Effectiveness of Different Types of Core Decompression in Early-Stage Osteonecrosis of the Femoral Head: A Systematic Review and Meta-Analysis

by Wojciech Konarski

Med. Sci. 2025, 13(4), 258; https://doi.org/10.3390/medsci13040258 - 3 Nov 2025

Viewed by 109

Abstract

Background: Osteonecrosis of the femoral head is a progressive disorder leading to femoral head collapse and early disability, often affecting young adults. Core decompression (CD) is the most established hip-preserving treatment for early-stage disease, yet the comparative benefits of biological and structural augmentation [...] Read more.

Background: Osteonecrosis of the femoral head is a progressive disorder leading to femoral head collapse and early disability, often affecting young adults. Core decompression (CD) is the most established hip-preserving treatment for early-stage disease, yet the comparative benefits of biological and structural augmentation remain uncertain. Methods: This systematic review and meta-analysis, registered in PROSPERO (CRD420251108396), evaluated 14 studies encompassing 1210 patients treated with CD alone or CD combined with biological (e.g., platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate) or structural (e.g., bone grafting, fibular support) augmentation. Results: Pooled random-effects models demonstrated that biological augmentation yielded significant improvements in Harris Hip Score and pain reduction (VAS) up to 24 months, with early peaks and subsequent stabilization, whereas structural augmentation showed no functional advantage at any time point. Radiological progression and conversion to total hip arthroplasty were not significantly reduced, though long-term trends favored biologically augmented CD. Conclusions: Overall, biological augmentation provides durable functional and symptomatic benefits in early-stage osteonecrosis, supporting its use as a first-line adjunct to CD, while structural augmentation appears less consistent and warrants further evaluation through large, standardized trials. Full article

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16 pages, 3443 KB

Open AccessArticle

Automated Detection and Grading of Renal Cell Carcinoma in Histopathological Images via Efficient Attention Transformer Network

by Hissa Al-kuwari, Belqes Alshami, Aisha Al-Khinji, Adnan Haider and Muhammad Arsalan

Med. Sci. 2025, 13(4), 257; https://doi.org/10.3390/medsci13040257 - 1 Nov 2025

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Abstract

Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer [...] Read more.

Background: Renal Cell Carcinoma (RCC) is the most common type of kidney cancer and requires accurate histopathological grading for effective prognosis and treatment planning. However, manual grading is time-consuming, subjective, and susceptible to inter-observer variability. Objective: This study proposes EAT-Net (Efficient Attention Transformer Network), a dual-stream deep learning model designed to automate and enhance RCC grade classification from histopathological images. Method: EAT-Net integrates EfficientNetB0 for local feature extraction and a Vision Transformer (ViT) stream for capturing global contextual dependencies. The architecture incorporates Squeeze-and-Excitation (SE) modules to recalibrate feature maps, improving focus on informative regions. The model was trained and evaluated on two publicly available datasets, KMC-RENAL and RCCG-Net. Standard preprocessing was applied, and the model’s performance was assessed using accuracy, precision, recall, and F1-score. Results: EAT-Net achieved superior results compared to state-of-the-art models, with an accuracy of 92.25%, precision of 92.15%, recall of 92.12%, and F1-score of 92.25%. Ablation studies demonstrated the complementary value of the EfficientNet and ViT streams. Additionally, Grad-CAM visualizations confirmed that the model focuses on diagnostically relevant areas, supporting its interpretability and clinical relevance. Conclusion: EAT-Net offers an accurate, and explainable framework for RCC grading. Its lightweight architecture and high performance make it well-suited for clinical deployment in digital pathology workflows. Full article

(This article belongs to the Special Issue Artificial Intelligence in Oncologic Imaging: Advances in Medical Image Segmentation and Predictive Modelling)

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10 pages, 233 KB

Open AccessArticle

Mismatch Repair System Gene Expression in FFPE Samples from Breast Cancer Patients

by Ricardo Quidute, Patricia Quidute, Matheus Moreira Perez, Carlos Henrique F. Peiró, Glaucia Luciano da Veiga, Beatriz da Costa Aguiar Alves and Fernando Luiz Affonso Fonseca

Med. Sci. 2025, 13(4), 256; https://doi.org/10.3390/medsci13040256 - 31 Oct 2025

Viewed by 148

Abstract

Background/Objectives: Cancer characteristics are mainly due to mutations in genes that regulate key pathways. One mechanism for identifying and correcting these mutations is the Mismatch Repair System. Given the lack of data on MMR in breast cancer FFPE samples, this study aims [...] Read more.

Background/Objectives: Cancer characteristics are mainly due to mutations in genes that regulate key pathways. One mechanism for identifying and correcting these mutations is the Mismatch Repair System. Given the lack of data on MMR in breast cancer FFPE samples, this study aims to examine hMSH2 and hMSH6 gene expression in FFPE tumor biopsies. Methods: One hundred patients with breast cancer were included in this study, from which tumor samples were obtained. Expression of the hMSH2 and hMSH6 genes was evaluated by qPCR. Results: Out of 100 tumor samples, 89 were suitable for molecular analysis. Of these, 10 (11.23%) expressed the hMSH2 gene and 4 (4.5%) expressed the hMSH6 gene. No associations were found between hMSH2 and hMSH6 expression and tumor staging, HER2, ER, PR, or Ki-67 expression. Conclusions: Our results suggest that the expression of the proposed markers is decreased in breast tumorigenesis. Full article

17 pages, 1734 KB

Open AccessSystematic Review

Exploring the Cardiovascular Impacts of Agmatine: A Systematic Review

by Oana-Mădălina Manole, Gabriela Rusu-Zota, Amin Bazyani and Viviana Onofrei

Med. Sci. 2025, 13(4), 255; https://doi.org/10.3390/medsci13040255 - 31 Oct 2025

Viewed by 185

Abstract

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and [...] Read more.

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and is involved in cognitive functions and withdrawal. The cardiovascular effects of AG began to be explored after the hypotensive effect of clonidine, an imidazoline agonist, was demonstrated. The current study aimed to systematize the effects of AG on the cardiovascular system obtained in previous preclinical studies. Methods: We searched three databases, PubMed, Cochrane, and Embase, using the keywords “agmatine” and “cardiac” or “vascular.” Results: Sixty studies were eligible and included in the analysis. Initially identified as Clonidine Displacing Substance (CDS), AG has demonstrated dual effects—an increase or decrease in blood pressure or in heart rate. Conclusions: The effects exerted by AG depend on the dose and route of administration, as well as on the receptors involved and the pathophysiological pathway used. Full article

(This article belongs to the Section Cardiovascular Disease)

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18 pages, 960 KB

Open AccessReview

MicroRNAs Regulating Oxidative Stress in Human Fertility: A Narrative Review of Mechanistic Insights and Clinical Potential

by Ioanna Vassilaki, Anastasios Potiris, Ekaterini Domali, Theodoros Karampitsakos, Despoina Mavrogianni, Themos Grigoriadis, Athanasios Zikopoulos, Efthalia Moustakli, Argyro Papadopoulou, Ismini Anagnostaki, Eriketi Kokkosi, Nikolaos Thomakos and Sofoklis Stavros

Med. Sci. 2025, 13(4), 254; https://doi.org/10.3390/medsci13040254 - 31 Oct 2025

Viewed by 187

Abstract

Human infertility represents a multifaceted condition, with oxidative stress (OS) and microRNAs (miRNAs) emerging as key contributors to its pathophysiology. This comprehensive review explores the complex interplay between reactive oxygen species (ROS) and miRNAs in male and female reproductive dysfunctions. ROS overproduction damages [...] Read more.

Human infertility represents a multifaceted condition, with oxidative stress (OS) and microRNAs (miRNAs) emerging as key contributors to its pathophysiology. This comprehensive review explores the complex interplay between reactive oxygen species (ROS) and miRNAs in male and female reproductive dysfunctions. ROS overproduction damages DNA, lipids, and proteins, impairing sperm quality and oocyte maturation. In males, OS is a leading cause of infertility, especially in conditions like varicocele, where key miRNAs such as miR-21, miR-34a, and miR-155 are dysregulated. In females, oxidative imbalance affects granulosa cells and follicular environments in disorders such as PCOS, premature ovarian insufficiency (POI), and endometriosis. Several miRNAs (e.g., miR-132-3p, let-7, miR-642a-5p) regulate mitochondrial function, steroidogenesis, and apoptosis through redox-sensitive signaling pathways (PI3K/Akt, NF-κB, FOXO1). Their altered expression in ovarian and seminal environments correlates with poor reproductive outcomes. Emerging evidence supports their potential role as diagnostic biomarkers and therapeutic targets, although most findings are based on animal models or in vitro studies. This review highlights the therapeutic potential of miRNA modulation and calls for further clinical research to validate miRNA-based interventions. Ultimately, understanding the miRNA–OS nexus offers promising avenues for improving diagnosis, prognosis, and treatment of infertility across both sexes. Full article

(This article belongs to the Section Gynecology)

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17 pages, 1482 KB

Open AccessReview

Should We Fear the Frail? A Review on the Impact of Frailty on Liver Surgery

by Sorinel Lunca, Stefan Morarasu, Raluca Zaharia, Ana Maria Musina, Wee Liam Ong, Gabriel Mihail Dimofte and Cristian Ene Roata

Med. Sci. 2025, 13(4), 253; https://doi.org/10.3390/medsci13040253 - 31 Oct 2025

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Abstract

Background: Frailty is a multidimensional syndrome characterized by reduced physiological reserve and resilience and has become a crucial predictor of outcomes in liver surgery. Unlike chronological age, frailty reflects broader vulnerabilities that significantly influence postoperative recovery. Aim: To review and synthesize current evidence [...] Read more.

Background: Frailty is a multidimensional syndrome characterized by reduced physiological reserve and resilience and has become a crucial predictor of outcomes in liver surgery. Unlike chronological age, frailty reflects broader vulnerabilities that significantly influence postoperative recovery. Aim: To review and synthesize current evidence on the relationship between frailty and postoperative outcomes following liver resection, with an emphasis on short-term complications, mortality, and long-term survival. Methods: A comprehensive literature review was performed, drawing on recent meta-analyses, large-scale cohort studies, and prospective observational data. Frailty was evaluated using a range of assessment tools, including the Modified Frailty Index (mFI), Clinical Frailty Scale (CFS), Kihon Checklist (KCL), and claims-based measures such as the Johns Hopkins Frailty Indicator. Results: Across studies, frailty has been consistently linked to a higher incidence of postoperative complications, such as post-hepatectomy liver failure (PHLF), infections, extended hospital stays, and increased mortality. In patients undergoing liver resection for cancer, frailty is also associated with poorer long-term survival. Importantly, frailty serves as an independent risk factor, even after adjusting for age, comorbid conditions, and tumor characteristics. Preoperative identification of frailty enhances risk stratification, informs surgical planning, potentially favoring parenchymal-sparing or minimally invasive approaches, and highlights patients who may benefit from prehabilitation. Conclusions: Frailty is a strong and independent predictor of poor outcomes after liver resection. Incorporating frailty assessment into routine preoperative evaluation can improve surgical decision-making, facilitate informed patient counseling, and optimize perioperative care strategies. Full article

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20 pages, 1548 KB

Open AccessArticle

Impact of Corticosteroids in Suprascapular Nerve Block on Pain and Function in Chronic Rotator Cuff Disease: A Retrospective, Observational, Longitudinal, Analytical Cohort Study

by Javier Muñoz-Paz, Ana Belén Jiménez-Jiménez, Antonio Hidalgo-Jorge, María Nieves Muñoz-Alcaraz, José Peña-Amaro and Fernando Jesús Mayordomo-Riera

Med. Sci. 2025, 13(4), 252; https://doi.org/10.3390/medsci13040252 - 31 Oct 2025

Viewed by 265

Abstract

Background/Objectives: Suprascapular nerve block (SSNB) is a useful therapeutic option for chronic shoulder pain, although the synergistic use of corticosteroids with anesthetics to prolong its effect is a controversial topic. The primary objective of this study was to compare the evolution of [...] Read more.

Background/Objectives: Suprascapular nerve block (SSNB) is a useful therapeutic option for chronic shoulder pain, although the synergistic use of corticosteroids with anesthetics to prolong its effect is a controversial topic. The primary objective of this study was to compare the evolution of pain and functionality using the visual analog scale (VAS) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire between patients treated with SSNB with corticosteroids (cSSNB) and without them (sSSNB). Methods: A retrospective, observational, longitudinal, analytical cohort study was conducted in 28 patients (14 n per group) aged 50–80 years who had undergone SSNB with 4 mL of 0.25% bupivacaine and 40 mg/mL triamcinolone during 2024 for chronic shoulder pain lasting more than 6 months. The variables to be collected were VAS, DASH, range of motion (ROM) and Lattinen Index (LI) at baseline, the first and the third month. Patients were grouped according to the type of SSNB (cSSNB vs. sSSNB) and analyzed longitudinally and cross-sectionally using IBM-SPSS Statistics version 28.0.0. Results: Regarding pain, the cSSNB obtained a significant reduction in the median VAS of 4 points in the first month (p = 0.001) and in the third month (p = 0.002). In addition, significantly lower evaluations in VAS were obtained in the third month of 3 points (p = 0.04) in favor of the cSSNB. Regarding functionality, a reduction in evaluations with respect to the initial DASH were observed only in the cSSNB, with a difference in the first month of 21.80 points (p = 0.001) and 21.35 points (p = 0.003) in the third month. In addition, differences between groups were found, in favor of the cSSNB, of 19.20 points (p = 0.017) in the first month and 12.55 points (p = 0.012) in the third month. Conclusions: The combined use of corticosteroids in SSNB appears to be associated with better short-to medium-term outcomes in terms of pain and function, compared to the use of SSNB without corticosteroids in chronic rotator cuff pathologies. Full article

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15 pages, 1305 KB

Open AccessArticle

Temporal Trends in Cardiovascular Health Metrics in Italy, 2015–2024: A Ten-Year Report from the Longevity Check-Up (Lookup) 8+ Study

by Stefano Cacciatore, Elena Levati, Riccardo Calvani, Matteo Tosato, Francesca Ciciarello, Vincenzo Galluzzo, Sara Salini, Andrea Russo, Emanuele Marzetti and Francesco Landi

Med. Sci. 2025, 13(4), 251; https://doi.org/10.3390/medsci13040251 - 30 Oct 2025

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Abstract

Background/Objectives: The objective of this ten-year report is to describe temporal trends in the cardiovascular health (CVH) score and its individual components across ages and sexes. We also examined the impact of the post-COVID-19 period on ideal CVH and identified demographic predictors of [...] Read more.

Background/Objectives: The objective of this ten-year report is to describe temporal trends in the cardiovascular health (CVH) score and its individual components across ages and sexes. We also examined the impact of the post-COVID-19 period on ideal CVH and identified demographic predictors of favorable cardiovascular risk profiles. Methods: Data for this cross-sectional study were collected between 2015 and 2024 as part of the Lookup 8+ project, an ongoing initiative integrating field-based CVH assessments across Italy. CVH was operationalized using a modified CVH score (0–7 points) inspired by Life’s Simple 7, combining behavioral and clinical metrics. Trends over time and across demographic groups were examined using descriptive statistics and multivariable models adjusted for age, sex, and year of assessment. Results: The study included 18,491 participants (mean age 56.1 ± 14.8 years; 55.2% women). After an initial decline in CVH score between 2015 and 2017 (mean score from 4.39 to 3.95), a gradual improvement followed, reaching 4.41 in 2024. Younger adults (18–39 years; 71.9% in 2024) and women (56.8%) consistently showed the highest prevalence of ideal CVH (score ≥ 5). The post-COVID-19 period was independently associated with higher odds of ideal CVH (OR 1.32; 95% CI 1.24–1.40). While blood pressure and cholesterol metrics improved, dietary quality and glycemic control worsened over time. Conclusions: From 2015 to 2024, overall CVH improved among Lookup participants, particularly among younger individuals after the COVID-19 pandemic. However, substantial age- and sex-related gaps remain, requiring targeted and equity-oriented prevention efforts. Full article

(This article belongs to the Section Cardiovascular Disease)

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20 pages, 3809 KB

Open AccessArticle

Elevated NIS Expression Correlates with Chemoresistance in Triple-Negative Breast Cancer: Potential Link to FOXA1 Activity

by Grigory Demyashkin, Anastasia Guzik, Mikhail Parshenkov, Dmitriy Belokopytov, Vladimir Shchekin, Maxim Batov, Petr Shegai and Andrei Kaprin

Med. Sci. 2025, 13(4), 250; https://doi.org/10.3390/medsci13040250 - 30 Oct 2025

Viewed by 209

Abstract

Background: Sodium/iodide symporter (NIS) is a membrane protein involved in iodide transport into cells, making it a key component of thyroid physiology and radioiodine therapy for thyroid cancer. Although NIS is expressed in many extrathyroidal tissues, including breast tumors, its functional role and [...] Read more.

Background: Sodium/iodide symporter (NIS) is a membrane protein involved in iodide transport into cells, making it a key component of thyroid physiology and radioiodine therapy for thyroid cancer. Although NIS is expressed in many extrathyroidal tissues, including breast tumors, its functional role and prognostic significance in these contexts remain a subject of active investigation. Understanding the mechanisms regulating NIS, its influence on cellular processes such as migration and metastasis, and its connection with transcription factors like FOXA1 could contribute to the development of new therapeutic strategies for breast cancer treatment. This study aims to investigate the correlation between sodium/iodide symporter (NIS) expression and response to neoadjuvant chemotherapy in patients with triple-negative breast cancer (TNBC). Methods: The current retrospective study included 161 TNBC patients who received neoadjuvant chemotherapy followed by mastectomy. NIS expression was assessed via immunohistochemistry, graded semi-quantitatively from 0 to 3+. The Residual Cancer Burden (RCB) scale was used to evaluate the response to chemotherapy. Statistical analysis included Lilliefors tests and Kendall’s tau correlation coefficient. Publicly available Cancer Genome Atlas datasets were analyzed to assess the relationship between NIS and FOXA1 expression. Results: NIS immunopositivity was observed in 69.5% of TNBC samples compared to 63.3% GATA-3-positive and 31.0% of Mammaglobin-positive samples. While no significant correlation was found between NIS expression and age, TNM stage, or Ki-67, a statistically significant moderate positive correlation (τ = 0.481, p < 0.01) was identified between NIS expression and RCB index, indicating that higher NIS expression was associated with a poorer response to neoadjuvant chemotherapy. TCGA data analysis revealed a statistically significant increase in NIS mRNA expression in FOXA1-mutated TNBC samples compared to FOXA1-wild-type samples (p < 0.05). Younger patients exhibited higher Ki-67 levels (τ = −0.416, p < 0.05). Conclusions: Higher NIS expression correlates with chemoresistance to neoadjuvant chemotherapy in TNBC patients. This phenomenon may be linked to FOXA1 activity, suggesting that NIS may represent a potential biomarker for chemoresistance in TNBC. The inverse correlation between patient age and Ki-67 levels may be associated with a different mutational landscape in younger patients. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

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15 pages, 2305 KB

Open AccessArticle

Association Between Peritoneal Dialysis-Associated Peritonitis and the Risk of All-Cause Mortality and Cardiovascular Death: A Time-Matched Retrospective Cohort Study

by Surapon Nochaiwong, Kajohnsak Noppakun, Manish M. Sood, Kednapa Thavorn, Greg A. Knoll, Chidchanok Ruengorn and Apichat Tantraworasin

Med. Sci. 2025, 13(4), 249; https://doi.org/10.3390/medsci13040249 - 30 Oct 2025

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Abstract

Background/Objectives: Although peritoneal dialysis (PD) practices have improved over the past decades, limited evidence exists on all-cause mortality and cardiovascular death following PD-associated peritonitis. This study aimed to investigate the association between PD-associated peritonitis and the risk of all-cause mortality and cardiovascular [...] Read more.

Background/Objectives: Although peritoneal dialysis (PD) practices have improved over the past decades, limited evidence exists on all-cause mortality and cardiovascular death following PD-associated peritonitis. This study aimed to investigate the association between PD-associated peritonitis and the risk of all-cause mortality and cardiovascular death. Methods: This multicenter, retrospective cohort study included adult patients who newly initiated PD between 1 January 2006 and 31 December 2020, with follow-up through 30 September 2022. Patients were matched 1:1 by time from PD initiation to index date (the occurrence date of PD-associated peritonitis for the exposure group and the corresponding matched time on PD for the non-exposure group [individuals without any peritonitis event]), age, and sex. Multivariable Cox proportional hazards models with shared frailty correction and competing risk models were used to estimate hazard ratio (HR) and subdistribution hazard ratio (SHR), respectively. Subgroup analyses were conducted by age, sex, PD modality, and comorbid conditions. Results: The cohort included 1510 matched pairs (total sample, 3020; mean age [SD], 58.6 [14.2] years; 1618 males [53.6%]), with a median follow-up of 5.6 years. After adjusting for sociodemographic, PD, and clinical characteristics and laboratory profiles, patients with any PD-associated peritonitis episode had significantly higher risk of all-cause mortality (HR, 2.17 [1.78–2.66], p < 0.001; SHR, 2.00 [1.74–2.29], p < 0.001) and cardiovascular death (HR, 2.90 [2.05–4.59], p < 0.001; SHR, 2.25 [1.66–3.05], p < 0.001) compared to those without PD-associated peritonitis. Subgroup analyses revealed no significant interactions (all p values for interaction > 0.05). Conclusions: PD-associated peritonitis was independently associated with substantially increased risk of all-cause and cardiovascular mortality among patients undergoing PD. These findings support the need for targeted interventions and clinical strategies aimed at reducing adverse outcomes following PD-associated peritonitis. Full article

(This article belongs to the Section Nephrology and Urology)

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26 pages, 1212 KB

Open AccessArticle

Identification and Computational Analysis of BRCA2 Variants in Mexican Women from Jalisco, Mexico, with Breast and Ovarian Cancer

by Patricia Montserrat García-Verdín, José Elías García-Ortiz, Asbiel Felipe Garibaldi-Ríos, Ingrid Patricia Dávalos-Rodríguez, Sandra del Carmen Mendoza-Ruvalcaba, María Teresa Magaña-Torres, Luis E. Figuera, Mónica Alejandra Rosales-Reynoso, Cesar de Jesús Tovar-Jácome, Guillermo Moisés Zúñiga-González, Belinda Claudia Gómez-Meda, Blanca Miriam Torres-Mendoza, Raquel Villegas-Pacheco, René Gómez-Cerda, Julio César Cárdenas Valdez, Sergio Osvaldo Meza-Chavolla and Martha Patricia Gallegos-Arreola

Med. Sci. 2025, 13(4), 248; https://doi.org/10.3390/medsci13040248 - 29 Oct 2025

Viewed by 386

Abstract

Background: Breast and ovarian cancers (BC and OC) are prevalent malignancies in women globally, with germline variants in the BRCA2 gene significantly increasing the risk of developing these cancers. Despite extensive studies, the frequency and impact of BRCA2 variants in women from Jalisco, [...] Read more.

Background: Breast and ovarian cancers (BC and OC) are prevalent malignancies in women globally, with germline variants in the BRCA2 gene significantly increasing the risk of developing these cancers. Despite extensive studies, the frequency and impact of BRCA2 variants in women from Jalisco, Mexico, remain underexplored. Objective: The aim of this study was to identify and characterize BRCA2 gene variants in Mexican women diagnosed with BC and OC and to assess their functional and structural consequences using computational analyses. Methodology: Genomic DNA from 140 Mexican women with BC and/or OC, selected based on clinical criteria suggestive of BRCA2 variants, was sequenced using NGS targeting BRCA2 coding regions. Functional effects were predicted with Ensembl VEP, SIFT, and PolyPhen-2. Structural impacts of missense variants were assessed using HOPE and AlphaFold models. Results: BRCA2 variants were identified in 12.86% of patients, with higher frequency in OC (21.05%) than BC (12%). Several mapped to key functional domains, including BRC repeats and the DNA-binding domain. Many were predicted as deleterious or probably damaging, though clinical classifications were often conflicting. Structural analysis indicated potential disruptions in protein stability or interactions for most missense variants. Clinically, BRCA2-positive BC patients were younger at diagnosis and showed a trend toward lower complete response. Conclusion: BRCA2 variants were found in 12.86% of patients, including six VUSs not reported in other populations. Several affected key functional domains with predicted deleterious effects. Findings support the need for genetic panels tailored to the Mexican population. Full article

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7 pages, 694 KB

Open AccessCommunication

A Prospective Cohort Study Comparing Microscopy and Culture in the Diagnosis of Superficial Fungal Skin Infections

by Amelia Yuting Monteiro, Hui Mei Cheng, Larissa Lim, Jiun Yit Pan, Kun Liang and Hong Liang Tey

Med. Sci. 2025, 13(4), 247; https://doi.org/10.3390/medsci13040247 - 29 Oct 2025

Viewed by 257

Abstract

Superficial fungal skin infections are common but often misdiagnosed, which may result in inappropriate treatment and the worsening of symptoms. An accurate and timely diagnosis is essential to differentiate these infections from similar conditions such as secondary syphilis, annular psoriasis, and pityriasis rosea. [...] Read more.

Superficial fungal skin infections are common but often misdiagnosed, which may result in inappropriate treatment and the worsening of symptoms. An accurate and timely diagnosis is essential to differentiate these infections from similar conditions such as secondary syphilis, annular psoriasis, and pityriasis rosea. This single-centre prospective cohort study at the National Skin Centre, Singapore, evaluated the diagnostic agreement between direct microscopy and fungal culture. Between August and December 2022, 268 skin scrape samples were collected from 149 patients with suspected fungal infections. Microscopy identified 67 (25.0%) positives, while fungal culture detected 42 (16.7%) positives. Among the 252 samples tested with both methods, 213 (84.5%) showed concordant results (κ = 0.487, p < 0.0001), a finding that indicates moderate agreement. The most commonly cultured organisms were Trichophyton rubrum and T. mentagrophytes. Our findings suggest that both microscopy and fungal culture may be performed to prevent true-positive cases from being missed. However, in cases where cost is a concern, microscopy can be selected as an initial diagnostic tool. Should microscopy be negative in cases with high clinical suspicion for fungal infection or when empirical treatment fails, culture remains a valuable follow-up test. These findings support a stepwise diagnostic approach—using microscopy first, then followed by culture when necessary—to improve diagnostic accuracy while enabling timely treatment. Full article

(This article belongs to the Section Immunology and Infectious Diseases)

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20 pages, 3622 KB

Open AccessReview

Nuclear CaMKII Isoforms as Regulators of Transcription: From Developmental to Pathological Persistence

by Areli Marlene Gaytán-Gómez, Claudio Adrián Ramos-Cortés, Ricardo Xopan Suarez-García, Diego Alberto Martínez-Islas, Axel Tonatiuh Marroquin-Aguilar, Fernanda Avelino-Vivas, Dafne Montserrat Solis-Galván, Alexis Arturo Laguna-González, Bruno Manuel García-García, Eduardo Minaya-Pérez, Efren Quiñones-Lara, Axel Eduardo Muciño-Galicia, Olga Villamar-Cruz, Luis Enrique Arias-Romero, Sonia León-Cabrera, Leonel Armas-López and Héctor Iván Saldívar-Cerón

Med. Sci. 2025, 13(4), 246; https://doi.org/10.3390/medsci13040246 - 27 Oct 2025

Viewed by 770

Abstract

Calcium/calmodulin-dependent protein kinase II (CaMKII) comprises multiple isoforms with distinct nuclear variants that exert transcriptional control in a context-dependent manner. Among them, CaMKIIδB and δ9 in the heart, and CaMKIIγ in the nervous system, have emerged as regulators of chromatin dynamics, transcription factor [...] Read more.

Calcium/calmodulin-dependent protein kinase II (CaMKII) comprises multiple isoforms with distinct nuclear variants that exert transcriptional control in a context-dependent manner. Among them, CaMKIIδB and δ9 in the heart, and CaMKIIγ in the nervous system, have emerged as regulators of chromatin dynamics, transcription factor activity, and developmental gene programs. Nuclear localization is driven by splice-dependent nuclear localization sequences, with phosphorylation at defined serine residues modulating import and retention. Evidence supports CaMKII-dependent phosphorylation of class IIa HDACs (Ser467/Ser632 in HDAC4), linking CaMKII to MEF2 activation in cardiac hypertrophy, and interactions with NF-κB and HSF1 further expand its nuclear repertoire. In the nervous system, CaMKIIγ contributes to kinase-dependent gene expression, potentially influencing plasticity and disease susceptibility. While these mechanisms highlight nuclear CaMKII as an isoform-specific regulator of transcription, direct evidence remains elusive, and several CaMKII putative substrates require further validation. This review synthesizes current knowledge on nuclear CaMKII isoforms, emphasizes established mechanistic pathways, and outlines unsolved questions critical for understanding their roles in development, disease progression, and therapeutic targeting. Full article

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14 pages, 4980 KB

Open AccessArticle

Multimodal Imaging of Ductal Carcinoma In Situ: A Single-Center Study of 75 Cases

by Fabrizio Urraro, Nicoletta Giordano, Vittorio Patanè, Maria Chiara Brunese, Carlo Varelli, Carolina Russo, Luca Brunese and Salvatore Cappabianca

Med. Sci. 2025, 13(4), 245; https://doi.org/10.3390/medsci13040245 - 27 Oct 2025

Viewed by 315

Abstract

Introduction: Ductal carcinoma in situ (DCIS) is a non-invasive precursor of breast cancer, usually detected on mammography as clustered microcalcifications. Many cases, however, lack calcifications and require complementary imaging. This study aimed to describe the multimodal imaging features of DCIS and evaluate the [...] Read more.

Introduction: Ductal carcinoma in situ (DCIS) is a non-invasive precursor of breast cancer, usually detected on mammography as clustered microcalcifications. Many cases, however, lack calcifications and require complementary imaging. This study aimed to describe the multimodal imaging features of DCIS and evaluate the radiology–pathology correlation. Methods: We retrospectively reviewed 75 women (aged 36–52 years) with biopsy-proven DCIS (January 2023–June 2025). All underwent mammography, targeted ultrasound, and dynamic contrast-enhanced 1.5T MRI. Imaging findings were correlated with histopathology, and logistic regression was used to explore predictors of MRI kinetics. Results: Mammography detected microcalcifications in 53.8% of patients, while 46.2% showed no calcifications. Ultrasound frequently revealed non-mass, duct-oriented hypoechoic abnormalities in non-calcified cases. MRI consistently demonstrated non-mass enhancement, with weak or persistent kinetics without washout in 69.2% and washout in 30.8%. A moderate correlation between MRI and histological extent was found (r = 0.62, p < 0.001), with MRI tending to overestimate lesion size. Oral contraceptive use was common (61.5%) but not significantly associated with kinetic pattern or grade. Conclusions: Mammography remains essential for calcified DCIS, whereas MRI enhances detection of non-calcified lesions. Persistent kinetics without washout may represent a typical imaging feature of DCIS. However, moderate radiology–pathology concordance and frequent overestimation highlight the need for careful interpretation. These findings support a multimodal diagnostic approach that can improve detection accuracy and assist in more tailored surgical planning. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

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13 pages, 740 KB

Open AccessArticle

Derivation of a Simple Risk Scoring Scheme for Prediction of Severe Dengue Infection in Adult Patients in Thailand

by Surangrat Pongpan, Patcharin Khamnuan, Pantitcha Thanatrakolsri, Supa Vittaporn and Punnaphat Daraswang

Med. Sci. 2025, 13(4), 244; https://doi.org/10.3390/medsci13040244 - 26 Oct 2025

Viewed by 285

Abstract

Background/Objectives: Severe dengue infection remains a major public health burden in Thailand, where timely identification of high-risk patients is essential for effective clinical management. Existing predictive models are often complex and less feasible in routine practice. This study aimed to develop a simple [...] Read more.

Background/Objectives: Severe dengue infection remains a major public health burden in Thailand, where timely identification of high-risk patients is essential for effective clinical management. Existing predictive models are often complex and less feasible in routine practice. This study aimed to develop a simple risk scoring system to predict dengue severity based on patient characteristics and routine clinical data. Methods: Retrospective data of adult dengue patients from nine general hospitals in Thailand from 2019 to 2022 were reviewed. Dengue infection was classified into two groups using the WHO 2009 modified criteria: non-severe (n = 577) and severe (n = 107). Demographic data, clinical characteristics, and laboratory findings were analyzed using logistic regression. Regression coefficients of significant predictors of severe dengue were converted into weighted item scores. Total scores were categorized into three risk levels based on probability distribution cut-off points. Results: The severity score stratified patients into three risk groups with significantly different prognoses: ≤2.0 points (low risk), 2.5–5.0 points (moderate risk), and ≥5.5 points (high risk). The positive likelihood ratios for low-, moderate-, and high-risk groups were 0.12, 1.05, and 28.76, respectively. The distribution of severity scores differed significantly between non-severe and severe cases. The scoring system discriminated between non-severe and severe dengue with an area under the receiver operating characteristic curve (AUROC) of 88.04% (95% CI, 83.99–92.08). Conclusions: The derived dengue severity scoring system classified patients into low, moderate, and high risk with excellent discriminatory performance, effectively distinguishing non-severe from severe dengue infection. Full article

(This article belongs to the Section Critical Care Medicine)

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13 pages, 344 KB

Open AccessArticle

Identifying Cardio-Metabolic Subtypes of Prediabetes Using Latent Class Analysis

by Gulnaz Nuskabayeva, Yerbolat Saruarov, Karlygash Sadykova, Mira Zhunissova, Nursultan Nurdinov, Kumissay Babayeva, Mariya Li, Akbota Zhailkhan, Aida Kabibulatova and Antonio Sarria-Santamera

Med. Sci. 2025, 13(4), 243; https://doi.org/10.3390/medsci13040243 - 25 Oct 2025

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Abstract

Background/Objectives: Prediabetes (PreDM) is a heterogeneous condition, impacting hundreds of millions worldwide, associated with a substantially high risk of Type 2 Diabetes Mellitus (T2DM) and cardiovascular complications. Early identification of subgroups within the PreDM population may support tailored prevention strategies. Methods: We conducted [...] Read more.

Background/Objectives: Prediabetes (PreDM) is a heterogeneous condition, impacting hundreds of millions worldwide, associated with a substantially high risk of Type 2 Diabetes Mellitus (T2DM) and cardiovascular complications. Early identification of subgroups within the PreDM population may support tailored prevention strategies. Methods: We conducted a cross-sectional study using data from annual health check-ups of 419 university staff (aged 27–69) in Kazakhstan. Latent Class Analysis (LCA) was applied to identify subgroups of individuals with PreDM based on cardiovascular risk factors. Differences in glucose metabolism markers (fasting glucose, OGTT, HOMA-IR, HOMA-β) were compared across identified classes. Results: PreDM prevalence was 43.4%. LCA revealed four distinct classes: Class 1: healthy, low-risk individuals; Class 2: overweight with moderate metabolic risk; Class 3: older, overweight individuals with high cardio-metabolic risk; and Class 4: obese, middle-aged to older individuals with very high cardio-metabolic risk. Significant differences were found in glucose metabolism profiles across the classes. IFG predominated in Class 1 (95%), while Classes 3 and 4 had higher rates of β-cell dysfunction and combined IFG/IGT patterns. HOMA-β differed significantly between classes (p < 0.001), while HOMA-IR did not. Conclusions: PreDM is highly prevalent in this working-age Kazakh population and demonstrates marked heterogeneity. Based on easily obtainable cardiovascular risk factors, we have identified four subgroups with distinct glucose profiles that may inform personalized interventions. These distinct subgroups may require differentiated prevention strategies, moving beyond a one-size-fits-all approach. Full article

(This article belongs to the Section Endocrinology and Metabolic Diseases)

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21 pages, 1744 KB

Open AccessArticle

Virtual Biomarkers and Simplified Metrics in the Modeling of Breast Cancer Neoadjuvant Therapy: A Proof-of-Concept Case Study Based on Diagnostic Imaging

by Graziella Marino, Maria Valeria De Bonis, Marisabel Mecca, Marzia Sichetti, Aldo Cammarota, Manuela Botte, Giuseppina Dinardo, Maria Imma Lancellotti, Antonio Villonio, Antonella Prudente, Alexios Thodas, Emanuela Zifarone, Francesca Sanseverino, Pasqualina Modano, Francesco Schettini, Andrea Rocca, Daniele Generali and Gianpaolo Ruocco

Med. Sci. 2025, 13(4), 242; https://doi.org/10.3390/medsci13040242 - 24 Oct 2025

Viewed by 244

Abstract

Background: Neoadjuvant chemotherapy (NAC) is a standard preoperative intervention for early-stage breast cancer (BC). Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a critical tool for evaluating treatment response and pathological complete response (pCR) following NAC. Computational modeling offers a robust framework [...] Read more.

Background: Neoadjuvant chemotherapy (NAC) is a standard preoperative intervention for early-stage breast cancer (BC). Dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a critical tool for evaluating treatment response and pathological complete response (pCR) following NAC. Computational modeling offers a robust framework to simulate tumor growth dynamics and therapy response, leveraging patient-specific data to enhance predictive accuracy. Despite this potential, integrating imaging data with computational models for personalized treatment prediction remains underexplored. This case study presents a proof-of-concept prognostic tool that bridges oncology, radiology, and computational modeling by simulating BC behavior and predicting individualized NAC outcomes. Methods: CE-MRI scans, clinical assessments, and blood samples from three retrospective NAC patients were analyzed. Tumor growth was modeled using a system of partial differential equations (PDEs) within a reaction–diffusion mass transfer framework, incorporating patient-specific CE-MRI data. Tumor volumes measured pre- and post-treatment were compared with model predictions. A 20% error margin was applied to assess computational accuracy. Results: All cases were classified as true positive (TP), demonstrating the model’s capacity to predict tumor volume changes within the defined threshold, achieving 100% precision and sensitivity. Absolute differences between predicted and observed tumor volumes ranged from 0.07 to 0.33 cm³. Virtual biomarkers were employed to quantify novel metrics: the biological conversion coefficient ranged from 4 × 10⁻⁷ to 6 × 10⁻⁶ s⁻¹, while the pharmacodynamic efficiency coefficient ranged from 1 × 10⁻⁷ to 4 × 10⁻⁴ s⁻¹, reflecting intrinsic tumor biology and treatment effects, respectively. Conclusions: This approach demonstrates the feasibility of integrating CE-MRI and computational modeling to generate patient-specific treatment predictions. Preliminary model training on retrospective cohorts with matched BC subtypes and therapy regimens enabled accurate prediction of NAC outcomes. Future work will focus on model refinement, cohort expansion, and enhanced statistical validation to support broader clinical translation. Full article

(This article belongs to the Special Issue Feature Papers in Section “Cancer and Cancer-Related Research”)

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16 pages, 771 KB

Open AccessReview

Effectiveness of Selenium Supplementation in the Treatment of Graves–Basedow Disease: A Scoping Review

by Hernando Vargas-Uricoechea, Alejandro Castellanos-Pinedo, Karen Urrego-Noguera, María V. Pinzón-Fernández, Ivonne A. Meza-Cabrera and Hernando Vargas-Sierra

Med. Sci. 2025, 13(4), 241; https://doi.org/10.3390/medsci13040241 - 24 Oct 2025

Viewed by 590

Abstract

Background: Graves–Basedow disease (GBD) is an autoimmune thyroid disorder characterized by loss of tolerance to the thyrotropin receptor, with clinical manifestations such as a hyperadrenergic state, goiter, orbitopathy, and myxedema, inter alia. Selenium is a micronutrient, essential for the synthesis of selenoproteins. Selenium [...] Read more.

Background: Graves–Basedow disease (GBD) is an autoimmune thyroid disorder characterized by loss of tolerance to the thyrotropin receptor, with clinical manifestations such as a hyperadrenergic state, goiter, orbitopathy, and myxedema, inter alia. Selenium is a micronutrient, essential for the synthesis of selenoproteins. Selenium deficiency has been linked to an increased risk and exacerbation of GBD and GBD orbitopathy; therefore, it has been suggested that supplementation with this micronutrient could modify some outcomes associated with both conditions. Objectives: The objective of this scoping review was to synthesize and analyze the clinical trials that have evaluated the effectiveness of selenium on different outcomes in patients with GBD or GBD orbitopathy. Methods: The following databases were consulted: PubMed/Medline, Scopus, Biosis, ProQuest, Web of Science, and Google Scholar; and the search terms ‘Graves-Basedow disease’ or ‘Graves’ disease’ or ‘hyperthyroidism’ or ‘Graves’ hyperthyroidism’ or ‘selenium or selenium supplementation’ and ‘effectiveness’ were used. The search was limited to articles published in English between January 2000 and March 2025. To reduce selection bias, each article was reviewed independently by three authors using the Rayyan web tool and the JBI Critical Appraisal Checklist. Results: A total of 15 studies were identified (11 on patients with GBD and 4 on patients with GBD orbitopathy). In GBD, selenium supplementation was associated with significant improvements in TSH, FT4, FT3, TPOAb, TgAb, and TRAb levels; while in GBD orbitopathy, a positive effect of selenium supplementation was found on multiple clinical outcomes. Conclusions: Selenium supplementation in patients with GBD or GBD orbitopathy is associated with favorable biochemical and clinical outcomes. Full article

(This article belongs to the Section Endocrinology and Metabolic Diseases)

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14 pages, 1891 KB

Open AccessArticle

Comparison of Risk Stratification Tools for Atherosclerotic Cardiovascular Disease and Cardiovascular–Kidney–Metabolic Syndrome in Primary Care

by Victor Hugo Vázquez Martínez, Humberto Martínez Bautista, Patricia Muñoz Villegas, Jesús III Loera Morales and María del Rosario Padilla Salazar

Med. Sci. 2025, 13(4), 240; https://doi.org/10.3390/medsci13040240 - 23 Oct 2025

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Abstract

Background/Objectives: Cardiovascular disease is the leading cause of death in Mexico; this is due to the high prevalence of chronic non-communicable diseases (NCDs), including obesity, type 2 diabetes mellitus (T2DM), systemic arterial hypertension (SAH), cardiovascular disease, chronic kidney disease (CKD), and dyslipidemia. [...] Read more.

Background/Objectives: Cardiovascular disease is the leading cause of death in Mexico; this is due to the high prevalence of chronic non-communicable diseases (NCDs), including obesity, type 2 diabetes mellitus (T2DM), systemic arterial hypertension (SAH), cardiovascular disease, chronic kidney disease (CKD), and dyslipidemia. Primary care physicians require a classification tool that enables them to gain a broader understanding of their patients’ risks, thereby allowing them to make more informed clinical decisions. This study compared risk stratification for atherosclerotic cardiovascular disease (ASCVD) and Cardiovascular–Kidney–Metabolic (CKM) syndrome in a primary care setting in Mexico. Methods: An observational, descriptive, cross-sectional study analyzed 500 patients with T2DM, SAH, dyslipidemia, and/or CKD. Two ordinal logistic regression models were developed using a Chi-square test, Kruskal–Wallis test, and tetrachoric, polychoric, polyserial, and Pearson correlations. Results: Associations were found between ASCVD risk and factors like sex, age, and T2DM; for CKM syndrome, the associations were with age, T2DM, and dyslipidemia. Interestingly, 22% of advanced CKM patients had a low ASCVD risk. Alcohol consumption showed a strong positive relationship (42%) with CKM stages, while there was a negative relationship (33%) with the glomerular filtration rate. Conclusions: The ASCVD risk classification effectively identifies cardiac conditions, but the CKM syndrome score provides a broader assessment of comorbidities at earlier stages. Key factors like age, hypertension, T2DM, and smoking are crucial for cardiovascular risk but less so for CKM syndrome, highlighting the need for a broader stratification of risk. Full article

(This article belongs to the Section Cardiovascular Disease)

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14 pages, 1371 KB

Open AccessArticle

Immunoregulatory Imbalance in Preeclampsia: A Cross-Sectional Study of B7-H3 and Decidual NK Cell Interactions

by Khanisyah Erza Gumilar, Alexander Indra Humala, Manggala Pasca Wardhana, Ernawati Ernawati, Agus Sulistyono, Budi Utomo, Grace Ariani, Ming Tan, Erry Gumilar Dachlan and Gus Dekker

Med. Sci. 2025, 13(4), 239; https://doi.org/10.3390/medsci13040239 - 22 Oct 2025

Viewed by 1169

Abstract

Background: Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality, yet its pathophysiology is not fully understood. Recent studies suggest that dysregulated maternal immune responses, particularly involving decidual Natural Killer (dNK) cells and immune checkpoint molecules such as B7-H3, may [...] Read more.

Background: Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality, yet its pathophysiology is not fully understood. Recent studies suggest that dysregulated maternal immune responses, particularly involving decidual Natural Killer (dNK) cells and immune checkpoint molecules such as B7-H3, may play a role in the pathogenesis of this heterogeneous syndrome, particularly in the development of early-onset preeclampsia (EOP). Objective: The aim of this study was to investigate the expression patterns of B7-H3 on extravillous trophoblasts (EVTs) and the abundance of dNK cells in preeclamptic versus normotensive pregnancies and to analyze the relationship between these two immune parameters. Methods: A cross-sectional study was conducted using 42 placental samples (21 preeclampsia, 21 controls). Immunohistochemistry (IHC) was performed to detect CD56 (dNK cells) and CD276 (B7-H3) expression. Expression was semi-quantitatively evaluated using the Remmele Immunoreactive Score (IRS). Statistical comparisons and correlation analyses were conducted. Results: Preeclamptic placentas exhibited significantly higher dNK cell expression (IRS 7.19 ± 2.16) and significantly lower B7-H3 expression (IRS 2.63 ± 0.90) compared to controls (p < 0.001 and p = 0.002, respectively). A positive correlation was found between B7-H3 and dNK cell expression in both groups, with a stronger correlation in normotensive pregnancies (r = 0.605; p = 0.004) and preeclampsia (r = 0.465; p = 0.034). Conclusions: The inverse expression pattern and reduction in B7-H3 expression compared to dNK cells in preeclampsia suggest a loss of immune tolerance at the maternal–fetal interface. These findings highlight the potential of B7-H3 as a biomarker and immunoregulatory target for early prediction and prevention of preeclampsia. Full article

(This article belongs to the Section Gynecology)

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14 pages, 995 KB

Open AccessReview

Emerging Innovations in the Treatment of Fuchs Endothelial Corneal Dystrophy: A Narrative Review

by Magdalena Niestrata, James Jackson, Shehnaz Bazeer, Mingya Alexa Gong and Zahra Ashena

Med. Sci. 2025, 13(4), 238; https://doi.org/10.3390/medsci13040238 - 22 Oct 2025

Viewed by 652

Abstract

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of endothelial failure requiring keratoplasty in industrialised nations. Descemet membrane endothelial keratoplasty (DMEK) has become the gold-standard surgical therapy, yet it is constrained by limited donor tissue and a steep learning curve. This narrative [...] Read more.

Fuchs endothelial corneal dystrophy (FECD) is the leading cause of endothelial failure requiring keratoplasty in industrialised nations. Descemet membrane endothelial keratoplasty (DMEK) has become the gold-standard surgical therapy, yet it is constrained by limited donor tissue and a steep learning curve. This narrative review summarises current and emerging therapeutic strategies for FECD. We describe conventional endothelial keratoplasty and its outcomes, tissue-sparing procedures such as descemetorhexis without endothelial keratoplasty (DWEK) and quarter-DMEK, regenerative approaches including cultured endothelial cell injection and synthetic corneal substitutes, and adjunctive innovations ranging from Rho-associated kinase inhibitors to artificial intelligence-assisted diagnostics. Challenges surrounding donor shortages, variable clinical outcomes, regulatory hurdles and cost are critically appraised. We conclude by outlining future directions that are likely to combine advanced surgical techniques with cell-based and biomaterial solutions to deliver accessible, long-term restoration of vision for patients with FECD. Full article

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14 pages, 253 KB

Open AccessArticle

Subclinical Myocardial Dysfunction in Type 2 Diabetes Mellitus: Insights from Left Ventricular Diastolic Function and Global Longitudinal Strain Assessment

by Thao Phuong Nghiem, Hoang Minh Tran, Dung Ngoc Quynh Nguyen, Liem Thanh Dao, Cuong Cao Tran and Tuan Minh Vo

Med. Sci. 2025, 13(4), 237; https://doi.org/10.3390/medsci13040237 - 21 Oct 2025

Viewed by 307

Abstract

Background/Objectives: Diabetic cardiomyopathy in type 2 diabetes mellitus (T2DM) often progresses silently, manifesting as diastolic dysfunction or subtle systolic impairment despite preserved ejection fraction (EF). Detecting these changes early is critical to prevent symptomatic heart failure. This study assessed the prevalence of left [...] Read more.

Background/Objectives: Diabetic cardiomyopathy in type 2 diabetes mellitus (T2DM) often progresses silently, manifesting as diastolic dysfunction or subtle systolic impairment despite preserved ejection fraction (EF). Detecting these changes early is critical to prevent symptomatic heart failure. This study assessed the prevalence of left ventricular (LV) diastolic dysfunction and impaired global longitudinal strain (GLS) in T2DM patients with preserved EF and identified related risk factors. Methods: We performed a cross-sectional study of 232 adults with T2DM and EF > 50% at a tertiary hospital. Standard transthoracic and speckle-tracking echocardiography were used to evaluate LV diastolic function and GLS. Logistic regression identified predictors of myocardial dysfunction. Results: LV diastolic dysfunction was found in 53.9% of patients, while 13.4% showed impaired GLS (>–17.9%). Independent predictors of diastolic dysfunction were age ≥ 60 years (OR = 2.51, 95% CI: 1.25–5.07, p = 0.010) and diabetes duration of 5–10 years (OR = 3.06, 95% CI: 1.46–6.40, p = 0.003). Reduced GLS was independently associated with male sex (OR = 2.45, p = 0.040) and the presence of diastolic dysfunction (OR = 3.14, p = 0.010). Conclusions: Subclinical myocardial dysfunction is common in Vietnamese T2DM patients with preserved EF. Both diastolic dysfunction and reduced GLS may occur independently or together, influenced by age, sex, and diabetes duration. Incorporating GLS into echocardiographic evaluation may enhance early detection and support tailored cardiovascular risk management in this high-risk group. Full article

18 pages, 971 KB

Open AccessReview

Gut–Brain Axis and Perioperative Gut Microbiome in Postoperative Cognitive Dysfunction: Implications for Neurosurgical Patients

by Ismail A. Abdullah, Sariya Khan and Fatma E. Hassan

Med. Sci. 2025, 13(4), 236; https://doi.org/10.3390/medsci13040236 - 21 Oct 2025

Viewed by 603

Abstract

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut–brain axis as the main mechanism for the regulation of perioperative [...] Read more.

Background: Postoperative cognitive dysfunction (POCD) is a common postoperative condition after neurosurgery, and in patients of advancing age, with far-reaching implications for recovery and quality of life. Current evidence points to the gut–brain axis as the main mechanism for the regulation of perioperative neuroinflammation and cognition. Objective: The aim of this review is to consolidate the existing evidence for perioperative gut microbiome dysbiosis in POCD, specifically in neurosurgical patients. Methods: A review of preclinical and clinical evidence on the gut microbiome, surgical stress, and cognitive recovery was conducted. Both mechanistic and therapeutic evidence were examined. Results: Surgery and anesthesia enhance gut microbial diversity, intestinal permeability, and systemic inflammation, thereby compromising neuroplasticity and the integrity of blood–brain barriers. Preclinical models show that interventions to reestablish microbial homeostasis with probiotics, prebiotics, or fecal microbiota transplantation decrease postoperative cognition. Clinical studies offer evidence supporting the associations between decreased short-chain fatty acid-producing bacteria and POCD risk. Randomized controlled trials have demonstrated that perioperative probiotics lower the incidence and markers of POCD. Multi-omic approaches to integrating microbiome, metabolome, and neuroimaging signatures are being engineered to discern recovery phenotypes prior to surgery. Conclusions: Perioperative gut microbiota are a modifiable target for the optimization of cognitive recovery from neurosurgery. The inclusion of microbiome treatments and diagnostics into standard surgical care pathways is one potential pathway to POCD minimization, but large randomized trials will be necessary to establish this. Full article

(This article belongs to the Section Neurosciences)

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24 pages, 2310 KB

Open AccessArticle

Optimizing Mycophenolate Therapy in Renal Transplant Patients Using Machine Learning and Population Pharmacokinetic Modeling

by Anastasia Tsyplakova, Aleksandra Catic-Djorđevic, Nikola Stefanović and Vangelis D. Karalis

Med. Sci. 2025, 13(4), 235; https://doi.org/10.3390/medsci13040235 - 20 Oct 2025

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Abstract

Background/Objectives: Mycophenolic acid (MPA) is used as part of first-line combination immunosuppressive therapy for renal transplant recipients. Personalized dosing approaches are needed to balance efficacy and minimize toxicity due to the pharmacokinetic variability of the drug. In this study, population pharmacokinetic (PopPK) modeling [...] Read more.

Background/Objectives: Mycophenolic acid (MPA) is used as part of first-line combination immunosuppressive therapy for renal transplant recipients. Personalized dosing approaches are needed to balance efficacy and minimize toxicity due to the pharmacokinetic variability of the drug. In this study, population pharmacokinetic (PopPK) modeling and machine learning (ML) techniques are coupled to provide valuable insights into optimizing MPA therapy. Methods: Using data from 76 renal transplant patients, two PopPK models were developed to describe and predict MPA levels for two different formulations (enteric-coated mycophenolate sodium and mycophenolate mofetil). Covariate effects on drug clearance were assessed, and Monte Carlo simulations were used to evaluate exposure under normal and reduced clearance conditions. ML techniques, including principal component analysis (PCA) and ensemble tree models (bagging and boosting), were applied to identify predictive factors and explore associations between MPA plasma/saliva concentrations and the examined covariates. Results: Total daily dose and post-transplant time (PTP) were identified as key covariates affecting clearance. PCA highlighted MPA dose as the primary determinant of plasma levels, with urea and PTP also playing significant roles. Boosted tree analysis confirmed these findings, demonstrating strong predictive accuracy (R² > 0.91). Incorporating saliva MPA levels improved predictive performance, suggesting that saliva may be a complementary monitoring tool, although plasma monitoring remained superior. Simulations allowed exploring potential dosing adjustments for patients with reduced clearance. Conclusions: This study demonstrates the potential of integrating machine learning with population pharmacokinetic modeling to improve the understanding of MPA variability and support individualized dosing strategies in renal transplant recipients. The developed PopPK/ML models provide a methodological foundation for future research toward more personalized immunosuppressive therapy. Full article

(This article belongs to the Section Translational Medicine)

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13 pages, 815 KB

Open AccessArticle

Influence of Saharan Dust Intrusions on Respiratory Medication Dispensing

by Ruperto González-Pérez, Ainhoa Escuela-Escobar, Mario A. González-Carracedo and Paloma Poza-Guedes

Med. Sci. 2025, 13(4), 234; https://doi.org/10.3390/medsci13040234 - 20 Oct 2025

Viewed by 444

Abstract

Background: Saharan dust intrusions (SDIs) are associated with poor air quality and adverse respiratory outcomes. However, their impact on real-world inhaler utilization remains insufficiently characterized. We aimed to examine the association between SDI and the dispensing of short-acting beta-agonists (SABA) and inhaled corticosteroid–long-acting [...] Read more.

Background: Saharan dust intrusions (SDIs) are associated with poor air quality and adverse respiratory outcomes. However, their impact on real-world inhaler utilization remains insufficiently characterized. We aimed to examine the association between SDI and the dispensing of short-acting beta-agonists (SABA) and inhaled corticosteroid–long-acting beta-agonist (ICS–LABA) combinations in the Canary Islands, Spain. Methods: Pharmaceutical sales data for SABA and ICS–LABA were collected from 60 pharmacies in Santa Cruz de Tenerife (TF) and Las Palmas de Gran Canaria (GC) between June 2017 and May 2022. SDI days were identified based on daily PM₁₀ concentrations > 40 µg/m³ from the regional air quality monitoring network. Linear regression models evaluated associations between drug dispensations and SDI presence, frequency, and intensity, adjusting for seasonality (winter vs. summer). Results: Over 60 months, SABA sales were 14.8% lower in TF compared with GC, while ICS–LABA sales were 10.9% higher. SDI presence was associated with significantly higher ICS–LABA dispensations in both provinces (+5.7% in TF, +10.2% in GC), whereas no association was found for SABA. ICS–LABA sales correlated weakly but significantly with both SDI frequency and PM₁₀ levels. Seasonal analysis revealed stronger effects in winter, with ICS–LABA dispensations increasing by 14.3% (TF) and 9.6% (GC) during SDI months. For SABA, seasonal differences were independent of SDI exposure. Conclusions: SDIs in the Canary Islands are independently associated with increased dispensing of ICS–LABA maintenance therapy, particularly during winter months. Dispensing data offer a valuable population-level indicator of respiratory impact from natural airborne pollution and support the integration of environmental alerts into preventive respiratory care strategies. Full article

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15 pages, 1162 KB

Open AccessArticle

Incidence and Survival of IDH-Wildtype Glioblastoma and IDH-Mutant Astrocytoma by Treatment and Sex: A Regional Study in Spain (2011–2021)

by J. A. Encarnación, C. Manso, M. Royo-Villanova, P. Ruiz, M. I. De la Fuente, E. Cárdenas, S. Ros and J. L. Alonso-Romero

Med. Sci. 2025, 13(4), 233; https://doi.org/10.3390/medsci13040233 - 14 Oct 2025

Viewed by 845

Abstract

Background: The incidence and prognosis of high-grade gliomas differ according to histopathological and molecular features. The WHO 2021 CNS classification emphasized IDH status, but historical cohorts often lacked systematic molecular profiling. Methods: We conducted a retrospective population-based study including adult patients diagnosed with [...] Read more.

Background: The incidence and prognosis of high-grade gliomas differ according to histopathological and molecular features. The WHO 2021 CNS classification emphasized IDH status, but historical cohorts often lacked systematic molecular profiling. Methods: We conducted a retrospective population-based study including adult patients diagnosed with IDH-wildtype glioblastoma or IDH-mutant astrocytoma in a Spanish tertiary center (2011–2021). Incidence trends and survival outcomes were analyzed according to treatment modality and sex. Results: A total of 1057 patients were included: 530 (50.1%) with IDH-wildtype glioblastoma and 137 (13%) with IDH-mutant astrocytoma. Incidence of both subtypes significantly increased during the study period (p < 0.01). Median overall survival (OS) was 12.3 months for IDH-wildtype glioblastoma and 38.4 months for IDH-mutant astrocytoma. Multimodal therapy (surgery, radiotherapy, chemotherapy) significantly improved OS and progression-free survival (PFS) in both subgroups (p < 0.001). Male sex was associated with longer OS in both tumor types (p < 0.05). Conclusions: IDH-wildtype glioblastoma shows persistently poor outcomes despite increasing incidence, while IDH-mutant astrocytoma demonstrates better survival, particularly in male patients and those receiving multimodal therapy. These findings reflect real-world practice and provide epidemiological and survival data from Southern Europe to guide future clinical and public health strategies. Full article

(This article belongs to the Section Cancer and Cancer-Related Research)

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Med. Sci., Volume 13, Issue 4 (December 2025) – 57 articles

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