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20 pages, 831 KB  
Article
Bullying and Harassment in a University Context: Impact on the Mental Health of Medical Students
by Margarita L. Martinez-Fierro, Lorena Avila-Carrasco, Joselin M. Basconcelos-Sanchez, Isabel Peralta-Trejo, Yolanda Ortiz-Castro, María Elena Luna-Morales, Leticia A. Ramirez-Hernandez, Maria C. Martinez-Vazquez, Mentali Mental Health Collaborative Network and Idalia Garza-Veloz
Psychiatry Int. 2026, 7(1), 8; https://doi.org/10.3390/psychiatryint7010008 - 4 Jan 2026
Viewed by 210
Abstract
Background: Bullying in university settings is a significant yet understudied contributor to psychological distress. Differentiating the sources of victimization, may reveal distinct risk profiles associated with mental health and substance use outcomes. Objective: To evaluate the frequency and risk factors associated [...] Read more.
Background: Bullying in university settings is a significant yet understudied contributor to psychological distress. Differentiating the sources of victimization, may reveal distinct risk profiles associated with mental health and substance use outcomes. Objective: To evaluate the frequency and risk factors associated with bullying victimization among medical students, and to identify associations with mental disorders and substance use. Methods: A nested case–control cohort study was conducted with 124 medical students. Participants completed nine validated psychometric instruments evaluating neurobehavioral traits, emotional distress, substance use, and scholar bullying. Bivariate and multivariate regression models were used to estimate coefficients and odds ratios for key outcomes. Results: 42.7% of the students reported victimization, with teacher harassment (37.1%) more frequent than peer harassment (27.4%); 22.6% experienced both. Teacher harassment was primarily characterized by intentional harm (78%); peer harassment involved abuse of authority (63%). ADHD, severe stress, and substance use were associated with teacher-related victimization, while peer victimization was linked to ADHD, stress, impulsivity, and suicide risk. Childhood abuse, high stress levels, and non-heterosexual orientation as predictors of teacher harassment (p < 0.05). Notably, students with a non-heterosexual orientation were over six times more likely to report teacher harassment, highlighting the disproportionate vulnerability of sexual minorities within academic power dynamics. Conclusions: Teacher- and peer-related harassment are prevalent and often co-occur, with teacher-perpetrated bullying emerging as both more frequent and more strongly associated with mental health and identity-based vulnerabilities. Students with ADHD, high stress levels, and non-heterosexual orientation are at significantly greater risk. These findings emphasize the need for institutional accountability, inclusive academic policies, and targeted mental health support to protect vulnerable students and prevent harm within educational environments. Full article
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18 pages, 798 KB  
Article
Exploring the Risk: Investigating the Association Between Elderly-Onset Sarcoidosis (EOS) and Malignancy
by Ahmed Ehab, Axel T. Kempa, Ahmad Shalabi, Noha Elkateb, Nesrine Saad Farrag and Heba Wagih Abdelwahab
Adv. Respir. Med. 2026, 94(1), 3; https://doi.org/10.3390/arm94010003 - 2 Jan 2026
Viewed by 145
Abstract
Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between [...] Read more.
Background: Elderly-onset sarcoidosis > 65 (EOS) is rare and occurs in patients over 65. Studies on its incidence, clinical features, and treatment are limited, and its link to malignancy remains complex. Objectives: In this study, we aimed to analyze the possible association between malignancy and the occurrence of sarcoidosis in elderly patients over 65 years old. Design: Monocentric, nested retrospective case–control study. Material and Methods: A retrospective study analyzed newly diagnosed sarcoidosis patients in the Loewenstein Lung Center, Baden-Württemberg, Germany, categorizing them into younger-onset (<65 years) and elderly-onset (≥65 years). Demographic data, smoking status, medical history, symptoms, diagnostic methods, and any prior malignancy history were collected. Results: A total of 447 patients were included (365 patients within the group of younger-onset sarcoidosis and 82 patients with EOS). The median age of the younger-onset group was 47 (47 [23–63] years), compared to 69 (69 [65–84] years), p ≤ 0.001. Female patients were more prevalent in the group of elderly-onsets (54.9%) compared to the younger-onset group (35.9%), corresponding to an odds ratio of 2.2 (95% CI: 1.3–3.5, p: 0.002). Regarding the past history of malignancy, patients who had a positive history of malignancy were more prevalent among the elderly-onset group (29.6%) compared to the younger-onset group (5%) [OR (95% CI): 8.1 (4.1–15.8), p ≤ 0.001]. In multivariable logistic regression analysis with malignancy as the outcome, increasing age at sarcoidosis diagnosis was independently associated with a higher likelihood of prior malignancy (adjusted OR 1.08 per year, 95% CI 1.04–1.12), whereas sex, smoking status, and cardiometabolic comorbidity (diabetes and/or hypertension) were not independently associated. Conclusions: Elderly-onset sarcoidosis (EOS) is a less frequent variant of sarcoidosis with limited data regarding the possible risk factors. The increased prevalence of malignancy observed among patients with elderly-onset sarcoidosis appeared to be largely driven by age rather than a distinct EOS-specific effect. Age-adjusted analyses are essential when interpreting malignancy risk in sarcoidosis, and future age-matched prospective studies are needed to clarify potential biological links and guide evidence-based screening strategies. Full article
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9 pages, 1016 KB  
Article
Risk Factors Associated with the Development of Thrombotic Microangiopathy in Patients with Dermatomyositis
by Fabiola Cassiano-Quezada, Daniel Alberto Carrillo-Vázquez, Jiram Torres-Ruiz, Nancy Raquel Mejía-Domínguez, Karina Santana-de Anda, Ericka Abigail Guevara-Rojas and Diana Gómez-Martín
Int. J. Mol. Sci. 2026, 27(1), 315; https://doi.org/10.3390/ijms27010315 - 27 Dec 2025
Viewed by 217
Abstract
Thrombotic microangiopathy (TMA) is an infrequent and poorly understood manifestation in dermatomyositis (DM) associated with poor outcomes and refractoriness to treatment. The aim of this study is to describe the clinical characteristics and risk factors for its development. We conducted a nested case–control [...] Read more.
Thrombotic microangiopathy (TMA) is an infrequent and poorly understood manifestation in dermatomyositis (DM) associated with poor outcomes and refractoriness to treatment. The aim of this study is to describe the clinical characteristics and risk factors for its development. We conducted a nested case–control study comparing patients with DM who developed TMA to those with DM without this complication. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT), the Manual Muscle Test of eight muscle groups (MMT8), and muscle enzyme levels. A binomial logistic regression analysis was performed to identify risk factors for the development of TMA among patients with DM. All patients with TMA had DM. Patients with DM/TMA had a shorter time since disease onset (p = 0.033), lower levels of C3 (p = 0.07) and C4 (p = 0.046), as well as higher leukocyte (p = 0.044), neutrophil (p = 0.033), and creatine phosphokinase (CK) levels (p = 0.005). They also exhibited higher constitutional (p = 0.0008), pulmonary (p = 0.008), and muscle disease activity (p = 0.027). In the univariate analysis, a shorter time since disease onset (OR 0.42, p = 0.0042) indicated an increased risk for TMA, as did low complement levels (C3: OR 1.11, p = 0.01; C4: OR 1.18, p = 0.02) and higher constitutional (OR 2.27, p = 0.0014), pulmonary (OR 5.50, p = 0.0004), and muscle disease activity (OR 2.1, p = 0.003). Although elevated CK levels (OR 1.001, p = 0.0008) reached statistical significance, the effect size was minimal and should not be interpreted as a clinically relevant increase in risk. Confocal microscopy of muscle biopsy specimens demonstrated neutrophil extracellular traps (NETs) infiltrating muscle tissue. Patients with DM who develop TMA appear to exhibit a distinct clinical phenotype characterized by leukocytosis, neutrophilia, hypocomplementemia, shorter disease duration, and greater constitutional, pulmonary, and muscular disease activity. Although limited by the small sample size, these findings suggest a potential role of NETs in microvascular and tissue injury associated with DM-related TMA. Larger studies are warranted to validate these observations and further elucidate the underlying pathogenic mechanisms. Full article
(This article belongs to the Special Issue Advances in the Genetics, Epidemiology and Management of Myopathies)
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16 pages, 1636 KB  
Article
A Digital Twin Strategy Combined with a Monte Carlo Simulation Framework to Predict Outcomes in Patients with Unusual-Site Venous Thrombosis Treated with Direct Oral Anticoagulants Versus Vitamin K Antagonists Using Data from Real-World Populations
by Anabel Franco-Moreno, Luis Escobar-Curbelo, Juan Torres-Macho, Nuria Muñoz-Rivas, Cristina Lucía Ancos-Aracil, Ana Martínez de la Casa-Muñoz, Ana Bustamante-Fermosel, Paz Arranz-García and Miguel Ángel Casado-Suela
Clin. Pract. 2025, 15(12), 237; https://doi.org/10.3390/clinpract15120237 - 17 Dec 2025
Viewed by 308
Abstract
Background/Objectives: Unusual-site venous thrombosis (USVT) lacks robust evidence guiding anticoagulant selection between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This study aimed to evaluate recanalization, recurrence, and major bleeding outcomes in real-world USVT patients and to replicate these findings through a [...] Read more.
Background/Objectives: Unusual-site venous thrombosis (USVT) lacks robust evidence guiding anticoagulant selection between vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). This study aimed to evaluate recanalization, recurrence, and major bleeding outcomes in real-world USVT patients and to replicate these findings through a validated digital twin model with Monte Carlo simulation. Methods: We conducted a retrospective study of 90 USVT patients (72% VKAs, 28% DOACs). A conditional generative adversarial network was used to generate digital twins matched on age, sex, thrombosis site, and malignancy. Logistic regression was applied to estimate treatment-specific outcome probabilities for recanalization, recurrence, and major bleeding. A nested stochastic simulation framework simulated 500 iterations across clinical scenarios, including increased DOAC use, cancer prevalence, cerebral vein thrombosis proportion, and optimized VKA control. Results: The mean age was 67.5 years, and 54.4% were female. 61.1% of splanchnic vein thrombosis, 36.7% of upper extremity deep vein thrombosis, and 2.2% of cerebral vein thrombosis were included. In the real cohort, complete recanalization occurred in 40.0% of patients with DOACs and 36.0% with VKAs. Recurrence was 8.0% with DOACs and 7.7% with VKAs, and major bleeding occurred in 8.0% and 10.8% of cases, respectively. All-cause mortality was 20% in DOAC-treated patients and 60% in those receiving VKAs. Digital Twin-based predictions replicated these results (recanalization 40.3% versus 38.0%; recurrence 10.9% versus 8.6%; bleeding 7.6% versus 9.1%). Simulated scenarios preserved the directionality effect, with the most significant differences observed in high-cerebral vein thrombosis and cancer-enriched patients. Conclusions: DOACs showed comparable efficacy and slightly lower bleeding risk than VKAs in USVT. Digital twin and Monte Carlo modeling provided robust, reproducible simulations of treatment effects under varying clinical conditions. Separating empirical and simulation-based findings, the digital twin supported the internal consistency of real-world observations and demonstrated the potential of in silico modeling as a complementary tool in rare thrombotic diseases. Full article
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13 pages, 557 KB  
Article
Synolitic Graph Neural Networks of High-Dimensional Proteomic Data Enhance Early Detection of Ovarian Cancer
by Alexey Zaikin, Ivan Sviridov, Janna G. Oganezova, Usha Menon, Aleksandra Gentry-Maharaj, John F. Timms and Oleg Blyuss
Cancers 2025, 17(24), 3972; https://doi.org/10.3390/cancers17243972 - 12 Dec 2025
Viewed by 390
Abstract
Background: Ovarian cancer is characterized by high mortality rates, primarily due to diagnosis at late stages. Current biomarkers, such as CA125, have demonstrated limited efficacy for early detection. While high-dimensional proteomics offers a more comprehensive view of systemic biology, the analysis of [...] Read more.
Background: Ovarian cancer is characterized by high mortality rates, primarily due to diagnosis at late stages. Current biomarkers, such as CA125, have demonstrated limited efficacy for early detection. While high-dimensional proteomics offers a more comprehensive view of systemic biology, the analysis of such data, where the number of features far exceeds the number of samples, presents a significant computational challenge. Methods: This study utilized a nested case–control cohort of longitudinal pre-diagnostic serum samples from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) profiled for eight candidate ovarian cancer biomarkers (CA125, HE4, PEBP4, CHI3L1, FSTL1, AGR2, SLPI, DNAH17) and 92 additional cancer-associated proteins from the Olink Oncology II panel. We employed a Synolitic Graph Neural Network framework that transforms high-dimensional multi-protein data into sample-specific, interconnected graphs using a synolitic network approach. These graphs, which encode the relational patterns between proteins, were then used to train Graph Neural Network (GNN) models for classification. Performance of the network approach was evaluated together with conventional machine learning approaches via 5-fold cross-validation on samples collected within one year of diagnosis and a separate holdout set of samples collected one to two years prior to diagnosis. Results: In samples collected within one year of ovarian cancer diagnosis, conventional machine learning models—including XGBoost, random forests, and logistic regression—achieved the highest discriminative performance, with XGBoost reaching an ROC-AUC of 92%. Graph Convolutional Networks (GCNs) achieved moderate performance in this interval (ROC-AUC ~71%), with balanced sensitivity and specificity comparable to mid-performing conventional models. In the 1–2 year early-detection window, conventional model performance declined sharply (XGBoost ROC-AUC 46%), whereas the GCN maintained robust discriminative ability (ROC-AUC ~74%) with relatively balanced sensitivity and specificity. These findings indicate that while conventional approaches excel at detecting late pre-diagnostic signals, GNNs are more stable and effective at capturing subtle early molecular changes. Conclusions: The synolitic GNN framework demonstrates robust performance in early pre-diagnostic detection of ovarian cancer, maintaining accuracy where conventional methods decline. These results highlight the potential of network-informed machine learning to identify subtle proteomic patterns and pathway-level dysregulation prior to clinical diagnosis. This proof-of-concept study supports further development of GNN approaches for early ovarian cancer detection and warrants validation in larger, independent cohorts. Full article
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13 pages, 359 KB  
Article
Population Attributable Fraction of Tobacco Use and Type 2 Diabetes Mellitus: An Analysis of the ENSANUT 2021
by Julio Cesar Campuzano, Jorge Martin Rodríguez, Luz Myriam Reynales, Anaid Hernández and Diana Carolina Urrego
Epidemiologia 2025, 6(4), 84; https://doi.org/10.3390/epidemiologia6040084 - 2 Dec 2025
Viewed by 470
Abstract
Background: Robust evidence demonstrates that tobacco use acts as a causal and, therefore, modifiable risk factor for the development of type 2 diabetes mellitus (T2DM). However, its specific population-level impact in Mexico has not yet been quantified. Objective: This study aimed to estimate [...] Read more.
Background: Robust evidence demonstrates that tobacco use acts as a causal and, therefore, modifiable risk factor for the development of type 2 diabetes mellitus (T2DM). However, its specific population-level impact in Mexico has not yet been quantified. Objective: This study aimed to estimate the population attributable fraction (PAF) of T2DM associated with tobacco use among Mexican adults, utilizing data from the 2021 National Health and Nutrition Survey (ENSANUT). Methods: A nested case–control analysis was conducted within the complex sampling design of the ENSANUT. Adults aged 20 years or older were included. Cases were defined as individuals with a self-reported medical diagnosed T2DM diagnosis; controls were individuals without T2DM. Exposure status was categorized as current person who smokes, former person who smokes, and never person who smokes. A logistic regression model was employed, adjusting for key covariates including age, sex, socioeconomic status, and comorbidities. The PAF was subsequently calculated using the Miettinen formula. Results: The adjusted PAF for T2DM attributable to smoking was 10.1% (95% CI: 4.07–14.97). This finding suggests that approximately one in eight T2DM cases could be prevented through the elimination of tobacco use. The association was more pronounced among men and individuals with a history of heavy tobacco use. Conclusion: The estimated PAF for T2DM due to tobacco use underscores the significant contribution of policies established within the WHO Framework Convention on Tobacco Control to the prevention of chronic diseases. The implementation and strengthening of such policies, including increased tobacco taxes, comprehensive smoking bans in public places, on-package warnings, and advertising prohibitions, would prove highly beneficial. These findings show a strong population-level association between tobacco use and T2DM, but causality cannot be established. Future longitudinal studies in Mexico are needed to confirm these results. Full article
(This article belongs to the Special Issue Advances in Environmental Epidemiology, Health and Lifestyle)
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11 pages, 383 KB  
Article
Mandatory Biological/Targeted Synthetic Disease-Modifying Antirheumatic Drugs Dose Reduction on Risk of Serious Infections in Patients with Rheumatoid Arthritis: A Nationwide Nested Case–Control Study
by Der-Yuan Chen, Ching-Heng Lin, Hsin-Hua Chen, Yi-Ming Chen and Kuo-Tung Tang
Biomedicines 2025, 13(12), 2891; https://doi.org/10.3390/biomedicines13122891 - 26 Nov 2025
Viewed by 559
Abstract
Background: We aimed to investigate the risk for a serious infection in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This nested case–control study investigated the risk for a serious infection in RA [...] Read more.
Background: We aimed to investigate the risk for a serious infection in rheumatoid arthritis (RA) patients after tapering the dose of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Methods: This nested case–control study investigated the risk for a serious infection in RA patients who underwent mandatory b/tsDMARDs dose reduction 2.5 years after starting therapy with a single b/tsDMARD in the National Health Insurance Research Database (NHIRD). Cases were those patients who developed a serious infection afterwards. Matched controls were selected from those patients who did not develop a serious infection. We used unconditional logistic regression to analyze the odds ratios (ORs) of b/tsDMARDs dose reduction and discontinuation between cases and controls. Results: RA patients underwent an average dose reduction of 60%. Among a total of 268 cases and 1072 controls, we did not observe a lower risk for a serious infection in those patients who tapered or discontinued b/tsDMARDs. However, those patients who had discontinued b/tsDMARDs had a higher risk for a serious infection when compared with those who had not and had reduced their b/stDMARDs dose reduction below the average (i.e., ≤60%), with an adjusted OR of 1.48 (95%CI: 1.05, 2.09). Conclusions: Dose reduction in b/tsDMARDs in RA patients might not be associated with a lower risk for serious infection. Discontinuation of b/tsDMARDs, however, was likely associated with a higher risk for serious infection. Full article
(This article belongs to the Special Issue Diagnosis, Management and Treatment of Rheumatoid Arthritis)
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11 pages, 1319 KB  
Article
Common Molecular Detection of the Neglected Human Malaria Parasite Among Febrile Patients in Southern Regions in Senegal
by Babacar Souleymane Sambe, Serigne Ousmane Mbacké Diaw, Aissatou Diagne, Arona Sabène Diatta, Hélène Ataume Mawounge Diatta, Ibrahima Sarr, Rokhaya Sané, Patindé Yann Bianca Guigma, Bruno Senghor, Babacar Diouf, Papa Mbacke Sembene, Ines Vigan-Womas and Makhtar Niang
Pathogens 2025, 14(12), 1201; https://doi.org/10.3390/pathogens14121201 - 25 Nov 2025
Viewed by 514
Abstract
Background: In sub-Saharan Africa, Plasmodium falciparum is unequivocally responsible for almost all malaria cases and deaths. However, the long-neglected human P. vivax, P. ovale, and P. malariae parasites also emerge as relevant, though their prevalence and contribution to the burden of the [...] Read more.
Background: In sub-Saharan Africa, Plasmodium falciparum is unequivocally responsible for almost all malaria cases and deaths. However, the long-neglected human P. vivax, P. ovale, and P. malariae parasites also emerge as relevant, though their prevalence and contribution to the burden of the disease are very poorly appreciated. This study aimed to bridge this gap and surveyed the circulation of non-falciparum malaria parasites among febrile patients in four regions in south Senegal. Methods: Blood samples were obtained from 1990 febrile patients during the malaria transmission seasons of 2020, 2021, and 2022 in four southern regions in Senegal (Kedougou, Kolda, Tambacounda, and Ziguinchor). Genomic DNA was isolated and tested for Plasmodium infections by using a combination of Plasmodium genus-specific qPCR and Plasmodium species-specific nested PCR. Frequencies and distribution of Plasmodium species according to region, period, and patient demographics were analyzed using R. Spatial patterns of infection were further explored and visualized with QGIS software version 3.30.2. Results: The Plasmodium positivity rate was 73.43% of which 67.92% were unique Plasmodium species infections and 32.08% were co-infections by two or three Plasmodium species. The results described the ongoing circulation of all non-falciparum species in three of the four study regions, the non-detection of P. vivax and P. malariae parasites among the samples tested in Ziguinchor, the first evidence of non-falciparum infections in Kolda and Tambacounda, as well as the first report of P. ovale in Ziguinchor. Conclusions: Our data call on clinicians to account for these species in clinical prognoses, but also on the National Malaria Control Programme to consider these species in their policy of reducing the incidence of the disease with a view to eliminating malaria in Senegal. Full article
(This article belongs to the Section Parasitic Pathogens)
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12 pages, 957 KB  
Article
Determination of the Number of Circulating Small Extracellular Vesicles in Pregnancy Using the Novel Marker CD9
by Risa Narumi, Hirotada Suzuki, Manabu Ogoyama, Yasushi Saga, Shohei Tozawa, Syunya Noguchi, Akihide Ohkuchi, Toshihiro Takizawa, Hiroyuki Fujiwara and Hironori Takahashi
Int. J. Mol. Sci. 2025, 26(22), 10906; https://doi.org/10.3390/ijms262210906 - 10 Nov 2025
Viewed by 623
Abstract
Small extracellular vesicles (small EVs) play pivotal roles in intercellular communication and pregnancy maintenance, but their clinical significance in preeclampsia (PE) remains unclear. We obtained plasma samples from non-pregnant women, healthy pregnant women, and patients with early-onset (EoPE) and late-onset PE (LoPE). Small [...] Read more.
Small extracellular vesicles (small EVs) play pivotal roles in intercellular communication and pregnancy maintenance, but their clinical significance in preeclampsia (PE) remains unclear. We obtained plasma samples from non-pregnant women, healthy pregnant women, and patients with early-onset (EoPE) and late-onset PE (LoPE). Small EVs were isolated using ultracentrifugation and validated using transmission electron microscopy and nanoparticle tracking analysis; in addition, Western blotting was performed to identify suitable surface markers for plasma-derived small EVs. In our analysis, we consistently detected cluster of differentiation 9 (CD9), whereas classical markers such as cluster of differentiation 63 (CD63) and tumor susceptibility gene 101 (TSG101) were absent. In a prospective, nested case–control study, we analyzed first-trimester samples by using a CD9-based ELISA for small-EV quantification. The number of small EVs did not significantly differ between non-pregnant and healthy pregnant women regardless of the gestational age. However, EVs were significantly elevated in both EoPE (3.5-fold) and LoPE (1.5-fold) compared with matched controls. First-trimester EV levels did not show differences between women who later developed PE and normal controls. These findings indicate that CD9 is a promising marker for plasma-derived small EVs and that an elevated number of small EVs is associated with established PE but has limited predictive value in early pregnancy. Further studies are required to elucidate the cellular origin and clinical implications of small EVs in PE. Full article
(This article belongs to the Special Issue Cellular and Molecular Targets of Preeclampsia)
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25 pages, 3099 KB  
Article
Joint Energy–Resilience Optimization of Grid-Forming Storage in Islanded Microgrids via Wasserstein Distributionally Robust Framework
by Yinchi Shao, Yu Gong, Xiaoyu Wang, Xianmiao Huang, Yang Zhao and Shanna Luo
Energies 2025, 18(21), 5674; https://doi.org/10.3390/en18215674 - 29 Oct 2025
Cited by 1 | Viewed by 720
Abstract
The increasing deployment of islanded microgrids in disaster-prone and infrastructure-constrained regions has elevated the importance of resilient energy storage systems capable of supporting autonomous operation. Grid-forming energy storage (GFES) units—designed to provide frequency reference, voltage regulation, and black-start capabilities—are emerging as critical assets [...] Read more.
The increasing deployment of islanded microgrids in disaster-prone and infrastructure-constrained regions has elevated the importance of resilient energy storage systems capable of supporting autonomous operation. Grid-forming energy storage (GFES) units—designed to provide frequency reference, voltage regulation, and black-start capabilities—are emerging as critical assets for maintaining both energy adequacy and dynamic stability in isolated environments. However, conventional storage planning models fail to capture the interplay between uncertain renewable generation, time-coupled operational constraints, and control-oriented performance metrics such as virtual inertia and voltage ride-through. To address this gap, this paper proposes a novel distributionally robust optimization (DRO) framework that jointly optimizes the siting and sizing of GFES under renewable and load uncertainty. The model is grounded in Wasserstein-metric DRO, allowing worst-case expectation minimization over an ambiguity set constructed from empirical historical data. A multi-period convex formulation is developed that incorporates energy balance, degradation cost, state-of-charge dynamics, black-start reserve margins, and stability-aware constraints. Frequency sensitivity and voltage compliance metrics are explicitly embedded into the optimization, enabling control-aware dispatch and resilience-informed placement of storage assets. A tractable reformulation is achieved using strong duality and solved via a nested column-and-constraint generation algorithm. The framework is validated on a modified IEEE 33-bus distribution network with high PV penetration and heterogeneous demand profiles. Case study results demonstrate that the proposed model reduces worst-case blackout duration by 17.4%, improves voltage recovery speed by 12.9%, and achieves 22.3% higher SoC utilization efficiency compared to deterministic and stochastic baselines. Furthermore, sensitivity analyses reveal that GFES deployment naturally concentrates at nodes with high dynamic control leverage, confirming the effectiveness of the control-informed robust design. This work provides a scalable, data-driven planning tool for resilient microgrid development in the face of deep temporal and structural uncertainty. Full article
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20 pages, 8426 KB  
Article
Metabolomic Profile of Weight Gain of People Living with HIV Treated with Integrase Strand Transfer Inhibitor Regimens Reveals Dysregulated Lipid Metabolism and Mitochondrial Dysfunction
by Ana Miriam Ascencio-Anastacio, Violeta Larios-Serrato, José Antonio Mata-Marín, Mara Rodríguez Evaristo, Mireya Núñez-Armendáriz, Ana Luz Cano-Díaz, Alberto Chaparro-Sánchez, Gloria Elizabeth Salinas-Velázquez, Angélica Maldonado-Rodríguez, Javier Torres, María Martha García-Flores, Zuriel Eduardo Martínez-Valencia, Beatriz Irene Arroyo-Sánchez, Viridiana Olin-Sandoval, Fernando Minauro, Jesus Enrique Gaytán-Martínez and Ericka Nelly Pompa-Mera
Metabolites 2025, 15(11), 695; https://doi.org/10.3390/metabo15110695 - 25 Oct 2025
Viewed by 1806
Abstract
Background/Objectives: Excessive weight gain is a growing concern among people living with HIV (PWH) receiving integrase strand transfer inhibitor (INSTI)-based regimens as first-line antiretroviral therapy (ART), as it may contribute to multimorbidity. The mechanisms driving weight gain in INSTI users are not [...] Read more.
Background/Objectives: Excessive weight gain is a growing concern among people living with HIV (PWH) receiving integrase strand transfer inhibitor (INSTI)-based regimens as first-line antiretroviral therapy (ART), as it may contribute to multimorbidity. The mechanisms driving weight gain in INSTI users are not fully understood but are thought to be multifactorial. This study examines the plasma metabolome associated with weight gain in PWH on INSTI-based regimens. Methods: We conducted a nested case–control study within the randomized clinical trial MICTLAN (NCT06629480). Sixty-six participants were randomized to receive INSTI-based regimens, either bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), and followed for 18 months. Weight gain >10% relative to baseline was considered a primary endpoint and used as a criterium to categorize cases (n = 28) and controls (n = 38). Anthropometric and clinical measurements, plasma insulin, and metabolomic profiles were assessed at baseline and 18 months post-ART. Plasma untargeted metabolomics was performed using liquid chromatography–mass spectrometry (LC-MS/MS) to identify metabolomic changes linked to weight gain. Bioinformatic tools, including Partial Least Squares Discriminant Analysis (PLS-DA), volcano plots, and KEGG pathway enrichment analysis, were used to analyze plasma metabolomes and identify significant differential metabolites. Results: Weight gain at 18 months in PWH on INSTI-based ART was associated with insulin resistance, as measured by HOMA-IR (OR 3.23; 95% CI 1.14–9.10; p = 0.023), and visceral adipose tissue thickness > 4 cm (OR 4.50; 95% CI 1.60–13.03; 9.10; p = 0.004), and hypertriglyceridemia (OR 3.9; 95% CI 1.38–10.94; p = 0.008). Baseline HIV RNA viral load >50,000 copies/mL (OR 8.05; 95% CI 2.65–24.43; p = 0.0002) was identified as a baseline predictor of weight gain (aOR 6.58 (1.83–23.58); p = 0.004). In addition, accumulation of circulating medium-chain acylcarnitines, indicative of mitochondrial dysfunction, and insulin resistance were linked to weight gain in PWH on INSTI-based regimens after 18 months of therapy. Conclusions: This metabolomic study identified metabolites reflecting mitochondrial dysfunction, dysregulated lipid metabolism, and altered amino acid metabolism as key mechanisms underlying insulin resistance and weight gain in PWH on INSTI-based ART. Full article
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12 pages, 938 KB  
Article
Association Between Atopic Dermatitis and Colorectal Cancer Risk: A Korean Population-Based Study
by Ho Suk Kang, Kyeong Min Han, Joo-Hee Kim, Ji Hee Kim, Hyo Geun Choi, Dae Myoung Yoo, Ha Young Park, Nan Young Kim and Mi Jung Kwon
Biomedicines 2025, 13(10), 2538; https://doi.org/10.3390/biomedicines13102538 - 17 Oct 2025
Cited by 1 | Viewed by 817
Abstract
Background/Objectives: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that may influence cancer risk through immune dysregulation and chronic inflammation. The association between AD and colorectal cancer (CRC) remains unclear, with previous studies reporting conflicting results. Evidence from East Asian populations, [...] Read more.
Background/Objectives: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that may influence cancer risk through immune dysregulation and chronic inflammation. The association between AD and colorectal cancer (CRC) remains unclear, with previous studies reporting conflicting results. Evidence from East Asian populations, where CRC incidence is rapidly rising, is particularly limited. Methods: We conducted a nested case–control study using the Korean National Health Insurance Service–National Sample Cohort (2002–2019). A total of 9920 incident CRC cases were identified and matched 1:4 with 39,680 controls by age, sex, income, and residential region. AD was defined using diagnostic codes and prescription records. Overlap propensity score weighting was applied to minimize confounding, and weighted logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: AD was not significantly associated with CRC risk (adjusted OR = 0.97, 95% CI: 0.91–1.04). The null association was consistent across subgroups stratified by age, sex, comorbidity burden, and allergic comorbidities. Sensitivity analyses yielded similar results. Conclusions: In this large, nationwide, population-based study, AD did not exhibit a significant connection with the risk of CRC. This null association remained consistent across multiple subgroups and sensitivity analyses, suggesting that AD may not play a substantial role in colorectal carcinogenesis. However, the observational design and lack of detailed lifestyle information may limit causal interpretation. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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12 pages, 598 KB  
Article
Beyond the Skin: Atopic Dermatitis and Increased Gastric Cancer Risk in Korea
by Ho Suk Kang, Kyeong Min Han, Joo-Hee Kim, Ji Hee Kim, Hyo Geun Choi, Dae Myoung Yoo, Ha Young Park, Nan Young Kim and Mi Jung Kwon
Cancers 2025, 17(19), 3214; https://doi.org/10.3390/cancers17193214 - 2 Oct 2025
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Abstract
Background/Objectives: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, but its relationship with gastric cancer (GC) remains unclear. This study aimed to investigate the association between AD and GC using a nationwide Korean database. Methods: Using the Korean National Health Insurance [...] Read more.
Background/Objectives: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, but its relationship with gastric cancer (GC) remains unclear. This study aimed to investigate the association between AD and GC using a nationwide Korean database. Methods: Using the Korean National Health Insurance Service-National Sample Cohort, we conducted a nested case–control study including 10,174 GC patients and 40,696 matched controls (1:4 by age, sex, income, and region). Overlap propensity score weighting was used to control for confounders. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated via logistic regression. Results: AD was significantly associated with an increased risk of GC (adjusted OR = 1.08; 95% CI: 1.01–1.15). Subgroup analyses revealed stronger associations among individuals aged ≥ 65 years (OR = 1.12), men (OR = 1.10), rural residents (OR = 1.14), and those without comorbidities (CCI = 0, OR = 1.15). Higher risks were also observed in participants with non-allergic rhinitis (OR = 1.43) or no asthma (OR = 1.12). Conclusions: AD may be associated with an increased risk of GC in the Korean population. These findings may highlight the importance of considering dermatological conditions in the context of systemic cancer risk. Full article
(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)
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13 pages, 1455 KB  
Article
Alterations in the Metabolic and Lipid Profiles Associated with Vitamin D Deficiency in Early Pregnancy
by Yiwen Qiu, Boya Wang, Nuo Xu, Shuhui Wang, Xialidan Alifu, Haoyue Cheng, Danqing Chen, Lina Yu, Hui Liu and Yunxian Yu
Nutrients 2025, 17(19), 3096; https://doi.org/10.3390/nu17193096 - 29 Sep 2025
Cited by 1 | Viewed by 931
Abstract
Objective: Vitamin D deficiency (VDD) is common in pregnancy and may affect lipid metabolism. The underlying mechanisms are multifactorial, but most evidence so far comes from non-pregnant populations. This study aims to identify metabolites and metabolic patterns associated with VDD in early pregnancy [...] Read more.
Objective: Vitamin D deficiency (VDD) is common in pregnancy and may affect lipid metabolism. The underlying mechanisms are multifactorial, but most evidence so far comes from non-pregnant populations. This study aims to identify metabolites and metabolic patterns associated with VDD in early pregnancy and to evaluate their relationships with maternal lipid profiles. Methods: A nested case–control research was carried out in the Zhoushan Pregnant Women Cohort (ZPWC). Cases were defined as women with VDD (25(OH)D < 20 ng/mL), and controls (≥20 ng/mL) were matched 1:1 using propensity scores based on age, pre-pregnancy BMI, gestational week, and calendar year at blood sampling. The untargeted metabolomics of first-trimester maternal plasma were measured. Metabolic profiles were analyzed using partial least squares-discriminant analysis (PLS-DA). Principal component analysis (PCA) was applied to visualize group separation, and metabolite set enrichment analysis (MSEA) was performed to reveal biologically relevant metabolic patterns. Associations between VDD-related metabolite components in early pregnancy and lipid levels in mid-pregnancy were assessed using linear regression models. Results: 44 cases and 44 controls were selected for the study. There were 60 metabolites identified as being connected to VDD. Among these, 26 metabolites, primarily glycerophospholipids and fatty acyls, exhibited decreased levels in the VDD group. In contrast, 34 metabolites showed increased levels, mainly comprising benzene derivatives, carboxylic acids, and organooxygen compounds. PCA based on these metabolites explained 52.8% of the total variance (R2X = 0.528) across the first six principal components (PC1: 16.4%, PC2: 10.6%, PC3: 9.2%, PC4: 6.3%, PC5: 5.7%, PC6: 4.6%). PC2, dominated by lineolic acids and derivatives, was negatively associated with total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (all p < 0.01). PC3, dominated by glycerophosphocholines, was negatively associated with TC, TG, and high-density lipoprotein cholesterol (HDL-C) (all p < 0.05). MSEA revealed significant enrichment of the pantothenate and CoA biosynthesis pathway after multiple testing correction (FDR < 0.05). Conclusions: This study reveals distinct metabolic alterations linked to VDD and suggests potential mechanisms underlying its association with maternal lipid metabolism in early pregnancy. Full article
(This article belongs to the Section Nutrition and Metabolism)
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10 pages, 217 KB  
Article
Middle East Deployment and Lymphoid Malignancies in US Veterans: A Matched Case-Control Analysis
by Helen Ma and Pankaj Gupta
Cancers 2025, 17(19), 3161; https://doi.org/10.3390/cancers17193161 - 29 Sep 2025
Viewed by 716
Abstract
Background/Objective: US military personnel deployed to the Middle East were potentially subjected to harmful exposures, such as carcinogens from burn pits, which may increase the risk of lymphoid malignancies. Our objective was to determine the association between deployment and the risk of developing [...] Read more.
Background/Objective: US military personnel deployed to the Middle East were potentially subjected to harmful exposures, such as carcinogens from burn pits, which may increase the risk of lymphoid malignancies. Our objective was to determine the association between deployment and the risk of developing lymphoid malignancies. Methods: This was a retrospective nested matched case-control study from a cohort of 3.5 million veterans who enlisted in the military after September 2001 and were followed until death or last follow up through September 2024. Cases of lymphoid malignancies were identified by the VA Central Cancer Registry and controls were randomly selected from the same base cohort, matched by year of birth, year of enlistment, sex, race, and ethnicity. Exposure was defined as deployment to the Middle East as determined by identification on the VA Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) roster with confirmed dates of deployment or paystubs. Results: There were 1037 cases of lymphoid malignancies and 3572 matched controls. Deployment was not associated with a higher risk of developing lymphoid malignancies compared to non-deployment. Exposure to OEF/OIF was not associated with a higher risk of developing certain types of lymphoid malignancies. Conclusions: In this large, matched case-control study of US veterans, deployment to the Middle East was not associated with increased risk of developing lymphoid malignancies. While these findings do not support an increased lymphoid malignancy risk, important limitations remain, including the absence of detailed exposure and potential confounding variables. Prospective monitoring of specific types and doses of exposures during military deployment, development of lymphoid and other malignancies, and their underlying pathophysiology is indicated. Full article
(This article belongs to the Special Issue Chronic Lymphocytic Leukemia: From Genetics to Therapy)
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