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Search Results (67,012)

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24 pages, 828 KB  
Review
Modern Approaches to Diagnosis and Evaluation of Survival Prognosis in Patients with Pancreatic Cancer
by Maria Getsina, Nikolay Tsyba and Ekaterina Chernevskaya
Int. J. Mol. Sci. 2026, 27(13), 5867; https://doi.org/10.3390/ijms27135867 (registering DOI) - 29 Jun 2026
Abstract
Pancreatic cancer is among the most aggressive malignancies, and late diagnosis remains a key challenge. For a systematic review of pancreatic cancer diagnosis and prognosis, Scopus and Web of Science databases were used for the period from 2016 to 2026. The search query [...] Read more.
Pancreatic cancer is among the most aggressive malignancies, and late diagnosis remains a key challenge. For a systematic review of pancreatic cancer diagnosis and prognosis, Scopus and Web of Science databases were used for the period from 2016 to 2026. The search query included the following keywords and their combinations: pancreatic cancer, diagnosis, early detection, prognosis, biomarkers, metabolomic profiling, CA19-9, microbiome, metagenomic changes, circulating tumor DNA, genomic analysis. Inclusion criteria included only articles published in English. Exclusion criteria included case reports and studies that did not examine pancreatic cancer. Our analysis demonstrates that integrating multi-omics data, particularly combining traditional CA19-9 with circulating tumor DNA (ctDNA) and metabolomic profiles (lipids, amino acids, carbohydrates), significantly improves diagnostic accuracy. Microbiome composition and genomic alterations further refine risk stratification and prognostic assessment. The synergistic use of these biomarkers may facilitate the development of screening, early diagnosis, risk stratification, and treatment optimization. However, the introduction of new diagnostic approaches into clinical practice requires additional verification, standardization and prospective clinical studies. Full article
(This article belongs to the Special Issue Molecular Advances in Cancer and Cell Metabolism—3rd Edition)
13 pages, 583 KB  
Article
Association of Academic Stress, Physical Activity, Sedentary Behavior, and Diabetes Risk Among University Students
by Siti Nur Asiyah, Atik Qurrota A’yunin Al Isyrofi, Ayu Mei Wulandari, Ambarwati, Aini Nurul Fatimatuz Zahroh and Achmad Ilham Fanany Al Isyrofie
Healthcare 2026, 14(13), 1894; https://doi.org/10.3390/healthcare14131894 (registering DOI) - 29 Jun 2026
Abstract
Background: The increasing prevalence of diabetes mellitus and metabolic risk factors among young adults has become a major public health concern. University students are particularly vulnerable to unhealthy lifestyle changes, including sedentary behavior, insufficient physical activity, and academic stress, all of which may [...] Read more.
Background: The increasing prevalence of diabetes mellitus and metabolic risk factors among young adults has become a major public health concern. University students are particularly vulnerable to unhealthy lifestyle changes, including sedentary behavior, insufficient physical activity, and academic stress, all of which may be associated with an elevated risk of metabolic disorders. Objective: This study aimed to examine the associations of academic stress, physical activity, and sedentary behavior with diabetes risk among university students. Methods: A cross-sectional analytical study was conducted among 264 university students recruited through an online survey. Academic stress was assessed using a six-item Likert-scale instrument, while diabetes risk was evaluated using a composite score derived from indicators adapted from the modified Finnish Diabetes Risk Score (modified FINDRISC). Statistical analyses included descriptive statistics, Cronbach’s alpha reliability testing, exploratory factor analysis (EFA), Spearman’s correlation analysis, and multivariable logistic regression. Results: The academic stress instrument demonstrated good internal consistency (Cronbach’s alpha = 0.85). Exploratory factor analysis supported the construct validity of the instrument, with all six items loading substantially on a common academic stress factor. Correlation analysis revealed that academic stress was positively associated with sedentary behavior and diabetes risk, whereas physical activity was negatively associated with diabetes risk. Multivariable logistic regression showed that academic stress was significantly associated with an increased risk of diabetes (adjusted odds ratio [aOR] = 1.18, 95% confidence interval [CI]: 1.02–1.36; p = 0.028). Moderate-to-vigorous physical activity was associated with a lower risk of diabetes (aOR = 0.74, 95% CI: 0.60–0.92; p = 0.011), while longer sitting duration was associated with an increased risk of diabetes. Conclusions: Academic stress, sedentary behavior, and physical activity were significantly associated with diabetes risk among university students. These findings highlight the importance of developing university-based health promotion programs that integrate stress management, physical activity promotion, and sedentary behavior reduction to support the prevention of metabolic risk factors in young adults. Full article
(This article belongs to the Section Healthcare and Sustainability)
35 pages, 15888 KB  
Review
Biobehavioral Responses to the Built Environment: A Technology-Driven Review of Health Outcomes
by Naibin Jiang, Chao Chen, Zhen Peng, Xinyu Li and Jianmin Du
Buildings 2026, 16(13), 2611; https://doi.org/10.3390/buildings16132611 (registering DOI) - 29 Jun 2026
Abstract
Urbanization underscores the critical role of the built environment in shaping human health outcomes. Recently, technology-driven assessment enables a more precise, dynamic, and objective evaluation of individuals’ biobehavioral responses to built environments and their health. However, existing reviews are limited to single technologies, [...] Read more.
Urbanization underscores the critical role of the built environment in shaping human health outcomes. Recently, technology-driven assessment enables a more precise, dynamic, and objective evaluation of individuals’ biobehavioral responses to built environments and their health. However, existing reviews are limited to single technologies, single health outcomes, or specific environmental features. As a result, this narrative review summarizes 269 studies (2003–2025) to examine how such technology-driven methodologies capture the effects of built environments on psychophysiological well-being. Findings reveal a four-stage evolution in methodology from subjective evaluations and single-device monitoring to integrated subjective-objective measures and, more recently, multimodal synergistic frameworks. Accordingly, based on a technology-driven assessment of biobehavioral responses, this review synthesizes a dual-pathway framework linking the built environment to health: (1) psychological responses are mediated through emotion-arousal mechanisms, encompassing 22 key emotions across both positive and negative valences; and (2) physiological outcomes are influenced by behavioral–psychological mediation and direct environmental exposure, encompassing six categories that span from subclinical dysfunction to clinical disease risk. This review thereby provides a framework derived from the reviewed evidence that connects built environments to health through measurable biobehavioral pathways, directly supporting human-centered urban design and assessment. Full article
(This article belongs to the Special Issue Green Cities: Designs for Health and Sustainability)
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27 pages, 2323 KB  
Article
Corrosion and Erosion Risks in Biomass–Coal Cofiring Boilers: A CFD-Based Safety Assessment of a 660 MW Tangentially Fired Boiler
by Yuqiu Tian, Xiaomeng Xu, Lingjie Zhu, Lei Zhang, Qiang Wang and Zhian Li
Energies 2026, 19(13), 3080; https://doi.org/10.3390/en19133080 (registering DOI) - 29 Jun 2026
Abstract
Achieving the co-combustion of biomass and coal in utility boilers while reducing carbon dioxide emissions poses significant challenges owing to the divergent physicochemical properties of the fuels. These differences can induce high-temperature corrosion and erosion of heating surfaces, threatening boiler safety. Despite this, [...] Read more.
Achieving the co-combustion of biomass and coal in utility boilers while reducing carbon dioxide emissions poses significant challenges owing to the divergent physicochemical properties of the fuels. These differences can induce high-temperature corrosion and erosion of heating surfaces, threatening boiler safety. Despite this, integrated CFD-based assessments of sulfidic corrosion and particle erosion risks remain insufficiently addressed under realistic biomass–coal cofiring conditions. In this study, an integrated CFD-based risk assessment framework was established for biomass–coal cofiring boilers. The main novelty lies in the combined evaluation of high-temperature sulfidic corrosion and particle erosion risks under different biomass injection strategies. Specifically, user-defined functions were developed to classify high-temperature sulfidic corrosion risks based on local O2, CO, and H2S concentrations; the effects of biomass injection layers were quantitatively compared; the Oka erosion model was coupled with CFD particle tracking to predict wall wear; and an entropy-weighted multi-indicator method was used to rank the overall safety of different cofiring strategies. This study found that sufficiently high near-wall H2S concentrations in the main combustion zone indicate an increased risk of sulfidic corrosion under reducing-atmosphere conditions. Compared with pure coal combustion, biomass injection through layer A exacerbates wall corrosion, whereas biomass injection through layer AB mitigates it. Erosion is primarily localized near burner nozzles. Notably, biomass cofiring reduces the average erosion rate by 7.9–30.2% but increases the local maximum erosion rate by 7.1–25.1%. The comprehensive evaluation indicates that the condition with 30% RS injected from layer AB, mixed with coal, yields the best overall performance. The corrosion assessment is limited to sulfidic corrosion risks associated with reducing atmospheres and does not explicitly model alkali- or chlorine-induced corrosion. This study provides a theoretical foundation for biomass cofiring optimization and offers practical guidance for boiler operational safety and maintenance. Full article
16 pages, 2210 KB  
Article
Effects of Leaf Removal on Photosynthetic Activity, Fruit Yield, and Quality of Micro-Dwarf Tomatoes
by Dmitrii Usenko, Chen Giladi, Carmit Ziv and David Helman
Horticulturae 2026, 12(7), 792; https://doi.org/10.3390/horticulturae12070792 (registering DOI) - 29 Jun 2026
Abstract
Micro-dwarf tomato cultivars are increasingly considered for urban and controlled-environment agriculture due to their compact architecture and suitability for high-density planting. In this study, we evaluated the effects of different leaf removal intensities on leaf-level physiological performance, fruit yield, and fruit quality in [...] Read more.
Micro-dwarf tomato cultivars are increasingly considered for urban and controlled-environment agriculture due to their compact architecture and suitability for high-density planting. In this study, we evaluated the effects of different leaf removal intensities on leaf-level physiological performance, fruit yield, and fruit quality in three micro-dwarf tomato cultivars (Mohamed, Hahms Gelbe Topftomate, and Red Robin) grown under contrasting seasonal light conditions. Plants were subjected to low (15%), moderate (30%), or severe (90%) leaf removal, and leaf-level gas exchange was measured across canopy layers, along with yield and fruit quality assessments. Severe leaf removal (90%) increased carbon assimilation, transpiration, and stomatal conductance in middle and lower canopy leaves by up to approximately twofold compared with control plants, indicating improved light availability at the leaf level. However, these physiological enhancements did not consistently translate into higher yield, reflecting reduced whole-plant source capacity under excessive leaf removal. Low to moderate leaf removal (15–30%) generally increased or maintained yield and fruit number, whereas severe leaf removal reduced yield in Hahms Gelbe and Red Robin, particularly under low seasonal radiation. Fruit quality was largely unaffected by leaf removal, except for total soluble solids, which declined by approximately 12% under severe leaf removal across cultivars, consistent with sugar dilution under source limitation. Overall, these results demonstrate that optimal leaf removal in micro-dwarf tomatoes requires balancing improved canopy light distribution with maintenance of sufficient leaf area for carbon assimilation. For the tested compact canopies, LR15–30% represented a generally safe, practical range, whereas LR90% posed a substantial risk of source limitation, particularly at lower radiation; the exact threshold, however, remained cultivar- and light-dependent. Full article
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26 pages, 3010 KB  
Article
Attention Under Fire: The Effect of Wartime Public Focus on Israel’s Stock and Exchange Rate
by Nikolaos Papanikolaou, Evangelos Vasileiou and Themistoclis Pantos
Risks 2026, 14(7), 148; https://doi.org/10.3390/risks14070148 (registering DOI) - 29 Jun 2026
Abstract
This study examines the impact of public attention on financial markets during the Israel–Hamas conflict, focusing on the TA35 stock index and the Israeli Shekel (ILS) exchange rate over the period October 2023 to April 2025. By distinguishing between global and domestic Google [...] Read more.
This study examines the impact of public attention on financial markets during the Israel–Hamas conflict, focusing on the TA35 stock index and the Israeli Shekel (ILS) exchange rate over the period October 2023 to April 2025. By distinguishing between global and domestic Google search activity, the analysis investigates whether the origin of attention differentially affects market performance and currency dynamics. Public attention is treated as a real-time proxy for investor sentiment and perceived risk. Methodologically, the study combines Google Trends data with EGARCH(1,1) models to capture both return effects and asymmetric volatility responses. To enhance robustness, Principal Component Analysis (PCA) is applied separately to global and domestic search datasets, generating latent indices that reflect conflict-related and humanitarian narratives. These indices are subsequently incorporated into the empirical models. The findings reveal that global search intensity related to conflict topics exerts a significant negative effect on stock returns and contributes to currency depreciation, reflecting heightened uncertainty and risk aversion. In contrast, domestic search activity is associated with stabilizing or positive effects, suggesting local resilience and confidence. PCA-based models improve explanatory power and confirm that the geographical origin of attention plays a crucial role in shaping financial outcomes. Additionally, the results indicate that attention-driven shocks influence volatility asymmetrically, amplifying downside risk during periods of intensified global concern. Overall, the study contributes to the literature by integrating behavioral indicators into financial risk modeling and providing a novel, real-time framework for assessing how digital attention transmits geopolitical risk into asset prices. Full article
(This article belongs to the Special Issue Risk-Based and Behavioral Approaches to Stock Market Investment)
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10 pages, 845 KB  
Article
Admission BNP as a Dominant Prognostic Signal in Acute Decompensated Heart Failure with Frequent Renal Dysfunction: An Exploratory Multivariable Analysis
by Muneera O. AlTaweel, Elbadri I. Abdelgadir, Shahinaz Mohamed, Khamess O. Khamees, Waleed Gado and Lulwah Al Turki
J. Clin. Med. 2026, 15(13), 5079; https://doi.org/10.3390/jcm15135079 (registering DOI) - 29 Jun 2026
Abstract
Background: Risk stratification for acute decompensated heart failure (ADHF) at admission remains clinically challenging, particularly in patients with concomitant renal dysfunction. Although B-type natriuretic peptide (BNP) is a well-established biomarker in ADHF, its prognostic dominance in prespecified multivariable analyses of cohorts with frequent [...] Read more.
Background: Risk stratification for acute decompensated heart failure (ADHF) at admission remains clinically challenging, particularly in patients with concomitant renal dysfunction. Although B-type natriuretic peptide (BNP) is a well-established biomarker in ADHF, its prognostic dominance in prespecified multivariable analyses of cohorts with frequent cardiorenal dysfunction remains incompletely characterized. Methods: We conducted a single-center retrospective cohort study of 220 index admissions for ADHF. A prespecified multivariable logistic regression model was developed to estimate in-hospital mortality using admission variables, including age, sex, heart failure phenotype, systolic blood pressure, estimated glomerular filtration rate, serum albumin, and log-transformed BNP. Model performance was evaluated using discrimination (AUC), bootstrap optimism correction (200 iterations), calibration assessment, and decision curve analysis, in accordance with the TRIPOD guidelines. Results: In-hospital mortality occurred in 7.7% of patients (n = 17). In multivariable analysis, ln(BNP) was the only variable that reached statistical significance as an independent predictor of in-hospital mortality (OR 2.39 per unit increase; 95% CI 1.25–4.59; p = 0.009), representing the dominant prognostic signal in this dataset. Albumin and eGFR showed consistent but non-significant associations. The exploratory model demonstrated apparent discrimination (AUC 0.81), which decreased to 0.73 after optimism correction. A prespecified simplified model including albumin and ln(BNP) yielded an AUC of 0.77. Conclusions: In this exploratory multivariable analysis, admission BNP emerged as the primary prognostic factor for in-hospital mortality in an ADHF cohort with a high prevalence of renal dysfunction. The small number of outcome events limits confidence in model stability and precludes clinical deployment. These findings are hypothesis-generating and support BNP as the strongest prognostic signal observed in this cohort. External validation in larger cohorts is required before any clinical application. Full article
(This article belongs to the Section Cardiology)
21 pages, 735 KB  
Review
Cell Culture Adaptation of Porcine Group A Rotavirus: Advances and Challenges for Vaccine Development
by Zhen Zhang, Baihe Ma, Shuhua Liu, Xin Chen, Meiliang Guo, Fanxin Liang and Lianrui Li
Viruses 2026, 18(7), 718; https://doi.org/10.3390/v18070718 (registering DOI) - 29 Jun 2026
Abstract
Porcine group A rotavirus (PoRVA) is a significant cause of viral diarrhea in piglets, necessitating urgent global implementation of effective control strategies. This review assesses advancements in PoRVA in vitro cultivation and amplification, crucial for PoRVA vaccine development. Traditional PoRVA cultivation commonly employs [...] Read more.
Porcine group A rotavirus (PoRVA) is a significant cause of viral diarrhea in piglets, necessitating urgent global implementation of effective control strategies. This review assesses advancements in PoRVA in vitro cultivation and amplification, crucial for PoRVA vaccine development. Traditional PoRVA cultivation commonly employs primary porcine kidney cells or finite cell lines like MA-104, posing well-documented challenges in scalability, production cost, and their ability to recapitulate the natural intestinal microenvironment. Consequently, research has increasingly focused on adapting PoRVA to alternative systems, particularly immortalized porcine cell lines or physiologically relevant porcine intestinal organoids. This adaptation process, involving serial passaging, can induce genomic alterations and virulence attenuation in piglets, essential for generating live attenuated vaccine (LAV) candidates. Modern biotechnological tools, such as reverse genetics and synthetic genomics, have expedited the creation of recombinant PoRVA strains with defined antigenic profiles and enhanced in vitro growth characteristics. However, a significant concern regarding LAV candidates derived from cell culture adaptation is the risk of virulence reversion upon pig back-passage, necessitating thorough safety and genetic stability evaluations. Nevertheless, utilizing stable cell lines or organoid platforms presents a feasible and cost-effective approach for large-scale PoRVA vaccine production. Future research should focus on identifying vaccine candidates that provide broad protection and exceptional safety, with an emphasis on cross-protection against divergent epidemic genotypes, while ensuring the economic feasibility of innovative manufacturing approaches. Full article
(This article belongs to the Section Animal Viruses)
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17 pages, 1705 KB  
Article
Oxidative Potential of Water-Soluble Fractions in Road Dust from Huainan, a Typical Coal Resource-Based City in East China: Characteristics and Influencing Factors
by Nini Pang, Jingfeng Wu, Wandong Chu, Xianlin Mo, Zhao Lv, Guichun Zhou, Jie Wu and Jinggang Wang
Water 2026, 18(13), 1587; https://doi.org/10.3390/w18131587 (registering DOI) - 29 Jun 2026
Abstract
The oxidative potential (OP) of atmospheric particulate matter serves as an effective indicator for assessing the health risks posed by reactive oxygen species (ROS). Existing studies have mainly focused on conventional particulate matter including PM2.5, whereas systematic investigations into the OP [...] Read more.
The oxidative potential (OP) of atmospheric particulate matter serves as an effective indicator for assessing the health risks posed by reactive oxygen species (ROS). Existing studies have mainly focused on conventional particulate matter including PM2.5, whereas systematic investigations into the OP of road dust in coal–resource–based cities are still limited. Taking Huainan City, China as the study area, this paper explored the characteristics and influencing factors of OP in water–soluble fractions of road dust from different functional zones. The results indicated that the OP of water-soluble fractions in road dust from Huainan City was 0.162 ± 0.079 pmol/min/μg, with the value in the coal mining zone being significantly lower than that in the commercial and industrial zones. The average concentration of water–soluble organic carbon (WSOC) was 67.3 ± 59.4 mg/kg, with lower levels observed in the coal mining and power plant zones. WSOC was primarily dominated by fulvic acid–like (C1) and tryptophan–like (C2) components. C1 prevailed in coal mining, power plant, and other functional zones, whereas C2 was dominant in commercial, park and residential zones. Overall, the WSOC showed a mixed-source signature dominated by endogenous sources and characterized by a low degree of humification. The total concentration of water–soluble heavy metals in road dust was 43.46 mg/kg, dominated by Fe, Sr, Cu, Ba, and Mn, with relatively lower concentrations observed in the industrial and coal mining zones. The influencing factors of OP exhibited differentiation among functional zones: in industrial zones, it was regulated by As, Mn, TC (total carbon), WSOC and its fluorescent components, while in non-industrial zones, it was closely associated with Co, TC, and WSOC. These findings indicate that road dust toxicity and its key chemical drivers in coal mining and power plant zones of coal resource–based cities exhibit distinctive characteristics. This study provides a scientific basis for the precise management of road dust pollution and the prevention of associated health risks. Full article
(This article belongs to the Section Water and One Health)
19 pages, 5510 KB  
Review
Escaping the Efficiency Trap in Semiconductor–Biological Hybrid Systems
by Jianghua Yang, Peihang Wu, Yanhong Li and Shujuan Zhang
Catalysts 2026, 16(7), 595; https://doi.org/10.3390/catal16070595 (registering DOI) - 29 Jun 2026
Abstract
Semiconductor–biological hybrid systems (SBHS) have emerged as a disruptive technology for solar-driven chemical manufacturing, effectively bypassing the thermodynamic bottlenecks of natural photosynthesis. However, the aggressive pursuit of record-breaking solar-to-chemical conversion efficiencies has inadvertently fostered an efficiency trap. A profound interdisciplinary schism exists wherein [...] Read more.
Semiconductor–biological hybrid systems (SBHS) have emerged as a disruptive technology for solar-driven chemical manufacturing, effectively bypassing the thermodynamic bottlenecks of natural photosynthesis. However, the aggressive pursuit of record-breaking solar-to-chemical conversion efficiencies has inadvertently fostered an efficiency trap. A profound interdisciplinary schism exists wherein the acute environmental toxicity and long-term interfacial instability of these hybrid architectures are frequently overlooked. This review provides a critical appraisal of the oft-ignored environmental risks inherent in current SBHS designs. We systematically dissect the heavy metal leaching toxicity of first-generation inorganic photosensitizers and unveil the complex, bidirectional degradation mechanisms at the abiotic–biotic interface. Specifically, we highlight the dual threats of photogenerated reactive oxygen species inducing cellular oxidative stress and active, microbially induced material dismantling via reductive dissolution driven by extracellular electron transfer. To navigate beyond this purely performance-driven paradigm, we propose a multidimensional, standardized evaluation matrix that systematically balances catalytic efficiency with biological safety and life-cycle sustainability. Ultimately, this review offers a comprehensive roadmap to transition biohybrid platforms from fragile laboratory concepts into robust, scalable, and ecologically benign negative-emission technologies. Full article
(This article belongs to the Special Issue Bioinspired Photocatalysis and Photoenzymatic Catalysis)
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18 pages, 987 KB  
Article
Is It Too Late? Machine Learning for Predicting Orchiectomy Versus Testicular Preservation in Acute Torsion
by Onursal Varlikli, Ozan Can Tatar, Mustafa Alper Akay, Semih Metin, Fahriye Nur Cuce and Gulsen Ekingen Yildiz
Diagnostics 2026, 16(13), 2034; https://doi.org/10.3390/diagnostics16132034 (registering DOI) - 29 Jun 2026
Abstract
Objectives: Testicular torsion is a time-critical pediatric urological emergency in which delayed presentation may increase the likelihood of orchiectomy. However, preoperative estimation of the immediate intraoperative outcome remains challenging. This study aimed to develop and internally validate machine-learning models integrating ischemic timing variables [...] Read more.
Objectives: Testicular torsion is a time-critical pediatric urological emergency in which delayed presentation may increase the likelihood of orchiectomy. However, preoperative estimation of the immediate intraoperative outcome remains challenging. This study aimed to develop and internally validate machine-learning models integrating ischemic timing variables and complete blood count-derived inflammatory indices to predict orchiectomy versus testicular preservation at index surgical exploration in pediatric and adolescent testicular torsion. Methods: We retrospectively analyzed 165 children and adolescents who underwent surgical exploration for confirmed testicular torsion. The primary endpoint was orchiectomy at index exploration versus testicular preservation through detorsion and/or orchiopexy. Clinical timing variables and complete blood count-derived indices, including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, white blood cell-to-monocyte ratio, monocyte-to-mean platelet volume ratio, hemoglobin-to-monocyte ratio, systemic inflammatory response index, and aggregate index of systemic inflammation, were evaluated. Five supervised machine-learning algorithms—logistic regression, random forest, XGBoost, LightGBM, and support vector machine—were assessed using nested stratified cross-validation with an outer 5-fold loop and inner 3-fold hyperparameter selection. Model performance was estimated from out-of-fold predictions. Results: Orchiectomy was performed in 37 patients (22.4%), whereas testicular preservation through detorsion and/or orchiopexy was performed in 128 patients (77.6%). Symptom duration was significantly longer in the orchiectomy group than in the preservation group (48.00 [30.00–72.00] vs. 6.00 [2.00–24.00] h, p < 0.001). Monocyte count was also higher in the orchiectomy group (0.92 [0.68–1.23] vs. 0.65 [0.50–0.93] × 109/L, p < 0.001). Among the combined models, XGBoost achieved the highest numerical discrimination, with a ROC-AUC of 0.926 ± 0.066 and a bootstrap 95% confidence interval of 0.856–0.966. Feature-block and interpretability analyses identified symptom duration as the dominant predictor, followed by emergency department waiting time and selected monocyte-centered inflammatory indices. Conclusions: Immediate intraoperative orchiectomy in pediatric and adolescent testicular torsion was most strongly associated with prolonged symptom duration, while selected complete blood count-derived inflammatory indices provided complementary risk information. The combined XGBoost model showed strong internal discrimination and clinically interpretable predictor patterns. However, the model was internally validated only and requires external validation before clinical implementation. Full article
12 pages, 3872 KB  
Brief Report
The Beneficial Effects of Berberine on Vascular Dysfunction in Type 2 Diabetes Are Enhanced by HSP70 Inhibition
by Valentina Ochoa Mendoza, Swasti Rastogi, Conner Weaver, Micheline Rosa Silveira and Kenia Pedrosa Nunes
Biomolecules 2026, 16(7), 959; https://doi.org/10.3390/biom16070959 (registering DOI) - 29 Jun 2026
Abstract
Type 2 diabetes (T2D) is a chronic metabolic disorder leading to increased cardiovascular risk and vascular dysfunction. Hyperglycemia, a hallmark of T2D, drives hypercontractility, thereby compromising vascular function. Heat shock protein 70 (HSP70) has emerged as an important player in vascular reactivity under [...] Read more.
Type 2 diabetes (T2D) is a chronic metabolic disorder leading to increased cardiovascular risk and vascular dysfunction. Hyperglycemia, a hallmark of T2D, drives hypercontractility, thereby compromising vascular function. Heat shock protein 70 (HSP70) has emerged as an important player in vascular reactivity under physiological conditions via its interaction with calcium mobilization, and in T2D, blocking this protein prevents hypercontractility. Circulating extracellular HSP70 (eHSP70) has also been proposed as a biomarker in chronic diseases, as it can function as a damage-associated molecular pattern (DAMP) to activate the innate immune system and promote low-grade inflammation. Berberine (BBR), a natural alkaloid with anti-inflammatory properties, has been shown to attenuate vascular contraction by modulating intracellular calcium handling. Yet the link between HSP70 and BBR in modulating vascular contraction in T2D remains unknown. Therefore, we investigated whether acute and/or chronic BBR treatment modulates HSP70 to prevent vascular hypercontractility in the T2D mouse model. For acute ex vivo treatment, db/+ and db/db aortic rings were incubated for 30 min with or without the HSP70 inhibitor VER155008, in the presence or absence of BBR or vehicle. For chronic in vivo treatment, db/+ and db/db mice received intraperitoneal BBR injections (10 mg/kg, 3 times per week) and BBR in their drinking water (0.5 mg/mL) for 28 days. Following chronic (4 weeks, in vivo) or acute ex vivo (30 min) BBR treatment, vascular function was assessed in aortic rings isolated from male T2D (db/db) and age-matched non-diabetic (db/+) mice using wire myography. Rings were incubated with or without the HSP70 inhibitor VER155008, in the presence or absence of BBR or vehicle. Overt hyperglycemia and hypercontractility were observed in diabetic animals compared with non-diabetic controls. While acute BBR treatment attenuated vasoconstriction in both diabetic and nondiabetic groups, the combination of BBR and VER155008 produced a stronger inhibitory effect only in the diabetic group. Chronic BBR treatment prevented aortic hypercontractility in diabetic mice; however, the synergistic effect with VER155008 was no longer observed. Additionally, BBR reduced systemic HSP70 levels. Collectively, these findings indicate that BBR improves vascular smooth muscle cells’ function in T2D, at least in part, through HSP70-dependent mechanisms during chronic treatment. Full article
(This article belongs to the Section Molecular Biomarkers)
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14 pages, 463 KB  
Article
Adolescent Δ9-THC Exposure Differentially Affects Mice Depending on Their Personality
by Dilorom Begmatova, Liudmila Vinnikova, Natalya Zemliana, Kenneth Blum, Panayotis K. Thanos, Natalya M. Kogan and Albert Pinhasov
Pharmaceuticals 2026, 19(7), 1009; https://doi.org/10.3390/ph19071009 (registering DOI) - 29 Jun 2026
Abstract
Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ9-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. [...] Read more.
Background: Adolescence is a sensitive period for brain maturation during which exposure to Δ9-tetrahydrocannabinol (THC) can induce long-lasting neurobehavioral alterations. Yet, preclinical and clinical studies report inconsistent long-term outcomes of adolescent THC exposure, ranging from clear impairments to apparently normalizing effects. We hypothesize that these discrepancies reflect stable individual differences in stress-coping abilities. Methods: To test this, selectively bred Dominant (Dom; stress-resilient, risk-prone) and Submissive (Sub; stress-vulnerable, depressive-like) Sabra mice received THC or vehicle during adolescence and were assessed in adulthood. Results: Anxiety-like and exploratory behavior, measured in the hole-board test, were differentially affected by THC as a function of stress vulnerability: in Sub mice, THC increased exploration and reduced anxiety-like behavior, whereas in Dom mice THC produced the opposite pattern. Recognition memory, evaluated by the novel object recognition test, showed modest, line-dependent alterations. Sensitivity to N-methyl-D-aspartate (NMDA) receptor hypofunction, a widely used index of vulnerability to schizophrenia-like symptoms, was examined using MK-801-induced locomotion. Adolescent THC potentiated MK-801-evoked hyperlocomotion in Dom mice but attenuated it in Sub mice. Conclusions: In the context of increasing medical and recreational cannabis exposure, these in vivo findings suggest that stress-vulnerability-related traits may be an important variable to consider in future preclinical and translational studies of adolescent THC exposure. Full article
(This article belongs to the Section Natural Products)
14 pages, 2181 KB  
Case Report
Multimodal Analysis of Aggressive Multifocal Cutaneous Squamous Cell Carcinoma Associated with a Germline COL6A3 Truncating Variant: A Case Report
by Mircea Negrutiu, Stefan Cristian Vesa, Bogdan Florea, Diana Miclea, Razvan Bucur, Adrian Baican, Monica Focșan and Sorina Danescu
Diagnostics 2026, 16(13), 2032; https://doi.org/10.3390/diagnostics16132032 (registering DOI) - 29 Jun 2026
Abstract
Background: Cutaneous squamous cell carcinoma (cSCC) is commonly regarded as a sporadic malignancy primarily driven by ultraviolet exposure. However, the occurrence of multiple, aggressive tumors at a relatively young age suggests the presence of underlying genetic susceptibility. The role of germline variants affecting [...] Read more.
Background: Cutaneous squamous cell carcinoma (cSCC) is commonly regarded as a sporadic malignancy primarily driven by ultraviolet exposure. However, the occurrence of multiple, aggressive tumors at a relatively young age suggests the presence of underlying genetic susceptibility. The role of germline variants affecting extracellular matrix organization, pigmentation pathways, and tumor metabolism in aggressive cSCC remains incompletely understood. Case Presentation: We describe a 53-year-old patient with a long-standing history of multiple aggressive cutaneous squamous cell carcinomas involving the scalp and facial regions, characterized by recurrent and multifocal disease. A comprehensive diagnostic approach was undertaken, including histopathological examination, fluorescence confocal microscopy, high-frequency cutaneous ultrasound, and genetic analysis using whole-exome sequencing (WES). Results: Histopathology confirmed high-risk features consistent with aggressive cSCC. Cutaneous ultrasound and fluorescence confocal microscopy provided complementary, non-invasive insights into tumor depth, architecture, and invasive patterns. Whole-exome sequencing identified a heterozygous truncating variant in COL6A3 (NM_004369.4:c.5645C>A, p.Ser1882Ter), classified as likely pathogenic according to ACMG criteria. Additionally, two heterozygous variants of uncertain significance were detected in TYR (NM_000372.5:c.1569C>A, p.Ser523Arg) and FH (NM_000143.4:c.1237-5_1237-4insTCTCCCTCCCTC). Although individually inconclusive, the combined germline genetic background may have contributed to the patient’s aggressive and multifocal cutaneous phenotype. Discussion: This case report supports a potential role of extracellular matrix remodeling, pigmentation-related susceptibility, and metabolic dysregulation in cutaneous carcinogenesis and tumor aggressiveness. This case illustrates how integrating WES with advanced non-invasive imaging techniques can enhance the understanding of biologically aggressive cSCC. Conclusions: This report highlights a unique case of multifocal aggressive cSCC characterized by a distinct germline genetic profile identified by WES and multimodal imaging assessment. Comprehensive molecular and imaging evaluation may be beneficial in selected patients with atypical or aggressive cutaneous squamous cell carcinoma, with implications for personalized surveillance and management. Full article
(This article belongs to the Special Issue Ultrasound and Multimodal Diagnostics in Personalized Medicine)
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18 pages, 300 KB  
Article
Oral Health, Polypharmacy and Nutritional Status in Institutionalized Dementia Patients: A Multicenter Cross-Sectional Study
by Joana Pombo-Lopes, Diogo Sousa-Catita, Paulo Mascarenhas, Jorge Fonseca and José Grillo-Evangelista
Biomedicines 2026, 14(7), 1476; https://doi.org/10.3390/biomedicines14071476 (registering DOI) - 29 Jun 2026
Abstract
Background: As the population ages, dementia poses a critical public health challenge. This study examined the oral health and nutritional status of institutionalized Portuguese adults with dementia, exploring their interrelated predictors. Methods: This multicenter, cross-sectional study assessed institutionalized patients using the Decayed, Missing, [...] Read more.
Background: As the population ages, dementia poses a critical public health challenge. This study examined the oral health and nutritional status of institutionalized Portuguese adults with dementia, exploring their interrelated predictors. Methods: This multicenter, cross-sectional study assessed institutionalized patients using the Decayed, Missing, and Filled Teeth (DMFT) index, posterior functional units (PFUs), plaque (PI) and gingival (GI) indices, the Short Xerostomia Inventory (SXI-5), and the Mini Nutritional Assessment (MNA). DMFT was modeled using multivariable ordinary least squares (OLS) regression for demographic and clinical predictors and separate negative binomial models for medication-related predictors. Other outcomes were analyzed using outcome-specific multivariable models. Results: The study included 71 participants (mean age: 82.5 ± 6.9 years). A high dental disease burden (mean DMFT score of 24.3 ± 7.5) was observed, independently predicted by advanced age (β = 0.48, p = 0.002) and residence in public long-term care units (LTCUs) (β = 6.65, p = 0.001). Total edentulism affected 28.2% of the sample. Polypharmacy emerged as a significant predictor of tooth loss; each additional medication was associated with an 18% decrease in the likelihood of retaining natural teeth (OR = 0.82, p = 0.008). Higher cognitive decline (GDS) was associated with increased plaque (p = 0.043), and modified-texture diets were associated with lower plaque levels (β = −0.64, p = 0.021). The mean MNA score (16.9 ± 3.8) indicated a high risk of malnutrition, with a trend toward lower gingival inflammation with better nutritional status (p = 0.061). Conclusions: Institutionalized dementia patients face severe oral and nutritional risks associated with age, polypharmacy and institutional environment. This emphasizes the need for multidisciplinary protocols and caregiver training. Full article
(This article belongs to the Special Issue New Advances in Oral Pathology and Medicine)
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