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Search Results (1,366)

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12 pages, 739 KB  
Article
Groundwater Radionuclide Contamination in the Saumalkol Settlement Located near Decommissioned Uranium Mining Sites
by Danara Ibrayeva, Madina Kairullova, Masahiro Hosoda, Yasutaka Omori, Yerlan Kashkinbayev, Kuralay Ilbekova, Assel Bagramova, Aigerim Shokabayeva and Meirat Bakhtin
Environments 2026, 13(3), 161; https://doi.org/10.3390/environments13030161 - 13 Mar 2026
Abstract
Groundwater used for drinking in settlements located near decommissioned uranium mining facilities may contain elevated naturally occurring radioactive materials, posing long-term public-health concerns. The purpose of this study was to evaluate the radiological quality of groundwater used for drinking in the Saumalkol settlement [...] Read more.
Groundwater used for drinking in settlements located near decommissioned uranium mining facilities may contain elevated naturally occurring radioactive materials, posing long-term public-health concerns. The purpose of this study was to evaluate the radiological quality of groundwater used for drinking in the Saumalkol settlement by applying gross alpha–beta screening and isotope-specific analysis of 226Ra and 228Ra to identify the main contributors to groundwater radioactivity and estimate the associated radiation dose from water consumption. Groundwater samples were analyzed using gross alpha–beta screening and isotope-specific determination of 226Ra and 228Ra by radiochemical separation and low-background counting, and ingestion doses were estimated using international dose coefficients. Gross alpha activity averaged 2.26 ± 0.96 Bq/L, with most samples exceeding the WHO screening value of 0.5 Bq/L, while gross beta activity averaged 0.65 ± 0.17 Bq/L. Mean activity concentrations of 226Ra and 228Ra were 0.17 ± 0.03 Bq/L and 1.47 ± 0.9 Bq/L, respectively, with significantly higher 228Ra in deep boreholes and a systematic predominance of 228Ra over 226Ra (p < 0.05), indicating a thorium-controlled geochemical signature in fractured crystalline aquifers. The estimated annual committed effective ingestion dose from radium isotopes was 0.46 mSv, exceeding the reference level of 0.1 mSv for drinking-water exposure. These findings demonstrate that groundwater radioactivity in Saumalkol is dominated by radium from the thorium series and highlight the need for sustained radionuclide-specific monitoring and targeted water management strategies in uranium-affected regions. Full article
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19 pages, 2381 KB  
Article
RTP004 Peptide Binds to Botulinum Neurotoxin, Increases Cell Surface Binding, and Enhances Cellular SNAP-25 Cleavage
by Andre F. Batista, Ratnesh Singh, Frank Lee, Shaoqiu Zhuo, Dmitri Leonoudakis and Conor J. Gallagher
Toxins 2026, 18(3), 134; https://doi.org/10.3390/toxins18030134 - 10 Mar 2026
Viewed by 161
Abstract
DaxibotulinumtoxinA for injection (DAXI) is a botulinum neurotoxin (BoNT) drug product comprising the 150 kDa pure BoNT/A1 as the drug substance formulated with a proprietary stabilizing excipient, RTP004. We hypothesized that RTP004 facilitates localization of BoNT/A1 to the neuronal membrane, resulting in increased [...] Read more.
DaxibotulinumtoxinA for injection (DAXI) is a botulinum neurotoxin (BoNT) drug product comprising the 150 kDa pure BoNT/A1 as the drug substance formulated with a proprietary stabilizing excipient, RTP004. We hypothesized that RTP004 facilitates localization of BoNT/A1 to the neuronal membrane, resulting in increased BoNT internalization and cleavage of the synaptosomal-associated protein of 25 kDa (SNAP-25) within synaptic terminals. We characterized the interaction between RTP004 and BoNT/A1 using in silico and in vitro techniques. In vitro analyses revealed that negative charges on the BoNT/A1 surface were located on the light chain (LC, the catalytic domain) and the C-terminus of the heavy chain (HC, the receptor-binding domain), potentially providing sites for interaction with the positively charged RTP004 peptide. RTP004 bound to BoNT/A1, but not to human serum albumin (HSA), in both static and dynamic conditions. RTP004, not HSA, enhanced binding of BoNT to artificial membranes and RTP004 dissociated from BoNT under conditions that mimicked physiological conditions of the synaptic vesicle. RTP004 also increased binding of BoNT to the synaptosomal cell membrane and enhanced cleavage of SNAP-25 in a dose-dependent manner. These findings demonstrate that RTP004, not the excipient HSA common in other BoNT/A1 drug products, enhances binding of BoNT to the cell surface, facilitates internalization of BoNT into the cell, and increases SNAP-25 cleavage. Full article
(This article belongs to the Section Bacterial Toxins)
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13 pages, 241 KB  
Hypothesis
From Molecular Cleavage to Clinical Effect: A Probabilistic Field Model of Botulinum Toxin Action
by Andrea Felice Armenti and Francesco Armenti
Biology 2026, 15(5), 446; https://doi.org/10.3390/biology15050446 - 9 Mar 2026
Viewed by 178
Abstract
Botulinum toxin (BoNT) is a highly specific molecular enzyme whose therapeutic action is based on the proteolytic cleavage of SNARE proteins, most notably SNAP-25. Despite the deterministic nature of this molecular mechanism, the clinical effects of BoNT exhibit substantial variability in efficacy, spatial [...] Read more.
Botulinum toxin (BoNT) is a highly specific molecular enzyme whose therapeutic action is based on the proteolytic cleavage of SNARE proteins, most notably SNAP-25. Despite the deterministic nature of this molecular mechanism, the clinical effects of BoNT exhibit substantial variability in efficacy, spatial extent, and duration that cannot be fully explained by dose–response relationships or diffusion-based models. In this work, we propose the Molecular Probability Field (MPF-BoNT) as a conceptual framework that bridges discrete molecular events and emergent functional outcomes. The MPF is defined as the spatial–temporal distribution of the probability that presynaptic terminals reach a functional silencing state (operationalized via SNAP-25 cleavage exceeding a threshold), shaped by exposure, uptake, target density, and temporal dynamics following toxin exposure. Within this framework, clinical effects arise from the integration of probabilistic molecular events across space and time, rather than from toxin presence or concentration alone. The MPF-BoNT framework accounts for key features of botulinum toxin action, including spread, nonlinearity of dose effects, variability in duration, and differences between technical and biological non-response. By explicitly incorporating molecular variables such as local concentration, exposure time, terminal density, internalization probability, and functional silencing thresholds, the framework provides an integrative interpretation of tissue-level behavior grounded in molecular biology. The MPF-BoNT offers a formal language to describe how established enzymatic events generate observable spatial, temporal, and functional patterns. As a generative framework grounded in explicit testable structure, it establishes a foundation for future experimental and clinical research. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
19 pages, 1288 KB  
Review
The Ergogenic Potential of Succinic Acid in Exercise Performance and Post-Exercise Recovery: A Systematic Review
by Karol Jędrejko, Oliver Catlin, Maciej Jędrejko, Bożena Muszyńska, Izabela Bat, Susan M. Kleiner, Dominika Granda, Andrzej Pokrywka and Ralf Jäger
Nutrients 2026, 18(5), 870; https://doi.org/10.3390/nu18050870 - 9 Mar 2026
Viewed by 270
Abstract
Background: Succinic acid plays a central role in human energy metabolism as a key intermediate of the Krebs cycle that releases energy accumulated as guanosine triphosphate (GTP). Through its conversion via succinate dehydrogenase (SDH), succinate directly links the Krebs cycle to oxidative [...] Read more.
Background: Succinic acid plays a central role in human energy metabolism as a key intermediate of the Krebs cycle that releases energy accumulated as guanosine triphosphate (GTP). Through its conversion via succinate dehydrogenase (SDH), succinate directly links the Krebs cycle to oxidative phosphorylation (OXPHOS), contributing to adenosine triphosphate (ATP) production. Exercise induces pronounced changes in succinate concentrations in skeletal muscle, blood, and saliva, with responses influenced by training status, exercise modality, and intensity. Objective: This systematic review evaluated the effects of succinate-containing supplements or sole-ingredient succinic acid supplementation on exercise performance and post-exercise recovery in healthy trained individuals. Methods: The review was conducted in accordance with PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar were searched without date restrictions. Interventional studies assessing succinate-containing supplementation with outcomes related to exercise performance or recovery were included. Methodological quality was evaluated using the Cochrane Risk of Bias 2 tool. This study was registered in advance with the International Prospective Register of Systematic Reviews (PROSPERO, CRD420251237042). Results: Six studies involving 153 participants (mean age: 23 years) met the inclusion criteria. Five of the six included studies were rated as having a high risk of bias, while the only study judged to be at low risk of bias reported no beneficial effects on exercise performance outcomes. Supplementation protocols included daily doses of 300–2040 mg for up to 21 days and a single acute dose of 30 mg/kg, with most interventions administering succinate as part of multi-ingredient formulations rather than as an isolated compound. Three studies reported ergogenic effects in direct performance metrics, including improvements in maximal oxygen uptake, oxygen consumption, anaerobic threshold power, and total work performed. Two additional studies demonstrated favorable physiological adaptations indirectly relevant to exercise performance, including improved acid-base regulation, hematological markers related to oxygen transport, and antioxidant status, although validated performance outcomes were not assessed. Substantial heterogeneity and overall methodological limitations precluded meta-analysis. Conclusions: Current evidence suggests that succinate-containing supplements or sole-ingredient succinic acid supplementation may enhance direct performance outcomes such as aerobic performance, total workload, and indirect physiological markers, e.g., acid-base balance, hematological indicators and antioxidant capacity in healthy trained individuals. However, given that the majority of included studies were at high risk of bias and the only low-risk study reported no ergogenic effects, current evidence does not provide reliable support for performance-enhancing benefits of succinate supplementation. Interpretation is further limited by the predominant use of multi-ingredient formulations, making it difficult to isolate the effects of succinic acid. While biologically plausible mechanisms exist, well-controlled trials using isolated succinic acid are required before conclusions regarding efficacy can be drawn. Full article
(This article belongs to the Special Issue Nutritional Supplements for Endurance Exercise)
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17 pages, 1861 KB  
Article
Characterisation of a Novel Bioactive Strontium Bioglass-Based Endodontic Sealer
by Sheena Parekh, Arjun Haria, Simon Rawlinson, Robert Hill and Samira Al-Salehi
Appl. Sci. 2026, 16(5), 2443; https://doi.org/10.3390/app16052443 - 3 Mar 2026
Viewed by 186
Abstract
New hard tissue formation helps create a more stable seal in endodontic treatment. To achieve this, a novel class of endodontic sealers containing the pro-osteogenic element, strontium (within a BG), embedded in a polydimethylsiloxane matrix (Sr-PDMS) was produced. The properties of this sealer [...] Read more.
New hard tissue formation helps create a more stable seal in endodontic treatment. To achieve this, a novel class of endodontic sealers containing the pro-osteogenic element, strontium (within a BG), embedded in a polydimethylsiloxane matrix (Sr-PDMS) was produced. The properties of this sealer were compared with a commercially available bioactive endodontic sealer, Guttaflow Bioseal (GFBS). Glass was prepared via the melt quench method and incorporated into the GFBS matrix. Its physical properties were tested against the International Organisation for Standardisation (ISO) 6876. For biocompatibility assessment, dose–response proliferation of OCCM-30 cells was quantified by measuring DNA levels in varying concentrations of exogenous calcium and strontium, in culture media conditioned with the novel BG powder, and in sealer discs of the GFBS and novel Sr-PDMS. Two-way ANOVA followed by one-way ANOVA and the Bonferroni post hoc test were applied to the cell viability data. Both the GFBS and novel Sr-PDMS sealants demonstrated physical properties that met ISO 6876, but Sr-PDMS displayed greater radiopacity (p < 0.05), lower solubility, and increased setting time. Both sealants released ions into the immersion solution, with the additional release of Sr from the novel sealer. GFBS displayed evidence of apatite formation. As expected, high concentrations of BG-conditioned media were cytotoxic, but the levels released by the BG in the Sr-PDMS were not cytotoxic with 1:000 dilution and resulted in significantly increased (p < 0.01) cell proliferation compared to the control group. Full article
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39 pages, 5408 KB  
Review
Advances in Membrane, Dialyzer Design, and Related Monitoring Technologies for Hemodiafiltration: Translating Bench-Side Innovations to Bedside Applications
by Alfred Gagel, Gerhard Wiesen, Stefano Stuard and Bernard Canaud
J. Clin. Med. 2026, 15(5), 1921; https://doi.org/10.3390/jcm15051921 - 3 Mar 2026
Viewed by 351
Abstract
Background: Online hemodiafiltration (HDF) represents the most advanced form of kidney replacement therapy, combining diffusive and convective transport to enhance the removal of uremic toxins across a wide molecular spectrum. Achieving high convective volumes is a key determinant of treatment efficacy and [...] Read more.
Background: Online hemodiafiltration (HDF) represents the most advanced form of kidney replacement therapy, combining diffusive and convective transport to enhance the removal of uremic toxins across a wide molecular spectrum. Achieving high convective volumes is a key determinant of treatment efficacy and has been associated with improved survival. Beyond small solutes, HDF targets middle molecules and protein-bound uremic toxins (PBUTs), including β2-microglobulin, inflammatory cytokines, and other large uremic compounds implicated in cardiovascular and systemic complications. Aims: This narrative review examines advances in dialysis membrane materials, dialyzer design, and monitoring technologies that optimize mass transfer in HDF. It focuses on the interplay between membrane permeability, hemocompatibility, and convective dose delivery, and discusses how these engineering developments translate into clinical performance. Key mechanisms: Recent progress in synthetic polymer membranes, particularly polysulfone- and polyethersulfone-based systems, and hollow-fiber manufacturing has enabled improved control of pore size distribution, hydraulic permeability, and sieving characteristics. These developments enhance the clearance of middle molecules and selected PBUTs while preserving essential proteins such as albumin. Mechanistic insights into internal filtration, protein polarization, and Donnan effects highlight the complex transport processes occurring within the dialyzer and their interaction with automated HDF systems. Expanded hemodialysis and high-volume HDF approaches further increase the removal of larger solutes but require careful management to limit albumin loss and maintain hemocompatibility. Clinical implications: Optimized membrane design, combined with advanced HDF machine algorithms, allows delivery of high convective volumes under safe and stable conditions, improving removal of β2-microglobulin, cytokines, and other clinically relevant toxins associated with inflammation and cardiovascular risk. However, treatment must remain individualized, considering electrolyte balance, albumin preservation, and patient-specific factors such as inflammation and nutritional status. Mechanistic modeling supports understanding of transport phenomena but must be interpreted cautiously when translated into clinical practice. Conclusions: Advances in membrane science, dialyzer engineering, and monitoring technologies have strengthened the role of HDF as a precision-based renal replacement therapy. Continued innovation aimed at optimizing middle-molecule and PBUT clearance while preserving albumin and treatment stability is essential to improve patient outcomes and support the broader implementation of HDF as a mainstream dialysis modality. Full article
(This article belongs to the Special Issue Redefining Hemodialysis: Beyond Diffusion to Precision Therapy)
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19 pages, 1633 KB  
Article
Evaluation of Urinary Tubular Biomarkers in Dogs with Myxomatous Mitral Valve Disease Across ACVIM Stages
by Pablo Cardenal-Morales, José Ignacio Cristóbal, Rafael Barrera, Alberto Ezquerra-Durán, Paloma Nicolas, Patricia Ruiz, Ángela Durán-Galea and Francisco Javier Duque
Vet. Sci. 2026, 13(3), 243; https://doi.org/10.3390/vetsci13030243 - 3 Mar 2026
Viewed by 387
Abstract
Myxomatous mitral valve disease (MMVD) is the most common acquired heart valve disease in dogs and it may contribute to cardiovascular–renal axis disorders (CvRD) in dogs. Sensitive and early biomarkers of renal involvement are needed. In this prospective and observational study, 84 dogs [...] Read more.
Myxomatous mitral valve disease (MMVD) is the most common acquired heart valve disease in dogs and it may contribute to cardiovascular–renal axis disorders (CvRD) in dogs. Sensitive and early biomarkers of renal involvement are needed. In this prospective and observational study, 84 dogs were enrolled (20 healthy dogs and 64 dogs with MMVD), categorised using the American College of Veterinary Internal Medicine guidelines. Serum and urinary parameters were analysed, including tubular biomarkers expressed as creatinine-ratios: urinary alkaline phosphatase (uALPc), gamma-glutamyl transferase (uGGTc), N-acetyl-β-D-glucosaminidase (uNAGc), and cystatin C (uCystc). uALPc, uGGTc, and uNAGc were higher in MMVD than in controls; uALPc and uGGTc were increased from stage B1, uNAGc was higher in stages with cardiomegaly (B2 and C+D), and uCystc increased mainly in clinical stages (C+D). Serum renal markers increased only in clinical stages. ROC analysis showed good discrimination for MMVD with uALPc (AUC 0.87) and uGGTc (0.86); for cardiomegaly with uALPc (0.77) and uNAGc (0.75); and for congestive heart failure with SDMA (0.85) and uCystc (0.75). No urinary biomarker was associated with daily furosemide dose. Urinary tubular biomarkers, particularly uALPc and uGGTc, detect early CvRD in dogs with MMVD and complement traditional serum markers. Full article
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10 pages, 378 KB  
Proceeding Paper
Sustainable Cold-Chain Logistics for Vaccine and Blood Supply in East Malaysia
by Yuan Zhi Leong and Wai Yie Leong
Eng. Proc. 2026, 129(1), 15; https://doi.org/10.3390/engproc2026129015 - 2 Mar 2026
Viewed by 250
Abstract
Ensuring product integrity across Malaysia’s East Malaysian states (Sabah and Sarawak) requires a cold chain that is resilient to tropical heat, long multimodal routes, intermittent power, and dispersed rural populations. This paper proposes a sustainability-first architecture for vaccine and blood component logistics that [...] Read more.
Ensuring product integrity across Malaysia’s East Malaysian states (Sabah and Sarawak) requires a cold chain that is resilient to tropical heat, long multimodal routes, intermittent power, and dispersed rural populations. This paper proposes a sustainability-first architecture for vaccine and blood component logistics that combines World Health Organization and the United Nations International Children’s Emergency Fund Effective Vaccine Management (EVM 2.0) criteria with energy-aware transport planning, solar-hybrid edge refrigeration, phase-change materials, and digital temperature monitoring compliant with ISO 23412 for temperature-controlled delivery services. In this study, a mixed-methods methodology was employed, including (1) route and mode optimization under temperature risk and carbon intensity constraints; (2) equipment right-sizing using duty-cycle energy models and IEC 60068 environmental tests as design baselines; (3) governance with real-time earned value management (EVM) and key performance indicators (KPIs); and (4) scenario analysis for riverine, road, air, and drone last-mile segments relevant to remote East Malaysian communities. Results from realistic logistic scenarios indicate a 45–65% reduction in dose-weighted temperature-excursion minutes, 28–41% reduction in CO2e per successful dose delivered, and 35–52% reduction in product loss compared with status quo planning. For blood components, solar-hybrid storage and mixed-mode routing reduced breach risk by 37% while maintaining red cells (2–6 °C), platelets (20–24 °C, continuous agitation surrogate), and fresh frozen plasma (≤−18 °C) requirements aligned with WHO guidance and Malaysia’s national transfusion policies. We provide a reference architecture, implementation bill of materials, and an EVM-aligned KPI dashboard to guide scale-up. Full article
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17 pages, 973 KB  
Review
A Multi-Dimensional Analysis of the Changing Role of Clinical and Community Pharmacists in Romanian Healthcare
by Alexandra Cristina Tocai (Moțoc), Felicia Dragan, Daria Marina Dragan, Andrei George Teodorescu, Cristina Oana Daciana Teodorescu, Camelia Florentina Ciobanu, Diana Uivarosan and Dana Carmen Zaha
Healthcare 2026, 14(5), 624; https://doi.org/10.3390/healthcare14050624 - 1 Mar 2026
Viewed by 381
Abstract
Community and hospital pharmacists in Romania are valuable to healthcare, but their involvement in multidisciplinary teams is still not up to the mark when measured against international standards. A systematic literature review search was conducted using the PubMed, Embase, Web of Science, and [...] Read more.
Community and hospital pharmacists in Romania are valuable to healthcare, but their involvement in multidisciplinary teams is still not up to the mark when measured against international standards. A systematic literature review search was conducted using the PubMed, Embase, Web of Science, and Scopus databases, following the PRISMA 2020 guidelines, complemented by a bibliometric analysis with VOSviewer, to identify research trends and key contributors in the field. This review examines studies such as counseling effectiveness, clinical contribution, and professional obstacles faced by pharmacists in Romania published between 2014 and 2025 that mainly focus on community practice, integration into hospitals, and new areas such as pharmacogenetics and pharmacovigilance. The studies surveyed patients on how they evaluated counseling, tracked clinical pharmacists who adjusted drug doses through therapeutic monitoring, checked whether healthcare professionals followed safety warnings, and checked management systems within institutions. High costs and the removal of pharmacovigilance from compulsory university courses add to the obstacles. Romanian pharmacists already possess the knowledge or skills to raise treatment success and shield patients from unsafe self-medication through timely clinical advice. To use this capacity fully, the system must change, including health insurance covering pharmaceutical services, compulsory updating of course content, and official interdisciplinary protocols for this potential to be fully exploited. Full article
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17 pages, 1414 KB  
Article
Cost-Effectiveness and Budget Impact Analysis of the Trivalent Adjuvanted Influenza Vaccine in People over 50 Years of Age for Argentina
by Leandro Javier Pastori, Constanza Silvestrini Viola, Tomas Alconada, Gonzalo Pereira, José Luis Montes, Joaquin Mould-Quevedo, Carolina Saenz, Nathalia Katz, Ariel Bardach and Natalia Espinola
Vaccines 2026, 14(3), 227; https://doi.org/10.3390/vaccines14030227 - 28 Feb 2026
Viewed by 380
Abstract
Background: Influenza imposes a substantial burden on Argentina, particularly among adults aged 50–64 with comorbidities and those aged ≥65. The adjuvanted trivalent influenza vaccine (aTIV) has shown superior effectiveness compared with non-adjuvanted vaccines; however, its cost-effectiveness and budget impact in the 50–64 high-risk [...] Read more.
Background: Influenza imposes a substantial burden on Argentina, particularly among adults aged 50–64 with comorbidities and those aged ≥65. The adjuvanted trivalent influenza vaccine (aTIV) has shown superior effectiveness compared with non-adjuvanted vaccines; however, its cost-effectiveness and budget impact in the 50–64 high-risk population have not been assessed nationally. This study evaluates the cost-effectiveness and budget impact of introducing aTIV for high-risk adults aged 50–64, alongside its use in adults aged ≥65, compared with standard-dose trivalent influenza vaccine (SD-TIV) from the Argentine health care system perspective. Methods: A decision-analytic static model was used to compare aTIV with SD-TIV over a single influenza season. In addition, a 5-year budget impact analysis (BIA) was conducted under scenarios of progressive uptake. Model inputs were derived from international literature, local data, and expert opinion. Deterministic and probabilistic sensitivity analyses were performed. Results: Compared with SD-TIV, aTIV yielded a lifetime gain of 1489 quality-adjusted life-years (QALYs) at an incremental cost of USD 8.34 million, resulting in an incremental cost-effectiveness ratio (ICER) of USD 5599 per QALY gained—well below Argentina’s cost-effectiveness threshold (USD 11,059/QALY). Higher vaccine acquisition costs were largely offset by reductions in outpatient visits and hospitalizations. The BIA showed a modest average annual per-member-per-month increase of USD 0.0025, remaining below the estimated budget impact threshold (USD 0.0065). Conclusions: Implementing aTIV in adults aged ≥50 with risk factors would be cost-effective and affordable in Argentina. These findings support the consolidation and potential expansion of current vaccination strategies to reduce influenza burden. Full article
(This article belongs to the Special Issue Vaccines and Vaccine Preventable Diseases)
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16 pages, 2265 KB  
Article
Development and Validation of an Interpretable Model for Predicting Postoperative Hyperlactatemia in Young Children Following Congenital Heart Surgery
by Yuchan Chen, Wenxin Ge, Lixin Hu, Jiaqi Chen and Yajun Chen
J. Clin. Med. 2026, 15(5), 1846; https://doi.org/10.3390/jcm15051846 - 28 Feb 2026
Viewed by 172
Abstract
Objectives: Postoperative hyperlactatemia (POHL) is a common complication after pediatric cardiac surgery, yet its perioperative risk factors remain unclear. This study developed and internally validated an interpretable machine learning (ML) model to identify young children at risk for POHL. Methods: We [...] Read more.
Objectives: Postoperative hyperlactatemia (POHL) is a common complication after pediatric cardiac surgery, yet its perioperative risk factors remain unclear. This study developed and internally validated an interpretable machine learning (ML) model to identify young children at risk for POHL. Methods: We retrospectively analyzed 3224 children aged 0 to 36 months from 2018 to 2023. Four ML models, including logistic regression (LR), random forest (RF), support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost), were trained and validated. Model performance was assessed using discrimination, calibration, and classification metrics, and decision curve analysis evaluated clinical utility. SHapley Additive exPlanation (SHAP) provided both global and local interpretability. Results: Of the 3224 children, 731 (22.7%) developed POHL, with a median age of 5 months. The RF model performed best (AUC, 0.821; 95% CI, 0.787–0.854; sensitivity, 69.7%; specificity, 84.1%; Brier score, 0.146). SHAP analysis identified 8 key predictors of POHL. Established factors included cardiopulmonary bypass duration, lowest bypass temperature, epinephrine dose, and RACHS-1 category. Novel contributors comprised low body weight, reduced left ventricular end-diastolic diameter, plasma transfusion, and continued mechanical ventilation within the first 24 postoperative hours. Conclusions: We developed and internally validated an interpretable RF model that integrates established and novel predictors to estimate POHL risk in young children after cardiac surgery. Pending external validation, it may support earlier risk recognition and more personalized perioperative management in this high-risk pediatric population. Full article
(This article belongs to the Special Issue Management of Congenital Heart Disease (CHD))
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11 pages, 630 KB  
Article
Associations Between Early Neurosurgical Workflow and Survival in Primary Central Nervous System Lymphoma: A Single-Center Retrospective Study
by Emre Ozkara, Eray Horoz, Zuhtu Ozbek, Deniz Arik, Funda Canaz, Suzan Saylisoy, Hava Uskudar Teke and Murat Vural
Curr. Oncol. 2026, 33(3), 139; https://doi.org/10.3390/curroncol33030139 - 27 Feb 2026
Viewed by 196
Abstract
Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which early management decisions frequently occur within neurosurgical workflows prior to oncologic treatment. In this retrospective single-center study, we aimed to explore whether early neurosurgical workflow characteristics are associated with survival outcomes [...] Read more.
Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which early management decisions frequently occur within neurosurgical workflows prior to oncologic treatment. In this retrospective single-center study, we aimed to explore whether early neurosurgical workflow characteristics are associated with survival outcomes in patients with PCNSL. Consecutive adult patients diagnosed with PCNSL between 2012 and 2022 were included, and the variables of interest comprised pre-biopsy corticosteroid exposure, the interval between diagnostic magnetic resonance imaging (MRI) and stereotactic biopsy, and the time from biopsy to initiation of high-dose methotrexate–based induction therapy. All patients were treated under a standardized hematology protocol to limit systemic treatment heterogeneity. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of diagnostic biopsy, and survival analyses were performed using Kaplan–Meier methods and log-rank testing. Twenty-nine patients met the inclusion criteria. Median OS and PFS were not reached in steroid-naïve patients, whereas pre-biopsy corticosteroid exposure was associated with consistently shorter survival trajectories, with a clear separation of the survival curves, despite conventional statistical significance not being reached. Similarly, median OS and PFS were not reached in patients undergoing biopsy within 7 days of MRI, and an MRI-to-biopsy interval exceeding 7 days demonstrated an unfavorable survival trajectory compared with earlier biopsy; biopsy-to-induction timing did not show a measurable association with early survival outcomes. Established prognostic stratification using Memorial Sloan–Kettering Cancer Center classes showed expected survival discrimination within the cohort, supporting internal validity. Given the limited sample size and retrospective design, all findings should be interpreted as exploratory associations rather than evidence of causality. These results suggest that early neurosurgical workflow characteristics, particularly empiric pre-biopsy corticosteroids avoidance and diagnostic delay minimization, may be associated with early survival trajectories in PCNSL and warrant further evaluation in larger prospective studies. Full article
(This article belongs to the Section Neuro-Oncology)
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18 pages, 9019 KB  
Article
The Influence of Ambient Particulate Matter on the Human Respiratory Tract in Major Academic Centers
by Patryk Grzywa, Filip Mucha, Anna Chlebowska-Styś, Łukasz Pachurka, Vânia Martins, Lucyna Samek, Susana Marta Almeida, Mihalis Lazaridis and Izabela Sówka
Atmosphere 2026, 17(3), 237; https://doi.org/10.3390/atmos17030237 - 25 Feb 2026
Viewed by 313
Abstract
The impact of air pollution on human health remains a critical issue. This study investigates the concentrations of PM2.5 and PM2.5–10 and translates measured exposure concentrations to internal human dose using the Exposure Dose Model 2 (ExDoM2). The cities analyzed (Poznań, [...] Read more.
The impact of air pollution on human health remains a critical issue. This study investigates the concentrations of PM2.5 and PM2.5–10 and translates measured exposure concentrations to internal human dose using the Exposure Dose Model 2 (ExDoM2). The cities analyzed (Poznań, Wrocław) were selected based on their demographic and functional significance and the structure of dominant emission sources. These are large academic centers with a significant influx of residents, leading to the seasonal increase in the number of people exposed to air pollution. The total deposited doses of PM2.5 in the human respiratory tract (HRT) for adult males varied seasonally, with the highest dose recorded in winter and autumn equal to 180 µg in Wrocław and Poznań, and the lowest in spring and summer equal to 30 µg and 65 µg in Wrocław and Poznań, respectively. These findings highlight the significant impact of seasonal variability on exposure to particulate matter and its potential health implications. In particular, the deposited doses of particulate matter in Wrocław and Poznań were found to be within a similar range during certain seasons, indicating comparable urban exposure levels. During the heating season, municipal and residential emissions related to the combustion of solid fuels in individual heat sources play a key role, while during the non-heating season, traffic emissions and secondary particulate matter resuspension are more significant. Further research is required to determine the extent to which these similarities reflect shared emission sources or meteorological conditions. Full article
(This article belongs to the Section Air Quality and Health)
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14 pages, 1131 KB  
Article
Mycophenolate Mofetil for Treatment of Ipilimumab-Induced Colitis in Patients with Metastatic Melanoma
by Christina Naoum, Julia K. Winkler, Pawel Majenka, Carmen Loquai, Annika Brekner, Milena Fuchß, Katharina C. Kähler, Marilena Petersen, Ralf Gutzmer, Imke von Wasielewski and Jessica C. Hassel
Cancers 2026, 18(5), 734; https://doi.org/10.3390/cancers18050734 - 25 Feb 2026
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Abstract
Background/Objectives: Treatment with immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has greatly improved clinical outcomes but can induce immune-related adverse events (irAEs). ICI-induced immune-related (ir) colitis is one of the most common severe irAEs and is primarily managed by treatment with [...] Read more.
Background/Objectives: Treatment with immune checkpoint inhibitors (ICIs) in patients with advanced melanoma has greatly improved clinical outcomes but can induce immune-related adverse events (irAEs). ICI-induced immune-related (ir) colitis is one of the most common severe irAEs and is primarily managed by treatment with high-dose corticosteroids. Some patients are steroid-refractory and require additional immunosuppressants. Infliximab is commonly used as the additional treatment of choice, while data for other immunosuppressants such as mycophenolate mofetil (MMF) are sparse. Methods: We used MMF to treat ir colitis in a cohort of patients in Heidelberg and compared clinical data with patients who received standard irAE management with infliximab in the Cancer Centers of Heidelberg, Hannover, Mainz, and Kiel. Outcome measures included response rate, time to response, duration and amount of steroid intake, and recurrence of colitis, as well as progression-free survival (PFS) and overall survival (OS) measured from the start of steroid intake. Results: Out of 52 patients refractory to steroids, 31 were treated with additional MMF and 21 with additional infliximab. A total of 24 out of 31 patients (77.4%) experienced bowel habit normalization during treatment with MMF after a median of seven days. Seven patients required additional infliximab to achieve a resolution of symptoms. Twenty out of 21 patients (95.2%) showed a normalization of stool frequency with infliximab after a median of eleven days. One patient required additional MMF to achieve a normal bowel habit. Hence, resolution of symptoms was achieved during both treatment regimens (p = 0.081) in a comparable period of time (p = 0.858). Neither recurrence of colitis after additional immunosuppression (p = 0.760) nor rate of CMV positivity after recurrence of colitis (p = 0.898) differed between groups. We observed a tendency towards longer treatment duration (108 vs. 85 days, p = 0.052) and significantly higher cumulative corticosteroid intake (7585 mg vs. 3485 mg, p = 0.002) in the MMF group compared to the infliximab group. However, we observed significantly higher cumulative steroid intake and a longer duration of corticosteroid therapy in patients treated at the Heidelberg center compared with those treated at the other participating centers within the infliximab group. In contrast, no significant differences in corticosteroid duration or cumulative dose were observed in the center-internal comparison between MMF- and infliximab-treated patients at Heidelberg. These subgroup analyses may indicate that the observed differences in corticosteroid exposure are more likely related to center-specific management strategies rather than substance-specific effects. Neither median PFS nor OS differed between the groups (mPFS: MMF: 3.2 months; infliximab: 2.1 months (p = 0.978); mOS MMF: 12 months; infliximab: 9.5 months (p = 0.561)). Conclusions: The data point to MMF as a well-tolerated, oral treatment alternative for patients with ICI-induced ir colitis, especially in patients where infliximab is contra-indicated. Full article
(This article belongs to the Special Issue Adverse Effects During Cancer Treatment)
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Article
A Comprehensive Study on Radiological Hazard Assessment and Geological Features of Gypsum Deposits
by Mohamed Y. Hanfi, Mohammad W. Marashdeh, Masoud S. Masoud, Hassan A. A. Shahin, Haitham Alrajhi and Ahmed E. Abdel Gawad
Toxics 2026, 14(3), 191; https://doi.org/10.3390/toxics14030191 - 25 Feb 2026
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Abstract
This study assessed natural radioactivity values and corresponding radiological hazards in gypsum samples collected from the investigated area. The geologic context mainly includes tertiary and quaternary sedimentary formations with gypsum horizons of Early Messinian age, interbedded with layers of limestone and marl. A [...] Read more.
This study assessed natural radioactivity values and corresponding radiological hazards in gypsum samples collected from the investigated area. The geologic context mainly includes tertiary and quaternary sedimentary formations with gypsum horizons of Early Messinian age, interbedded with layers of limestone and marl. A total of thirty-five gypsum samples were collected and analyzed for the 238U, 232Th, and 40K activity concentration using High-Purity Germanium (HPGe) gamma-ray spectrometry. The mean activity concentrations for the gypsums are reported at 73 ± 87 Bq kg−1, 14 ± 17 Bq kg−1, and 35 ± 201 Bq kg−1 for 238U, 232Th, and 40K, respectively. Several related radiological hazard indices were estimated from the various activity concentrations, including radium equivalent activity (Raeq) and absorbed dose rate (Dair). All gypsum analyzed fell below international safety limits for radiological risk, as evidenced by the observed radium equivalent activity (Raeq), with a maximum value of 456 Bq kg−1, and the total annual effective dose (AED) values from 0.09 to 1.26 mSv y−1 remaining between these two values. The results indicate the levels of radioactive hazards of the gypsum samples were generally below global safety standards, but individual samples (i.e., S17, S20, S24, S26, S30, S35) exceeded one or more of the hazard indices. Statistical assessment of the samples, with respect to their radiological hazard and natural radioactivity, was also undertaken as a way of seeking further insights into their relationships, productivity, and characteristics. This included Pearson correlation, hierarchical cluster analysis (HCA) and principal component analysis (PCA). The evidence suggests that for the gypsums, 238U was the greatest contributor to radiological hazards, influencing all hazard indices. Full article
(This article belongs to the Section Metals and Radioactive Substances)
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