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11 pages, 772 KB  
Article
Beyond Coiling: A Comparative Analysis of Survey-Reported Preferences for Endovascular Cerebral Aneurysm Occlusion
by Sanjana R. Salwi, Thilan Tudor, Oleg Shekhtman, Georgios S. Sioutas, Pious D. Patel, Irina-Mihaela Matache, Mohamed Salem, Sonia Ajmera, Sandeep Kandregula, Jan-Karl Burkhardt and Visish M. Srinivasan
Clin. Pract. 2026, 16(6), 112; https://doi.org/10.3390/clinpract16060112 (registering DOI) - 15 Jun 2026
Abstract
Background: Aneurysm treatment options are rapidly evolving, as evidenced by the recent introduction and widespread adoption of flow diversion and intrasaccular devices. However, there is a need to understand how these newer technologies are used for difficult-to-treat aneurysms. The main aims of this [...] Read more.
Background: Aneurysm treatment options are rapidly evolving, as evidenced by the recent introduction and widespread adoption of flow diversion and intrasaccular devices. However, there is a need to understand how these newer technologies are used for difficult-to-treat aneurysms. The main aims of this study were to investigate the variation in aneurysm treatment recommendations among neurosurgeons, interventional radiologists, and interventional neurologists and to generally describe trends in endovascular treatment. Methods: In this survey-based study conducted from June to September 2024, participants were presented with clinical vignettes and asked to choose preferred treatment options, with responses analyzed based on demographic variables including specialty, age, and training prior to and after the introduction of flow diversion. Results: A total of 108 respondents completed the study with a representative mix of specialties—(45 (42.5%) radiologists, 22 (20.8%) neurologists, and 39 (36.8%) neurosurgeons. Sixty-six (61.1%) trained after the introduction of flow diversion. Treatment recommendations were significantly different by specialty (p < 0.001). The Kappa statistic to assess variation in responses showed significant variation in treatment preferences across aneurysm subtypes, ranging from poor (κ = 0.07) to fair (0.31). Treatment of ruptured aneurysms varied by specialty with radiologists opting for stent-assisted coiling at a higher rate than neurologists or neurosurgeons (p < 0.001). There was no significant difference in rates of recommending flow diversion or intrasaccular devices between those who had trained before and after their introduction (p = 0.97). Conclusion: The study highlights the dynamic nature of aneurysm management and considerable variability among different specialties. Further exploration into the rationale for each decision is needed to understand how specialty training affects these decisions. Full article
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19 pages, 4590 KB  
Article
Oxidative-Stress Biomarkers and Pathologic Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer: A Prospective Cohort Study
by Hayriye Şahinli, Galip Can Uyar, Yakup Düzköprü, Özlem Aydın İsak, Ayşe Arzu Eren and Salim Neşelioğlu
Cancers 2026, 18(12), 1939; https://doi.org/10.3390/cancers18121939 (registering DOI) - 14 Jun 2026
Abstract
Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational [...] Read more.
Background: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) varies considerably, and oxidative stress may modulate radiosensitivity. This study evaluated ischemia-modified albumin (IMA) and thiol–disulfide homeostasis as potential biochemical predictors of pathological tumor regression. Methods: A prospective observational cohort study was conducted to assess pre- and post-treatment oxidative stress biomarkers in patients with LARC receiving capecitabine-based long-course CRT. Serum IMA, native thiol, total thiol, and disulfide levels were quantified spectrophotometrically. Pathologic regression was graded according to the Modified Ryan system as good (TRG 0–1) or poor (TRG 2–3). Receiver operating characteristic (ROC) analyses, Firth-penalized logistic regression, and internal validation using cross-validation, calibration, and decision-curve analyses were performed. Results: Of 38 screened patients, 31 met eligibility criteria and completed CRT, alongside 31 matched healthy controls. Compared with controls, patients had higher baseline disulfide (15.7 ± 5.2 vs. 11.9 ± 3.1 µmol/L; p = 0.012) and IMA levels (0.886 ± 0.062 vs. 0.798 ± 0.048 ABSU; p = 0.006). Poor responders exhibited higher pre-treatment IMA (0.927 ± 0.045 vs. 0.842 ± 0.050 ABSU; p = 0.020) and disulfide levels (18.4 ± 5.2 vs. 13.0 ± 3.8 µmol/L; p = 0.012). Pre-treatment IMA demonstrated the highest predictive accuracy for poor tumor regression (AUC = 0.872; 95% CI 0.751–0.993). In multivariable Firth-penalized logistic regression, elevated baseline IMA was independently associated with poor pathological response (OR = 3.63; 95% CI 1.22–16.20; p = 0.043), whereas negative circumferential resection margin (CRM) status was independently associated with favorable regression (OR = 0.21; 95% CI 0.02–0.71; p = 0.003). The internally validated model demonstrated excellent discrimination (AUC = 0.948; 95% CI 0.866–0.966) and good calibration. Conclusions: Baseline IMA and CRM status were independently associated with pathological response after CRT in LARC. These findings suggest that oxidative-stress biomarkers may have potential value for response stratification; however, the results should be considered exploratory and require external validation in larger independent cohorts before clinical application. Full article
(This article belongs to the Special Issue Advancements in “Cancer Biomarkers” for 2025–2026)
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24 pages, 296 KB  
Article
Enhancing HACCP Decisions: A Comparative Risk Assessment for Table Olive Processing
by Cristina Campanero Pintado, Kharla Andreina Segovia Bravo, Antonio Benítez Cabello, Francisco Noé Arroyo-López and Efrén Pérez-Santín
Foods 2026, 15(12), 2153; https://doi.org/10.3390/foods15122153 (registering DOI) - 14 Jun 2026
Abstract
Table olive processing comprises multiple stages in which physical, chemical, and biological hazards may occur. Although risk assessment is a core element of Hazard Analysis and Critical Control Points (HACCP) systems, the selection of assessment tools remains insufficiently standardized. This study compared a [...] Read more.
Table olive processing comprises multiple stages in which physical, chemical, and biological hazards may occur. Although risk assessment is a core element of Hazard Analysis and Critical Control Points (HACCP) systems, the selection of assessment tools remains insufficiently standardized. This study compared a 4 × 4 risk matrix and Failure Mode and Effects Analysis (FMEA) for hazard evaluation in Spanish-style and Californian-style table olive processing. Hazards were assessed across 41 processing stages for Spanish-style olives and selected key stages for Californian-style olives using probability × severity in the 4 × 4 matrix and severity × occurrence × detection in FMEA. Significant hazards were further evaluated using the Codex Alimentarius decision tree to identify critical control points (CCPs) and strengthened prerequisite programs (PRPs). Both tools identified similar significant hazards, including biological hazards associated with fermentation, brine management, storage, container sealing, and heat treatment, as well as physical hazards from foreign bodies and chemical hazards related to heavy metals, pesticide residues, mycotoxins, and food-contact material migration. FMEA provided greater analytical detail through the detection parameter, whereas the 4 × 4 matrix was simpler and more practical for complex flow diagrams. Overall, both tools were suitable for HACCP-based risk assessment in table olive processing. Full article
(This article belongs to the Section Food Quality and Safety)
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13 pages, 63394 KB  
Case Report
Metastatic Anaplastic Thyroid Carcinoma Presenting with Gastrointestinal Bleeding: A Case Report and Literature Review
by Hassan Al-Thani, Husham Abdelrahman, Maryam Al-Sulaiti, Abdelhakem Tabeb, Mahir Petkar, Noora Al-Thani and Ayman El-Menyar
Reports 2026, 9(2), 185; https://doi.org/10.3390/reports9020185 (registering DOI) - 14 Jun 2026
Abstract
Background: Thyroid cancer is increasing, particularly the differentiated type, with decreasing incidence of the anaplastic type. Anaplastic thyroid carcinoma (ATC) is a rare, aggressive, and often lethal form. It frequently presents with metastatic disease, regional and systemic, with common distant metastasis to [...] Read more.
Background: Thyroid cancer is increasing, particularly the differentiated type, with decreasing incidence of the anaplastic type. Anaplastic thyroid carcinoma (ATC) is a rare, aggressive, and often lethal form. It frequently presents with metastatic disease, regional and systemic, with common distant metastasis to the lung, bone, brain, and adrenal, and rarely to other places. Case presentation: A 74-year-old Arab male presented with symptomatic anemia and melena and was admitted for investigation of the cause. The patient was found to have a large retrosternal goiter and gastric tumor. CT scan showed a pedunculated, nonobstructive mass, suggestive of a GIST or leiomyoma. The neck mass presented with compressive symptoms. He underwent a combined neck and abdominal surgical resection based on a multidisciplinary team decision, as prior biopsies were not conclusive. The final pathology report identified similar tumors in the two specimens and suggested an anaplastic thyroid carcinoma as the primary tumor with metastasis to the stomach. Furthermore, the workup, including a PET scan 2 weeks post-surgery, revealed widespread metastases in the bone, lung, and liver, and the treatment was palliative. He was followed up in the outpatient clinic for 4 and a half months post-operatively. The patient developed sepsis and cardiopulmonary arrest and died. Conclusions: ATC can metastasize to many places in the body, including the stomach (as shown in our case), which can cause significant upper gastrointestinal bleeding and anemia. Metastatic ATC carries a poor prognosis; thus, physicians need to keep a high index of suspicion in approaching similar cases. A multidisciplinary approach for the management is of utmost importance for appropriate treatment. This disease’s pathology, behavior, and targeted new treatment modalities must be explored further. Full article
(This article belongs to the Collection Clinical Research in Oncology)
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13 pages, 794 KB  
Review
An Individualized Right-to-Left Tunneling “Bail-Out” for Complex ICD Upgrade in a Pacemaker-Dependent Patient: A Case Report and Literature Review
by Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Sotiria G. Giotaki, Christos Piperis, Maria S. Kousta, Ioannis Anagnostopoulos, Christos Karavasilis, Gerasimos Deftereos, Georgios Giannopoulos, Sotirios Patsilinakos, Gerasimos Siasos and Spyridon Deftereos
J. Pers. Med. 2026, 16(6), 318; https://doi.org/10.3390/jpm16060318 (registering DOI) - 14 Jun 2026
Abstract
Inadequate vein access is a frequent obstacle during cardiac implantable electronic device (CIED) upgrade procedures; thus, bail-out strategies are employed. A 71-year-old male with dilated cardiomyopathy bearing a 7-year-old right-sided dual-chamber pacemaker was scheduled for upgrade to an implantable cardioverter defibrillator. The case [...] Read more.
Inadequate vein access is a frequent obstacle during cardiac implantable electronic device (CIED) upgrade procedures; thus, bail-out strategies are employed. A 71-year-old male with dilated cardiomyopathy bearing a 7-year-old right-sided dual-chamber pacemaker was scheduled for upgrade to an implantable cardioverter defibrillator. The case presented two main challenges—first, pacemaker dependency, and second, an occluded right subclavian vein. In a shared decision-making approach, the decision was made to “abandon” the right-sided ventricular lead in situ, reposition the right-sided atrial lead by tunneling over the sternum into the left pectoral area, and implant a new left-sided defibrillator lead. During the 2-year follow-up our patient remained clinically stable and the CIED fully functional. Herein, beyond case presentation we also elaborate on individualized alternative treatment strategies for patients with venous access site occlusion in a literature review. Full article
(This article belongs to the Special Issue New Insights into Cardiac Electrophysiology and Personalized Medicine)
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22 pages, 983 KB  
Article
Short-Term Profitability Pressure Following Green Bond Issuance: Evidence from China’s Listed Heavy-Polluting Enterprises
by Yilin Cai, Meng Feng, Yueming Qiu and Yi David Wang
Sustainability 2026, 18(12), 6114; https://doi.org/10.3390/su18126114 (registering DOI) - 14 Jun 2026
Abstract
Green bonds have become an important financial instrument for supporting environmental investment and industrial transformation. This paper examines short-term profitability dynamics around first green bond issuance among heavy-polluting firms listed on China’s A-share market. Using a staggered-adoption framework based on the group-time average [...] Read more.
Green bonds have become an important financial instrument for supporting environmental investment and industrial transformation. This paper examines short-term profitability dynamics around first green bond issuance among heavy-polluting firms listed on China’s A-share market. Using a staggered-adoption framework based on the group-time average treatment effect estimator of Callaway and Sant’Anna we compare issuing firms after issuance with never-issuing and not-yet-issuing firms while controlling for firm characteristics, firm fixed effects, and year fixed effects. The estimates show that issuing firms experience an average post-issuance ROE decline of approximately 4.9 percentage points during the four years following issuance. Given that the average ROE in the sample is 0.0702, this estimate is economically substantial. Because green bond issuance is a voluntary corporate financing decision rather than an externally assigned policy shock, the estimates are interpreted as treatment-on-the-treated effects under the assumptions of no anticipation, overlap, and conditional parallel trends. Additional diagnostics and a DuPont-style mechanism analysis suggest that the post-issuance ROE decline is mainly associated with lower net profit margins and, to a lesser extent, lower asset turnover. Heterogeneity analyses indicate that the post-issuance profitability pressure varies across ownership types, regions, and industries. Full article
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18 pages, 655 KB  
Article
Effect of ESG Awareness on Sustainable Investment Decisions: An Experimental Study
by Mostafa E. Shahen, Mahmoud Otaify, Hanan Amin Mohamed and Ahmed Rady
J. Risk Financial Manag. 2026, 19(6), 427; https://doi.org/10.3390/jrfm19060427 (registering DOI) - 13 Jun 2026
Abstract
The future of Earth depends on the investment choices of companies and individuals. Over the past decade, investment decisions of individuals have been intensely studied by researchers in developed countries. Yet, very few studies focused on these investment decisions in developing countries using [...] Read more.
The future of Earth depends on the investment choices of companies and individuals. Over the past decade, investment decisions of individuals have been intensely studied by researchers in developed countries. Yet, very few studies focused on these investment decisions in developing countries using an experimental approach. This study adopts an experimental approach to examine the impact of ESG awareness on the sustainable investment decisions of undergraduate students in Egypt. In the experiment, subjects were asked to watch a video on investment basics (control) and investment and ESG basics (treatment). After that, the subjects were asked to choose between two choices, one sustainable (ESG choice) and one unsustainable with and without a return difference. After controlling for demographic characteristics, personal traits, financial knowledge, and risk tolerance, the results indicate that ESG awareness increases the probability of making sustainable investment decisions. Moreover, the findings indicate that sustainable investing among individuals is conditional on higher or equal returns than conventional investing. The study provides practical insights for professionals and policy recommendations. Full article
(This article belongs to the Special Issue Bridging Financial Integrity and Sustainability)
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30 pages, 4874 KB  
Review
Beyond SINS: A Critical Review of Biomechanical, Microstructural, and Radiomic Biomarkers for Predicting Fracture Risk in Spinal Metastases
by An Sen Tan, Calvin Kai En Tjio, Jonathan Jiong Hao Tan, Naresh Kumar, Wilson Ong, Shuliang Ge, Yi Liang Tan, Eric Fang, Balamurugan A Vellayappan and James Thomas Patrick Decourcy Hallinan
Diagnostics 2026, 16(12), 1835; https://doi.org/10.3390/diagnostics16121835 (registering DOI) - 13 Jun 2026
Abstract
Background/Objectives: Although the Spinal Instability Neoplastic Score (SINS) is widely used to estimate spinal metastases fracture risk and guide decisions on stabilisation procedures, prior studies have demonstrated mixed results. Patients with the same score exhibit clinically heterogeneous outcomes, with some SINS criteria correlating [...] Read more.
Background/Objectives: Although the Spinal Instability Neoplastic Score (SINS) is widely used to estimate spinal metastases fracture risk and guide decisions on stabilisation procedures, prior studies have demonstrated mixed results. Patients with the same score exhibit clinically heterogeneous outcomes, with some SINS criteria correlating less well with the estimated fracture risk than others. There are also barriers to implementation such as the time burden required for manual calculation and interobserver variability associated with qualitative morphological criteria. SINS also lacks sensitivity for detecting latent structural compromise in treatment-naive patients and those susceptible to the iatrogenic effects of stereotactic body radiation therapy. This review aims to evaluate emerging imaging, biomechanical, and microstructural markers with the potential to improve fracture risk stratification and prognostication for spinal oncology patients. Methods: We synthesise evidence across three innovative frontiers: (1) biomechanical modelling, including CT-derived finite element analysis and failure-load pattern models; (2) radiomics, utilizing radiomics features from radiological imaging to develop a predictive model; and (3) microstructural MRI biomarkers, exploring the translatability of the Vertebral Bone Quality score, fat fraction, and paraspinal muscle atrophy from osteoporosis to the metastatic spine. Results: Emerging biomechanical, radiomic and microstructural imaging markers show potential in addressing some limitations of traditional SINS criteria for fracture risk stratification across the spinal oncology treatment continuum, from initial diagnosis to post-radiation surveillance, thereby facilitating more precise risk assessment. However, current evidence remains largely retrospective and heterogeneous, and further validation is required before clinical adoption. Conclusions: We propose a framework that shifts the paradigm from conventional morphological scoring toward a multiparametric assessment of spinal stability. Full article
(This article belongs to the Special Issue Contemporary Spine Diagnostics and Management)
22 pages, 2880 KB  
Systematic Review
Real-World Outcomes of Switching to Aflibercept 8 mg in Previously Treated Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis
by Abdullah Bousamri, Mohammad Kana’an, Faisal Alharbi and Noor Alqudah
J. Clin. Med. 2026, 15(12), 4599; https://doi.org/10.3390/jcm15124599 (registering DOI) - 13 Jun 2026
Abstract
Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously [...] Read more.
Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: −0.017 logMAR; 95% CI: −0.027 to −0.007; +0.83 ETDRS letters; I2 = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I2 = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I2 = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes. Full article
(This article belongs to the Section Ophthalmology)
22 pages, 1584 KB  
Review
Understanding CT Perfusion in Acute Ischemic Stroke: How Algorithms Shape Perfusion Maps
by Nicola Morelli, Marco Spallazzi, Marina Biondi, Eugenia Rota and Davide Colombi
Diagnostics 2026, 16(12), 1831; https://doi.org/10.3390/diagnostics16121831 (registering DOI) - 12 Jun 2026
Viewed by 89
Abstract
CT perfusion (CTP) is widely used in acute ischemic stroke imaging, particularly for treatment selection beyond conventional time windows. However, automated perfusion maps are not direct measurements of irreversible tissue injury, but estimates shaped by deconvolution strategy, temporal correction, dispersion handling, and software-specific [...] Read more.
CT perfusion (CTP) is widely used in acute ischemic stroke imaging, particularly for treatment selection beyond conventional time windows. However, automated perfusion maps are not direct measurements of irreversible tissue injury, but estimates shaped by deconvolution strategy, temporal correction, dispersion handling, and software-specific thresholds. This review provides a clinically oriented explanation of how CTP algorithms influence the estimation of ischemic core and hypoperfused tissue. Particular attention is given to singular value decomposition (SVD) methods, Bayesian approaches, and timing parameters, including time to maximum (Tmax), Delay, time to peak (TTP), and mean transit time (MTT). Differences in residue function estimation and threshold definition may generate variable outputs across software platforms, even from the same source dataset. Perfusion thresholds should therefore not be treated as universally interchangeable. CTP findings should be integrated with clinical status, non-contrast CT, CT angiography (CTA), collateral status, occlusion site, and imaging-to-treatment context, serving as decision-support tools rather than isolated measures of tissue viability. Full article
(This article belongs to the Special Issue Clinical Advances and Applications in Neuroradiology: 2nd Edition)
17 pages, 921 KB  
Article
The Societal Burden of Breast Cancer in Working-Age Women in Croatia: A Multicentre Cross-Sectional Study
by Vid Duplančić, Ana Bobinac, Luka Vončina, Katarina Hraste, Ana Tečić Vuger, Robert Šeparović and Eduard Vrdoljak
Healthcare 2026, 14(12), 1693; https://doi.org/10.3390/healthcare14121693 (registering DOI) - 12 Jun 2026
Viewed by 148
Abstract
Background/Objectives: Breast cancer affects working-age women not only through treatment and survival but also through health-related quality of life (HRQoL), work capacity and informal caregiving needs. Evidence from Central and Eastern Europe remains limited. This study estimated the indirect societal burden of breast [...] Read more.
Background/Objectives: Breast cancer affects working-age women not only through treatment and survival but also through health-related quality of life (HRQoL), work capacity and informal caregiving needs. Evidence from Central and Eastern Europe remains limited. This study estimated the indirect societal burden of breast cancer among working-age women in Croatia and reported economic indirect costs separately from monetised HRQoL/welfare loss. Methods: A multicentre cross-sectional study conducted in 2024 included women aged 18–65 years receiving outpatient oncology care at two tertiary centres in Croatia. HRQoL was assessed with the EuroQol five-dimension five-level instrument (EQ-5D-5L) and compared with Croatian general-population norms. Utility decrements were annualised and monetised using a national willingness-to-pay threshold of €17,000 per quality-adjusted life year (QALY). Work productivity impairment was measured using the Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire and valued, together with informal care, using the human-capital approach. Deterministic sensitivity analyses and approximate 95% confidence intervals were used to show how the estimates changed under key assumptions. Results: A total of 271 women participated (mean age 51.3 years among age-eligible records). Mean EQ-5D-5L utility was 0.76 versus 0.91 in the general population, corresponding to an annual QALY loss of 0.15 and a monetised HRQoL/welfare loss of €2550 per patient-year (95% CI €2083–€3017). Among employed participants, mean overall work productivity loss was 43.9% (842.9 h/year), equivalent to €7333 annually (95% CI €6311–€8355). Informal caregiving was reported by 54.7% of participants, with mean annual costs of €1566 (95% CI €1269–€1863). Economic indirect costs were €8899 per patient-year (95% CI €7835–€9963). In an extended welfare-inclusive scenario, the estimated burden was €11,449 per patient-year (95% CI €10,287–€12,611), corresponding to an illustrative national estimate of €86 million (95% CI €77–€95 million; 0.11% of gross domestic product). Conclusions: Breast cancer in working-age women imposes a substantial societal burden in Croatia, driven by reduced HRQoL, productivity losses and informal caregiving needs. These findings support taking societal burden into account in public health planning, survivorship care and health policy decision-making. Full article
(This article belongs to the Section Public Health and Preventive Medicine)
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18 pages, 5960 KB  
Article
Mutational Signatures and Machine Learning for Risk Stratification of Acute Myeloid Leukaemia Based on Targeted Sequencing Data
by Heba Elhaddad, Claudia Chiriches, Shuvro Prokash Nandi, Patrick van Eijk, Amanda Gilkes, Katie Watts, Amy Houseman, Charlotte S. Wilhelm-Benartzi, Oliver Gerhard Ottmann, Simon H. Reed and Martin Ruthardt
Cancers 2026, 18(12), 1925; https://doi.org/10.3390/cancers18121925 (registering DOI) - 12 Jun 2026
Viewed by 150
Abstract
Background/Objectives: To date, no validated scoring system can accurately predict the responses of acute myeloid leukaemia (AML) patients to induction chemotherapy (CTX). Current risk assessment relies on complex cytogenetic and molecular abnormalities and focuses on mutations in genes considered fundamental to leukaemogenesis. Methods: [...] Read more.
Background/Objectives: To date, no validated scoring system can accurately predict the responses of acute myeloid leukaemia (AML) patients to induction chemotherapy (CTX). Current risk assessment relies on complex cytogenetic and molecular abnormalities and focuses on mutations in genes considered fundamental to leukaemogenesis. Methods: We performed bioinformatic analysis of targeted sequencing (TS) data from 111 genes in 1552 AML patients, focusing on mutational patterns derived from single-nucleotide variant (SNV) catalogues. The SNV catalogues were analysed using non-negative matrix factorisation (NNMF), a linear dimensionality-reduction approach, to extract risk-defining recursive signatures (RSs) and to distinguish responders from resistant patients following induction CTX. To enable patient-level prediction, we complemented NNMF with a Random Forest (RF) model. Given the class imbalance between responders and resistant cases, model performance was improved by applying the Synthetic Minority Over-sampling Technique (SMOTE) and by incorporating germline variants alongside somatic mutations. Results: NNMF-derived RSs captured clinically relevant structures in patients’ mutational profiles and clustered patients by treatment response, indicating that the diagnostic targeted sequencing data contain sufficient information for risk stratification and treatment response prediction. At the single-patient level, RF models incorporating balanced data and germline variation improved predictive performance compared with unbalanced somatic-only models. Conclusions: These findings demonstrate that machine learning applied to targeted sequencing data can extract clinically informative mutational structures and improve risk stratification in AML, supporting its potential integration into precision treatment decision-making. Full article
(This article belongs to the Special Issue Machine Learning and Artificial Intelligence in Leukemia)
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27 pages, 951 KB  
Article
Explainable Multi-Agent LLM Framework for Phishing Email Detection via Role-Specialized Evidence Decomposition
by Tanya Yadav and Mohammad Masum
Electronics 2026, 15(12), 2606; https://doi.org/10.3390/electronics15122606 (registering DOI) - 12 Jun 2026
Viewed by 126
Abstract
Phishing email remains a persistent and operationally critical cybersecurity threat, yet existing detection approaches, including traditional machine learning and single-pass large language model systems, either lack native interpretability or provide explanations that are difficult to standardize and audit. This paper introduces an explainable [...] Read more.
Phishing email remains a persistent and operationally critical cybersecurity threat, yet existing detection approaches, including traditional machine learning and single-pass large language model systems, either lack native interpretability or provide explanations that are difficult to standardize and audit. This paper introduces an explainable multi-agent LLM framework that decomposes phishing evidence across three role-specialized agents focused on linguistic patterns, psychological manipulation, and sender identity consistency. The framework then aggregates specialist outputs through schema-governed synthesis, enabling each intermediate and final decision to be structured, comparable, and auditable. The central contribution is the treatment of role-specialized evidence decomposition and explanation structure as first-class design constraints rather than post hoc additions. The framework is evaluated on a fixed 1000-email subset drawn from a unified TREC/Nazario corpus of 56,212 emails under controlled zero-shot conditions. The full multi-agent Meta-Judge system achieves Macro-F1 = 98.28% and phishing recall = 99.45%, improving Macro-F1 by 6.3 percentage points over a zero-shot single-model GPT-4o-mini baseline. Paired statistical testing confirms that this improvement is significant and is driven primarily by reduced false positives on legitimate emails while preserving high phishing recall. Additional evaluation on an independent LLM-attributed email benchmark shows a consistent Macro-F1 improvement of 0.0773 over the zero-shot baseline under distribution shift. Ablation results show that role-specialized decomposition is the primary performance driver, while deterministic voting provides a competitive raw-classification aggregator and Meta-Judge synthesis provides structured, analyst-facing explanations. These results indicate that role-specialized evidence decomposition combined with schema-governed explanation can improve both detection reliability and auditability in phishing classification workflows. Full article
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19 pages, 515 KB  
Review
Emerging Pathways to Non-Invasive Diagnosis in Endometriosis: Integrating Machine Learning, Deep Learning and Multi-Omics Biomarkers
by Daniel Markov, Jasmin Gurung, Usman Khalid, Kristian Bechev, Vladimir Aleksiev, Galabin Markov and Elena Poryazova
Diagnostics 2026, 16(12), 1823; https://doi.org/10.3390/diagnostics16121823 (registering DOI) - 12 Jun 2026
Viewed by 117
Abstract
Endometriosis is a chronic, debilitating condition affecting approximately 10–15% of reproductive-aged women and it is often associated with significant diagnostic delays due to its heterogeneity and unreliable non-invasive tests. Artificial intelligence (AI) offers innovative methods for improving endometriosis diagnosis, prognosis and research via [...] Read more.
Endometriosis is a chronic, debilitating condition affecting approximately 10–15% of reproductive-aged women and it is often associated with significant diagnostic delays due to its heterogeneity and unreliable non-invasive tests. Artificial intelligence (AI) offers innovative methods for improving endometriosis diagnosis, prognosis and research via advanced pattern recognition and data analysis capabilities. The integration of AI in diagnostic workflow has the potential to improve efficiency, accuracy, and patient outcomes. This review summarises current developments of AI—including machine learning, deep learning, and natural language processing—in the diagnostic workflow of endometriosis. It analyses different fields of diagnostics ranging from AI-assisted imaging in detection of pouch of Douglas to multi-omics biomarkers assisting the clinical decision process. AI can enhance accuracy, reducing diagnostic delays and supporting personalised treatment planning. However, there are multiple limitations, such as small datasets, overfitting, and lack of external validation and variability. Further research and evaluation are required before it can be implemented into healthcare systems. AI holds promise as a non-invasive, scalable adjunct to current diagnostics, potentially reducing the economic and personal burden endometriosis carries. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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13 pages, 3603 KB  
Article
Physiological Responses of Apple to Nitrogen Fertilization Regimes: Roles of Calcium Metabolism in Fruit Quality and Bitter Pit Development
by Yue Xing, Zhanling Zhu, Ge Tian, Minghui Du, Hui Cao and Shunfeng Ge
Plants 2026, 15(12), 1820; https://doi.org/10.3390/plants15121820 (registering DOI) - 12 Jun 2026
Viewed by 126
Abstract
Excessive or improper nitrogen (N) fertilization can disrupt calcium (Ca) nutrition in apple trees and induce Ca-related physiological disorders, yet its effects on Ca availability and partitioning remain unclear. This study evaluated the impact of different N fertilization regimes on soil Ca availability, [...] Read more.
Excessive or improper nitrogen (N) fertilization can disrupt calcium (Ca) nutrition in apple trees and induce Ca-related physiological disorders, yet its effects on Ca availability and partitioning remain unclear. This study evaluated the impact of different N fertilization regimes on soil Ca availability, Ca partitioning, and Ca bioavailability in fruit tissues of 10-year-old ‘Fuji’ apple trees, using Ca fractionation analysis combined with multi-criteria decision-making (TOPSIS). High N applied as a single dose (H1) significantly reduced soil water-soluble and exchangeable Ca, while increasing Ca oxalate (CaOx) accumulation in fruit pedicels, particularly at maturity. Although total CaOx in fruit flesh decreased, its relative proportion increased, indicating enhanced Ca sequestration. In contrast, split application of moderate N (M3) maintained more stable soil Ca availability, reduced CaOx accumulation, and improved Ca allocation to fruit tissues. Integrated evaluation ranked treatments as M3 > M1 > H3 > H1. Overall, moderate and split N fertilization reduced Ca sequestration into CaOx, enhanced Ca availability, and improved Ca distribution in fruit tissues, providing a physiological basis for optimizing N management to mitigate Ca-related disorders and improve fruit quality. Full article
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