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24 pages, 10494 KB  
Article
ECG-Gated 4D-CTA Assessment of Intracranial Aneurysm Wall Dynamics and Longitudinal Size Change: An Exploratory Study
by Peter Jankovič, Kamil J. Chodzyński, Axel E. Vanrossomme, Karim Zouaoui Boudjeltia, Andrej Šteňo, Christian R. Wirtz, Ján Šulaj and Andrej Paľa
Neurol. Int. 2026, 18(5), 81; https://doi.org/10.3390/neurolint18050081 (registering DOI) - 27 Apr 2026
Abstract
Background: The risk stratification of unruptured intracranial aneurysms (UIAs) relies largely on static clinical and morphological parameters, which may not fully capture aneurysm-specific wall behavior. ECG-gated four-dimensional computed tomography angiography (4D-CTA) enables the time-resolved assessment of aneurysm wall motion, but reliable interpretation requires [...] Read more.
Background: The risk stratification of unruptured intracranial aneurysms (UIAs) relies largely on static clinical and morphological parameters, which may not fully capture aneurysm-specific wall behavior. ECG-gated four-dimensional computed tomography angiography (4D-CTA) enables the time-resolved assessment of aneurysm wall motion, but reliable interpretation requires the differentiation of biological motion from measurement uncertainty. Methods: In this prospective exploratory pilot study, ECG-gated 4D-CTA was used to evaluate the longitudinal aneurysm size change, global volumetric pulsation (GVP), spatial wall pulsation (SWP), intrinsic wall deformability and variability. Size change and pulsation were defined using predefined resolution- and noise-based thresholds. Spatial wall motion was assessed using phase-resolved three-dimensional displacement maps. Harmonic modeling isolated periodic pulsation, and residual variability exceeding empirically derived uncertainty limits was conservatively interpreted as deformability. Associations with aneurysm growth and ELAPSS scores were analyzed using exploratory statistics. Results: Eleven UIAs in ten patients were followed for 4.3 ± 1.1 years. A longitudinal size change occurred in six aneurysms (54.5%). Baseline GVP was present in eight aneurysms (73%) and SWP in nine (82%). GVP was not associated with a size change (p = 1.00). All aneurysms with a size change exhibited baseline SWP, whereas no size change was observed in aneurysms without SWP; however, this association did not reach statistical significance in this small exploratory cohort (p = 0.18). Conservative variability metrics were not associated with growth but correlated with baseline shape irregularity, particularly the undulation index (Spearman’s ρ up to ~0.90). Conclusions: In this small exploratory pilot cohort, spatial wall pulsation showed a descriptive directional pattern with longitudinal aneurysm size changes, whereas global volumetric pulsation did not. These findings are preliminary, should be interpreted cautiously, and require confirmation in larger, adequately powered longitudinal studies before clinical application. Full article
(This article belongs to the Section Brain Tumor and Brain Injury)
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12 pages, 597 KB  
Article
CSF Amyloid and Tau Biomarkers Distinguish Mixed from Vascular Dementia by Identifying Alzheimer’s Disease Co-Pathology
by Zuzana André, Andrea Kopániová, Barbora Gaštanová, Petra Brandoburová, Veronika Režnáková, Martin Fabian, Pavol Povinec, Jozef Hanes and Karin Gmitterová
Medicina 2026, 62(5), 833; https://doi.org/10.3390/medicina62050833 (registering DOI) - 27 Apr 2026
Abstract
Background and Objectives: Vascular dementia (VaD) and mixed dementia (MD) represent prevalent causes of cognitive decline in the elderly, as they share similar pathological pathways and clinical features. Distinguishing between these two conditions remains a challenge, due to their frequent clinical and neuroimaging [...] Read more.
Background and Objectives: Vascular dementia (VaD) and mixed dementia (MD) represent prevalent causes of cognitive decline in the elderly, as they share similar pathological pathways and clinical features. Distinguishing between these two conditions remains a challenge, due to their frequent clinical and neuroimaging overlap. Nevertheless, it is important from a prognostic perspective. Materials and Methods: The study comprised 114 participants, including patients with VaD (n = 33), MD (n = 26), Alzheimer’s disease (AD; n = 26), and 29 cognitively healthy controls (C). We evaluated routinely used cerebrospinal fluid (CSF) biomarkers (total tau, p-tau181, Aβ1-42) and their ratios to assess inter-group differences, diagnostic accuracy, and correlations with cognitive score. Results: Patients with MD demonstrated significantly higher levels of t-tau and p-tau181, and lower levels of Aβ1-42, compared to VaD (p < 0.004 for all analyses). With the exception of p-tau181/t-tau, all calculated ratios enabled differentiation between these groups. ROC analysis confirmed the high diagnostic accuracy of CSF Aβ1-42 and t-tau (AUC 0.82 and 0.79 respectively) for detecting AD pathology in dementia patients. Furthermore, the t-tau/Aβ1-42, p-tau181/Aβ1-42 ratios were the most effective in differentiating AD-related from vascular pathologies (AUC 0.78 and 0.80 respectively), and in differentiating MD from VaD (AUC 0.79 and 0.77 respectively). A significant correlation was observed between CSF biomarkers (especially tau markers) and cognitive impairment severity. Conclusions: CSF biomarkers effectively differentiate mixed from vascular dementia by identifying underlying AD pathology independent of the clinical phenotype. This supports the use of CSF biomarkers in clinical practice to reveal the neurodegenerative component in patients with cerebrovascular disease, which is of fundamental importance for emerging disease-modifying treatment strategies in mixed neuropathologies. Full article
(This article belongs to the Section Neurology)
20 pages, 1483 KB  
Article
Beyond Binary Cutoffs: An Explainable Machine Learning Framework for Individualized Diagnostic Reasoning in Suspected Urolithiasis
by Kyungman Cha, Sang Hoon Oh, Jaekwang Shin and Jee Yong Lim
Diagnostics 2026, 16(9), 1313; https://doi.org/10.3390/diagnostics16091313 - 27 Apr 2026
Abstract
Background: Emergency department evaluation of suspected urolithiasis increasingly relies on non-contrast CT, yet not all patients require imaging. Existing clinical prediction rules help stratify stone probability, but by converting continuous measurements into fixed binary indicators, they offer little insight into why a [...] Read more.
Background: Emergency department evaluation of suspected urolithiasis increasingly relies on non-contrast CT, yet not all patients require imaging. Existing clinical prediction rules help stratify stone probability, but by converting continuous measurements into fixed binary indicators, they offer little insight into why a particular patient is at risk or how much uncertainty remains after each testing stage—questions that bear directly on individualized diagnostic decisions. Methods: We retrospectively analyzed 1000 ED patients with suspected urolithiasis who underwent non-contrast CT (stone prevalence 85.0%). A gradient boosting classifier was trained on 17 continuous clinical and laboratory features and compared against binary-thresholded counterparts and an established scoring system; the 17-feature model achieved AUC 0.771 (95% CI 0.726–0.813) versus 0.723 (95% CI 0.675–0.771) for the reference score on this cohort (DeLong p = 0.001). Individual predictions were explained using an interventional Shapley value approach, and a Shannon entropy-based framework was applied to quantify the marginal diagnostic contribution of each sequential testing stage. Results: Held-out permutation importance identified red blood cell count on microscopy, age, pain duration, and prior stone history as the most influential predictors. Several features showed non-linear contributions that diverged from conventional binary thresholds: creatinine effect crossed zero near 0.90 mg/dL and pain duration peaked between 2 and 5 h. C-reactive protein, absent from existing scoring systems, emerged as a meaningful negative predictor. Sequential entropy analysis showed that dipstick urinalysis provided the largest marginal information gain among non-history stages (6.1% of prior entropy), while physical examination contributed 2.3%. A prevalence sensitivity analysis projected that the framework’s threshold behavior would differ substantially in lower-prevalence populations, underscoring that the cohort-specific cut-points are not portable decision rules. We therefore position the framework as a reasoning aid that complements clinical judgment and imaging, not as a stand-alone triage tool. Conclusions: Explainable machine learning can address questions that aggregate discrimination metrics cannot: which features drive risk for a given patient, how those effects behave across the continuous measurement range, and how much diagnostic uncertainty each testing stage resolves. The Shapley-based explanations and entropy framework developed here offer a structured approach to individualized diagnostic reasoning in the ED evaluation of suspected urolithiasis, functioning as an interpretive adjunct to, rather than a replacement for, existing clinical tools and CT imaging. Full article
(This article belongs to the Special Issue Clinical Diagnosis and Management in Urology)
19 pages, 588 KB  
Review
Vagus Nerve Stimulation in Alzheimer’s Disease and Mild Cognitive Impairment: Current Evidence and Future Directions
by Ruth Narramore, Mudasar Aziz, Sheharyar Baig, Joyce S. Balami, Arshad Majid and Ali N. Ali
NeuroSci 2026, 7(3), 52; https://doi.org/10.3390/neurosci7030052 (registering DOI) - 27 Apr 2026
Abstract
Vagus nerve stimulation (VNS) may improve cognition and promote underlying brain health through various mechanisms including the noradrenaline and cholinergic pathways. Whilst early human studies used invasive devices (iVNS), recent decades have seen the emergence of non-invasive devices that stimulate the vagus nerve [...] Read more.
Vagus nerve stimulation (VNS) may improve cognition and promote underlying brain health through various mechanisms including the noradrenaline and cholinergic pathways. Whilst early human studies used invasive devices (iVNS), recent decades have seen the emergence of non-invasive devices that stimulate the vagus nerve transcutaneously (tVNS) via either the cervical branches in the neck (tcVNS) or the auricular branch in the ear (taVNS). With this increase in more accessible devices, tVNS is gaining interest as a novel therapy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This targeted review aims to understand the current evidence in human trials in this specific population. PubMed, Cochrane, EMBASE, MEDLINE, and Google Scholar were searched. Six human interventional studies were found (one iVNS; five taVNS). VNS is well tolerated and study designs demonstrate feasibility within this population for future blinded and appropriately powered long-term studies with participants applying tVNS at home. However, protocols and tVNS settings remain variable. Working memory domains such as verbal fluency and 3D processing show the most promise but global cognitive scores were also sensitive in some cases. The role of biomarkers of tVNS activity and its effect on AD markers and neuroinflammation should be considered in the design of future studies. Full article
(This article belongs to the Special Issue New Therapeutic Approaches in Neurological Conditions)
12 pages, 628 KB  
Article
The Impact of Maternal Dietary Avoidance During Breastfeeding on Physical Growth and Social–Emotional Development in Infants with Food Allergies: A Prospective Cohort Study
by Jun Fang, Rui’an Wang, Zhanzhan Zhang, Yuanfeng Zhong, Yannan Wan, Qian Chen, Xuelin Xia and Xuan Zhang
Children 2026, 13(5), 603; https://doi.org/10.3390/children13050603 (registering DOI) - 27 Apr 2026
Abstract
Background: Maternal dietary avoidance during breastfeeding of infants with food allergies (FA) is common, but its impact on growth and development is unclear. Methods: This prospective cohort study enrolled infants aged 4–6 months who were mainly breastfed from the child health care clinic [...] Read more.
Background: Maternal dietary avoidance during breastfeeding of infants with food allergies (FA) is common, but its impact on growth and development is unclear. Methods: This prospective cohort study enrolled infants aged 4–6 months who were mainly breastfed from the child health care clinic of Children’s Hospital of Chongqing Medical University, Chongqing, China. The participants were classified into a group with clinically diagnosed FA and a non-food allergies (NFA) group. To analyze avoidance extent, the FA group was stratified into high (≥5 types) and low (<5 types) avoidance subgroups based on the median number of avoided food categories. Outcomes included anthropometric Z-scores and ASQ:SE-2 social–emotional scores at 12 months, analyzed using Generalized Estimating Equations. Results: High avoidance mothers comprised 50% of the FA group. Compared to the high avoidance group, the non-FA group showed significantly better linear growth (β = 0.84, 95% CI 0.38–1.30, p < 0.001). Weight and head circumference showed no differences. High avoidance was associated with higher ASQ:SE-2 scores versus both the low avoidance and non-FA groups (p < 0.001), indicating greater social–emotional concerns. Conclusions: Extensive maternal dietary avoidance was associated with suboptimal linear growth and higher social–emotional risk scores in infants with FA, underscoring the need for integrated nutritional and developmental monitoring. These findings warrant cautious interpretation given the exploratory nature of this single-center study. Full article
(This article belongs to the Section Pediatric Neonatology)
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36 pages, 637 KB  
Article
Cognitive Grounding for Perspective Integration in Multi-LLM Systems
by Lev Sukherman, Yetunde Longe-Folajimi and Marina Konkol
Computers 2026, 15(5), 277; https://doi.org/10.3390/computers15050277 (registering DOI) - 27 Apr 2026
Abstract
This paper investigates whether structured collaboration between multiple large language models (LLMs), each assigned a distinct cognitive role grounded in psychological theory, produces benefits beyond simple answer aggregation. We propose the Parallel Synthesis architecture, in which three cognitively specialized roles Analyzer (hierarchical decomposition), [...] Read more.
This paper investigates whether structured collaboration between multiple large language models (LLMs), each assigned a distinct cognitive role grounded in psychological theory, produces benefits beyond simple answer aggregation. We propose the Parallel Synthesis architecture, in which three cognitively specialized roles Analyzer (hierarchical decomposition), Creative (divergent thinking), and Critic (critical evaluation) process each task independently and in parallel, and a Synthesizer integrates their outputs into a final response. To evaluate collaborative reasoning, we introduce the Emergent Reasoning Score (ERS), a composite metric that separates perspective integration (Synthesis Effectiveness) from novel concept generation (Emergent Value). Experiments on Experiments on the AI2 Reasoning Challenge (ARC-Challenge) (1172 questions) and and the Massive Multitask Language Understanding benchmark (MMLU) (1531 questions) show two consistent findings. First, the architecture achieves high Synthesis Effectiveness (SE=0.7110.744), indicating reliable integration of all three cognitive perspectives. Second, Emergent Value remains low (EV=0.0960.112), indicating that synthesis primarily recombines existing concepts rather than generating substantial novel content. A Majority Voting baseline achieves comparable or slightly higher answer accuracy than the Synthesizer on both benchmarks, showing that the architecture’s main contribution lies not in answer selection but in producing integrated reasoning traces that draw on multiple perspectives. These findings suggest that the practical value of cognitively grounded multi-agent architectures lies in reliable perspective integration, while ERS provides a reusable framework for distinguishing integration from genuinely novel reasoning in multi-agent LLM systems. The empirical results reported here constitute a pilot validation of the proposed framework on closed-form benchmarks, intended to establish a proof of concept and motivate larger-scale evaluation. Full article
18 pages, 721 KB  
Article
Relationships Between Sleep Quality, Perceived Stress, and Premenstrual Syndrome Among Medical and Nursing Students: A Cross-Sectional Study in Palestine
by Malak Abu Khashan, Shahd Aldarak, Marwa Zahdeh, Ayah Alawneh, Nada Abo Dyak, Shahd Qazae, Shahd Ghanem, Mohammad N. S. Al-Mohtaseb, Hadeel Ayesh, Abdallah Alwawi and Azzam Zrineh
Healthcare 2026, 14(9), 1168; https://doi.org/10.3390/healthcare14091168 - 27 Apr 2026
Abstract
Background: Premenstrual syndrome (PMS) significantly impacts daily functioning among women of reproductive age. Medical and nursing students face exceptional stressors that may exacerbate PMS, yet the interrelationships between sleep quality, perceived stress, and PMS remain understudied in Middle Eastern contexts. This study aimed [...] Read more.
Background: Premenstrual syndrome (PMS) significantly impacts daily functioning among women of reproductive age. Medical and nursing students face exceptional stressors that may exacerbate PMS, yet the interrelationships between sleep quality, perceived stress, and PMS remain understudied in Middle Eastern contexts. This study aimed to investigate the relationships between sleep quality, perceived stress, and self-reported PMS symptoms among Palestinian female medical and nursing students, to assess their prevalence and severity, and to examine variations across sociodemographic and lifestyle factors. Methods: This cross-sectional correlational study recruited 708 female medical and nursing students from three Palestinian universities. Validated Arabic instruments assessed sleep quality (PSQI), perceived stress (PSS-10), and PMS symptoms (A-PMSS). Analyses included Spearman’s correlations, non-parametric tests (Mann–Whitney U Test, Kruskal–Wallis Test), and multivariable linear regression. Results: Nearly all participants (98%) reported some degree of self-reported PMS symptoms at any severity level, with 76% experiencing moderate-to-severe symptoms. Poor sleep quality (PSQI > 5) affected 62.1%, while 94.5% reported moderate-to-high perceived stress. Significant positive correlations were identified between PSQI and PMS (rho = 0.295, p < 0.001) and between PSS-10 and PMS (rho = 0.483, p < 0.001). Multivariable regression revealed that perceived stress and sleep quality were significant independent predictors of PMS severity after adjusting for covariates, with the overall model explaining 27.5% of variance in PMS scores. Conclusions: This study reveals a substantial burden of PMS, poor sleep quality, and stress among Palestinian female medical and nursing students. Perceived stress and sleep quality were independently associated with PMS severity. These findings highlight need for integrated wellness programs in healthcare education for Palestinian students. Full article
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19 pages, 481 KB  
Article
Long-Term Outcome of Patients with a Floating Hip Injury of Müller Type A: An Analysis of Prognostic Factors Linked to Functional Outcomes
by Beytullah Unat, Cagrı Karabulut, Musa Alperen Bilgin, Ramazan Erol, Ilkan Kisi, Ibrahim Halil Rızvanoglu and Nevzat Gönder
J. Clin. Med. 2026, 15(9), 3321; https://doi.org/10.3390/jcm15093321 (registering DOI) - 27 Apr 2026
Abstract
Background/Objectives: A floating hip injury, defined as an ipsilateral fracture of the pelvis or acetabulum combined with a femoral fracture, represents a rare and devastating musculoskeletal injury resulting from high-energy trauma. Although Müller type A floating hip injuries comprising an acetabular fracture [...] Read more.
Background/Objectives: A floating hip injury, defined as an ipsilateral fracture of the pelvis or acetabulum combined with a femoral fracture, represents a rare and devastating musculoskeletal injury resulting from high-energy trauma. Although Müller type A floating hip injuries comprising an acetabular fracture with an ipsilateral femoral fracture are recognized for their clinical complexity, the long-term prognostic factors influencing functional outcomes remain poorly elucidated. This study aimed to identify independent prognostic factors associated with unsatisfactory long-term functional outcomes in patients with Müller type A floating hip injuries. Methods: A retrospective study was performed on 68 consecutive patients with Müller type A floating hip injuries who underwent surgical fixation at a single tertiary trauma center, with a minimum follow-up period of 5 years. Functional outcomes were assessed using the Majeed score, and patients were dichotomized into satisfactory (n = 48; 70.6%) and unsatisfactory (n = 20; 29.4%) outcome groups. Acetabular fractures were classified according to the Judet–Letournel system, and femoral fractures were classified by fracture level (proximal, shaft, or distal). Radiological outcomes were evaluated using Matta’s radiological grading system. Demographic, injury-specific, and treatment-related variables were compared between groups using the Mann–Whitney U test and chi-square test with Bonferroni correction. A multivariate binary logistic regression model was constructed to determine independent predictors of unsatisfactory outcomes. Results: The mean age was 37.15 ± 12.07 years, with a male predominance (67.6%). The predominant mechanism of injury was pedestrian struck by vehicle (54.4%), followed by motor vehicle collision (27.9%) and fall from height (17.6%); collectively, high-energy vehicular trauma accounted for 82.3% of cases. In the univariate analysis, transverse with posterior wall acetabular fracture pattern (p = 0.001), proximal femur fracture level (p = 0.001), associated lower extremity fractures (p = 0.001), nerve damage (p = 0.001), higher body mass index (BMI) (p = 0.001), and lower Matta’s radiological scores (p = 0.001) were significantly associated with unsatisfactory outcomes. Three independent predictors emerged in the multivariate logistic regression: BMI (OR = 1.50; 95% CI: 1.05–2.15; p = 0.025), the presence of associated lower extremity fractures (OR = 29.02; 95% CI: 2.83–297.67; p = 0.005), and Matta’s radiological score (OR = 0.06; 95% CI: 0.01–0.56; p = 0.014). The model yielded internal discriminatory metrics within the acceptable range (overall accuracy 89.7%, sensitivity 95.8%, specificity 75.0%, Nagelkerke R2 = 0.757); however, given the limited events-per-variable ratio (~6.7) and the wide confidence intervals observed for some predictors, these internal performance estimates are likely optimistic due to potential overfitting, and the findings should be interpreted as exploratory pending external validation. Conclusions: Elevated BMI, the presence of associated ipsilateral lower extremity fractures, and poor quality of acetabular reduction, assessed via Matta’s radiological criteria, are independent determinants of unsatisfactory long-term functional outcomes in Müller type A floating hip injuries. These findings underscore the critical importance of achieving anatomical reduction in the acetabulum and highlight the compounding effect of additional ipsilateral limb injuries on patient prognosis. Full article
(This article belongs to the Special Issue Acute Management and Surgical Strategies in Orthopedic Trauma)
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12 pages, 829 KB  
Article
Improvement in Antipsychotic-Related Sexual Dysfunction After Switching to Cariprazine: A Prospective Real-World Study
by Ángel L. Montejo, Juan C. Fiorini, Pedro Megía, Rubén Ochoa, Belén Arribas, Marc Peraire, Iván Echeverria, Eladio Aparicio and Llanyra García-Ullán
J. Clin. Med. 2026, 15(9), 3320; https://doi.org/10.3390/jcm15093320 (registering DOI) - 27 Apr 2026
Abstract
Background: Sexual dysfunction is a frequent adverse effect of antipsychotic treatment and a major contributor to poor adherence and reduced quality of life. Evidence regarding the impact of switching to prolactin-sparing antipsychotics in routine clinical practice remains limited. This study evaluated changes [...] Read more.
Background: Sexual dysfunction is a frequent adverse effect of antipsychotic treatment and a major contributor to poor adherence and reduced quality of life. Evidence regarding the impact of switching to prolactin-sparing antipsychotics in routine clinical practice remains limited. This study evaluated changes in sexual function following initiation or switch to cariprazine in real-world patients with schizophrenia spectrum disorders. Methods: In this prospective observational study, adult outpatients were either initiated on cariprazine de novo (Group A) or switched from a previous antipsychotic due to clinically significant sexual dysfunction (Group B). Sexual function was assessed using the Psychotropic-Related Sexual Dysfunction Questionnaire (SALSEX) at baseline and Month 3. Secondary measures included serum prolactin levels and Brief Psychiatric Rating Scale (BPRS) an CGI scores. Effect sizes were calculated using Cohen’s d. Results: Forty-two patients were included (Group A: n = 14; Group B: n = 28). In Group B, mean SALSEX total scores significantly decreased from 8.04 ± 2.76 to 2.41 ± 2.06 (Δ = −5.63; p < 0.001; d = 2.27). Prolactin levels also significantly decreased after switching (p = 0.012). In Group A, SALSEX scores showed a statistically significant but clinically modest reduction (2.79 ± 2.01 to 1.23 ± 1.24; p = 0.023; d = 0.93), with no evidence of treatment-emergent sexual dysfunction. Improvements in sexual function were not associated with changes either in BPRS or CGI scores, baseline symptom severity, sex, or testosterone levels. Conclusions: Switching to cariprazine in patients with antipsychotic-related sexual dysfunction was associated with large and clinically meaningful improvement in sexual function in routine practice. The effect appeared independent of overall symptom improvement and endocrine normalization thresholds, supporting the clinical value of prolactin-sparing switching strategies. Full article
(This article belongs to the Section Mental Health)
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24 pages, 5307 KB  
Article
Calibrating the Performance Assessment Mechanism in Virtual Laboratories with a Reinforcement Learning-Inspired Technique
by Vasilis Zafeiropoulos and Dimitris Kalles
Appl. Sci. 2026, 16(9), 4253; https://doi.org/10.3390/app16094253 (registering DOI) - 27 Apr 2026
Abstract
Science universities strive to offer efficient lab training to their students and at the same time secure their safety and minimize the damages to the lab equipment. Thus, the development of distance learning tools for students to be trained virtually and safely in [...] Read more.
Science universities strive to offer efficient lab training to their students and at the same time secure their safety and minimize the damages to the lab equipment. Thus, the development of distance learning tools for students to be trained virtually and safely in using the various lab instruments and performing experiments is necessary. Since the students are evaluated for their performance at the on-site labs, the assessment at the virtual labs is also needed and consequently, an embedded assessment mechanism for the evaluation of the user’s performance in the virtual lab is a necessary feature. For the assessment mechanism to be reliable and devoid of the designer’s bias, though, it may need calibration with Machine Learning. Hellenic Open University has developed its own virtual biology laboratory, Onlabs, which simulates its on-site one for its students to be trained and evaluated at. Considering the evaluation of the user’s performance in Onlabs, it is made with respect to particular experiments and is based on an embedded scoring algorithm. The latter is two-fold, measuring the extent to which the necessary steps have been made and the extent to which those steps were made in the correct order. Within the context of the experimental procedure of microscoping, the scoring algorithm has been recalibrated with the use of various Machine Learning techniques. In this paper, we propose the design of a Reinforcement Learning variant and recalibration of the scoring measure concerning the steps order. The results suggest that under specific parameters and Reinforcement Learning methods, a more efficient scoring mechanism may be achieved. Full article
(This article belongs to the Special Issue Reinforcement Learning for Real-World Applications)
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18 pages, 1186 KB  
Article
Systemic Immune Signatures of Endoscopic–Histologic Discordance in Inflammatory Bowel Disease: A Pilot Study
by Nikolaos Martinos, Christos Kroupis, Maria Gypari, Georgios Kranidiotis, Christos Karakoidas, Marina Konstantinou, Andreas C. Lazaris and Georgia-Eleni Thomopoulou
J. Clin. Med. 2026, 15(9), 3319; https://doi.org/10.3390/jcm15093319 (registering DOI) - 27 Apr 2026
Abstract
Background: Endoscopic remission is a central therapeutic target in inflammatory bowel disease (IBD); however, histologic inflammation may persist despite apparent mucosal healing. The biological mechanisms underlying endoscopic–histologic discordance remain incompletely defined. We aimed to characterize systemic cytokine patterns associated with discordant disease. Methods: [...] Read more.
Background: Endoscopic remission is a central therapeutic target in inflammatory bowel disease (IBD); however, histologic inflammation may persist despite apparent mucosal healing. The biological mechanisms underlying endoscopic–histologic discordance remain incompletely defined. We aimed to characterize systemic cytokine patterns associated with discordant disease. Methods: In this prospective cross-sectional study, 59 patients with IBD undergoing clinically indicated colonoscopy underwent concurrent endoscopic and histologic assessment. Endoscopic remission was defined as a Mayo endoscopic subscore ≤ 1 for ulcerative colitis and SES-CD ≤ 2 for Crohn’s disease. Histologic healing was defined as a Geboes score < 2.0. Patients were classified into concordant remission, discordant disease (endoscopic remission with persistent histologic activity), and concordant active disease. Circulating interleukin (IL)-10, IL-23, and C-reactive protein (CRP) levels were compared across phenotypes using nonparametric methods. Associations with discordant disease were evaluated using Firth penalized logistic regression, and model discrimination was assessed using receiver operating characteristic (ROC) analysis with bootstrap internal validation. Results: Among 36 patients in endoscopic remission, 14 (38.9%) exhibited persistent histologic activity. Discordant patients demonstrated significantly lower IL-10 and higher IL-23 concentrations compared with concordant remission (both p < 0.001), whereas CRP did not differ significantly. Across phenotypes, IL-10 decreased progressively, while IL-23 increased stepwise (both p < 0.001). In multivariable analysis, lower IL-10 (OR 0.0014; 95% CI 0.000003–0.576; p = 0.032) and higher IL-23 (OR 16.94; 95% CI 1.90–151.32; p = 0.011) were independently associated with discordant disease. A model incorporating IL-10 and CRP demonstrated strong discrimination (AUC 0.925), with further improvement after inclusion of IL-23 (AUC 0.994), although these estimates should be interpreted with caution given the limited sample size. Conclusions: Endoscopic–histologic discordance is associated with a distinct systemic cytokine profile characterized by reduced IL-10 and elevated IL-23 levels, despite low CRP concentrations. These findings suggest incomplete restoration of immune regulatory balance and highlight the potential role of circulating cytokines, particularly IL-10, in identifying ongoing microscopic inflammation. These results are exploratory and hypothesis-generating and require validation in larger, prospective cohorts before clinical application. Full article
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15 pages, 19143 KB  
Article
Revealing the Dynamic Association Between Lymphatic Endothelial Cell Markers and Intervertebral Disk Degeneration
by Qiang Zhang, Maoqiang Lin, Shishun Yan, Fei Huang and Haiyu Zhou
Biomedicines 2026, 14(5), 993; https://doi.org/10.3390/biomedicines14050993 (registering DOI) - 27 Apr 2026
Abstract
Objective: This study aims to analyze the dynamic changes in lymphatic endothelial cell (LEC) markers during the progression of intervertebral disk degeneration (IDD) and to investigate their association with the progression of IDD. Method: In this study, intervertebral disk (IVD) specimens were first [...] Read more.
Objective: This study aims to analyze the dynamic changes in lymphatic endothelial cell (LEC) markers during the progression of intervertebral disk degeneration (IDD) and to investigate their association with the progression of IDD. Method: In this study, intervertebral disk (IVD) specimens were first collected from patients who underwent open lumbar fusion surgery for spinal fractures (control group, n = 10) and lumbar disk herniation (IDD group, n = 10). Concurrently, a mouse IDD model was established, and IVD specimens were collected from mouse in the Sham group and the IDD group 1, 3, and 6 weeks after modeling (n = 5 per group at each time point). Pathological morphological changes in human and mouse IVD specimens were observed using Hematoxylin and Eosin (H&E) and Masson’s Trichrome staining. The degree of degeneration in the mouse IVD specimens was quantified using a histopathological scoring system. Subsequently, real-time quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), and immunofluorescence (IF) staining were employed to examine LEC markers in IVD tissue, including lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), podoplanin (PDPN), prospero homeobox protein 1 (PROX-1), and vascular endothelial growth factor receptor 3 (VEGFR-3), as well as matrix metabolism-related markers such as matrix metalloproteinase 13 (MMP-13) and collagen II (Col II). Finally, we performed Spearman’s rank correlation analysis between the histopathological scores of all mouse IVD specimens and the corresponding expression levels of LEC markers. Results: In human IVD tissue, expression levels of LYVE-1, PDPN, PROX-1, and VEGFR-3 were extremely low in the normal group. In contrast, expression of these markers was significantly upregulated in the IDD group. In the mouse IDD model, compared with the Sham group at the same time point, the IDD group exhibited higher histopathological scores in IVD tissue, accompanied by upregulation of LYVE-1, PDPN, PROX-1, and MMP-13, as well as downregulation of Col II. In-depth analysis revealed that these differences between the Sham and IDD groups were not static but exhibited a dynamic pattern of increasing magnitude over time. Concurrently, as the modeling period progressed, the histopathological scores of mouse IVD in the IDD group, as well as the expression levels of LYVE-1, PDPN, PROX-1, and MMP-13, showed a progressive upward trend, while Col II expression progressively decreased. In addition, Spearman’s rank correlation analysis revealed that the expression levels of LYVE-1, PDPN, and PROX-1 in mouse IVD tissue were all significantly positively correlated with histopathological scores. Conclusions: In the process of IDD, the dynamic upregulation of LEC markers is highly consistent with its severity in the time dimension. At the same time, there was also a significant positive correlation between the expression level of LEC markers and the severity of IDD. Taken together, these findings suggest that the dynamic upregulation of LEC markers may be potentially associated with the pathological progression of IDD. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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19 pages, 2161 KB  
Article
TLA-SleepNet: A Transformer–BiLSTM–Attention Network for Automatic Sleep Staging Using Single-Channel Ballistocardiogram Signals
by Jianfeng Wu, Banteng Liu and Ke Wang
Electronics 2026, 15(9), 1841; https://doi.org/10.3390/electronics15091841 (registering DOI) - 27 Apr 2026
Abstract
Traditional sleep staging studies typically rely on signals collected using contact-based sensors, which may interfere with the natural sleep state of subjects and thus affect the authenticity and reliability of the recorded data. To address this limitation, this study proposes an automatic sleep [...] Read more.
Traditional sleep staging studies typically rely on signals collected using contact-based sensors, which may interfere with the natural sleep state of subjects and thus affect the authenticity and reliability of the recorded data. To address this limitation, this study proposes an automatic sleep staging method based on non-contact single-channel ballistocardiogram (BCG) signals. First, band-pass filtering is applied to the raw BCG signals to separate the heart rate and respiratory components. Heart rate variability (HRV) and respiratory rate variability (RRV) features are then extracted, and mutual information is used to select key feature subsets that exhibit strong correlations with different sleep stages. Considering the complexity and prominent temporal characteristics of real-world sleep data, a temporal modeling network named TLA-SleepNet is constructed to enhance the model’s capability in capturing complex sequential features and improving robustness. Experiments conducted on 10 independent sleep recordings containing a total of 10,614 sleep epochs demonstrate that, under subject non-independent testing conditions with five-fold cross-validation, the proposed method achieves an accuracy of 87.1% in the sleep staging task, with precision, kappa coefficient, and F1-score reaching 92.4%, 81.9%, and 88.7%, respectively. The results indicate that the proposed method can achieve a reliable sleep staging performance without direct contact between sensors and the human body, providing a feasible solution for non-contact sleep monitoring in home-based and mobile healthcare applications. Full article
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22 pages, 3260 KB  
Article
Comparative Clinical Evaluation of Chamomile, Sage, and Ginger Mouthwashes in Reducing Plaque and Gingival Inflammation
by Ioana Elena Lile, Anda Olivia Jesamine Samoilă, Carolina Cojocariu, Gianina Tapalagă, Neli-Kinga Oláh, Otilia Lavinia Stana, Adelina Berari and Diana Marian
Antibiotics 2026, 15(5), 433; https://doi.org/10.3390/antibiotics15050433 (registering DOI) - 27 Apr 2026
Abstract
Background: Despite mechanical hygiene, plaque-related illnesses like gingivitis and periodontitis affect over 3.5 billion people globally. Natural mouthwashes are becoming increasingly popular as consumers shift toward plant-based alternatives to chlorhexidine, which may have drawbacks that limit long-term acceptability. This study aimed to evaluate [...] Read more.
Background: Despite mechanical hygiene, plaque-related illnesses like gingivitis and periodontitis affect over 3.5 billion people globally. Natural mouthwashes are becoming increasingly popular as consumers shift toward plant-based alternatives to chlorhexidine, which may have drawbacks that limit long-term acceptability. This study aimed to evaluate the short-term clinical potential of three herbal mouthwashes—Matricaria chamomilla (chamomile), Salvia officinalis (sage), and Zingiber officinale (ginger)—in reducing dental plaque and clinical signs of gingival inflammation in young adults. (2) Materials and Methods. A randomised controlled clinical trial was conducted on 175 systemically healthy participants, allocated equally into five groups (three herbal groups, placebo, and chlorhexidine). Each herbal group used a 2% aqueous infusion three times daily for twelve weeks. The 2% aqueous infusion concentration was selected based on commonly reported concentrations in previous phytotherapeutic and clinical studies evaluating herbal mouthwashes, balancing potential efficacy with safety and tolerability. The plant materials were sourced from certified suppliers, and standardized dried plant parts were used under controlled preparation conditions. Clinical assessments were performed at baseline (T0), week 1 (T1), week 5 (T2), and week 9 (T3), corresponding to the beginning of each evaluation interval within the 12-week study, using the Silness–Löe Plaque Index and the modified Löe–Silness Gingival Index. Data were analyzed using repeated-measures ANOVA with Bonferroni post hoc correction. (3) Results. Repeated-measures ANOVA revealed a significant main effect of time for both plaque accumulation and gingival index scores. For the Silness–Löe Plaque Index, a marked time-dependent reduction was observed across the active treatment groups (p < 0.001; η2p = 0.56), with a significant time × group interaction (p < 0.001; η2p = 0.49). Similarly, the modified Löe–Silness Gingival Index showed a significant reduction over time (p < 0.001; η2p = 0.22), with a significant interaction effect between time and mouthwash type (p < 0.001; η2p = 0.17). No statistically significant differences were found among the three herbal mouthwashes in post hoc Bonferroni comparisons (all p > 0.05), whereas all active treatments showed significantly better outcomes compared with the placebo. (4) Discussion. All three rinses showed similar clinical effects on plaque and gingival scores. However, without mechanistic assays, no claims can be made about comparable antibacterial or anti-inflammatory activity. Compared with conventional antiseptics such as chlorhexidine, herbal rinses offer important advantages in terms of biocompatibility, safety, and tolerability, with no staining, taste alteration, or mucosal irritation reported. At T3, the correlation between plaque and gingival indices was weak (Spearman’s ρ = 0.18, p = 0.09), suggesting limited linear association; this finding should be interpreted cautiously, as the low end-range values and limited variability of both indices at this time point may have masked a true association. This exploratory observation raises, but does not confirm, the possibility that factors other than plaque reduction may contribute to gingival improvement. (5) Conclusions. Significant reductions in dental plaque and clinical signs of gingival inflammation were observed following regular use of chamomile, sage, and ginger mouthwashes for twelve weeks. All herbal formulations exhibit similar clinical results. Longer-term controlled trials incorporating microbiological and phytochemical analyses are recommended to validate these findings further. Full article
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16 pages, 2063 KB  
Article
Comparison of Stromal Tumor-Infiltrating Lymphocyte (sTIL) Levels and Clinicopathological Features in Neoadjuvant-Naive HER2-Low and HER2-Negative Primary Breast Cancers
by Mümin Emiroğlu, Esra Canan Kelten Talu, Cem Karaali, Olçun Ümit Ünal and Mihriban Erdoğan
Medicina 2026, 62(5), 826; https://doi.org/10.3390/medicina62050826 (registering DOI) - 27 Apr 2026
Abstract
Background and Objective: The clinical success of novel antibody-drug conjugates has led to the identification of a new subgroup within traditionally HER2-negative breast cancers, termed ‘HER2-low.’ The aim of this study was to investigate the clinicopathological differences between HER2-low and HER2-negative groups [...] Read more.
Background and Objective: The clinical success of novel antibody-drug conjugates has led to the identification of a new subgroup within traditionally HER2-negative breast cancers, termed ‘HER2-low.’ The aim of this study was to investigate the clinicopathological differences between HER2-low and HER2-negative groups in neoadjuvant-naive primary breast cancer patients, with a specific focus on stromal tumor-infiltrating lymphocyte (sTIL) density. Materials and Methods: The study included 731 neoadjuvant-naive invasive breast cancer patients. Tumors were classified as HER2-negative (IHC 0) and HER2-low (IHC 1+ or 2+/ISH-negative). sTIL levels were evaluated following the International TILs Working Group guidelines. Results: The HER2-low group (38.7%) demonstrated significantly higher histological grade (p = 0.033) and higher sTIL density (p = 0.006) compared to the HER2-negative group. A stepwise increase in sTIL rates was observed parallel to the HER2 immunohistochemical score (0 → 1+ → 2+) (p = 0.015). The HER2-low/hormone receptor (HR)-negative subgroup exhibited the highest sTIL density (median 35%). No statistically significant difference in overall or disease-free survival was found between the groups. Conclusions: HER2-low breast cancers were associated with a more immunogenic tumor microenvironment compared to HER2-negative tumors. This robust immune infiltration may offset the higher histological grade observed in the HER2-low cohort, potentially explaining the comparable survival outcomes. These findings provide a biological rationale for exploring the synergy between novel antibody–drug conjugates and immune checkpoint inhibitors, particularly in the highly immunogenic HER2-low/HR-negative subgroup. Full article
(This article belongs to the Special Issue Future Trends in Breast Cancer Management)
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