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16 pages, 636 KB  
Article
Effects of Adapted Aquatic Exercise on Autism-Related Behaviors, Flexibility, and Handgrip Strength in Boys with Autism Spectrum Disorder: A Randomized Controlled Trial
by Çalık Veli Koçak, Murat Ergin, Can Koçak, Mehmet Savaş Nebol, Mustafa Kayıhan Erbaş, Umut Canlı and Monira I. Aldhahi
Healthcare 2026, 14(13), 1838; https://doi.org/10.3390/healthcare14131838 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impairments in social communication and the presence of restricted and repetitive behaviors, often accompanied by motor impairments. Previous research indicates that regular physical exercise may reduce autism-related behaviors and improve motor [...] Read more.
Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impairments in social communication and the presence of restricted and repetitive behaviors, often accompanied by motor impairments. Previous research indicates that regular physical exercise may reduce autism-related behaviors and improve motor competence. This study aimed to examine the effects of an adapted aquatic exercise program on autism-related behaviors, flexibility, and handgrip strength, key motor functions relevant to daily functioning. Methods: In this parallel-group randomized controlled trial, 35 boys with mild autism spectrum disorder (aged 8.4 ± 2.1 years) were enrolled. Participants were randomly assigned to an exercise group (n = 17) and a control group (n = 18). The exercise group completed a 16-week adapted aquatic exercise program (2 sessions/week, 50 min/session), while the control group received usual education only. The primary outcome was autism-related behaviors assessed by the Autism Behavior Checklist (ABC); secondary outcomes included flexibility and handgrip strength. Results: The exercise group showed significant improvements in Autism Behavior Checklist (ABC) scores, flexibility, and handgrip strength compared with the control group (p < 0.05). Large effect sizes were observed across all outcomes (partial eta squared, ηp2 > 0.14). These findings indicate that adapted aquatic exercise confers beneficial effects on behavioral and motor outcomes in children with mild ASD. Conclusions: Regular participation in adapted aquatic exercise reduces autism-related behaviors and improves flexibility and handgrip strength. These findings provide empirical support for the inclusion of aquatic exercise in intervention programs targeting children with ASD and may inform future research and practice. Full article
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15 pages, 692 KB  
Article
Prognostic Value of BUN-Based Ratios for Mortality and Prolonged Hospitalization in Acute Upper Gastrointestinal Bleeding: Comparison with Established Risk Scores
by Bayram İnan, Çağdaş Erdoğan, Emir Tuğrul Keskin, Yavuz Özden, Hulusi Can Karpuzcu, İhsan Ateş and Zeki Mesut Yalın Kılıç
Medicina 2026, 62(6), 1210; https://doi.org/10.3390/medicina62061210 (registering DOI) - 22 Jun 2026
Viewed by 68
Abstract
Background and Objectives: This study investigated the prognostic value of two simple blood urea nitrogen (BUN)-based ratios, BUN/hemoglobin (Hb) and BUN/Albumin, for predicting in-hospital mortality and prolonged hospitalization in patients with acute upper gastrointestinal bleeding (UGIB). Their performance was compared with established [...] Read more.
Background and Objectives: This study investigated the prognostic value of two simple blood urea nitrogen (BUN)-based ratios, BUN/hemoglobin (Hb) and BUN/Albumin, for predicting in-hospital mortality and prolonged hospitalization in patients with acute upper gastrointestinal bleeding (UGIB). Their performance was compared with established risk scores, including the Glasgow–Blatchford score (GBS), AIMS-65, ABC and Rockall scores. Materials and Methods: This retrospective cohort study included 486 patients evaluated for acute UGIB between March 2023 and February 2026. The diagnostic performance of BUN/Hb and BUN/Albumin ratios was assessed using receiver operating characteristic (ROC) analysis and compared with established risk scores. Associations with clinical outcomes were evaluated using logistic regression analyses. Results: The median age was 67 years, and 292 patients (60.1%) were male. In-hospital mortality occurred in 17 patients (3.5%), while prolonged hospitalization was observed in 207 patients (42.6%). AIMS-65 showed the highest Area Under the Curve (AUC) for mortality prediction (0.799; 95% CI 0.696–0.902), followed by the ABC score (0.731) and the BUN/Albumin ratio (0.711). For prolonged hospitalization, BUN/Hb showed the highest AUC (0.706; 95% CI 0.660–0.752), although differences from established scores were not statistically significant. In multivariable analysis, BUN/Albumin remained associated with mortality, whereas BUN/Hb did not reach statistical significance for prolonged hospitalization. However, mortality-related findings should be interpreted with caution because only 17 in-hospital deaths occurred in the study cohort. Conclusions: Simple BUN-based ratios may provide complementary prognostic information in acute UGIB. BUN/Albumin was associated with in-hospital mortality and showed modest discriminatory ability, but it did not demonstrate statistically significant superiority over established risk scores. BUN/Hb showed the numerically best discrimination for prolonged hospitalization, but without statistically significant superiority or persistent significance in multivariable analysis. Overall, these ratios may serve as supportive tools for early risk assessment rather than replacements for established risk scoring systems. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
20 pages, 6003 KB  
Review
Incidental Findings in [18F]-PSMA PET/CT for Prostate Cancer: Structured Reporting Across PET and Low-Dose CT, Clinical Relevance, and Cascade-Aware Management
by Katarzyna Sklinda, Marek Kasprowicz, Michał Małek, Bartlomiej Olczak, Tadeusz Budlewski, Malgorzata Kobylecka, Jerzy Walecki and Martyna Rajca
Uro 2026, 6(2), 17; https://doi.org/10.3390/uro6020017 - 17 Jun 2026
Viewed by 137
Abstract
[18F]-PSMA PET/CT is a high-impact modality for the staging and restaging of prostate cancer, but its wide anatomic coverage and tracer biology generate frequent incidental findings on both PET and the accompanying low-dose CT (LDCT). This narrative review is restricted in [...] Read more.
[18F]-PSMA PET/CT is a high-impact modality for the staging and restaging of prostate cancer, but its wide anatomic coverage and tracer biology generate frequent incidental findings on both PET and the accompanying low-dose CT (LDCT). This narrative review is restricted in scope to fluorine-18 PSMA tracers because tracer-specific biodistribution and pitfall profiles shape what is perceived as incidentaloma: how confidently lesions can be categorized, and how often borderline findings trigger downstream testing, particularly for skeletal foci with [18F]-PSMA-1007. Specifically, [18F]-PSMA-1007 shows substantially higher rates of focal unspecific bone uptake than [68Ga]-PSMA-11—reported in multicenter studies as affecting up to 40–50% of patients—which directly inflates the pool of potential incidentalomas and creates a tracer-specific false-positive problem with no parallel in gallium-68 practice. Additionally, [18F]-DCFPyL has different urinary clearance kinetics that affect bladder and ureteral uptake patterns, altering what qualifies as physiologic versus incidental in the pelvis. These differences mean that the threshold for Category B versus C classification—and the appropriate cascade-resistant language—must be tuned to the specific tracer in use. A framework built on [68Ga]-PSMA-11 data would systematically underestimate bone pitfall frequency in [18F]-PSMA-1007 practice and could therefore paradoxically increase rather than reduce cascades if applied uncritically across tracers. These biodistribution differences have direct and concrete consequences for reporting behaviour and downstream management. In [18F]-PSMA-1007 practice, a focal bone uptake without a CT correlate in a mechanically plausible location—such as an anterior rib or vertebral endplate—should trigger Category B language in the report conclusion: the finding is documented in the body with explicit safety netting (“most consistent with unspecific uptake; no routine workup unless interval growth, new pain, or aggressive CT morphology”), and no referral to bone scintigraphy or MRI is generated. Without tracer-specific awareness, the same finding would typically prompt a reflex bone scan or whole-body MRI referral, delaying definitive prostate cancer management by weeks and adding imaging costs without diagnostic gain. By contrast, in [68Ga]-PSMA-11 practice, an equivalent focal bone uptake without a CT correlate carries a higher prior probability of true metastatic disease given the lower background rate of unspecific uptake and should more often be reported at Category B with a lower threshold for escalation or more cautious language. For [18F]-DCFPyL, the higher urinary activity in the pelvis means that ureteral segments can mimic lymph node disease; recognizing this as a physiologic variant (Category C) rather than an equivocal nodal finding (Category B) avoids unnecessary pelvic MRI referrals that would otherwise be triggered by an uncontextualized report. In practical terms, the tracer-specific calibration of the overlay therefore changes not only the category assigned but also the specific safety-netting language and the escalation trigger, which directly modifies the downstream management pathway for each affected finding type. The scanned population—predominantly older men with a high prevalence of degenerative, inflammatory, and vascular abnormalities—creates substantial background noise that can drive low-value diagnostic cascades if incidental findings are communicated without actionability context. We integrate society-endorsed frameworks (EANM/SNMMI procedure guideline 2.0; E-PSMA; PSMA-RADS; and PROMISE/miTNM with miPSMA score) and propose a cascade-aware overlay for incidental findings that can be appended to existing PSMA reporting standards rather than replacing them. The A/B/C actionability overlay is a structured expert-consensus framework informed by existing evidence-based guidelines for specific finding types and by tracer-specific cohort data; it has not yet been prospectively validated as a standalone tool, and its current level of evidence is therefore analogous to a structured expert recommendation rather than an evidence-based clinical guideline. We operationalize a three-tier actionability scheme across PET- and CT-dominant findings, provide cascade-resistant language for conclusions, and clarify why SUVmax-only “probability scales” for lymph nodes are not recommended in routine reports. Three practical tables summarize PET incidental findings, lymph node reporting frameworks, and LDCT incidental findings, and two structured report templates are provided (concise and extended), with the extended version explicitly labelling actionability tiers and escalation triggers. Finally, we outline concrete AI use cases for standardization and triage while emphasizing governance to avoid the amplification of false positives and paradoxical growth of cascades. Full article
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19 pages, 9536 KB  
Article
Membrane Access and Orbital Localization Govern ABC Transporter Substrate Recognition
by Saad Harrizi, Imane Nait Irahal, Kaouthar El Birgui and Mostafa Kabine
Molecules 2026, 31(12), 2084; https://doi.org/10.3390/molecules31122084 - 13 Jun 2026
Viewed by 243
Abstract
The ATP-binding cassette transport protein Pdr5p is known to play a role in multidrug resistance in Saccharomyces cerevisiae by effluxing structurally diverse xenobiotics; yet the physicochemical determinants of substrate recognition remain poorly defined. To address this, density functional theory (DFT) calculations at the [...] Read more.
The ATP-binding cassette transport protein Pdr5p is known to play a role in multidrug resistance in Saccharomyces cerevisiae by effluxing structurally diverse xenobiotics; yet the physicochemical determinants of substrate recognition remain poorly defined. To address this, density functional theory (DFT) calculations at the B3LYP-D3BJ/def2-SVP level were combined with machine learning to derive a predictive model of substrate recognition using a curated dataset of 66 compounds spanning 9 functional categories. A hybrid support vector machine (SVM) classifier achieved 96.3% accuracy (95% CI: 81.0–99.9%, Clopper–Pearson exact) in discriminating substrates from non-substrates under leave-one-out cross-validation. Feature importance analysis identified lipophilicity (LogP, F-score = 37.5) as the dominant descriptor, suggesting that membrane partitioning constitutes the initial recognition step. The HOMO–LUMO gap contributed secondarily (F-score = 12.4). Substrates were further distinguished by high frontier orbital focalization, with frontier orbital spread of 1.8–2.6%, compared to 4.18–7.22% for non-substrates. Notably, a model trained exclusively on Pdr5p data achieved 87% prediction accuracy when applied without retraining to the human P-glycoprotein (ABCB1) dataset, suggesting conserved physicochemical principles of substrate recognition across evolutionarily distant ABC transporters. These findings provide a quantum chemical framework for understanding and potentially predicting MDR transporter substrate specificity. Full article
(This article belongs to the Section Computational and Theoretical Chemistry)
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16 pages, 2249 KB  
Article
Longitudinal Adaptive Functioning Outcomes in Children with Autism Spectrum Disorder During a 180 Day Open-Label Extension of K11-Tmax, a Consortium Probiotic Mix with Multivitamins
by Deivis O. Guimaraes, Racire S. Silva, Lara A. Ferreira, Larissa Martinelli, Rebeca M. M. Werly, Raphaela F. Amorim, Lívia B. S. S. Holzbach, Roberto Badaró, Alex A. B. Santos, Elisardo C. Vasquez and Sarha A. L. de Queiroz
Life 2026, 16(6), 940; https://doi.org/10.3390/life16060940 - 2 Jun 2026
Viewed by 339
Abstract
Autism spectrum disorder (ASD) is frequently associated with gastrointestinal symptoms, immune dysregulation, and altered microbiota-related signaling, supporting interest in microbiota-targeted interventions. This study evaluated adaptive functioning for over 180 days in children with ASD in a previously randomized controlled trial (RCT). After the [...] Read more.
Autism spectrum disorder (ASD) is frequently associated with gastrointestinal symptoms, immune dysregulation, and altered microbiota-related signaling, supporting interest in microbiota-targeted interventions. This study evaluated adaptive functioning for over 180 days in children with ASD in a previously randomized controlled trial (RCT). After the initial 90-day blinded phase, the study continued as an open-label extension (OLE) in which all participants received K11 TMAX, a kefir-derived probiotic consortium combined with a microencapsulated micronutrient blend. The study included 130 children (3–11 years of age) who continued from the RCT were followed-up in three different trajectories: (1) placebo → K11-TMAX; (2) K11 → K11-TMAX; and (3) continued K11-TMAX supplementation. Children’s adaptive functioning was assessed by the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3), Adaptive Behavior Composite (ABC) as well as by four core domains: (1) communication; (2) daily living skills; (3) socialization; and (4) motor skills. All three groups of children improved significantly on all of the parameters that were assessed with the effect sizes ranging from 0.13 to 0.43. The greatest improvement in the communication domain was seen in the transition group (1) and the greatest decrease in the externalizing behavior scores were seen in the continuous group (3) of children. Children’s adaptive functioning improved in clinically meaningful ways. Children’s improvement, however, was within the disability range and did not reach the level of typical development of children of the same age. These findings suggest supplementary therapeutic use of K11-TMAX, modulating the gut–brain axis, in children with autism spectrum disorder (ASD). Full article
(This article belongs to the Section Microbiology)
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19 pages, 1732 KB  
Article
Selective Hematological Profiles in Drug-Naïve Early Autism: Clinical and Developmental Correlates
by Dilek Altun Varmış, Cumali Yüksekkaya, Hülya Binokay, Serkan Güneş, Elif Gözde Yüce Antepüzümü, Yunus Kıllı, Nazmiye İnce and Hamide Kübra Özlük
Biomedicines 2026, 14(6), 1237; https://doi.org/10.3390/biomedicines14061237 - 29 May 2026
Viewed by 236
Abstract
Background/Objectives: Peripheral biomarkers for autism spectrum disorder (ASD) have shown mixed results in previous studies. In this study, complete blood count-derived immune-inflammatory markers, iron and micronutrient levels, and thyroid function were compared between drug-naïve preschoolers newly diagnosed with ASD and healthy controls. [...] Read more.
Background/Objectives: Peripheral biomarkers for autism spectrum disorder (ASD) have shown mixed results in previous studies. In this study, complete blood count-derived immune-inflammatory markers, iron and micronutrient levels, and thyroid function were compared between drug-naïve preschoolers newly diagnosed with ASD and healthy controls. Additionally, the relationships between these markers, symptom severity, and developmental skills were examined. Methods: This retrospective case–control study included 62 children with ASD (aged 24–72 months) and 61 age-matched healthy controls. Symptom severity, behavioral traits, and developmental status were assessed using the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), and Denver II Developmental Screening Test (DDST), respectively. Composite inflammatory indices were calculated from hemogram data. Statistical analyses incorporated Holm–Bonferroni corrections for multiple comparisons and sex-stratified exploratory analyses of conditional associations using 95% bootstrap confidence intervals based on 5000 resamples. Results: Children with ASD demonstrated significantly lower mean corpuscular volume (MCV; d = 0.66, adj. p = 0.019), lower mean platelet volume (MPV; d = 0.58, adj. p = 0.034), and higher absolute lymphocyte counts (LYMPH; d = 1.10, adj. p = 0.019). Initial group differences in ferritin, serum iron, and transferrin saturation did not survive adjustment (adj. p > 0.05). Composite inflammatory indices were not significantly associated with clinical or developmental scores. Higher CARS and ABC scores correlated with lower personal–social and language scores on the DDST (p < 0.01). Furthermore, exploratory sex-stratified, conditional association analyses suggested preliminary basophil- and lymphocyte-related patterns in girls; however, these findings are strictly hypothesis-generating due to the small female sample size (n = 12). Conclusions: Newly diagnosed, drug-naïve preschoolers with ASD showed a distinct baseline blood profile, including lower MCV and MPV and higher lymphocyte counts. Clinical challenges were most evident in personal–social and language domains. While the primary diagnostic value of routine hemograms in this context appears limited, the exploratory sex-stratified basophil- and lymphocyte-related patterns require validation in adequately powered future cohorts. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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26 pages, 13790 KB  
Article
Reading Between the ABCs: Intrinsic Disorder and Evolutionary Dynamics of Non-Canonical Regions in ABC Transporters
by Ichda Arini Dinana, Yukihiko Kubota and Masahiro Ito
Int. J. Mol. Sci. 2026, 27(11), 4699; https://doi.org/10.3390/ijms27114699 - 23 May 2026
Viewed by 223
Abstract
ATP-binding cassette (ABC) transporters are one of the largest superfamilies of membrane proteins, but little is known about the structural and evolutionary features of their non-domain regions. To clarify the diversity of these non-canonical regions across evolutionary lineages, we performed an analysis of [...] Read more.
ATP-binding cassette (ABC) transporters are one of the largest superfamilies of membrane proteins, but little is known about the structural and evolutionary features of their non-domain regions. To clarify the diversity of these non-canonical regions across evolutionary lineages, we performed an analysis of intrinsically disordered regions, site-specific selection and predicted post-translational modification (PTM) sites among five architectural classes involving 1581 prokaryotic and eukaryotic sequences. Linker and flanking regions were more disordered than transmembrane and nucleotide-binding domains in all architectures. Disorder fraction was significantly different between region types after phylogenetic correction (Pagel’s λ ≈ 0.97). Predicted PTM sites are enriched in disordered non-domain segments, with N-linked glycosylation and phosphoserine showing the strongest positive enrichment. A total of 140 sites satisfied a tiered conservation criterion (MusiteDeep score ≥ 0.5; cross-species conservancy ≥ 30%), including 40 high-confidence or moderate-confidence sites (conservancy ≥ 50%) as well as novel phosphotyrosine candidates in half transporters and NBD-only proteins. Site-specific selection analyses showed pervasive purifying selection across domain cores and architecture-dependent enrichment of episodic positive selection in non-domain regions, with significant non-domain enrichment in full reverse and half forward transporters (Fisher’s exact, BH-adjusted p < 0.05). In summary, these findings establish that non-canonical regions of ABC transporters are evolutionarily dynamic and contain conserved predicted modification sites, supporting the idea that these regions are evolutionary dynamic segments that deserve experimental characterization as candidate regulatory interfaces. Full article
(This article belongs to the Special Issue New Insights in Translational Bioinformatics: 3rd Edition)
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16 pages, 876 KB  
Article
Adaptive Behavior Change in Autism: Outcomes from a Comprehensive, Interdisciplinary Clinical Care Cohort
by Kelly Olvany, Annie Aitken, Elysa J. Marco, Neil Hattangadi and Kevin A. Shapiro
J. Pers. Med. 2026, 16(5), 242; https://doi.org/10.3390/jpm16050242 - 30 Apr 2026
Viewed by 831
Abstract
Purpose: The purpose of this study was to examine the effects of a medically centered, interdisciplinary treatment model on adaptive behavior in children with Autism Spectrum Disorder (ASD). The Cortica model involves a comprehensive program including behavioral and developmental therapies, overseen by a [...] Read more.
Purpose: The purpose of this study was to examine the effects of a medically centered, interdisciplinary treatment model on adaptive behavior in children with Autism Spectrum Disorder (ASD). The Cortica model involves a comprehensive program including behavioral and developmental therapies, overseen by a neurodevelopmental physician. Here, we investigated how adaptive behaviors change over time during care at Cortica. Methods: We analyzed changes in the Vineland Adaptive Behavior Scales over the course of Cortica care compared to a community sample comprising longitudinal data from the National Database for Autism Research (NDAR). Results: Using propensity score weights to match cohorts based on baseline functioning, multilevel growth curve models showed significant Cohort × Time interactions for the Adaptive Behavior Composite (ABC) score and all subscale scores, indicating increased growth in adaptive behavior skills for children in the Cortica cohort relative to NDAR. Conclusions: Results of this study highlight the importance of using adaptive behaviors as a primary outcome in clinical research studies and suggest that a personalized, multidisciplinary approach to intervention can result in improved adaptive behavior skills over time. Full article
(This article belongs to the Special Issue Mental Health: Clinical Advances in Personalized Medicine)
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18 pages, 1165 KB  
Article
Characteristics, Risk Stratification, and Outcomes of Upper Gastrointestinal Bleeding in Patients Receiving Antithrombotic Therapy
by Ragaey Ahmad Eid, Michael Nady Naguib, Amr Ahmed Abd El Bary, Mohamed Medhat Mohamed Zaki, Marwa O. Elgendy, Anwar M. Alnakhli, Mohammed Gamal and Mohamed Mohamed Tawfik
Biomedicines 2026, 14(4), 935; https://doi.org/10.3390/biomedicines14040935 - 20 Apr 2026
Viewed by 561
Abstract
Background/Objectives: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a major clinical emergency, particularly among patients receiving antiplatelet or anticoagulant therapy, whose use has increased substantially in recent years. This study aimed to evaluate the clinical characteristics, endoscopic findings, risk stratification, and [...] Read more.
Background/Objectives: Non-variceal upper gastrointestinal bleeding (NVUGIB) remains a major clinical emergency, particularly among patients receiving antiplatelet or anticoagulant therapy, whose use has increased substantially in recent years. This study aimed to evaluate the clinical characteristics, endoscopic findings, risk stratification, and outcomes of NVUGIB in patients receiving antithrombotic therapy, and to compare the predictive performance of commonly used prognostic scores. Methods: This prospective cohort study included 89 patients receiving antithrombotic therapy who presented with NVUGIB at Beni-Suef University Hospitals between March 2023 and March 2025. Clinical presentation, laboratory findings, and endoscopic characteristics were recorded. Risk stratification was assessed using Glasgow–Blatchford (GBS), Rockall, Baylor, AIMS65, ABC, and PNED scores. The optimal cut-off values for prediction of rebleeding and mortality were determined using receiver operating characteristic (ROC) analysis and the Youden index. Area under the curve (AUC) values were reported with 95% confidence intervals. Results: Endoscopy revealed that peptic ulcers were the most common lesion (41/89, 46%), followed by erosive disease (27/89, 30%), with the stomach being the most frequently involved site (76.5%). Rebleeding occurred in 16 patients (18.0%), while mortality was observed in 2 patients (2.2%). The Glasgow–Blatchford score demonstrated the most consistent performance for predicting rebleeding, with an optimal cutoff value of 5.5 (derived using the Youden index), yielding 92.9% sensitivity and 78.8% specificity. For mortality prediction, AIMS65, ABC, and PNED scores showed very high AUC values, although these findings should be interpreted cautiously due to the small number of mortality events (n = 2). No statistically significant difference in rebleeding or mortality was observed between single and dual antithrombotic therapy, although patients receiving dual therapy required longer hospitalization and more transfusion units. Conclusions: In patients with antithrombotic-related GI bleeding, ulcers and erosions predominate, with minimal differences between single and dual therapy outcomes. Concomitant NSAID use trends toward higher mortality. Glasgow–Blatchford score offers optimal performance for both rebleeding and mortality prediction, with a cutoff of 5.5 providing excellent sensitivity (92.9%) and specificity (78.8%) for rebleeding risk assessment. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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24 pages, 2502 KB  
Article
Repurposing Coronary Risk Scores to Identify Increased Likelihood of Atrial Fibrillation in Chronic Coronary Syndrome
by Alexandru-Florinel Oancea, Mathilde Leonard, Paula Cristina Morariu, Maria Godun, Alexandru Jigoranu, Ionela-Larisa Miftode, Radu Stefan Miftode, Aurelia Mihaela Nica, Alexandra Rotaru, Paul Simion, Ana Maria Buburuz, Diana-Elena Floria, Raluca Mitea, Cristina Gena Dascalu, Elena Cojocaru, Antoniu Octavian Petriș, Irina-Iuliana Costache-Enache and Mariana Floria
Med. Sci. 2026, 14(2), 161; https://doi.org/10.3390/medsci14020161 - 24 Mar 2026
Viewed by 720
Abstract
Atrial fibrillation (AF) frequently coexists with chronic coronary syndrome (CCS), reflecting shared cardiovascular risk factors and structural remodeling pathways. Identifying CCS patients at increased likelihood of AF remains clinically relevant, particularly when arrhythmia is silent or paroxysmal. Background: We hypothesized that established clinical [...] Read more.
Atrial fibrillation (AF) frequently coexists with chronic coronary syndrome (CCS), reflecting shared cardiovascular risk factors and structural remodeling pathways. Identifying CCS patients at increased likelihood of AF remains clinically relevant, particularly when arrhythmia is silent or paroxysmal. Background: We hypothesized that established clinical and angiographic risk scores used in CCS may capture cumulative cardiovascular burden and could therefore assist in AF risk stratification. The biomarker-based ABC-stroke score was incorporated as a biological reference framework reflecting myocardial stress and injury. Methods: This prospective, single-center proof-of-concept study included 131 consecutive patients undergoing invasive coronary angiography for suspected myocardial ischemia. Patients were classified according to rhythm status, irrespective of AF subtype. Coronary artery disease severity was quantified using the Gensini and SYNTAX (PCI and CABG) scores. Global cardiovascular risk was assessed using Framingham, ASCVD, SCORE2, and SCORE2-OP. Correlation analyses, ROC curves, and multivariable logistic regression were performed to evaluate associations between risk scores, coronary complexity, and AF. Results: Clinical and angiographic risk scores differed significantly according to rhythm status and AF phenotype. Patients with AF exhibited higher global cardiovascular risk and greater coronary anatomical complexity compared with those in sinus rhythm. SYNTAX PCI and SYNTAX CABG demonstrated moderate discriminative performance for AF detection (AUC 0.745 and 0.760, respectively), with SYNTAX CABG remaining independently associated with AF in multivariable analysis. Significant correlations were observed between traditional cardiovascular risk scores and SYNTAX-derived measures of coronary complexity, whereas correlations with the Gensini score were weaker. The ABC-stroke reference model showed a strong discriminative signal, consistent with its biological proximity to AF-related myocardial stress. Conclusions: Established clinical and angiographic risk scores used in CCS are associated with the presence and phenotype of AF. These findings suggest that routinely available coronary risk assessment tools may serve as practical instruments for identifying CCS patients at increased likelihood of AF, potentially facilitating targeted rhythm screening and earlier risk stratification. Full article
(This article belongs to the Section Cardiovascular Disease)
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15 pages, 1105 KB  
Article
Systemic Inflammation Response Index (SIRI) and Aggregate Index of Systemic Inflammation (AISI) as Predictors of Mortality in Patients with Upper Gastrointestinal Bleeding
by Çağdaş Erdoğan, Bayram İnan, İhsan Ateş and Zeki Mesut Yalın Kılıç
J. Clin. Med. 2026, 15(6), 2245; https://doi.org/10.3390/jcm15062245 - 16 Mar 2026
Cited by 1 | Viewed by 683
Abstract
Background/Objectives: Systemic inflammatory markers have recently gained attention as prognostic indicators in various acute conditions. However, their predictive value in non-variceal upper gastrointestinal bleeding (UGIB) remains uncertain. This study aimed to evaluate the prognostic performance of the Systemic Inflammation Response Index (SIRI) [...] Read more.
Background/Objectives: Systemic inflammatory markers have recently gained attention as prognostic indicators in various acute conditions. However, their predictive value in non-variceal upper gastrointestinal bleeding (UGIB) remains uncertain. This study aimed to evaluate the prognostic performance of the Systemic Inflammation Response Index (SIRI) and the Aggregate Index of Systemic Inflammation (AISI) for in-hospital mortality among patients with non-variceal UGIB and to compare them with established clinical scoring systems. Methods: This retrospective cohort study included 531 adult patients admitted with non-variceal UGIB between April 2023 and February 2025. Demographic, clinical, and laboratory data were collected at presentation. Inflammatory indices (SIRI, AISI, AISI/Hb) and established risk scores (Glasgow-Blatchford, Rockall, AIMS-65, and ABC) were calculated. The primary outcome was all-cause in-hospital mortality. Discriminatory ability was assessed using receiver operating characteristic (ROC) curve analysis, and independent predictors were identified by multivariable logistic regression. Results: The overall in-hospital mortality rate was 4.7% (25/531). Non-survivors were older and had lower systolic blood pressure, higher serum urea, and elevated inflammatory indices. Among biomarkers, SIRI (AUC = 0.773, 95% CI: 0.737–0.809) and AISI (AUC = 0.709, 95% CI: 0.670–0.747) showed good discriminatory ability, comparable to AIMS-65 (AUC = 0.765) and ABC (AUC = 0.786). In multivariable models, SIRI (OR = 1.10, p = 0.011) and AISI (OR = 1.04 per 100 units, p = 0.003) remained independent predictors of mortality after adjustment for age, systolic blood pressure, hemoglobin, serum urea, and albumin. Conclusions: SIRI and AISI are independent predictors of in-hospital mortality in patients with non-variceal UGIB, demonstrating comparable prognostic performance to conventional risk scores. These readily available inflammatory indices may serve as simple and cost-effective adjuncts for early risk stratification in clinical practice. Full article
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21 pages, 4298 KB  
Article
Upregulated ZBP1 Is Associated with B-Cell Dysregulation in Systemic Lupus Erythematosus
by Yiying Yang, Ke Liu, Hao Ma, Litao Lu, Ganqian Zhu, Xiaoxia Zuo, Huali Zhang, Yaxi Zhu and Muyao Guo
Biomedicines 2026, 14(2), 451; https://doi.org/10.3390/biomedicines14020451 - 17 Feb 2026
Viewed by 1116
Abstract
Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperactivation and excessive autoantibody production. Z-DNA binding protein 1 (ZBP1), an innate immune sensor involved in nucleic acid recognition and cell death signaling, has been implicated in antiviral and inflammatory responses. [...] Read more.
Background/Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperactivation and excessive autoantibody production. Z-DNA binding protein 1 (ZBP1), an innate immune sensor involved in nucleic acid recognition and cell death signaling, has been implicated in antiviral and inflammatory responses. However, its role in B-cell dysregulation during SLE remains unclear. Methods: Integrative transcriptomic analyses were performed using public datasets (GSE61635, GSE235658, GSE136035, and GSE163497) to determine the expression pattern and biological functions of ZBP1 in SLE. Bulk RNA-seq and single-cell RNA-seq data were used to evaluate ZBP1 expression across B-cell subsets. Correlations between ZBP1 expression, disease activity, and immunological parameters were assessed. RNA-seq data following ZBP1 knockdown were analyzed to explore its potential downstream pathways and molecular networks. In addition, in vitro ZBP1 knockdown experiments were conducted to examine its effects on B-cell activation, plasma cell differentiation, and antibody production. Results: ZBP1 was significantly upregulated in peripheral blood and B cells from SLE patients and was enriched in pathways related to type I interferon signaling and cytokine-mediated immune responses. Single-cell transcriptomic profiling further revealed elevated ZBP1 expression across multiple B-cell subsets, including naïve B cells, memory B cells, age-associated B cells (ABCs), and plasma cells. Clinically, ZBP1 expression in peripheral B cells was positively correlated with CD86 mean fluorescence intensity (MFI), SLE Disease Activity Index (SLEDAI) scores, and serum IgG levels, suggesting a link between ZBP1 and B-cell activation. RNA-seq analysis following ZBP1 silencing demonstrated that ZBP1 regulates genes involved in the cell cycle, DNA replication, and p53 signaling, indicating its potential role in promoting B-cell proliferation and activation. Functionally, ZBP1 silencing impaired B-cell activation, reduced plasma cell differentiation, and decreased immunoglobulin production in vitro. Conclusions: Our study identifies ZBP1 as a molecule upregulated in SLE B cells and associated with B-cell activation and disease activity. Although direct causality remains to be established, the data indicate that ZBP1 may contribute to SLE pathogenesis by modulating cell cycle-related pathways and promoting aberrant B-cell responses, highlighting its potential as a biomarker and a candidate therapeutic target in SLE. Full article
(This article belongs to the Special Issue New Insights in Immunological Pathways)
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22 pages, 4698 KB  
Article
Neuroimmune Activation in a Goat Model of Intervertebral Disc Degeneration
by Janai A. Augustin, Kevin G. Burt, Caitlin Barrett, Matthew Fainor, Brianna S. Orozco, Thomas P. Schaer, Harvey E. Smith, Robert L. Mauck and Sarah E. Gullbrand
Cells 2026, 15(3), 286; https://doi.org/10.3390/cells15030286 - 3 Feb 2026
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Abstract
Intervertebral disc degeneration (IVDD) initiates a cascade of structural and biological changes that compromise mechanical function, often leading to chronic pain. While small animal models have provided insight into inflammatory and nociceptive mechanisms of IVDD, translational studies require large animal models that more [...] Read more.
Intervertebral disc degeneration (IVDD) initiates a cascade of structural and biological changes that compromise mechanical function, often leading to chronic pain. While small animal models have provided insight into inflammatory and nociceptive mechanisms of IVDD, translational studies require large animal models that more closely replicate human spine anatomy and physiology. This study induced cervical disc degeneration via intradiscal chondroitinase ABC (ChABC) injection in a large animal model and evaluated the associated disc pathology and neuroinflammatory responses across IVDs and within spinal cord and dorsal root ganglia (DRG) tissues. Results confirmed structural degeneration at ChABC-injected levels and revealed additional evidence of adjacent segment degeneration. Neuroinflammatory analyses revealed innervation, via deposition of PGP9.5 and NFH, throughout both ChABC-injected and adjacent IVDs. Monocyte markers were significantly increased in ChABC-degenerated IVDs. Across experimental groups, the level of monocyte (Ly6C) and macrophage (CD68) markers correlated with worsened histological scores and with reduced mechanical integrity. Similarly, increased production of the neuropeptide, Substance P, in IVDs was significantly positively correlated with compromised IVD mechanical function. Finally, we observed elevated production of the microglia marker, Iba1, and Substance P production in the spinal cord, with similar trends in DRGs, in degenerative spines. By establishing quantitative relationships between disc pathology, immune responses, and neural activation, this work established possible disease-contributing neuroinflammatory activation and further validated a clinically relevant model for preclinical evaluation of regenerative and therapeutic strategies. Full article
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27 pages, 5985 KB  
Article
Chemical Profiling, Ampicillin Interaction Patterns, and Exploratory Molecular Docking of Lauraceae Essential Oils
by Anca Hulea, Florin Imbrea, Doris Floares (Oarga), Iuliana Popescu, Mukhtar Adeiza Suleiman, Calin Hulea, Ilinca Merima Imbrea, Alina-Georgeta Neacșu, Marinel Horablaga, Cosmin Alin Popescu and Diana Obistioiu
Int. J. Mol. Sci. 2026, 27(3), 1447; https://doi.org/10.3390/ijms27031447 - 31 Jan 2026
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Abstract
This study compares the chemical composition, antimicrobial effects, and antibiotic-potentiating capacity of three Lauraceae essential oils (EO): Cryptocarya agathophylla (CAEO), Litsea cubeba (LCEO), and Laurus nobilis (LNEO). Gas chromatography–mass spectrometry (GC–MS) analysis revealed distinct chemotypes: CAEO and LCEO were dominated by oxygenated monoterpenes, [...] Read more.
This study compares the chemical composition, antimicrobial effects, and antibiotic-potentiating capacity of three Lauraceae essential oils (EO): Cryptocarya agathophylla (CAEO), Litsea cubeba (LCEO), and Laurus nobilis (LNEO). Gas chromatography–mass spectrometry (GC–MS) analysis revealed distinct chemotypes: CAEO and LCEO were dominated by oxygenated monoterpenes, while LNEO contained the highest levels of monoterpene hydrocarbons. Antibacterial testing against nine bacterial strains showed strain-dependent growth suppression trends, while true minimum inhibitory concentrations (MICs) were reached only in selected cases. EO–ampicillin interactions were evaluated using MIC-based checkerboard criteria, whereas OD-derived inhibition parameters were used exclusively to describe sub-MIC potentiation trends. In combination assays, LNEO exhibited the most pronounced potentiating effects against Streptococcus pyogenes, Shigella flexneri, and Haemophilus influenzae, while CAEO and LCEO showed moderate or strain-dependent enhancement. Hierarchical clustering highlighted distinct oil- and strain-specific interaction profiles. Overall, although CAEO displayed stronger intrinsic antibacterial effects when tested alone, LNEO emerged as the most effective potentiator of ampicillin activity in a strain-dependent manner. The effects of the major compounds identified in the Lauraceae EO were assessed in silico against protein targets of some microorganisms using the AutoDock software version 4.2.6. The docking scores revealed binding affinities of the bioactive compounds towards Dpr protein (4.3–5.8 kcal/mol), DNA gyrase (4.7–7.1 kcal/mol), mono- diacylglycerol lipase (4.4–6.2 kcal/mol), CYP51 (5.8–8.0 kcal/mol), phage-encoded quorum sensing anti-activator (5.8–8.0 kcal/mol) and Chondroitin ABC lyase I (4.8–6.3 kcal/mol). Two (2) hit compounds (α-Citral, β-Citral) were finely defined by strong hydrophobic and hydrophilic interactions with the bacterial and fungal protein targets, respectively. Full article
(This article belongs to the Special Issue Rational Design and Synthesis of Bioactive Molecules, 2nd Edition)
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21 pages, 1919 KB  
Article
Comparative Evaluation of A4C, CHAMPS, and CAGIB Scores for Risk Stratification in Hemodialysis Patients with Acute Gastrointestinal Bleeding
by Mete Ucdal and Evren Ekingen
Diagnostics 2026, 16(3), 401; https://doi.org/10.3390/diagnostics16030401 - 27 Jan 2026
Viewed by 849
Abstract
Background/Objectives: Gastrointestinal bleeding (GIB) in hemodialysis (HD) patients carries substantial mortality risk. The A4C and CHAMPS scores are novel risk stratification tools, while CAGIB was developed for cirrhosis-associated GIB. We compared the discriminative performance of these scores in HD patients with acute [...] Read more.
Background/Objectives: Gastrointestinal bleeding (GIB) in hemodialysis (HD) patients carries substantial mortality risk. The A4C and CHAMPS scores are novel risk stratification tools, while CAGIB was developed for cirrhosis-associated GIB. We compared the discriminative performance of these scores in HD patients with acute GIB, stratified by variceal and non-variceal etiology. Methods: We conducted a retrospective cohort study of 57 HD patients with acute GIB (January 2020–December 2024) following STROBE and TRIPOD guidelines. Patients were stratified as non-variceal (n = 42) or variceal (n = 15). The primary outcome was 30-day mortality; secondary outcomes included ICU admission, rebleeding, and transfusion requirements. A4C, CHAMPS, CAGIB, ABC, AIMS65, and Glasgow–Blatchford scores were compared using AUROC analysis. Results: Mean age was 45.8 ± 13.2 years. Non-variceal GIB (73.7%) was predominantly caused by angiodysplasia (28.6%) and peptic ulcer disease (23.8%); variceal GIB (26.3%) was mainly from esophageal varices (80.0%). Overall 30-day mortality was 17.5%, significantly higher in variceal (26.7%) versus non-variceal GIB (14.3%, p = 0.048). For non-variceal GIB, CHAMPS demonstrated excellent mortality discrimination (AUROC 0.91), significantly outperforming CAGIB (AUROC 0.68, p = 0.02). Conversely, for variceal GIB, CAGIB showed superior performance (AUROC 0.89) compared to CHAMPS (AUROC 0.72, p = 0.04). A4C performed consistently for transfusion prediction across both groups (AUROC 0.75–0.78). Conclusions: Optimal risk stratification in HD patients with GIB requires etiology-specific scoring: CHAMPS for non-variceal and CAGIB for variceal bleeding. This complementary performance reflects distinct pathophysiological mechanisms underlying mortality. Prospective validation in larger multicenter cohorts is warranted. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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