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11 pages, 615 KB  
Article
Patellofemoral Joint Replacement for Isolated Patellofemoral Osteoarthritis: Mid- to Long-Term Survivorship and Functional Outcomes
by Fernando Diaz Dilernia, Mutaz Tageldein, Emad Anam, Aaron Campbell and Gavin Wood
J. Pers. Med. 2026, 16(7), 345; https://doi.org/10.3390/jpm16070345 (registering DOI) - 25 Jun 2026
Abstract
Background/Objectives: Patellofemoral joint (PFJ) replacement is a bone-preserving option for isolated patellofemoral osteoarthritis; however, reported survivorship and failure patterns remain variable. This study evaluated implant survivorship, functional outcomes, reoperations, and failure mechanisms following PFJ replacement using standard second-generation implant systems, with or without [...] Read more.
Background/Objectives: Patellofemoral joint (PFJ) replacement is a bone-preserving option for isolated patellofemoral osteoarthritis; however, reported survivorship and failure patterns remain variable. This study evaluated implant survivorship, functional outcomes, reoperations, and failure mechanisms following PFJ replacement using standard second-generation implant systems, with or without patellar resurfacing. Methods: We retrospectively reviewed a consecutive cohort of 39 patients (48 knees) who underwent PFJ replacement for isolated patellofemoral osteoarthritis between 2011 and 2021. Median age at surgery was 59 years, and median body mass index (BMI) was 31 kg/m2. Median follow-up for clinical and revision surveillance was 9 years (IQR 8–10). Functional outcomes were assessed using the Oxford Knee Score (OKS) and SF-12 Physical and Mental Component Scores (PCS and MCS). Implant survivorship was analyzed using Kaplan–Meier methodology, with conversion to total knee arthroplasty (TKA) as the endpoint. Statistical analyses were primarily descriptive and exploratory because only five TKA revisions occurred. Results: Median OKS improved from 19 (IQR 16–24) preoperatively to 36 (IQR 24–42) at the latest follow-up, with a median paired improvement of 17 points. SF-12 PCS improved from 25 to 47, and SF-12 MCS from 36 to 55. Eight knees (16.7%) underwent non-revision reoperation, and five knees (10.4%) underwent conversion to TKA. All TKA revisions were performed for the progression of tibiofemoral osteoarthritis. Kaplan–Meier survivorship free from TKA revision was 89.6% at 9 years (95% CI 76.8–95.5). No clear difference in TKA-free survivorship was detected between resurfaced and non-resurfaced knees. Conclusions: PFJ replacement demonstrated substantial functional improvement and mid- to long-term survivorship comparable to published registry ranges in a selected cohort with isolated patellofemoral osteoarthritis. TKA revision was uncommon and was attributable to the progression of tibiofemoral osteoarthritis. Because of the retrospective design, small cohort size, bilateral cases, and limited number of revision events, subgroup and risk-factor analyses should be interpreted as exploratory. Full article
(This article belongs to the Special Issue Knee Injuries: Personalized Diagnosis, Treatment and Management)
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18 pages, 658 KB  
Article
Internet Gaming Disorder, Problem Gambling Symptoms and Mental Health in Spanish Adolescents: A Cross-Sectional Study on the Role of Microtransactions and Loot Boxes
by Juan Manuel Díaz Peña, Richard Kjellgren, Joaquim A. Ferreira and Fernando Fajardo Bullón
Healthcare 2026, 14(13), 1846; https://doi.org/10.3390/healthcare14131846 (registering DOI) - 25 Jun 2026
Abstract
Background/Objectives: Adolescent mental health problems have increased in recent years, with growing concern about the impact of digital behaviors such as problematic video game use and gambling. Internet Gaming Disorder (IGD) and Problem Gambling Symptoms may share psychological risk markers, but evidence [...] Read more.
Background/Objectives: Adolescent mental health problems have increased in recent years, with growing concern about the impact of digital behaviors such as problematic video game use and gambling. Internet Gaming Disorder (IGD) and Problem Gambling Symptoms may share psychological risk markers, but evidence in Spanish adolescents is limited. This study aimed to examine the relationship between IGD, problem gambling symptoms, and mental health, and to identify sociodemographic, psychological, and behavioral factors associated, including microtransactions and loot boxes. Methods: A cross-sectional study was conducted with secondary education students from Extremadura (Spain). The final sample included 343 participants. Measures included an ad hoc questionnaire on video game use, the IGDS9-SF, SOGS-RA, and the Strengths and Difficulties Questionnaire (SDQ). Descriptive analyses, Spearman correlations, and multivariable regression (Poisson and negative binomial) were performed. Results: IGD and gambling were positively correlated (Spearman’s ρ = 0.386, p < 0.001) and associated with higher mental health difficulty scores (IGD: ρ = 0.299, p < 0.001; gambling: ρ = 0.214, p < 0.001). Male gender was associated with both outcomes (IGD: incidence rate ratio [IRR] = 1.21 [95% Confidence Interval: 1.13–1.30]; gambling: IRR = 2.90 [1.85–4.60]). Microtransactions were associated with both behaviors (IGD: IRR = 1.17 [1.09–1.25]; gambling: IRR = 1.74 [1.19–2.54]), while loot box use was related only to IGD (IRR = 1.13 [1.05–1.21]). Total SDQ score was positively associated with both IGD (IRR = 1.02 [1.02–1.03]) and gambling (IRR = 1.10 [1.06–1.13]). Younger age was associated with higher IGD scores (IRR = 0.97 [0.96–0.99]). Conclusions: There are similarities in the associations among the examined factors and increased scores of IGD and gambling in adolescents, particularly male gender, higher mental health difficulties scores, and involvement in monetized gaming systems. School-based, family, and public health prevention strategies may benefit from addressing the importance of psychological well-being and increase awareness of the potential risks associated with digital gaming practices. Full article
(This article belongs to the Special Issue The Relationship of Social Media and Cyberbullying with Mental Health)
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11 pages, 1728 KB  
Case Report
Multidisciplinary Orthodontic and Home Sleep Apnea Testing-Based Assessment of Sleep-Disordered Breathing in a Pediatric Patient with Gorlin–Goltz Syndrome: A Case Report
by Federica Guglielmi, Francesca Colacino, Anna Maria Raguso, Giulio Solimene, Beatrice Cognigni and Patrizia Gallenzi
Oral 2026, 6(4), 78; https://doi.org/10.3390/oral6040078 (registering DOI) - 25 Jun 2026
Abstract
Background: Gorlin–Goltz syndrome is a rare autosomal dominant condition with characteristic craniofacial and odontogenic anomalies. Orofacial alterations in childhood may precede dermatological findings, highlighting the relevance of early orthodontic and functional evaluation. Objective: This case describes a multidisciplinary orthodontic and Home [...] Read more.
Background: Gorlin–Goltz syndrome is a rare autosomal dominant condition with characteristic craniofacial and odontogenic anomalies. Orofacial alterations in childhood may precede dermatological findings, highlighting the relevance of early orthodontic and functional evaluation. Objective: This case describes a multidisciplinary orthodontic and Home Sleep Apnea Testing (HSAT)-based approach for the assessment of craniofacial morphology and sleep-disordered breathing (SDB) risk in a pediatric patient with Gorlin–Goltz syndrome. Methods: A 12-year-old male with a genetically confirmed PTCH1 mutation underwent digital intraoral scanning, orthodontic evaluation, and SDB screening using the Pediatric Sleep Questionnaire (PSQ). Following a positive screening score, HSAT with the Philips Alice NightOne® system was performed under specialist supervision. Results: The patient showed recurrent odontogenic cysts, a lateral open bite, and unilateral Class II canine relationship. The PSQ score was 0.579, exceeding the validated cut-off of 0.33 and indicating an elevated SDB risk. HSAT findings were suggestive of mild obstructive sleep apnea based on Respiratory Event Index (REI) values (REI 4.7/h), with an isolated SpO2 nadir of 77% and a maximum recorded apnea duration of 425 s, warranting cautious specialist interpretation and follow-up assessment. Conclusions: Integrating orthodontic assessment, digital documentation, validated screening tools, and objective HSAT-based evaluation may support the early recognition of functional compromise in syndromic pediatric patients. Positive screening results should prompt specialist referral and objective sleep assessment, while attended polysomnography remains indicated when comprehensive sleep architecture evaluation or definitive characterization is required. Full article
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13 pages, 1257 KB  
Article
Carpal Tunnel Syndrome Is Associated with Increased Risk of Fibromyalgia: A Retrospective Cohort Study
by Yu-Jung Su, Yun-Chen Liang, Yen-Po Chen, Wan-Yun Hsu, Hui-Chin Chang, Yu-Chao Tseng, Hsi-Chen Wei, Chun-Ming Chen and Shuo-Yan Gau
Life 2026, 16(7), 1059; https://doi.org/10.3390/life16071059 (registering DOI) - 25 Jun 2026
Abstract
Background: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder with multifactorial etiologies, while fibromyalgia is a chronic centralized pain condition characterized by widespread pain and central sensitization. Although shared mechanisms such as neurogenic inflammation and altered pain processing have been [...] Read more.
Background: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder with multifactorial etiologies, while fibromyalgia is a chronic centralized pain condition characterized by widespread pain and central sensitization. Although shared mechanisms such as neurogenic inflammation and altered pain processing have been proposed, longitudinal evidence evaluating whether CTS predisposes to subsequent fibromyalgia remains limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Adults aged ≥ 18 years with ≥2 clinical encounters between 2018 and 2023 were included. Patients with CTS formed the exposure cohort, while individuals without CTS undergoing routine health examinations served as controls. Those with prior fibromyalgia, malignancy, or death before index were excluded. One-to-one propensity score matching was performed to balance demographics, body mass index, psychiatric conditions, socioeconomic factors, healthcare utilization, and comorbidities including mood, anxiety, stress-related, and sleep disorders. The primary outcome was incident fibromyalgia. Sensitivity analyses included alternative matching strategies, extended washout periods, stricter exposure definitions, and active comparator analyses using osteoarthritis. Stratified analyses by age and sex were conducted. Associations were estimated using hazard ratios with 95% confidence intervals. Results: After matching, 217,208 patients were included in each cohort. CTS was associated with a significantly increased risk of fibromyalgia (HR 2.709, 95% CI 2.521–2.911). Consistent findings were observed across sensitivity analyses. Compared with osteoarthritis, CTS remained associated with higher fibromyalgia risk (HR 1.331, 95% CI 1.254–1.411). Stratified analyses demonstrated consistent associations across age groups (18–64 years: HR 2.820, 95% CI 2.595–3.065; ≥65 years: HR 2.717, 95% CI 2.337–3.159) and sexes (male: HR 3.018, 95% CI 2.482–3.672; female: HR 2.655, 95% CI 2.457–2.869). Conclusions: CTS was associated with coded fibromyalgia diagnosis in this large real-world cohort, and this association was observed across multiple sensitivity and stratified analyses. These findings should be interpreted as evidence of an epidemiologic association rather than a causal relationship. CTS may serve as a clinical marker for patients who warrant attention to broader pain-related symptoms, while future studies are needed to clarify temporality and underlying mechanisms. Full article
(This article belongs to the Section Medical Research)
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17 pages, 3011 KB  
Article
Architecture-Level Risk-Guided Fault-Injection Prioritization for Systolic AI Accelerators: A Fixed Candidate-Pool Evaluation
by Larisa Goffman-Vinopal
Electronics 2026, 15(13), 2792; https://doi.org/10.3390/electronics15132792 (registering DOI) - 25 Jun 2026
Abstract
Fault-injection campaigns are widely used to evaluate silent data corruption (SDC) in AI hardware, but exhaustive campaigns over workloads, dataflows, processing elements, and datapath roles are expensive. This paper presents an architecture-level risk-guided fault-injection prioritization method for systolic AI accelerators. The method ranks [...] Read more.
Fault-injection campaigns are widely used to evaluate silent data corruption (SDC) in AI hardware, but exhaustive campaigns over workloads, dataflows, processing elements, and datapath roles are expensive. This paper presents an architecture-level risk-guided fault-injection prioritization method for systolic AI accelerators. The method ranks candidate transient functional perturbations before downstream validation, with the goal of enriching the discovery of candidates that produce a thresholded relative-output-error outcome under a limited validation budget. The evaluation uses a fixed candidate fault pool: all ranking policies score the same 21,000 candidate faults across 30 workload/dataflow/array configurations, corresponding to five GEMM-derived workloads, three array sizes, and two dataflows. Fault magnitudes are sampled once per candidate and are independent of all ranking scores. Candidate faults are modeled as transient architecture-level perturbations in MAC, accumulator, or forwarding paths. The proposed full-risk score combines activity, composite spatial stress, tensor sensitivity, and a path-class weight. In the proposed architecture-level simulation environment and under the fixed-pool protocol, the proposed method achieves the highest mean top-10% SDC-proxy lift, AUPRC, NDCG@10%, and rank correlation with relative output error among the evaluated principle-based ranking policies. At the calibrated threshold, it achieves a mean top-10% lift of 5.65× [4.91, 6.38], compared with 4.61× for AVF-like exposure and 4.33× for output sensitivity. Paired configuration-level tests, threshold sensitivity, and outcome-model sensitivity analyses characterize the result while showing that the proposed score is not universally dominant under every synthetic outcome assumption. The method is intended as a front-end architecture-level screening tool for validation prioritization, not as a replacement for RTL, gate-level, FPGA, or silicon reliability signoff. Full article
(This article belongs to the Section Computer Science & Engineering)
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12 pages, 825 KB  
Article
Sequential Add-On Therapy Modifies Mortality Risk Stratification in Group 1.4 Pulmonary Arterial Hypertension: A Real-World, Single-Center Retrospective Cohort Study from Mexico
by Arturo Cortes-Telles, Yuliana Valeria Priego-Escamilla, Diana Lizbeth Ortíz-Farias, Saúl Vázquez-López, Yuri Noemí Pou-Aguilar and Esperanza Figueroa-Hurtado
J. Clin. Med. 2026, 15(13), 4924; https://doi.org/10.3390/jcm15134924 (registering DOI) - 24 Jun 2026
Abstract
Background: Dynamic risk stratification is fundamental to the modern management of pulmonary arterial hypertension (PAH). However, data on the impact of sequential add-on therapy in patients with Group 1.4 PAH—particularly in Latin American populations—remains limited. This study evaluated changes in risk classification using [...] Read more.
Background: Dynamic risk stratification is fundamental to the modern management of pulmonary arterial hypertension (PAH). However, data on the impact of sequential add-on therapy in patients with Group 1.4 PAH—particularly in Latin American populations—remains limited. This study evaluated changes in risk classification using COMPERA 2.0 and REVEAL Lite 2 scores in patients treated with endothelin receptor antagonist (ERA) and phosphodiesterase type 5 inhibitor (PDE5i) combination therapy (macitentan + sildenafil) at a referral center in Mexico. Methods: In this single-center, retrospective cohort study, 25 patients with a confirmed diagnosis of PAH between 1st January 2022 and 31st December 2024 were evaluated at baseline and after 24 weeks of treatment. Clinical, functional, and biochemical parameters were recorded. Within-patient changes were analyzed using the Wilcoxon signed-rank test, and agreement between risk assessment tools was assessed using Spearman’s correlation coefficient. Results: At 24 weeks, patients demonstrated significant improvement in World Health Organization functional class (p = 0.002) and a significant reduction in brain natriuretic peptide levels (p = 0.003). Both COMPERA 2.0 and REVEAL Lite 2 scores showed a consistent shift toward lower-risk categories. A strong concordance between the two tools was observed. Conclusions: Sequential add-on ERA + PDE5i therapy was associated with meaningful improvement in risk stratification among patients with Group 1.4 PAH. These findings support the clinical utility of simplified, noninvasive risk assessment tools in real-world settings, particularly in resource-constrained environments. Full article
(This article belongs to the Special Issue Clinical Research on Pulmonary Hypertension and Its Complications)
28 pages, 681 KB  
Article
The Link Between Dietary Indices, Sarcopenia, and Clinical Parameters in Diabetic and Non-Diabetic Hemodialysis Patients
by Yahya Faruk Karatas, Gulsum Gizem Topal, Damla Gumus and Mevlude Kizil
J. Clin. Med. 2026, 15(13), 4923; https://doi.org/10.3390/jcm15134923 (registering DOI) - 24 Jun 2026
Abstract
Background and Objectives: Sarcopenia is highly prevalent among maintenance hemodialysis (HD) patients, particularly in the presence of diabetes mellitus (DM). Dietary glycemic and insulinemic characteristics may contribute to metabolic disturbances associated with muscle deterioration, although evidence in HD populations remains limited. This [...] Read more.
Background and Objectives: Sarcopenia is highly prevalent among maintenance hemodialysis (HD) patients, particularly in the presence of diabetes mellitus (DM). Dietary glycemic and insulinemic characteristics may contribute to metabolic disturbances associated with muscle deterioration, although evidence in HD populations remains limited. This study aimed to investigate the associations between dietary indices, sarcopenia, nutritional status, and clinical outcomes in diabetic (DM+) and non-diabetic (DM−) HD patients. Materials and Methods: This cross-sectional study included 92 maintenance HD patients (43 DM+ and 49 DM−). Dietary intake was assessed using three-day food records, and dietary insulin index (DII), dietary insulin load (DIL), dietary glycemic index (DGI), and dietary glycemic load (DGL) were calculated. Sarcopenia was evaluated using handgrip strength, bioelectrical impedance analysis, gait speed, and SARC-F. Anthropometric, biochemical, nutritional, and sarcopenia-related parameters were compared across tertiles of dietary indices. Results: Sarcopenia was identified in 32.6% of patients with diabetes and 36.7% of those without diabetes. Diabetic patients exhibited significantly lower handgrip strength, slower walking speed, longer walking time, and higher SARC-F scores (p < 0.01). Across DGL tertiles in DM+ patients, significant progressive increases were observed in body weight (p < 0.05), body mass index (p < 0.05), lean mass (p < 0.05), mid-upper arm circumference (p < 0.01), and triceps skinfold thickness (p < 0.01). Higher DIL and DGL tertiles were also associated with elevated serum phosphorus, LDL cholesterol, triglycerides, and total cholesterol levels (p < 0.05). DIL and DGL showed stronger associations with overall energy and nutrient intake compared with DII and DGI. However, no significant associations were identified between dietary indices and sarcopenia diagnosis or sarcopenia-related risk indicators after adjustment for age and sex. Conclusions: Dietary indices were associated with various anthropometric, biochemical, and nutritional parameters in HD patients, with more pronounced associations observed among patients with DM, suggesting a potential role of dietary quality in the nutritional and metabolic profile of this population. Full article
(This article belongs to the Section Clinical Nutrition & Dietetics)
41 pages, 11772 KB  
Article
An Uncertainty-Aware Computational Framework for Dimensional Error Prediction in Ceramic Additive Manufacturing Under Variable Material and Process Conditions
by Mahmoud AlJamal, Nawal Louzi, Mohammad Q. Al-Jamal, Luay Tahat, Ala Mughaid and Qasim Aljamal
Computation 2026, 14(7), 144; https://doi.org/10.3390/computation14070144 (registering DOI) - 24 Jun 2026
Abstract
Ceramic additive manufacturing offers strong potential for fabricating geometrically complex and application-specific components, yet achieving reliable dimensional fidelity remains challenging because dimensional deviation is governed by highly coupled material, process, thermal, and environmental factors. To address this problem, this study proposes an uncertainty-aware [...] Read more.
Ceramic additive manufacturing offers strong potential for fabricating geometrically complex and application-specific components, yet achieving reliable dimensional fidelity remains challenging because dimensional deviation is governed by highly coupled material, process, thermal, and environmental factors. To address this problem, this study proposes an uncertainty-aware computational framework for dimensional error prediction in ceramic 3D printing under variable material and process conditions. The contribution is positioned as a system-level integration of established learning, uncertainty estimation, calibration, and reliability-interpretation components within a ceramic additive manufacturing dimensional-error prediction workflow, rather than as a fundamental methodological breakthrough. The validation is conducted using the publicly available Ceramic 3D Printing Process Control Dataset, a 1000-sample tabular dataset, and the resulting findings are therefore interpreted as dataset-specific computational evidence rather than direct proof of industrial deployment readiness. The methodology begins with a structured data-driven preprocessing pipeline that transforms the Ceramic 3D Printing Process Control Dataset into a multi-condition feature space through data cleaning, one-hot material encoding, min–max normalization, and engineered descriptors capturing extrusion–speed balance, thermal gradients, cooling intensity, deposition density, and material-conditioned interactions. A multi-branch deep computational architecture is then developed to encode material, process, thermal-environmental, and engineered-feature streams separately, followed by adaptive cross-condition fusion to learn nonlinear dependencies across ceramic printing regimes. To improve reliability beyond deterministic regression, the framework jointly models aleatoric and epistemic uncertainty and incorporates calibration refinement to align predictive confidence with observed error behavior, thereby enabling preliminary reliability-oriented interpretation of stable and high-risk operating conditions. Experimental results demonstrate that the full model achieves the best overall within-dataset performance, with a test MAE of 0.0118, RMSE of 0.0172, R2=0.999, MAPE of 1.74%, calibration error of 0.003, PICP of 0.996, reliability score of 0.992, and a stable prediction rate of 98.7%. Although these values indicate strong predictive behavior under the current structured dataset, the exceptionally high R2 should be interpreted cautiously because external experimental validation, larger measured datasets, and cross-machine ceramic printing trials are still required. These findings show that the proposed framework provides an effective system-level computational strategy for dataset-specific reliability-aware dimensional quality prediction in ceramic additive manufacturing and offers a preliminary data-driven foundation for uncertainty-aware intelligent process optimization. Full article
(This article belongs to the Special Issue Computational Methods in Structural Optimization)
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17 pages, 607 KB  
Article
Imaging-Based Risk Stratification of IPMN Using a Structured Imaging Score: A Retrospective Proof-of-Concept Study
by Stefano Fusco, Hannes F. Digomann, Sabrina Groß, Nisar Peter Malek, Eckhart Fröhlich and Tatjana Hoffmann
Curr. Oncol. 2026, 33(7), 383; https://doi.org/10.3390/curroncol33070383 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Accurate risk stratification of intraductal papillary mucinous neoplasms (IPMNs) remains clinically challenging. This study evaluates a structured imaging-based scoring approach for IPMN risk stratification, referred to as the Tübingen Dignity Score (TDS), and compares its diagnostic performance with established methods. Methods: In [...] Read more.
Background/Objectives: Accurate risk stratification of intraductal papillary mucinous neoplasms (IPMNs) remains clinically challenging. This study evaluates a structured imaging-based scoring approach for IPMN risk stratification, referred to as the Tübingen Dignity Score (TDS), and compares its diagnostic performance with established methods. Methods: In this retrospective study, imaging findings from patients with suspected IPMN were analyzed using MRI, CT, and ultrasound. The TDS was applied as an imaging-based scoring system. Diagnostic performance was assessed in a histopathological subset and compared with MRI-based assessment and Fukuoka criteria. Results: MRI showed high sensitivity (94.4%) but limited specificity (57.1%). Fukuoka criteria showed high sensitivity (100%) and high specificity (91.3%) in this cohort, although with a lower positive predictive value. In contrast, the TDS showed high specificity (100%) and positive predictive value, but lower sensitivity (40%), reflecting a different diagnostic profile. These findings indicate a trade-off between sensitivity and specificity across the evaluated approaches. However, the limited number of malignant cases limits the robustness and generalizability of these estimates. Conclusions: The TDS may serve as a complementary, imaging-based tool within a multimodal diagnostic framework for IPMN. Its potential value lies in supporting clinical decision-making in selected cases, particularly where established criteria yield inconclusive results. Given the limited sample size, retrospective single-center design, and exploratory nature of this study, external prospective multicenter validation is required before routine clinical application can be recommended. Full article
20 pages, 4461 KB  
Article
Immunogenetic and Transcriptomic Evidence Implicating the NKG2D-MICA/MICB Axis in CALR-Mutated Myeloproliferative Neoplasms
by Velizar Shivarov, Gergana Tsvetkova, Ilina Micheva, Evgueniy Hadjiev, Jasmina Petkova, Galia Madjarova and Milena Ivanova
Cancers 2026, 18(13), 2052; https://doi.org/10.3390/cancers18132052 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Immune surveillance is increasingly recognized as a modifier of myeloproliferative neoplasm (MPN) initiation and evolution, yet the contribution of the NKG2D receptor and its ligands MICA/MICB to CALR-mutated disease remains unclear. Methods: We performed high-resolution next-generation sequencing genotyping of MICA and MICB [...] Read more.
Background/Objectives: Immune surveillance is increasingly recognized as a modifier of myeloproliferative neoplasm (MPN) initiation and evolution, yet the contribution of the NKG2D receptor and its ligands MICA/MICB to CALR-mutated disease remains unclear. Methods: We performed high-resolution next-generation sequencing genotyping of MICA and MICB in 43 patients with CALR-mutated MPN (WHO 2022 criteria) and compared the allele and haplotype distributions with those of 156 healthy Bulgarian controls and 85 patients with JAK2 V617F-positive MPN. Associations were tested using age- and sex-adjusted additive generalized linear models; bi-locus haplotypes were evaluated using haplotype score methods. In a genotyped subgroup (35 CALR-mutated MPN patients and 105 controls), functional KLRK1 (NKG2D) polymorphisms were analyzed for haplotype-level associations. We also performed 700 ns molecular dynamics simulations of selected MICA variants in complex with NKG2D and reanalyzed publicly available single-cell RNA-sequencing data (GSE117826) and RNA-sequencing data from CRISPR/Cas9-edited CALR-mutant iPSC-derived megakaryocytes to evaluate MICA/MICB expression. Results: MICA*004:001 was significantly associated with CALR-mutated MPN versus controls (p = 0.004; Bonferroni-adjusted p = 0.047), while MICB*008:001 showed only nominal association. Exploratory haplotype analyses identified a MICA*009:01-MICB*004:001 haplotype associated with CALR-mutated status (p = 0.008) and a KLRK1 G-A-G-T haplotype (rs1049174-rs2617160-rs2246809-rs2617170) associated with increased CALR-mutated MPN risk (OR = 3.61; p = 0.029). Transcriptomic reanalysis indicated a higher fraction of CALR-mutant stem and progenitor cells expressing detectable MICA/MICB transcripts, and heterozygous CALR-mutant megakaryocytes exhibited higher MICA expression than the wild type. Conclusions: Together, these data support an exploratory immunogenetic and transcriptomic link between the NKG2D-MICA/MICB axis and CALR-mutated MPN, but direct protein-level and functional studies are required before mechanistic or therapeutic conclusions can be drawn. Full article
15 pages, 328 KB  
Article
Serum 25-Hydroxyvitamin D Deficiency Is Independently Associated with Cognitive Impairment, Depressive Symptoms, and Functional Dependency in Hospitalised Older Adults: A Cross-Sectional Study from Central Romania
by Valer Donca, Lucretia Avram, Tudor Cosma, Daniela Rus, Andrada Nemes, Andrei Balan, Adela Serban, Rodica Ungur and Dana Crisan
Nutrients 2026, 18(13), 2066; https://doi.org/10.3390/nu18132066 (registering DOI) - 24 Jun 2026
Abstract
Background: Vitamin D deficiency is highly prevalent in older adults and has been increasingly recognised as a potential contributor to cognitive decline, depressive symptomatology, and functional impairment. However, the clinical significance of specific 25-hydroxyvitamin D thresholds in relation to this multidomain geriatric [...] Read more.
Background: Vitamin D deficiency is highly prevalent in older adults and has been increasingly recognised as a potential contributor to cognitive decline, depressive symptomatology, and functional impairment. However, the clinical significance of specific 25-hydroxyvitamin D thresholds in relation to this multidomain geriatric phenotype remains incompletely characterised. Methods: We conducted a cross-sectional study of 1438 consecutive patients aged 65 years or older admitted for comprehensive geriatric assessment at a tertiary centre in Cluj-Napoca, Romania, between January 2023 and November 2025. Serum 25-hydroxyvitamin D [25(OH)D] was categorised as deficient (<20 ng/mL), insufficient (20–30 ng/mL), or sufficient (≥30 ng/mL). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), depressive symptoms using the Geriatric Depression Scale (GDS-30 and GDS-SF), and functional status using Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). Multivariable linear regression analyses were adjusted for age, body mass index, serum albumin, and estimated glomerular filtration rate (eGFR). Results: Suboptimal vitamin D status was highly prevalent in this geriatric cohort, with 43.3% of participants meeting criteria for frank deficiency (<20 ng/mL). Lower 25(OH)D concentrations were significantly associated with worse cognitive performance, greater depressive symptom burden, and higher functional dependency. Serum 25(OH)D correlated positively with MoCA and MMSE scores and inversely with ADL, IADL, and GDS scores. In adjusted models, vitamin D remained independently associated with MoCA, IADL, and GDS. Stratified analyses suggested that the main clinical deterioration occurred below 20 ng/mL, while the 20–30 ng/mL range behaved as an intermediate phenotype closer to sufficiency than to frank deficiency. Conclusions: In this large cohort of hospitalised older adults, serum 25(OH)D deficiency below 20 ng/mL was independently associated with poorer cognition, more depressive symptoms, and greater functional impairment. These findings support routine vitamin D assessment in geriatric practice and suggest that the <20 ng/mL threshold identifies a clinically relevant high-risk phenotype. Full article
(This article belongs to the Section Micronutrients and Human Health)
19 pages, 1540 KB  
Article
Significance of the Echocardiographic Assessment of Longitudinal Left Ventricular Systolic Function in Children and Adolescents with Hypertrophic Cardiomyopathy
by Jasna Kalanj, Ida Jovanovic, Milan Djukic, Vojislav Parezanovic, Igor Stefanovic, Maja Bijelic, Andrija Pavlovic, Nadja Cukanovic, Luka Zekovic, Ivana Jovanovic and Milorad Tesic
J. Clin. Med. 2026, 15(13), 4911; https://doi.org/10.3390/jcm15134911 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Hypertrophic cardiomyopathy (HCM) in childhood is associated with a risk of adverse cardiovascular events despite preserved left ventricular (LV) ejection fraction (EF). The aim of this study was to evaluate echocardiographic parameters of longitudinal LV systolic function and determine their relationship [...] Read more.
Background/Objectives: Hypertrophic cardiomyopathy (HCM) in childhood is associated with a risk of adverse cardiovascular events despite preserved left ventricular (LV) ejection fraction (EF). The aim of this study was to evaluate echocardiographic parameters of longitudinal LV systolic function and determine their relationship with cardiac magnetic resonance (CMR) findings and major adverse cardiovascular events (MACE) in children and adolescents with HCM. Methods: This single-centre prospective observational study enrolled 31 children and adolescents with HCM and preserved LV EF. Echocardiographic assessment included mitral annular plane systolic excursion (MAPSE), tissue Doppler mitral annulus systolic velocity (s′), mitral annular displacement index (MADI), and LV global longitudinal strain (GLS). Investigated CMR parameters encompassed LV mass, maximal wall thickness, and late gadolinium enhancement (LGE). Associations between echocardiographic and CMR findings were analyzed, and the discriminative value of longitudinal function parameters for MACE was assessed. Results: Impaired longitudinal systolic function was frequently detected in our cohort. Lower MAPSE and s′ z-scores were present in 61.3% of patients, reduced MADI in 96.8%, and reduced LV GLS in all subjects. Patients with MACE showed significantly lower MADI (p < 0.001) and worse LV GLS (p = 0.003). An exploratory LV GLS cut-off value of −12.1% showed discrimination for MACE in this cohort, with 75% sensitivity and 95.7% specificity. Echocardiographic parameters significantly correlated with CMR markers of hypertrophy and fibrosis, particularly LV GLS, which demonstrated the strongest associations with LV mass and the presence and extent of LGE. Conclusions: Echocardiographic parameters of longitudinal LV systolic function could contribute to closer clinical surveillance in children and adolescents with HCM. LV GLS may identify subtle myocardial dysfunction and provide exploratory prognostic information; however, its role in risk stratification requires prospective validation in larger pediatric HCM cohorts. Full article
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15 pages, 1491 KB  
Article
Focal Hepatic Hypoperfusion After Normothermic Machine Perfusion of Liver Grafts Is Associated with a Higher Comprehensive Complication Index
by Felicia Kneifel, Felix Becker, Qing Wen Lin, Carsten Szardenings, Sebastian Kubasch, Arne Riegel, Haluk Morgül, Isabelle Flammang, Shadi Katou, Andreas Pascher and Philipp Houben
Bioengineering 2026, 13(7), 729; https://doi.org/10.3390/bioengineering13070729 (registering DOI) - 24 Jun 2026
Abstract
Background: Normothermic machine perfusion (NMP) is increasingly being used to improve organ utilization in liver transplantation (LT). However, its non-physiological perfusion setting may cause focal hepatic hypoperfusion (FHH), which remains insufficiently characterized in terms of its incidence, risk factors, and clinical impact. Methods: [...] Read more.
Background: Normothermic machine perfusion (NMP) is increasingly being used to improve organ utilization in liver transplantation (LT). However, its non-physiological perfusion setting may cause focal hepatic hypoperfusion (FHH), which remains insufficiently characterized in terms of its incidence, risk factors, and clinical impact. Methods: Data on liver grafts that underwent NMP prior to LT at the Department of General, Visceral, and Transplant Surgery, University Hospital Münster, between October 2019 and August 2024 were retrospectively analyzed. Recipients who underwent contrast-enhanced computed tomography within 30 days post-LT were included. The primary outcomes were the Comprehensive Complication Index (CCI) and overall graft survival rate. Ninety-one patients met the inclusion criteria and were stratified according to the presence of FHH in the FHH+ (n = 27) and FHH- (n = 64) groups. Results: FHH was detected in 29.7% of the grafts. Higher graft weight was the only independent predictor of FHH. In addition, graft weight correlated with the extent of FHH (τ = 0.40, p < 0.001). FHH did not affect graft or patient survival but was associated with higher CCI scores (p = 0.001) and prolonged intensive care unit length of stay (p = 0.028). Conclusions: FHH is a common radiological finding after NMP. Although it does not affect graft loss, its association with a higher complication burden warrants further attention. Whether avoiding NMP in very heavy grafts could reduce the incidence of FHH remains to be determined. Full article
(This article belongs to the Special Issue Bioengineering Liver Transplantation—3rd Edition)
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17 pages, 2789 KB  
Article
The Sepsis ImmunoScore Predicts Sepsis, Mortality, and Deterioration Better than Clinical Scores and Widely Available Biomarkers
by Gregory L. Watson, Lincoln C. Updike, Carlos G. López-Espina, Akhil Bhargava, Lee A. Schmalz, Shah Khan, Dennys S. Urdiales, Matthew D. Sims, Ashok V. Palagiri, Adrian D. Haimovich, Alon Dagan, Benjamin P. Davis, Karen C. White, Paul A. Gurbel, Stockton M. Mayer, Anwaruddin Syed, Sihai Dave Zhao, Ruoqing Zhu, Rashid Bashir, Nathan I. Shapiro and Bobby Reddyadd Show full author list remove Hide full author list
Diagnostics 2026, 16(13), 1962; https://doi.org/10.3390/diagnostics16131962 (registering DOI) - 24 Jun 2026
Abstract
Background: Early and accurate risk stratification of patients suspected of serious infection is essential for improving outcomes, but existing diagnostic and predictive tools have limited accuracy. The objective was to compare the performance of an FDA-authorized AI diagnostic test, the Sepsis ImmunoScore, against [...] Read more.
Background: Early and accurate risk stratification of patients suspected of serious infection is essential for improving outcomes, but existing diagnostic and predictive tools have limited accuracy. The objective was to compare the performance of an FDA-authorized AI diagnostic test, the Sepsis ImmunoScore, against widely available biomarkers and clinical tools for diagnosis of sepsis and prediction of in-hospital mortality and intensive care unit (ICU) admission. Methods: This multicenter observational study included 6027 adult patients suspected of infection across 7 U.S. hospital sites. The Sepsis ImmunoScore’s predictive performance was compared to the sequential organ failure assessment (SOFA) score, procalcitonin (PCT), C-reactive protein (CRP), Systemic Inflammatory Response Syndrome (SIRS) score, National Early Warning Score (NEWS), and quick SOFA (qSOFA). Primary outcomes included sepsis as defined by Sepsis-3 criteria, in-hospital mortality, and ICU admission. Predictive accuracy was assessed using area under the receiver operating characteristic curve (AUC), and 95% confidence intervals were generated and hypothesis testing conducted using the bootstrap method. Results: The Sepsis ImmunoScore demonstrated statistically significant superior performance across all outcomes. For sepsis prediction, the Sepsis ImmunoScore achieved an AUC of 0.82, compared to SOFA (0.72), procalcitonin (PCT) (0.70), C-reactive protein (CRP) (0.61), SIRS (0.59), NEWS (0.69), and qSOFA (0.67). For in-hospital mortality prediction, the Sepsis ImmunoScore achieved an AUC of 0.80, outperforming SOFA (0.72), PCT (0.67), CRP (0.58), SIRS (0.60), NEWS (0.72), and qSOFA (0.69). For ICU admission, the Sepsis ImmunoScore reached an AUC of 0.74, superior to SOFA (0.63), PCT (0.64), CRP (0.54), SIRS (0.60), NEWS (0.70), and qSOFA (0.65). All differences between the Sepsis ImmunoScore and comparators were statistically significant. Conclusions: The Sepsis ImmunoScore significantly improved predictive accuracy for sepsis, in-hospital mortality, and ICU admission compared to six conventional clinical scores and biomarkers. This AI-based tool may enhance risk stratification and clinical decision-making, potentially leading to more timely sepsis interventions and improved outcomes. Full article
(This article belongs to the Special Issue Diagnosis and Prognosis of Sepsis)
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17 pages, 1325 KB  
Article
Adropin, S100A1, and SERCA2b Dysregulation in Coronary Artery Disease: Molecular and In Silico Insights into Calcium Signaling and Metabolic Dysfunction
by Onur Aslan, Harika Topal Önal, Meral Urhan Küçük and Emre Dirican
Biomedicines 2026, 14(7), 1430; https://doi.org/10.3390/biomedicines14071430 (registering DOI) - 24 Jun 2026
Abstract
Background/Objectives: Coronary artery disease (CAD) is a leading cause of cardiovascular morbidity and mortality worldwide. Type 2 diabetes mellitus (T2DM) further increases CAD risk through metabolic disturbances and endothelial dysfunction. Adropin, S100A1, and SERCA2b are important regulators of endothelial function, energy metabolism, and [...] Read more.
Background/Objectives: Coronary artery disease (CAD) is a leading cause of cardiovascular morbidity and mortality worldwide. Type 2 diabetes mellitus (T2DM) further increases CAD risk through metabolic disturbances and endothelial dysfunction. Adropin, S100A1, and SERCA2b are important regulators of endothelial function, energy metabolism, and calcium homeostasis. This study aimed to investigate the gene and protein expression levels of these biomarkers in CAD patients with and without T2DM. Methods: Gene and protein expression levels of adropin (ENHO), S100A1, and SERCA2b were evaluated in peripheral blood samples obtained from healthy controls (n = 50), CAD patients (n = 46), and CAD patients with T2DM (CAD+T2DM) (n = 40). Gene expression was determined using real-time PCR, while protein levels were measured with ELISA. Additionally, in silico bioinformatics analyses, such as protein–protein interaction networks and pathway enrichment analyses, were performed to explore potential molecular relationships among these biomarkers. Results: Adropin and ENHO gene expression levels were significantly lower in CAD patients and inversely related to the SYNTAX score. S100A1 levels were also reduced, and SERCA2b gene expression was significantly decreased, especially in the CAD+T2DM group. Bioinformatics analyses revealed that these molecules participate in interconnected pathways related to calcium signaling, cardiac muscle contraction, and metabolic regulation. Conclusions: These findings demonstrate links between altered levels of adropin, S100A1, and SERCA2b and CAD with or without T2DM. However, these observations are preliminary and need validation in larger prospective studies and mechanistic research before drawing definitive conclusions about their clinical utility, disease progression, or prognostic value. Full article
(This article belongs to the Special Issue New Insights into Biomarkers in Cardiovascular Diseases)
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