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Search Results (16,308)

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13 pages, 758 KB  
Article
Age-Stratified Long-Term Outcomes of Immune Checkpoint Inhibitors for Stage IV Melanoma and NSCLC in the Netherlands: A Population-Based Study
by Eline G. M. Steenhuis, Lieke M. van Disseldorp, Femke J. C. Jacobs, Nathalie van Schayk, Karijn Suijkerbuijk, Marieke Louwman, Julia N. S. d’Hooghe, Ronald A. M. Damhuis and Wouter H. van Geffen
Cancers 2026, 18(12), 2019; https://doi.org/10.3390/cancers18122019 (registering DOI) - 22 Jun 2026
Abstract
Background: Immune checkpoint inhibitors (ICIs) are standard treatment for melanoma and non-small cell lung cancer (NSCLC), yet evidence on their effectiveness in older adults remains limited due to underrepresentation in clinical trials. This study assessed long-term, age-stratified outcomes of ICI treatment in real-world [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) are standard treatment for melanoma and non-small cell lung cancer (NSCLC), yet evidence on their effectiveness in older adults remains limited due to underrepresentation in clinical trials. This study assessed long-term, age-stratified outcomes of ICI treatment in real-world clinical practice. Methods: This nationwide observational study used data from the Netherlands Cancer Registry on patients with synchronous stage IV melanoma or NSCLC who received first-line ICIs between 2018 and 2023. Melanoma treatments included nivolumab plus ipilimumab or anti-PD-1 monotherapy; NSCLC treatments included pembrolizumab with or without chemotherapy. Primary outcomes were five-year overall survival (5-yr OS) and three-year conditional survival (3-yr CS), stratified by age. Results: A total of 11,140 patients were included, consisting of 583 patients with melanoma and 10,557 with NSCLC. In the melanoma population, 5-yr OS was 43.8%. Patients aged ≥ 75 years had a 5-yr OS of 30.8% and a 3-yr CS of 58.7%. In NSCLC treated with pembrolizumab monotherapy, 5-yr OS was 23.1%; among patients aged ≥ 75 years, 5-yr OS was 15.6% and 3-yr CS was 46.6%. Pembrolizumab combined with chemotherapy resulted in a 5-yr OS of 14.6%, with corresponding 5-yr OS of 8.4% and 3-yr CS of 35.5% in patients aged ≥ 75 years. Conclusions: This registry-based analysis suggests that ICI are associated with durable long-term survival in real-world patients with stage IV melanoma or NSCLC, including selected older adults. These findings are in line with outcomes of clinical trials, but further research is needed on predictors of ICI effectiveness in the older population. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
15 pages, 1267 KB  
Article
One-Year Comparative Outcomes of Conventional Versus Accelerated Corneal Cross-Linking in Progressive Keratoconus
by Iva Bešlić, Sania Vidas Pauk, Martina Tomić, Miro Kalauz, Tomislav Kuzman, Sonja Jandroković, Ivan Škegro, Antonela Geber, Lorena Karla Šklebar, Dina Lešin Gaćina, Petar Bešlić and Sanja Masnec
Medicina 2026, 62(6), 1209; https://doi.org/10.3390/medicina62061209 (registering DOI) - 22 Jun 2026
Abstract
Background and Objectives: Corneal collagen cross-linking (CXL) halts keratoconus progression, yet potential differences between conventional and accelerated protocols at one year remain uncertain. We analyzed the completed 12-month follow-up of a previously reported 6-month cohort to compare conventional (3 mW/cm2 × [...] Read more.
Background and Objectives: Corneal collagen cross-linking (CXL) halts keratoconus progression, yet potential differences between conventional and accelerated protocols at one year remain uncertain. We analyzed the completed 12-month follow-up of a previously reported 6-month cohort to compare conventional (3 mW/cm2 × 30 min; CXL 30) versus accelerated (9 mW/cm2 × 10 min; CXL 10) CXL, interpreting outcomes within the ABCD framework alongside Kmax and curvature radii. Materials and Methods: In this single-center retrospective longitudinal analysis of prospectively collected routine clinical data, 22 eyes were included, with assessments performed at baseline and at 1, 3, 6, and 12 months of follow-up. Evaluated outcomes comprised ABCD stages (A–D), anterior and posterior radius of curvature (ARC and PRC), Kmax, pachymetric and elevation indices, as well as UDVA and BCVA. Within-group change used Friedman with Wilcoxon post hoc; between-group differences used Mann–Whitney (α = 0.05). Results: Both protocols resulted in significant visual improvement and Kmax reduction at 12 months (overall time effect: CXL 30 p < 0.001; CXL 10 p = 0.026). Median Kmax decreased 56.5 → 52.3 D (CXL 30) and 59.3 → 58.3 D (CXL 10). UDVA improved 0.2 → 0.6 (CXL 30) and 0.2 → 0.3 (CXL 10); BCVA 0.4 → 0.8 (CXL 30) and 0.2 → 0.5 (CXL 10). Tomographic analysis showed predominantly anterior changes, with a significant decrease in A stage in the CXL 30 group and an increase in ARC in both groups, more pronounced in CXL 30. In the late 6 → 12-month window, posterior metrics (PRC and posterior elevation) were largely stable; raw PRC change did not reach significance. Conclusions: Conventional and accelerated CXL both stabilized keratoconus at one year with meaningful functional gains. Beyond 6 months, remodeling was predominantly anterior; within-group findings suggested a more pronounced anterior tomographic response in the CXL 30 group. The 12-month visit may be useful for reassessing stability after CXL, although this study was not designed to determine optimal retreatment timing or optical rehabilitation strategy. Longer-term studies with standardized biomechanical and densitometric endpoints are warranted to assess durability and refine protocol selection. Full article
15 pages, 332 KB  
Review
Young Barley (Hordeum vulgare L.) Preparations: From Phytochemical Complexity to Clinical Relevance
by Wojciech Rzeski and Weronika Rzeska
Molecules 2026, 31(12), 2190; https://doi.org/10.3390/molecules31122190 (registering DOI) - 22 Jun 2026
Abstract
Young barley, derived from the early vegetative stage of Hordeum vulgare L., constitutes a plant-based functional ingredient whose phytochemical profile differs markedly from that of mature grain. Two principal commercial forms exist—dried grass powder and juice-derived products—differing in matrix composition and bioactive compound [...] Read more.
Young barley, derived from the early vegetative stage of Hordeum vulgare L., constitutes a plant-based functional ingredient whose phytochemical profile differs markedly from that of mature grain. Two principal commercial forms exist—dried grass powder and juice-derived products—differing in matrix composition and bioactive compound concentration. This narrative review critically evaluates the current knowledge on the phytochemical composition, biological activity, and translational relevance of young barley preparations considered as a functional plant food. The phytochemical spectrum is dominated by C-glycosyl flavones, particularly saponarin and lutonarin, alongside phenolic acids, chlorophylls, enzymatic antioxidants, vitamins, and minerals. Experimental evidence implicates the modulation of redox homeostasis, inflammatory signaling, and metabolic regulators as the primary biological mechanisms. In vitro studies additionally demonstrate antiproliferative activity in human cancer cell lines and immunomodulatory properties mediated by polysaccharide-rich fractions, extending the biological profile of young barley beyond classical antioxidant activity. Although preclinical models consistently demonstrate antioxidant and metabolic effects, high experimental doses and limited preparation standardization restrict the direct extrapolation to human supplementation contexts. Available clinical trials suggest modest improvements in selected lipid, glycemic, and oxidative stress markers; yet, most are small in scale and brief in duration. Agronomic variables including fertilization strategy and soil composition represent additional, underappreciated sources of phytochemical variability and safety concern. Overall, the current evidence supports the biological plausibility of young barley as a functional plant food; yet, the clinical data remain preliminary. Future research should prioritize preparation standardization, dose–response characterization, and agronomic transparency to strengthen translational reliability. In conclusion, young barley preparations represent a biologically plausible functional plant food ingredient with preliminary clinical support, pending confirmation from adequately powered, standardised randomised controlled trials. Full article
28 pages, 5987 KB  
Article
Textilinin-1, a Snake Venom-Derived Kunitz-Type Protease Inhibitor, Accelerates Wound Healing Through Anti-Inflammatory, Antibacterial, and Pro-Regenerative Activities
by Zhuo Chen, Huiwen Pang, Youzhi Wu, David M. Klyne, Xuqiang Nie, Pengfei Jiang, Xinfei Wu, Kong-Nan Zhao and Felicity Y. Han
Pharmaceutics 2026, 18(6), 762; https://doi.org/10.3390/pharmaceutics18060762 (registering DOI) - 22 Jun 2026
Abstract
Background/Objectives: Chronic wounds remain a formidable clinical challenge due to the suboptimal efficacy of conventional delivery systems and therapeutics. Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional [...] Read more.
Background/Objectives: Chronic wounds remain a formidable clinical challenge due to the suboptimal efficacy of conventional delivery systems and therapeutics. Textilinin-1, a venom-derived Kunitz-type serine protease inhibitor, has previously established its profile as a potent hemostatic agent. However, its potential as a multifunctional biopharmaceutical for wound management remains largely untapped. This study evaluates the pharmacological effects of Textilinin-1 in preclinical models of cutaneous wound repair. Methods: We employed an integrated platform comprising bioinformatics, in vitro cellular assays, and in vivo murine excisional wounds and a pilot porcine proof-of-concept model to assess the wound healing-promoting effects of Textilinin-1 and explore associated cellular responses associated with key stages of the wound healing cascade. Results: Textilinin-1 was associated with multiple cellular responses relevant to tissue repair. It attenuated M1-like inflammatory activation and showed preliminary growth-inhibitory activity against Staphylococcus aureus under the tested conditions. Concurrently, it enhanced the proliferative and migratory capacity of fibroblasts, endothelial cells, and keratinocytes, which are key cellular targets for wound closure. In pre-clinical pilot porcine and rodent models, Textilinin-1 treatment was associated with accelerated wound contraction and improved structural tissue quality. Conclusions: Our findings provide preclinical evidence that Textilinin-1 may promote cutaneous wound repair and modulate cellular responses relevant to key stages of the wound healing cascade. These results support further investigation of Textilinin-1 as a candidate for wound repair applications. Future studies are required to define its precise molecular mechanisms, evaluate its efficacy in chronic or otherwise compromised wound models, and optimize its topical formulation or hydrogel-based delivery. Full article
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23 pages, 33952 KB  
Article
A Prosthetically Coupled Tripod Fixation Concept for Edentulous Surgical Guides: A Three-Case Proof-of-Concept Study
by Ioan-Achim Borșanu, Ralph-Alexandru Erdelyi, Sergiu-Manuel Antonie, Remus Christian Bratu and Emanuel-Adrian Bratu
Dent. J. 2026, 14(6), 385; https://doi.org/10.3390/dj14060385 (registering DOI) - 22 Jun 2026
Abstract
Background: Stabilization of surgical guides in fully edentulous patients remains a clinical challenge due to mucosal resilience and potential micromovement, even when fixation pins are used. Guide instability may affect drilling accuracy and overall workflow predictability. This proof-of-concept case series describes a stabilization [...] Read more.
Background: Stabilization of surgical guides in fully edentulous patients remains a clinical challenge due to mucosal resilience and potential micromovement, even when fixation pins are used. Guide instability may affect drilling accuracy and overall workflow predictability. This proof-of-concept case series describes a stabilization approach based on pre-placed tripod reference implants with multi-unit coupling, designed to create a mechanically defined prosthetic docking platform for fully guided implant surgery. Methods: Three fully edentulous patients requiring implant-supported rehabilitation were treated using a two-stage protocol. Three temporary reference implants were inserted in a tripod configuration 7–10 days prior to definitive surgery. Multi-unit abutments were mounted on the reference implants, and intraoral scanning was performed to design a surgical guide indexed to the prosthetic interfaces. During implant placement, the guide was screw-retained to the reference implants via the multi-unit connections. Postoperative implant positions were evaluated radiographically by superimposing postoperative datasets onto the preoperative planning model. Intraoperative guide stability, surgical events, and early postoperative outcomes were recorded. Results: Stable guide fixation was achieved in all three cases without detectable intraoperative displacement. Implant placement was completed as planned in each patient, and removal of the temporary reference implants was uneventful. No intraoperative or early postoperative complications were observed. Mean coronal, apical, and angular deviations between planned and achieved implant positions were 0.70 ± 0.16 mm, 0.39 ± 0.13 mm, and 3.30 ± 0.59°, respectively. These preliminary findings, derived from four treated arches, were comparable to ranges reported in selected studies on fully guided implant surgery; however, no direct statistical comparison with previously published datasets was performed. Conclusions: Within the limitations of this proof-of-concept case series, temporary reference implants arranged in a tripod configuration provided a stable and reproducible prosthetic indexing platform for guided implant surgery in fully edentulous patients. Further prospective studies involving larger patient cohorts and controlled comparative designs with conventional mucosa-supported or fixation-pin-supported surgical guides are required to evaluate the reproducibility, clinical performance, and long-term applicability of this stabilization concept. Full article
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13 pages, 3926 KB  
Article
Structural Mapping of Disease-Level Community-Based Care Patterns in Rural Clinics on Remote Islands in Japan: A Questionnaire Survey
by Daisuke Matsubara and Kazuhiko Kotani
Healthcare 2026, 14(12), 1799; https://doi.org/10.3390/healthcare14121799 (registering DOI) - 22 Jun 2026
Abstract
Background/Objectives: Remote islands in Japan constitute a unique medical environment in which physicians often manage a broad spectrum of clinical conditions. However, physicians practicing on remote islands have diverse medical backgrounds, and disease-level community-based care patterns in these settings have not been [...] Read more.
Background/Objectives: Remote islands in Japan constitute a unique medical environment in which physicians often manage a broad spectrum of clinical conditions. However, physicians practicing on remote islands have diverse medical backgrounds, and disease-level community-based care patterns in these settings have not been systematically described. This study aimed to characterize community-based care patterns across diseases in clinics on remote islands in Japan using an exploratory conceptual framework and to examine whether facility- and physician-related attributes were associated with these patterns. Methods: We conducted a questionnaire survey in February 2023 involving rural clinics on remote islands in Japan. For each disease, respondents reported community involvement at three clinical stages—initial consultation, follow-up, and completion of care—yielding eight possible care patterns (000–111). Primary community completeness was defined as the proportion of clinics reporting community-based involvement in initial consultation and completion of care (P111 + P101). Diseases were ranked according to this metric and stratified into three predefined conceptual zones (upper, middle, and lower). Subgroup analyses examined differences in primary community completeness according to facility- and physician-related attributes, including deployment duration, prior rural practice experience, career length, and specialty composition. Results: We analyzed data from 23 clinics covering 167 diseases. Diseases formed a continuous gradient ranging from community-completable to specialist-dependent conditions. Differences in community-based care patterns were most pronounced in the middle zone. Deployment duration was associated with directional differences in community-based care patterns, whereas specialty composition was associated with larger subgroup differences. In contrast, diseases in the lower zone demonstrated relatively stable specialist-dependent patterns regardless of facility- or physician-related attributes. Conclusions: This exploratory study proposed a conceptual framework for characterizing community-based care patterns across diseases in clinics on remote islands in Japan. The findings suggest that community-based care patterns on remote islands may reflect differences in disease-related care structures as well as contextual factors. The proposed framework may support future discussions regarding education, workforce planning, and healthcare systems in remote island settings in Japan. Full article
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19 pages, 285 KB  
Article
Diagnostic Performance and Error Patterns of a Large Language Model and Neural Network in Periodontitis Classification: A Comparative Study
by Agata Ossowska, Aida Kusiak, Albert Camlet and Dariusz Świetlik
J. Clin. Med. 2026, 15(12), 4837; https://doi.org/10.3390/jcm15124837 (registering DOI) - 22 Jun 2026
Abstract
Background/Objectives: Periodontitis is a highly prevalent chronic disease requiring accurate diagnosis for effective treatment planning. Artificial intelligence (AI) has emerged as a potential tool to support clinical decision-making. This study aimed to compare the diagnostic performance and classification error patterns of a [...] Read more.
Background/Objectives: Periodontitis is a highly prevalent chronic disease requiring accurate diagnosis for effective treatment planning. Artificial intelligence (AI) has emerged as a potential tool to support clinical decision-making. This study aimed to compare the diagnostic performance and classification error patterns of a large language model (LLM) and a neural network (NN) in periodontitis classification according to the current staging and grading system. Methods: This retrospective study included 110 patients with periodontal disease. Clinical and demographic variables (age, sex, smoking status, number of teeth, API, BOP, PPD, and CAL) were analyzed. Reference diagnoses were established by two experts. Cases were evaluated using an LLM and a neural network. Model performance was assessed using accuracy, confusion matrices, and Cohen’s kappa coefficient, along with error analysis. Results: The LLM achieved 62% accuracy for stage and 63% for grade classification (κ = 0.48). The neural network showed higher performance, with 85% accuracy for stage and 79% for grade (κ = 0.79 and κ = 0.67, respectively). The LLM more often underestimated disease severity, whereas the neural network tended to overestimate progression. Differences between models were statistically significant (p < 0.0001). Conclusions: In this dataset and classification task, the task-specific neural network demonstrated higher diagnostic performance than the evaluated large language model. However, the findings should be interpreted in light of the fundamentally different training paradigms and intended applications of these AI systems. Further research is required to optimize and validate AI-based approaches for clinical use. Full article
13 pages, 1550 KB  
Case Report
Clinical Decision-Making and Multidisciplinary Management of Peristomal Pyoderma Gangrenosum in Stage IVB Rectal Cancer: A Case Report—Corticosteroid Response but Fatal Cancer Progression
by Hiroshi Tanabe, Mari Ogawa, Mari Kita and Takeshi Kotake
Reports 2026, 9(2), 194; https://doi.org/10.3390/reports9020194 (registering DOI) - 22 Jun 2026
Abstract
Background and Clinical Significance: Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum, most commonly associated with inflammatory bowel disease or haematologic disorders. Its occurrence in patients with solid malignancies is uncommon. PPG in an oncologic setting poses diagnostic and therapeutic [...] Read more.
Background and Clinical Significance: Peristomal pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum, most commonly associated with inflammatory bowel disease or haematologic disorders. Its occurrence in patients with solid malignancies is uncommon. PPG in an oncologic setting poses diagnostic and therapeutic challenges because systemic immunosuppressive therapy, wound care, and ongoing chemotherapy must be carefully balanced; Case Presentation: We report the case of a Japanese man in his 50s with stage IVB rectal adenocarcinoma who developed rapidly progressive peristomal ulceration clinically consistent with PPG around a colostomy 12 weeks after initiation of panitumumab-containing systemic chemotherapy. The diagnosis was made on clinical grounds and was strongly supported by the clinical morphology, exclusion of major mimickers, and response to systemic corticosteroid therapy, although histopathological confirmation was not obtained. Because existing diagnostic criteria for pyoderma gangrenosum are not specifically designed for peristomal disease, they were used as supportive rather than definitive diagnostic tools. Skin biopsy was avoided due to the risk of pathergy at the peristomal site. Superficial cultures were not obtained because frequent cleansing and faecal contamination were likely to compromise diagnostic accuracy. To minimise mechanical pathergy, the stoma appliance was changed from a one-piece soft convex system to a two-piece flat system. Multidisciplinary management, including systemic corticosteroids, meticulous stoma care, and selective ultrasonic debridement, resulted in complete epithelialisation by Week 26. Chemotherapy was temporarily withheld during the active inflammatory phase and later resumed. Despite successful control of the peristomal ulceration, the patient died from progressive malignancy at Week 34; Conclusions: This case highlights the clinical challenge of balancing immunosuppressive therapy for clinically suspected PPG with ongoing oncologic treatment. Mechanical pathergy related to stoma appliance use was considered a more likely precipitating factor than chemotherapy alone, although panitumumab may have contributed to impaired cutaneous repair. Close collaboration among dermatologists, oncologists, surgeons, WOC nurses, and family caregivers is essential for multidisciplinary decision-making in complex oncologic settings. Full article
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12 pages, 878 KB  
Article
Pure Nodal Small Lymphocytic Lymphoma: Clinical, Pathologic, and Outcome Features in a Single-Center Cohort
by Andreea Georgiana Stoica, Mariana Așchie, Miruna Gherase-Cristian, Anca Florentina Mitroi, Georgeta Camelia Cozaru, Mădălina Boșoteanu, Cristina Cioti, Sorin Deacu and Irina Tica
Medicina 2026, 62(6), 1200; https://doi.org/10.3390/medicina62061200 (registering DOI) - 22 Jun 2026
Abstract
Background and Objectives: Small lymphocytic lymphoma (SLL) represents the tissue-based manifestation of chronic lymphocytic leukemia (CLL). Despite their shared biological background, patients with SLL have been underrepresented in CLL-focused clinical trials, and data addressing the clinical behavior of pure nodal SLL remain [...] Read more.
Background and Objectives: Small lymphocytic lymphoma (SLL) represents the tissue-based manifestation of chronic lymphocytic leukemia (CLL). Despite their shared biological background, patients with SLL have been underrepresented in CLL-focused clinical trials, and data addressing the clinical behavior of pure nodal SLL remain scarce. The present study aimed to identify factors associated with time to first treatment (TTFT) and progression-only survival in patients with pure nodal SLL. Materials and Methods: In this prospective observational study, 46 patients with pure nodal SLL were included and followed for a median duration of approximately 5 years. Clinical, laboratory, histopathological, and TP53-related parameters were evaluated for their prognostic impact on TTFT and progression-only survival. Results: On univariable analysis, advanced-stage disease, hemoglobin < 10 g/dL, elevated serum β2M, elevated lactate dehydrogenase, del(17p), and aberrant p53 immunohistochemical expression were significantly associated with shorter TTFT and progression-only survival. Conclusions: Pure nodal SLL is a heterogeneous entity with a variable clinical course. Easily assessable clinical and biological parameters, including TP53 abnormalities, may help predict treatment requirement and disease progression, thereby contributing to better risk stratification and more individualized management. Kaplan–Meier analysis demonstrated significantly shorter time-to-first-treatment (TTFT) among patients with elevated β2M levels (≥3.5 mg/L), bulky lymphadenopathy (≥5 cm), and advanced-stage disease. Full article
(This article belongs to the Section Hematology and Immunology)
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17 pages, 1887 KB  
Article
Salivary RANKL/OPG and Periodontal Status Among Users of Heated Tobacco and Electronic Cigarettes Versus Non-Smokers: A Prospective Observational Study
by Alexandra Cornelia Teodorescu, Elena-Raluca Baciu, Irina-Georgeta Sufaru, Bogdan-Constantin Vasiliu, Alice Murariu and Sorina Mihaela Solomon
Healthcare 2026, 14(12), 1797; https://doi.org/10.3390/healthcare14121797 (registering DOI) - 22 Jun 2026
Abstract
Background/Objectives: This prospective observational cohort study aimed to evaluate the influence of heated tobacco (HT) and electronic cigarettes (ECs) on bone remodeling markers such as receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), and periodontal status, at baseline and at [...] Read more.
Background/Objectives: This prospective observational cohort study aimed to evaluate the influence of heated tobacco (HT) and electronic cigarettes (ECs) on bone remodeling markers such as receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), and periodontal status, at baseline and at 3 months after initial periodontal therapy. Methods: The sample comprised 236 participants (130 women, 106 men; mean age 38.96 ± 7.69 years), distributed across non-smokers (n = 72), heated tobacco/HT product users (n = 83), and electronic cigarette/EC users (n = 81). For each patient, the periodontal charting included periodontal probing depth (PPD), bleeding on probing (BOP), and clinical attachment loss (CAL). Unstimulated saliva samples were analyzed for RANKL and OPG levels. All patients underwent nonsurgical periodontal therapy (scaling and root planing). Between-group comparisons were performed using the Kruskal–Wallis test followed by Bonferroni-adjusted pairwise comparisons, while within-group changes over time were assessed using the Wilcoxon signed-rank test. To complement the primary nonparametric analyses, two-way mixed-design ANOVA and ANCOVA models adjusted for baseline values and periodontitis stage were performed as sensitivity analyses. Statistical significance was set at p < 0.05. Results: At baseline, both product user groups exhibited significantly higher PPD (p = 0.005) and CAL (p = 0.001) compared with non-smokers, with no differences between HT and EC users. Salivary RANKL levels were significantly higher in HT and EC users than in non-smokers, and OPG levels did not differ significantly. Following non-surgical periodontal therapy, all parameters improved significantly across groups (p < 0.001). At the 3-month follow-up, both product user groups maintained higher PPD (p = 0.008), CAL (p = 0.001), and salivary RANKL levels, compared with non-smoking individuals (p < 0.001). The RANKL/OPG ratio remained significantly different only for EC users compared with non-smokers (p < 0.001). Conclusions: HT and EC use were associated with differences in periodontal parameters and higher RANKL levels, while differences in the RANKL/OPG ratio were observed in EC users compared with non-smokers. Non-surgical periodontal therapy improved clinical parameters and reduced the RANKL/OPG ratio, highlighting the importance of biofilm control. Full article
(This article belongs to the Special Issue Oral Healthcare: Diagnosis, Prevention and Treatment—2nd Edition)
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15 pages, 886 KB  
Article
Evaluation of Clinical Outcomes in Dogs with Malignant Intranasal Tumors Treated with Radiotherapy: A Retrospective Study of 40 Cases
by Simone Carvalho dos Santos Cunha, Bianca Moreira Angelim, Rebeca Herdade, Karen Cristina de Souza da Rocha Dias, Laís Calazans Menescal Linhares, Rafael Costa Bitencourt, Guilherme Andraus Bispo, Felipe Noleto de Paiva and Andrigo Barboza de Nardi
Cancers 2026, 18(12), 2013; https://doi.org/10.3390/cancers18122013 (registering DOI) - 22 Jun 2026
Abstract
Background/Objectives: Intranasal tumors are common malignancies in dogs, characterized by locally aggressive behavior and clinical signs such as epistaxis, nasal discharge, and facial deformity. Radiotherapy (RT) is considered the treatment of choice due to anatomical limitations to surgical resection. This study aimed to [...] Read more.
Background/Objectives: Intranasal tumors are common malignancies in dogs, characterized by locally aggressive behavior and clinical signs such as epistaxis, nasal discharge, and facial deformity. Radiotherapy (RT) is considered the treatment of choice due to anatomical limitations to surgical resection. This study aimed to evaluate clinical outcomes, toxicity, and prognostic factors in dogs with primary malignant intranasal tumors treated with cobalt-60–based megavoltage radiotherapy. Methods: This retrospective study included 40 dogs with histopathologically confirmed primary malignant intranasal tumors treated between September 2018 and February 2025 at a veterinary radiotherapy clinic in Rio de Janeiro, Brazil. Medical records were reviewed for patient demographics, tumor characteristics, treatment protocols, response, toxicity, and survival outcomes. Tumors were staged using modified Adams criteria based on computed tomography. Definitive-intent protocols (n = 32) delivered 48–54 Gy in 10–13 fractions administered three to five times weekly, while palliative protocols consisted of either four fractions of 8 Gy delivered once weekly or five fractions of 4 Gy delivered daily. Results: Adenocarcinoma was the most common histologic subtype (42.5%), and 82.5% of dogs had stage III–IV disease. The objective response rate was 82.5% (CR: 17.5%; PR: 65.0%), with clinical benefit observed in 92.5% of cases. Acute toxicity was frequent but manageable, primarily affecting skin, oral mucosa, and eyes. Overall median progression-free interval (PFI) and survival time (MST) were 382 days and 430 days, respectively. Stage IV disease was significantly associated with shorter survival when compared to stage I-III (MST 345 vs. 1063 days, respectively; p = 0.016). Treatment response was significantly associated with PFI in univariate analysis (p < 0.05). Conclusions: Radiotherapy provided high response rates and meaningful clinical benefit with acceptable toxicity in dogs with malignant intranasal tumors, highlighting the importance of early diagnosis and treatment. Further prospective studies with standardized protocols are warranted. Full article
(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)
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31 pages, 2460 KB  
Review
Beyond DSM Categories: Criteria for Biologically Valid Disease Axes in Psychiatry
by Lukasz Szarpak, Bernard Rybczynski, Michal Pruc, Bartosz W. Maj, Maciej Maslyk, Iwona Niewiadomska and Wieslaw J. Cubala
J. Clin. Med. 2026, 15(12), 4830; https://doi.org/10.3390/jcm15124830 (registering DOI) - 22 Jun 2026
Abstract
Dimensional and transdiagnostic models have become central to contemporary efforts to move psychiatric nosology beyond DSM/ICD categories. This shift reflects persistent limitations of categorical syndromes as final biological targets, including within-diagnosis heterogeneity, cross-diagnostic comorbidity, developmental instability, and incomplete alignment with underlying mechanisms. This [...] Read more.
Dimensional and transdiagnostic models have become central to contemporary efforts to move psychiatric nosology beyond DSM/ICD categories. This shift reflects persistent limitations of categorical syndromes as final biological targets, including within-diagnosis heterogeneity, cross-diagnostic comorbidity, developmental instability, and incomplete alignment with underlying mechanisms. This article examines a central unresolved problem in this transition: when, if ever, a descriptive or predictive psychiatric dimension can be interpreted as a candidate disease axis. We conducted a conceptual synthesis of major dimensional and transdiagnostic frameworks, including Research Domain Criteria (RDoC), Hierarchical Taxonomy of Psychopathology (HiTOP), the general psychopathology factor, cross-disorder genomic models, clinical staging approaches, and data-driven subtyping. The analysis separates three levels of inference that are often conflated in psychiatric research: descriptive structure, predictive utility, and disease-level biological validity. The synthesis identifies a recurrent inferential error in which reproducible factors, clusters, or classifiers are prematurely treated as evidence of disease architecture. Such constructs may describe real covariance patterns or improve prognostic prediction without establishing biological validity. We propose an eight-domain hierarchical framework for promotion to candidate disease-axis status, organized into four core gatekeepers—replication across cohorts, ascertainment, and methods, developmental coherence, incremental prognostic value beyond diagnosis and nonspecific severity, and discriminability from nonspecific severity—and four supporting/disciplining domains: cross-level convergence, mechanistic constraint, clinical leverage, and explicit falsifiability/boundary conditions. On this basis, middle-level transdiagnostic spectra and selected cross-disorder genomic liabilities appear more defensible as candidate disease axes than highly global or weakly specified constructs. Psychiatry was justified in turning toward dimensional models, but dimensionality alone does not confer biological validity. The key task is not to choose between categories and dimensions, but to define the evidential thresholds under which dimensional constructs warrant ontological promotion. Full article
(This article belongs to the Special Issue Clinical Advances in Personalized Psychiatry)
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32 pages, 1694 KB  
Review
Comprehensive Review of Nystagmus and Vertigo Diagnostics: From Pathological Foundations to AI-Driven Telemedicine
by Kowshik Balasubramanian, Ali Danesh and Abhijit Pandya
Sensors 2026, 26(12), 3949; https://doi.org/10.3390/s26123949 (registering DOI) - 22 Jun 2026
Abstract
Nystagmus, the involuntary rhythmic oscillation of the eyes, is a critical diagnostic marker in vestibular medicine, distinguishing life-threatening central disorders such as stroke from benign peripheral conditions including Benign Paroxysmal Positional Vertigo (BPPV). Despite its clinical importance, accurate nystagmus assessment has long been [...] Read more.
Nystagmus, the involuntary rhythmic oscillation of the eyes, is a critical diagnostic marker in vestibular medicine, distinguishing life-threatening central disorders such as stroke from benign peripheral conditions including Benign Paroxysmal Positional Vertigo (BPPV). Despite its clinical importance, accurate nystagmus assessment has long been constrained by expensive infrared video-oculography equipment such as videonystagmography, specialist dependency, and the episodic nature of vestibular symptoms that are often resolved before a clinical encounter. This review synthesizes approximately 50 papers published between 1952 and 2026 across four thematic domains: AI-driven nystagmus analysis, clinical medicine, smartphone and portable hardware innovations, and telemedicine and remote monitoring. On the AI front, classical machine learning models achieve up to 98.77% nystagmus recognition accuracy using ensemble methods, while deep learning frameworks spanning CNNs, U-Nets, LSTMs, and optical flow networks demonstrate clinical-grade slow-phase velocity measurement equivalent to gold standard video-oculography on standard smartphone RGB video. Large language and vision models including GPT-4V and Gemini 2.0 show early-stage promise as zero-shot triage tools but currently fall well below specialist-level diagnostic accuracy. Concurrently, portable hardware innovations ranging from 3D-printed goggle systems to ARKit-based smartphone applications are narrowing the accessibility gap, while telemedicine frameworks enable ictal recording and cloud-based specialist review outside the clinic. Across all domains, the common barriers to clinical translation are dataset scarcity for rare BPPV subtypes, sensitivity to ambient conditions, and the absence of explainable AI mechanisms. This review maps the current state of the field and identifies multimodal data fusion, prospective clinical validation, and interpretable AI as the critical next steps toward equitable, specialist independent vestibular diagnostics. Full article
(This article belongs to the Section Biomedical Sensors)
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16 pages, 285 KB  
Review
Artificial Intelligence and the Evolving Paradigm of Lung Cancer Management
by Russell Seth Martins, Yousif Hanna and Andrea L. Axtell
Cancers 2026, 18(12), 2012; https://doi.org/10.3390/cancers18122012 (registering DOI) - 22 Jun 2026
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis, biological heterogeneity, and persistent challenges in staging and treatment selection. This narrative review summarizes current and emerging applications of AI across lung cancer screening and early detection, imaging-based [...] Read more.
Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis, biological heterogeneity, and persistent challenges in staging and treatment selection. This narrative review summarizes current and emerging applications of AI across lung cancer screening and early detection, imaging-based staging and prognostication, tissue and liquid biopsy-based tumor characterization, treatment planning, surgical and intraoperative guidance, and drug discovery. In imaging, deep learning models have demonstrated high performance in pulmonary nodule detection, risk stratification, and prediction of molecular alterations, while also showing promise in improving screening efficiency and reducing interpretive variability. In pathology and liquid biopsy domains, AI enables prediction of driver mutations, immunotherapy response, and survival outcomes directly from histopathology slides, circulating tumor DNA, and other blood-based biomarkers, facilitating minimally invasive precision oncology approaches. In treatment planning and delivery, AI systems are being developed to support clinical decision-making, surgical planning (through advanced image segmentation and delineation of operative anatomy), and intraoperative navigation through robotic and computer vision-enabled platforms. Despite these advances, significant barriers remain, including limited real-world validation, algorithmic biases, workflow integration issues, and unresolved ethical and legal concerns. Future progress will depend on the development of transparent, clinically validated, and generalizable AI systems that augment rather than replace the expertise of clinical providers and healthcare teams. Active engagement from pulmonologists, oncologists, radiologists, and thoracic surgeons will be essential in guiding safe implementation and ensuring that AI-driven innovations translate into meaningful improvements in patient outcomes. Full article
(This article belongs to the Section Methods and Technologies Development)
12 pages, 260 KB  
Article
Association Between Pain Self-Efficacy and Adherence to Hemodialysis Regimen
by Ioanna Mitsia, Vasiliki Matziou, Maria Polikandrioti, Sofia Zyga and Victoria Alikari
J. Clin. Med. 2026, 15(12), 4824; https://doi.org/10.3390/jcm15124824 (registering DOI) - 21 Jun 2026
Abstract
Background/Objectives: Pain is a common symptom in patients undergoing hemodialysis (HD) and may influence their quality of life. Pain self-efficacy may play an important role in self-management and adherence behaviors. This study aimed to examine the association between pain self-efficacy and adherence [...] Read more.
Background/Objectives: Pain is a common symptom in patients undergoing hemodialysis (HD) and may influence their quality of life. Pain self-efficacy may play an important role in self-management and adherence behaviors. This study aimed to examine the association between pain self-efficacy and adherence to the HD regimen in patients undergoing HD. Methods: In this descriptive and cross-sectional study, 199 patients undergoing HD from a single private hospital (convenience sample) in Athens, Greece, completed the Greek-Simplified Adherence Questionnaire-HD (GR-SMAQ-HD) to assess adherence and the Pain Self-efficacy Questionnaire (PSEQ) to assess pain self-efficacy. Sociodemographic and clinical data were also recorded. Bivariate analyses and multiple linear regression were performed to identify factors associated with adherence. Statistical significance was set at p < 0.05. Results: Patients demonstrated moderate levels of pain self-efficacy (mean PSEQ = 33.96 ± 9.74) and moderate adherence to the HD regimen (mean GR-SMAQ-HD = 4.78 ± 2.54). No significant correlation was found between pain self-efficacy and adherence in bivariate analysis (rho = 0.125, p = 0.221). However, in multivariate analysis, pain self-efficacy was a significant independent predictor of adherence (β = 0.056, p = 0.032). Longer duration of End-Stage Renal Disease (ESRD) (β = −0.158, p < 0.001), higher pill burden (rho = −0.237, p = 0.030) were associated with lower adherence. Marital status was also a significant predictor of adherence (β = 1.631, p = 0.016). The model explained 24% of the variance in adherence (Adjusted R2 = 0.24). Conclusions: Pain self-efficacy may indirectly affect adherence to the HD regimen, although its direct effect is modest. Adherence appears to be negatively influenced by pill burden and ESRD duration, while social support may play an important role. Full article
(This article belongs to the Special Issue A Holistic Approach to Management of Complications in Hemodialysis)
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