Search Results (6,752)

Background/Objectives: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with a 40% recurrence rate. However, reliable biomarkers for early recurrence detection or treatment guidance are lacking, especially for virus-negative tumors. Circulating tumor DNA (ctDNA), a fragment of tumor-derived cell-free DNA in blood, has emerged across multiple cancers as a minimally invasive precision biomarker to detect minimal residual disease (MRD); predict recurrence; and monitor treatment response. This review’s objective was to summarize recent advances in ctDNA as a tool for therapeutic decision-making in MCC, contextualized by findings in other malignancies. Methods: A comprehensive literature review was performed, focusing on studies published between 2016 and 2026 that evaluate ctDNA in MCC and other cancers. Key prospective trials, observational studies, and case reports were identified through PubMed and relevant conference proceedings. Data on ctDNA assay methods (tumor-informed vs. tumor-agnostic), clinical sensitivity, lead time for recurrence detection, and predictive value for therapy response were extracted and synthesized. Results: Across cancers such as colorectal, lung, and melanoma, ctDNA positivity after curative treatment predicts relapse months in advance of imaging and can guide adjuvant therapy decisions. In MCC, recent studies demonstrate that ctDNA levels correlate with MCC tumor burden and exhibit high sensitivity and specificity for clinically evident disease. Stage I-III MCC patients who were ctDNA-positive within four months of treatment had a 7.4-fold higher recurrence risk within the subsequent 12–18 months of follow-up. Serial ctDNA monitoring may enable earlier intervention in otherwise asymptomatic ctDNA-positive MCC cases, helping distinguish responders from non-responders. Conclusions: ctDNA is an emerging precision biomarker that offers significant prognostic and surveillance utility in MCC. It enables earlier detection of recurrence, potentially allowing treatment to begin before clinical disease manifests. It also helps stratify patients by risk and treatment response, informing personalized surveillance intensity and therapeutic choices. Integrating ctDNA monitoring into MCC management could improve outcomes by guiding timely interventions, although prospective trials are needed to confirm that ctDNA-guided decisions translate to improved patient survival. Formal cost-effectiveness analyses have not yet been conducted and represent an important area for future investigation. Full article

Background/Objectives: Verb anomia is a common symptom of primary progressive aphasia (PPA), particularly in the logopenic variant (lvPPA). Despite the central role of verbs in sentence construction, interventions specifically targeting verb anomia remain scarce. This study examined the effects of Personalized Observation, Execution and Mental Imagery (POEM) therapy, grounded in evidence that sensorimotor systems are recruited during action verb processing and may support verb retrieval. Methods: A 74-year-old woman with lvPPA completed pre- and post-POEM assessments (linguistic, cognitive, thymic, and motor). POEM consisted of 15 telepractice sessions delivered three times weekly using a systematic procedure with three sensorimotor strategies: action observation, gesture execution, and mental imagery. Results: No significant gains were observed in verb production across naming tasks, spontaneous speech, or functional communication contexts. However, co-verbal gesture use increased in frequency and quality, particularly during the naming of untrained verbs, suggesting that the gesture execution strategy was generalized. A delayed treatment effect was also noted, raising questions regarding the optimal duration of POEM in neurodegenerative conditions. Conclusions: While no statistically significant improvements in verb production were observed, qualitative analyses revealed increased use and quality of co-verbal gestures, suggesting that POEM had a compensatory effect. Future research involving larger cohorts and longer periods could help clarify the benefits of POEM therapy. It would also be relevant to compare in-person and remote delivery formats to evaluate POEM therapy’s robustness and adaptability in different clinical contexts. To conclude, these findings remain preliminary and should be interpreted with caution, particularly given the lack of significant improvement in primary verb production outcomes. Full article

Ulcerative colitis (UC) is a chronic disease marked by mucosal inflammation of the colon, and its prevalence has progressively increased worldwide. Gut dysbiosis is recognized as a key contributor to its pathogenesis. Although conventional treatments are effective in managing symptoms, they often fail to address the underlying gut microbial imbalance, prompting growing interest in microbiota-based therapies. Probiotic supplementation has demonstrated potential to modulate the disease. However, its clinical application is limited by variability in formulations and strain composition. Debate persists regarding the relative benefits of single-strain probiotics (SSPs), which depend on strain specificity, versus multi-strain probiotics (MSPs), which may provide synergistic effects. The literature remains inconclusive, with some studies indicating that MSPs outperform SSPs, while others emphasize the importance of strain specificity. This review describes the mechanistic basis of both approaches and descriptively synthesizes their clinical efficacy in UC management based on the clinical studies published between 2018 and 2025. Several studies report that both SSPs and MSPs are associated with clinical improvements, including reduced disease activity, symptom alleviation, and enhanced endoscopic outcomes. Given the methodological heterogeneity across included studies, comparative findings should be interpreted with appropriate caution. A direct head-to-head trial could provide a better understanding to determine the optimal approach. Advancing toward personalized probiotic therapy may further enhance the clinical application of probiotics for disease management. Full article

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction and impaired platelet production. Increasing evidence suggests that systemic inflammation plays a significant role in disease pathogenesis and clinical outcomes. This study aimed to evaluate the prognostic significance of inflammatory indices and their association with complications, mortality, treatment response, and relapse in patients with ITP. In this single-center retrospective study, 166 adult patients diagnosed with primary ITP between January 2015 and December 2024 were analyzed. Demographic, clinical, and laboratory data at diagnosis were collected. Inflammatory indices derived from complete blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were evaluated. Their associations with clinical outcomes were assessed using appropriate statistical methods. During the observation period based on retrospective medical records, complications occurred in 12% of patients, and mortality was observed in 6.6%. Patients with complications had significantly higher D-dimer levels and reduced bone marrow megakaryocyte production. In group comparisons, mortality was significantly associated with advanced age, male sex, and comorbidities. Laboratory findings revealed that lower hemoglobin, lymphocyte count, mean platelet volume, and albumin levels, along with higher PLR, erythrocyte sedimentation rate, bilirubin, and D-dimer levels, were significantly associated with mortality. Inflammatory indices such as NLR and PLR were not associated with complication development, but PLR was significantly associated with mortality. Response to intravenous immunoglobulin (IVIG) therapy was significantly associated with higher total protein, albumin, and fibrinogen levels, and lower erythrocyte sedimentation rate. Relapse was significantly associated in group comparisons with increased inflammatory activity, higher reticulocyte count, and positivity for antinuclear antibodies and Helicobacter pylori antigen. Systemic inflammation and impaired megakaryopoiesis play critical roles in the prognosis of ITP. While conventional inflammatory indices showed limited predictive value for complications, markers such as PLR, D-dimer, and albumin were associated with mortality and clinical outcomes. These findings suggest that readily available laboratory parameters may provide valuable insights for risk stratification and personalized management in patients with ITP. Full article

Developing functional foods that address both oxidative stress and physiological challenges like dysphagia is a critical frontier in personalized nutrition. This study investigates the multi-component synergy of Fu Ling Yin Zi (FLYZ), a traditional dietary therapy, and translates its functional properties into a 3D-printed dysphagia-friendly food. Using response surface methodology, the optimal FLYZ formulation was established at a 5:1:5 ratio of Poria cocos (Schw.) Wolf., Amygdalus communis Vas, and Citrus reticulata. Network pharmacology and molecular docking suggested that FLYZ’s active compounds (e.g., nobiletin, stigmasterol, tangeretin, l-SPD, glabridin, estrone) may mitigate oxidative stress via multiple targets (PTGS2, AKT1, TNF, ESR1, MMP9, and MAOA), with pathway analysis pointing to a potential role of the AKT1/GSK3β/HIF-1α axis. Subsequent in vitro cellular assays demonstrated that FLYZ enhanced antioxidant enzyme activities, reduced intracellular ROS, and modulated the expression of associated genes, supporting a potential link to this pathway. To actualize these functional benefits for patients with swallowing difficulties, a novel 3D-printing ink incorporating FLYZ and walnut oil within a hydrogel matrix (3% xanthan gum, 3% pectin, 1.5% carrageenan) was developed. The printed constructs exhibited excellent shape fidelity and, based on standardized IDDSI fork and spoon tests, were categorized as level 4 (pureed/extremely thick). Furthermore, a simulated in vitro digestion model showed that the colloidal network significantly protected FLYZ’s polyphenols and flavonoids, markedly improving their bioaccessibility and post-digestion antioxidant capacity. Collectively, this work establishes an integrated approach that combines predictive molecular profiling with advanced 3D food printing, thereby supporting the development of future foods tailored for personalized nutrition. Full article

Standard diagnostic categories (International Classification of Diseases (ICD) and Diagnostic and Statistical Manual of Mental Disorders (DSM)) were developed as a pragmatic compromise between competing theoretical schools in psychiatry and psychotherapy. Focused on recognizable patterns of symptoms, they produce reliable descriptions and facilitate clinical communication, research, and reimbursement. Such a focus, however, necessarily falls short of the etiological complexity of bodily, personal, interpersonal, and cultural processes that shape human suffering. This article argues that beneath the diversity of approaches seeking to address this gap, a fundamental complementarity emerges—one constitutive of human existence itself: the complementarity between two irreducible ways of being in the world. The first is the organismic–biological dimension, elaborated in Jakob von Uexküll’s biosemiotics: sign-governed, evolutionarily pre-formed processes of meaning-attribution that operate prior to and independent of language. The second is the symbolic–cultural dimension, developed in Ernst Cassirer’s philosophy of symbolic forms: the embedding of human beings in socially created, intersubjectively shared symbol systems through which the world is seen and understood. Although both approaches were published nearly a century ago, this article is not primarily a historical contribution. Rather, it argues that psychopathology and therapy can be understood more fully—and clinical practice enriched—when both dimensions are taken into account as genuinely complementary perspectives. Full article

Background/Objectives: In ketogenic therapy for children with refractory epilepsy—a special patient group—the quality of life of primary caregivers is often overlooked. This study aimed to explore the current state of primary caregivers’ quality of life and identify associated risk factors. Methods: A cross-sectional study was conducted from 21 January 2024 to 21 January 2025. A total of 117 primary caregivers of children with refractory epilepsy completed the World Health Organization Quality of Life (WHOQOL)-BREF (26 items) and Adherence questionnaire (6 items). Participants were divided into KD therapy groups (n = 51) and non-KD therapy groups (n = 66) according to the treatment. Factors associated with caregivers’ QoL in the ketogenic treatment were analyzed using the multifactor hierarchical regression. Results: There was no significant difference in QoL scores between the KD and non-KD caregiver groups (p > 0.05). KD adherence emerged as independently associated with caregivers’ QoL, particularly in the environmental domain (Model 1: β = −0.309, p = 0.022; Model 2: β = −0.306, p = 0.025). A higher KD cost was significantly associated with a lower social domain score in both models (Model 1: β = −0.285, p = 0.032; Model 2: β = −0.286, p = 0.034). Model 1 for the environmental domain demonstrated modest explanatory power (Adjusted R² = 0.246, p = 0.002). Conclusions: These findings underscore the need for clinical support systems to assess and address modifiable stressors early in treatment, including family structure, challenges with ketogenic diet therapy adherence, and financial burden. Such comprehensive evaluation is essential for developing effective and personalized interventions. Full article

Head and neck squamous cell carcinoma (HNSCC) remains one of the most aggressive and heterogeneous malignancies worldwide, characterized by high rates of locoregional recurrence, metastatic dissemination, and therapeutic resistance. Angiogenesis plays a central role in tumor progression by supporting vascular remodeling, hypoxia adaptation, invasion, immune evasion, and metastatic spread. In HNSCC, angiogenic activation is regulated through complex interactions involving hypoxia-inducible factors, vascular endothelial growth factor (VEGF) signaling, stromal remodeling, inflammatory pathways, and epigenetic mechanisms within the tumor microenvironment. Recent evidence has also highlighted the role of non-coding RNAs, particularly microRNAs, and exosome-mediated communication in modulating angiogenic and immune-related signaling pathways. Although antiangiogenic therapies, including monoclonal antibodies and tyrosine kinase inhibitors, have demonstrated biological activity in HNSCC, their clinical efficacy remains limited by tumor heterogeneity, adaptive resistance mechanisms, toxicity, and the lack of validated predictive biomarkers. Several emerging therapeutic strategies are under preclinical or early clinical investigation in HNSCC, including miRNA-based approaches, nanoparticle-assisted delivery systems, vascular normalization concepts, and combinations with immune checkpoint inhibitors; however, robust clinical evidence for most of these strategies remains limited, and their translation to routine practice requires further validation. This review provides a comprehensive overview of the molecular mechanisms regulating angiogenesis in HNSCC and critically discusses current and emerging pharmacological strategies targeting these pathways. Particular emphasis is placed on VEGF/VEGFR signaling, the integration of miRNA and exosome biology, resistance mechanisms, and translational perspectives for biomarker-guided personalized therapy. The novelty of this review lies in the systematic integration of miRNA- and exosome-mediated angiogenic regulation, therapeutic resistance pathways, and precision medicine strategies into a unified pharmacological framework, addressing gaps not fully covered by prior reviews focused primarily on VEGF-targeted agents. Full article

Background: Tinnitus is a prevalent auditory disorder associated with maladaptive cortical plasticity and aberrant neural synchronization across auditory and non-auditory brain networks. Acoustic desynchronization-based sound therapies, such as coordinated reset neuromodulation, aim to counteract pathological oscillatory patterns but commonly require prolonged daily listening sessions and specialized delivery formats, which may limit their accessibility and practicality in routine clinical settings. To address this limitation, a modified desynchronization protocol embedding therapeutic tones within music was developed to improve tolerability and engagement. This study aimed to evaluate the clinical effects of modified Music-Integrated Desynchronization Sound Therapy (mMIDST) on tinnitus severity in patients with chronic tinnitus. Methods: In this prospective, randomized, controlled, single-blind pilot trial conducted at the Otolaryngology Department of Hospital Clínico Universidad de Chile (Santiago, Chile) between July 2024 and July 2025, adults aged 18–75 years with chronic non-pulsatile tinnitus were assigned to receive either mMIDST or an active control intervention consisting of low-frequency stimulation (LFS) embedded within identical music tracks. Participants listened to personalized sound files for one hour daily, five days per week. Tinnitus severity was assessed using the Tinnitus Handicap Inventory (THI), with audiometric evaluations performed at baseline and after one, two, and three months. Between-group differences were analyzed using the Mann–Whitney U test. Results: Twenty-five participants completed the study (15 mMIDST, 10 LFS). Baseline audiometric thresholds and THI scores were comparable between groups. The mMIDST group showed significantly greater reductions in THI scores than the LFS group at two and three months of treatment (p < 0.05). Conclusions: mMIDST was associated with time-dependent improvements in tinnitus-related distress compared with an active control condition. Embedding desynchronization-based tonal stimulation within music may represent a promising and well-tolerated non-invasive approach for chronic tinnitus management. Full article

Background/Objectives: The accurate prediction of postprocedural mortality is critical for clinical decision-making; however, research on mortality risk models for patients undergoing mechanical thrombectomy remains limited. This study aimed to develop and validate machine learning models for predicting 90-day post-mechanical thrombectomy mortality. Methods: A retrospective-prospective cohort study involving 699 retrospective patients (January 2019–December 2022) and 274 prospective patients (January 2023–June 2024) from a single institution in Sichuan was conducted. The primary outcome was all-cause mortality within 90 days, ascertained via telephone follow-up. Predictors were identified using univariate analysis and LASSO regression. Eight predictive models were developed and evaluated using existing machine learning methods via 10-fold cross-validation. Model performance was assessed through discrimination, calibration, decision curve analysis, and interpretability via Shapley additive explanations. Results: The final dataset included 593 patients in the modeling set and 247 in the validation set. The 90-day mortality rates were 25.6% and 32.0%, respectively. Key predictors included age, hyperlipidemia, atrial fibrillation, pre-stroke statin use, antiplatelet/anticoagulant therapy within 48 h of onset, dysphagia, D-dimer levels, and activities of daily living scores. Logistic regression demonstrated superior performance in the modeling cohort (AUC = 0.87), whereas the multilayer perceptron model exhibited the greatest efficacy in the validation cohort (AUC = 0.77). Conclusions: Machine learning algorithms can accurately predict 90-day mortality among patients undergoing mechanical thrombectomy. The multilayer perceptron model demonstrated robust validation performance and offers a potential tool for personalized risk assessment and optimization of clinical decision-making. Full article

Opioids are first-line therapy for cancer pain, yet up to 30% of patients fail to achieve adequate control at standard doses. Opioid response is partly genetically mediated, and understanding these factors may improve symptom management. This project aimed to assess the feasibility of using tumor bank DNA for pharmacogenetic analyses and to validate previously identified genetic variants associated with opioid response using existing genetic and clinical data. In this retrospective cohort study, clinical data (morphine equivalent daily dose, demographics) and genetic data (single-nucleotide polymorphisms) were analyzed across 31 candidate loci. Adult deceased patients with melanoma, colorectal, or lung cancer treated with opioids between 2016 and 2021 and with available tumor bank DNA were included. Patients without sufficient DNA or not deceased were excluded. Of 3503 potential samples, 502 met the inclusion criteria. The median morphine equivalent daily dose was 40 mg (range 1–2140 mg). Eleven loci across six genes may be associated with higher (OPRM1, TAOK3, NFKBIA, COMT, and RHBDF2) and lower (COMT and GCH1) opioid dose requirements (p < 0.05, not significant after Bonferroni correction). Ultimately, tumor bank DNA is a feasible resource for pharmacogenetic research. Identified loci may contribute to variability in opioid response and support future personalized pain management strategies. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) represents one of the most common pregnancy-related disorders and it is correlated to increased risks of adverse maternal and neonatal outcomes. The prognostic role of initial glycemic values in predicting neonatal hypoglycemia and other complications remains underexplored. Methods: This retrospective study analyzed 233 women diagnosed with GDM between 2018 and 2024. Participants were stratified into three risk groups based on diagnostic oral glucose tolerance test (OGTT) values: low-risk group (fasting plasma glucose [FPG] 92–100 mg/dL, 1 h < 180 mg/dL, 2 h < 153 mg/dL), intermediate-risk group (FPG 101–110 mg/dL or 1 h 180–190 mg/dL or 2 h 153–163 mg/dL), and high-risk group (FPG > 110 mg/dL or 1 h > 190 mg/dL or 2 h > 163 mg/dL). Neonatal hypoglycemia was defined as the primary outcome, whereas secondary outcomes comprised insulin requirements, continuous glucose monitoring (CGM) use, macrosomia, polyhydramnios, and perinatal complications. Results: Non-significant differences across groups were observed except for Caucasian predominance in the high-risk group. Hypoglycemia trended higher in intermediate- and high-risk groups (26% and 21% vs. 17%), as well as polyhydramnios (14.3% and 13.8% vs. 4.5%) without statistical significance. Overall metabolic control was excellent, with almost 70% of patients maintaining HbA1c values ≤ 5.5% throughout the pregnancy with early and limited use of insulin therapy (17.3%). Conclusions: Diagnostic OGTT stratification provides limited prognostic value in optimized GDM care with early CGM and insulin use. Although trends for hypoglycemia and polyhydramnios suggest potential utility, the excellent metabolic control likely flattened the differences between groups. Prospective trials with CGM metrics are needed to develop more refined risk models, potentially enabling a more personalized management. Full article

Background: Lung cancer is a highly heterogeneous disease in which molecular characterization has become essential for guiding personalized therapies. The implementation of next-generation sequencing (NGS) allows for the simultaneous detection of multiple genomic alterations, improving tumor profiling and therapeutic decision-making. This study aimed to characterize the molecular landscape of lung cancer using NGS and to evaluate its association with histological subtypes and programmed death-ligand 1 (PD-L1) expression. Methods: A retrospective observational study was conducted on 96 patients diagnosed with lung cancer between 2023 and 2025. Molecular profiling was performed using the Action OncoKitDx panel. Associations between genetic alterations, histological subtypes, and PD-L1 expression were analyzed using Fisher’s exact test, with p < 0.05 considered statistically significant. Results: Adenocarcinoma was the most common histological subtype (67.7%), followed by squamous cell carcinoma (26%). The most common mutations were KRAS (34.4%), TP53 (29.2%), and EGFR (11.5%). KRAS mutations were significantly associated with adenocarcinoma (p = 0.001), while squamous cell carcinoma showed a higher frequency of cases without molecular alterations detected by the NGS panel (p = 0.002). Co-mutations were identified in 22.9% of cases, with KRAS–TP53 being the most common combination. Tumors harboring EGFR mutations showed a significantly lower frequency of co-mutations (p = 0.012). No significant associations were found between PD-L1 expression and either histological subtypes or the analyzed genetic alterations. Conclusions: Lung cancer exhibits marked molecular heterogeneity, with a predominance of KRAS mutations in adenocarcinoma. The low frequency of co-mutations in EGFR-mutated tumors supports their role as dominant driver alterations. The lack of association between PD-L1 expression and genomic alterations highlights the complexity of its regulation and suggests the involvement of multiple biological factors. These findings reinforce the clinical value of NGS in comprehensive tumor profiling and in the development of precision medicine strategies. Full article

Background/Objectives: The Systemic Immune–Inflammation Index (SII), derived from routine blood counts, has emerged as a potential marker of systemic inflammation in psoriasis. However, its longitudinal behavior across different systemic and biologic therapies remains poorly characterized. This study aimed to evaluate changes in SII over time, assess its relationship with Psoriasis Area and Severity Index (PASI) scores, and compare SII trajectories among different treatment classes. Methods: A retrospective single-center study included 210 adults with psoriasis treated for 12 months with cyclosporine, anti-TNF-α, anti-IL-17, or anti-IL-23 agents. SII and PASI were recorded at baseline, 16, 36, and 52 weeks. Correlations between SII and PASI were assessed using Spearman’s analysis. Longitudinal changes were evaluated using the Friedman test, and treatment-group differences were assessed using Kruskal–Wallis analysis. An adjusted multivariable linear regression model including age, sex, body mass index, psoriatic arthritis, baseline PASI, and treatment group was performed to identify factors associated with Δ%SII. Results: SII correlated with PASI at baseline (ρ = 0.406, p < 0.001) and at 52 weeks (ρ = 0.186, p = 0.007), whereas no significant associations were observed at intermediate timepoints. Longitudinal analyses demonstrated significant differences in SII trajectories among treatment groups (p < 0.001). SII increased over time in the cyclosporine and anti-TNF-α groups, while anti-IL-17 and anti-IL-23 therapies were associated with marked and sustained reductions. In the adjusted model, anti-IL-17 (β = −90.7, 95% CI −119.6 to −61.8, p < 0.001) and anti-IL-23 therapies (β = −97.9, 95% CI −126.2 to −69.6, p < 0.001) remained independently associated with greater reductions in SII compared with cyclosporine, whereas anti-TNF therapy showed no significant difference. Conclusions: SII is a dynamic marker of systemic inflammatory changes in psoriasis and exhibits distinct longitudinal patterns according to treatment class. The pronounced reductions observed with IL-17 and IL-23 inhibitors support the potential value of SII as an adjunctive measure of systemic inflammation. However, prospective studies are required to clarify its clinical utility and determine its role in routine patient management. Full article

Chemoradiotherapy plays an important role in the management of locally advanced head and neck squamous cell carcinoma. Unfortunately, a substantial fraction of patients experience treatment failure, while others suffer from significant treatment-related toxicity caused by intensive chemoradiotherapy regimens. This underscores the need for new biomarkers that can accurately capture the biological tumor heterogeneity and guide personalized therapy. Functional imaging combined with AI-based approaches such as radiomics and deep learning may offer a promising strategy for treatment stratification. However, a substantial number of challenges remain before clinical implementation can be achieved. Therefore, this review proposes a biology-driven framework for AI analysis of functional imaging in head and neck squamous cell carcinoma. In addition, it emphasizes the need for clinically oriented validation strategies to facilitate the translation of stratification models into clinical management. Full article