Biomedicines最新文献

{"title":"RETRACTED: Caffo et al. Molecular Investigation of DKK3 in Cerebral Ischemic/Reperfusion Injury. <i>Biomedicines</i> 2023, <i>11</i>, 815.","authors":"Maria Caffo, Roberta Fusco, Rosalba Siracusa, Gerardo Caruso, Valeria Barresi, Rosanna Di Paola, Salvatore Cuzzocrea, Antonino Francesco Germanò, Salvatore Massimo Cardali","doi":"10.3390/biomedicines14051016","DOIUrl":"10.3390/biomedicines14051016","url":null,"abstract":"<p><p>The journal retracts the article titled \"Molecular Investigation of DKK3 in Cerebral Ischemic/Reperfusion Injury\" [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond QRS Duration: Myocardial Work Indices for the Assessment of Left Bundle Branch Block.","authors":"Magdalena Potapowicz-Krysztofiak, Martyna Dąbrowska, Małgorzata Maciorowska, Zbigniew Orski, Paweł Krzesiński, Marek Kiliszek, Beata Uziębło-Życzkowska","doi":"10.3390/biomedicines14040941","DOIUrl":"10.3390/biomedicines14040941","url":null,"abstract":"<p><p><b>Background:</b> Left bundle branch block (LBBB) and QRS prolongation are markers of electrical dyssynchrony in heart failure, but they do not fully reflect its mechanical consequences. Myocardial work (MW)-derived indices may provide a more comprehensive assessment of left ventricular (LV) mechanical dyssynchrony. We evaluated associations between LV MW parameters, QRS duration, and LBBB in patients with heart failure with reduced ejection fraction (HFrEF) referred for ICD/CRT implantation. <b>Methods:</b> In this single-centre observational cross-sectional study, 96 consecutive patients referred for ICD or CRT implantation were screened. All patients underwent standardized baseline comprehensive echocardiography followed by advanced MW analysis. Myocardial work index (MWI) dispersion was assessed using two complementary methods. MWI dispersion (SD) was calculated as the standard deviation of segmental MWI values across all LV segments, and MWI dispersion (IQR) was defined as the interquartile range (IQR) of segmental MWI values. We evaluated the associations between QRS duration and MW-derived dyssynchrony parameters (individual and composite), as well as their discriminative performance for LBBB. Seven patients were excluded from further analysis due to inadequate echocardiography image quality. <b>Results:</b> The final study group comprised 89 patients with HFrEF (median age 65.5 years), of whom 67.4% were assigned to CRT. LBBB was present in 41.6%, and the median QRS duration was 142 ms (112-162). All analyzed LV MW indices were significantly associated with QRS duration (all q < 0.01). The strongest correlations were observed for MWI dispersion (IQR) (r = 0.58), peak strain dispersion (PSD) (r = 0.54), lateral-septal work asymmetry (r = 0.53), and MWI dispersion (SD) (r = 0.52) (all q < 0.0001). All MW indices differed significantly between patients with and without LBBB (all q ≤ 0.0001). MWI dispersion (IQR) showed the best single-marker discrimination of LBBB (AUC = 0.852). Composite indices achieved AUC = 0.84 but did not significantly improve discrimination versus MWI dispersion (IQR) alone. <b>Conclusions:</b> Myocardial work-derived indices of left ventricular dyssynchrony are strongly associated with QRS duration and the presence of LBBB in patients with HFrEF. Among them, MWI dispersion (IQR) was shown to be the best-performing MW marker for identifying LBBB. These findings suggest that MW dispersion may serve as a robust echocardiographic marker of mechanical dyssynchrony and warrants further investigation as a potential tool for predicting CRT response.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Interactions Between Medicinal Plant Bioactive and Standard Chemotherapy in Gastric Cancer: Preclinical Evidence and Translational Pitfalls.","authors":"Emilia Daliana Muntean, Daniela-Cornelia Lazăr, Ana-Maria Pah, Christian Banciu, Sorin-Dan Chiriac, Iasmina Denisa Boantă, Florin Muntean, Iulian-Alexandru Blidişel, George-Andrei Drăghici, Radu Jipa","doi":"10.3390/biomedicines14040947","DOIUrl":"10.3390/biomedicines14040947","url":null,"abstract":"<p><p>Gastric cancer remains a highly heterogeneous malignancy in which chemotherapy response is limited by intrinsic and acquired resistance, cumulative toxicity, and the restricted predictive value of conventional preclinical models. This review critically synthesizes evidence on selected medicinal plants and their bioactive phytocompounds as adjuncts to standard chemotherapy for gastric cancer, with an emphasis on mechanistic plausibility, preclinical synergy, and translational barriers. Across the reviewed literature, phytocompounds from <i>Curcuma longa</i>, <i>Scutellaria baicalensis</i>, <i>Camellia sinensis</i>, <i>Syzygium aromaticum</i>, <i>Glycyrrhiza glabra</i>, <i>Allium sativum</i>, <i>Marsdenia tenacissima</i>, and <i>Rhus verniciflua</i> showed anticancer or chemopreventive activity through multitarget effects on apoptosis, proliferation, invasion, inflammation, oxidative stress, and resistance-associated signaling. The most convincing chemosensitizing evidence involved curcumin, wogonin, baicalein, EGCG, which enhanced the activity of fluoropyrimidines, platinum agents, paclitaxel, doxorubicin, or related antitumor regimens in selected gastric cancer models. However, the evidence base remains heterogeneous and is constrained by variable extract standardization, incomplete dose reporting, poor bioavailability, insufficient pharmacokinetic/pharmacodynamic integration, and underuse of clinically relevant model systems. Overall, medicinal plant bioactives remain promising adjunct candidates in gastric cancer. Still, meaningful translation will require chemically defined interventions, rigorous synergy analysis, interaction-aware study design, and validation in advanced preclinical and clinical settings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Glucocorticosteroids for Proactive Therapy of Acute Radiation-Induced Skin Injury in Head and Neck Cancer: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.","authors":"Paweł Głuszak, Julia Woźna, Andrzej Bałoniak, Jakub Pazdrowski, Jan Stępka, Joanna Kaźmierska, Aleksandra Dańczak-Pazdrowska","doi":"10.3390/biomedicines14040942","DOIUrl":"10.3390/biomedicines14040942","url":null,"abstract":"<p><p><b>Background:</b> Acute radiation-induced skin injury (aRISI) is one of the most frequent adverse effects of radiotherapy (RT) in patients with head and neck cancer (HNC) and may compromise treatment delivery and quality of life. Topical glucocorticosteroids (GCS) are commonly used in clinical practice for aRISI management; however, evidence supporting their proactive use remains inconsistent. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of proactive topical GCS therapy during RT for HNC. <b>Methods:</b> A systematic search of PubMed, Embase, and the Cochrane Library was conducted from database inception to July 2025 in accordance with PRISMA 2020 guidelines. Randomized controlled trials comparing topical GCS with placebo or standard skin care in adult patients undergoing curative RT or RChT for HNC were included. The primary outcomes were incidence of clinically significant aRISI (grade ≥ 2) and severe aRISI (grade ≥ 3), assessed using validated grading systems (RTOG or CTCAE). Random-effects meta-analyses were performed to calculate pooled risk ratios (RRs) with 95% confidence intervals (CIs). Risk of bias was assessed using the Cochrane RoB 2 tool. <b>Results:</b> Three randomized controlled trials comprising 459 patients were included. Proactive topical GCS did not significantly reduce the pooled incidence of grade ≥ 2 aRISI compared with placebo or standard skin care (RR 0.87, 95% CI 0.60-1.27). Similarly, no statistically significant reduction in grade ≥ 3 aRISI was observed in pooled analysis (RR 0.81, 95% CI 0.22-3.06). Qualitative synthesis of secondary outcomes reported in individual trials suggested potential benefits of topical GCS, including delayed onset or slower progression of aRISI, and, in one large double-blind study, a reduced risk of severe reactions. No increase in treatment-related adverse events was observed in any included trial. <b>Conclusions:</b> Proactive topical GCS do not significantly reduce the overall incidence of aRISI in pooled analysis. Individual studies showed trend towards delayed onset, slower progression, and reduced severe aRISI without compromising safety. These findings support the judicious use of topical GCS as part of proactive supportive care in HNC RT, while highlighting the need for larger, standardized trials to define optimal regimens and patient selection.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autonomic Receptor Autoantibodies in Complex Regional Pain Syndrome and Other Chronic Pain Conditions: A Cross-Sectional Analysis.","authors":"Daniël P C van der Spek, Renée H Hoffenkamp, Frank J P M Huygen, Krishna D Bharwani, Niels Eijkelkamp, Maaike Dirckx","doi":"10.3390/biomedicines14040945","DOIUrl":"10.3390/biomedicines14040945","url":null,"abstract":"<p><p><b>Objectives</b>: Complex regional pain syndrome (CRPS) is a heterogeneous pain disorder with incompletely understood immunoinflammatory features. This study investigated whether autonomic receptor autoantibodies differentiate CRPS from other chronic pain conditions and healthy controls. <b>Methods</b>: We conducted a cross-sectional analysis of serum samples from patients referred with suspected CRPS. Patients were subsequently classified as having either CRPS or another chronic pain condition, based on the Budapest criteria. Healthy controls were included for comparison. Serum levels of autoantibodies targeting the muscarinic M2 receptor (M2R), β1-adrenergic receptor (β1AR), and the β2-adrenergic receptor (β2AR) were assessed using enzyme-linked immunosorbent assay. All analyses were performed blinded to group assignment. <b>Results</b>: Seventy participants were analyzed (CRPS = 22, other chronic pain = 25, healthy controls = 23). M2R autoantibody levels were higher in both CRPS and other chronic pain compared with healthy controls (mean difference [MD] = 0.37, 95%CI 0.22-0.51; and MD = 0.31 95%CI 0.19-0.44, respectively). β2AR levels were higher in other chronic pain compared with healthy controls (MD = 0.29, 95%CI 0.04-0.54), whereas no significant difference was observed in CRPS (MD = 0.21 95%CI -0.01-0.42). No meaningful differences were observed between CRPS and other chronic pain for any receptor. β1AR levels did not differ between groups. Seropositivity for any autoantibody was 55% in CRPS, 44% in other chronic pain, and 22% in healthy controls. <b>Conclusions</b>: Elevated autonomic receptor autoantibody levels were observed across chronic pain conditions but were not specific for CRPS.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty Kidney: The Interplay of Lipids and Diabetic Kidney Disease.","authors":"Zhiyue Zou, Pan Gao, Qian Yuan, Zhiwen Wang, Pengli Luo, Chun Zhang","doi":"10.3390/biomedicines14040944","DOIUrl":"10.3390/biomedicines14040944","url":null,"abstract":"<p><p>Diabetic nephropathy and diabetic atherosclerosis often develop together and share similar metabolic disturbances. Lipid abnormalities are common in diabetes, yet their roles in kidney and vascular injury are not fully understood. In diabetic kidney disease, altered lipid uptake, reduced fatty acid oxidation, and accumulation of harmful lipid species contribute to cellular stress, mitochondrial injury, inflammation, and fibrosis. In parallel, disordered lipid handling in the vasculature promotes endothelial dysfunction and atherosclerotic plaque development. However, not all lipid accumulation appears to be detrimental, and some findings suggest adaptive or context-dependent effects, leading to inconsistent results across studies. In this review, we summarize current evidence on lipid metabolism in diabetic nephropathy and atherosclerosis, compare shared and distinct features, and discuss ongoing controversies. We also briefly address the therapeutic relevance of targeting lipid pathways and highlight areas that require further investigation. Compared with prior reviews that mainly discussed fatty kidney as an emerging concept in chronic kidney disease research, this review specifically focuses on diabetic kidney disease and integrates kidney-specific lipid trafficking, kidney-vessel crosstalk, conflicting evidence, and mechanism-based therapeutic implications.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Cell and Bulk RNA-Seq Profiling of Non-Metastatic Versus Bone-Metastatic Prostate Cancer Identifies the CXCL10-CXCR3 Axis as a Key Determinant of Tumor Microenvironment and Treatment Resistance.","authors":"Zijian Song, Likai Ren, Hong Wang, Yanqing Wang, Xinxing Du, Wei Zhou, Qi Zhang, Jiyuan Yu, Zaixu Zhao, Linxiong Ye, Kaidi Jin, Ying Liu, Wei Xue","doi":"10.3390/biomedicines14040943","DOIUrl":"10.3390/biomedicines14040943","url":null,"abstract":"<p><p><b>Background:</b> Bone metastasis is a major determinant of morbidity and therapeutic failure in advanced prostate cancer (PCa); however, the transcriptional programs and tumor microenvironmental alterations driving metastatic progression remain incompletely understood. This study aimed to systematically characterize transcriptomic differences between non-metastatic and bone-metastatic PCa and to identify key microenvironmental signaling pathways involved in tumor survival and chemoresistance. <b>Methods:</b> Bulk RNA sequencing was performed on 49 non-metastatic and 28 bone-metastatic PCa specimens. Differential expression analysis was integrated with weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis, and immune/stromal deconvolution. Key findings were validated using in vitro functional assays, including Transwell co-culture models, small interfering RNA (siRNA)-mediated gene silencing, cell viability, apoptosis, and docetaxel resistance analyses. <b>Results:</b> Transcriptomic profiling identified 574 differentially expressed genes. Bone-metastatic tumors were enriched in ribosome-related and translational pathways, whereas non-metastatic tumors displayed immune-associated signatures, including natural killer (NK) cell-mediated cytotoxicity and cytokine signaling. WGCNA revealed immune-related gene modules preferentially enriched in non-metastatic disease. Immune deconvolution demonstrated significantly higher infiltration of NK cells and endothelial cells in non-metastatic tumors. Chemokine-receptor analysis highlighted upregulation of the CXCL10-CXCR3 axis in non-metastatic PCa. In vitro, PCa cells expressed CXCR3, while endothelial cells markedly increased CXCL10 expression upon co-culture. Functional assays showed that endothelial-derived CXCL10 promoted PCa cell survival, suppressed apoptosis, and conferred resistance to docetaxel via CXCR3-dependent signaling; these effects were reversed by CXCL10 or CXCR3 knockdown. <b>Conclusions:</b> These findings uncover a context-dependent endothelial-immune chemokine network distinguishing non-metastatic from bone-metastatic PCa and identify the CXCL10-CXCR3 axis as a critical mediator of tumor survival and chemoresistance, suggesting a potential therapeutic vulnerability in advanced prostate cancer.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory Variants in the KRAS 3'UTR and Intron 2 Are Associated with Breast Cancer Susceptibility Through Independent and Combinatorial Effects in a Mexican Population.","authors":"Asbiel Felipe Garibaldi-Ríos, Luis E Figuera, Belinda Claudia Gómez-Meda, Guillermo Moisés Zúñiga-González, Ingrid Patricia Dávalos-Rodríguez, Patricia Montserrat García-Verdín, Ana María Puebla-Pérez, Irving Alejandro Carrillo-Dávila, Martha Patricia Gallegos-Arreola","doi":"10.3390/biomedicines14040948","DOIUrl":"10.3390/biomedicines14040948","url":null,"abstract":"<p><p><b>Background:</b> Breast cancer (BC) is a leading cause of cancer-related mortality worldwide and a major public health concern in Mexico. Regulatory variants in <i>KRAS</i>, particularly within the 3'UTR and intronic regions, may influence gene expression through microRNA binding and transcriptional regulation. <b>Methods:</b> Five regulatory single-nucleotide variants (SNVs) in <i>KRAS</i> (rs12228277, rs1137196, rs8720, rs12587, and rs12245) were genotyped in BC patients and cancer-free controls. Associations were evaluated using odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for age, alcohol, and tobacco use. Multiple testing was corrected using the Benjamini-Hochberg false discovery rate (FDR). Linkage disequilibrium (LD), multilocus combinations, and in silico functional analyses were also performed. <b>Results:</b> Variants rs12228277, rs1137196, rs8720, and rs12245 showed significant genotype-level associations with BC susceptibility, all remaining significant after FDR correction (pFDR < 0.05). No clinicopathological associations remained significant after correction in single-variant analyses. Multilocus analysis identified specific high-risk combinations (e.g., involving rs12228277, rs1137196, and rs8720) associated with increased BC susceptibility. At the nominal level, these combinations showed associations with clinicopathological features, including hormone receptor-positive status (PR and ER), proliferation markers, and Luminal B subtype; however, none remained significant after FDR correction. LD analysis indicated weak linkage among variants. In silico analyses suggested potential regulatory effects on microRNA binding and <i>KRAS</i> expression. <b>Conclusions:</b> Regulatory variants in <i>KRAS</i> are associated with BC susceptibility through independent effects and potential combinatorial patterns. These findings support the relevance of non-coding variation in cancer risk and warrant further functional and replication studies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Network-Based Prediction of Residual Paravalvular Leak in Bicuspid Aortic Valve TAVI Using CT-Derived Anatomical Features.","authors":"Yijun Yao, Weili Jiang, Xinyue Yang, Jianyong Wang, Ruisi Tang, Yuan Feng, Yiming Li, Mao Chen","doi":"10.3390/biomedicines14040946","DOIUrl":"10.3390/biomedicines14040946","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve (BAV) remains associated with higher rates of residual paravalvular leak (PVL), which confers a two-fold increase in mortality. Despite procedural optimization including balloon post-dilatation, a subset of patients exhibit residual ≥moderate PVL. Pre-procedural identification of these patients could guide procedural planning. <b>Methods</b>: We retrospectively analyzed 402 BAV patients who underwent TAVI with self-expanding valves and balloon post-dilatation between January 2016 and June 2024. A multi-modal deep learning model (Model B) was developed, integrating a 3D ResNet encoder for computed tomography (CT) imaging features with a multilayer perceptron (MLP) for clinical variables, fused via a cross-attention mechanism. Its performance was compared against a conventional model (Model A) combining clinical variables with manually derived CT measurements. Both models were evaluated on identical test folds using 5-fold stratified cross-validation. <b>Results</b>: Of 402 patients, 36 (9.0%) had residual ≥moderate PVL, associated with significantly larger aortic root dimensions at all anatomical levels and greater aortic valve calcification volume (median 887.6 vs. 559.2 mm³; <i>p</i> = 0.004). Model A achieved a mean AUC of 0.694 (95% CI: 0.596-0.792). Model B achieved a mean AUC of 0.822 (95% CI: 0.680-0.964), with a specificity of 0.971, accuracy of 0.881, and PPV of 0.860, while sensitivity was 0.429, reflecting the limited number of outcome events in this cohort. <b>Conclusions</b>: A multi-modal deep learning model integrating expert-segmented CT imaging with clinical variables demonstrated significantly improved discrimination over the conventional approach in this internal cohort for predicting residual PVL in BAV-TAVI, supporting the integration of segmentation-guided deep learning into pre-procedural TAVI planning. However, given the modest number of outcome events, external validation is required to confirm the generalizability of these findings.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diffuse Midline Gliomas: Clinical, Diagnostic, and Therapeutic Perspectives.","authors":"Sanyukta Bihari, Dia Yang, Devarshi Mukherji, Aya Haggiagi","doi":"10.3390/biomedicines14040934","DOIUrl":"10.3390/biomedicines14040934","url":null,"abstract":"<p><p>Diffuse midline gliomas (DMGs) are rare but highly aggressive central nervous system (CNS) tumors that can present in both pediatric and adult populations. These tumors were redefined in the 2016 WHO classification of CNS tumors based on integrated histopathological and molecular features, and were initially designated as \"DMG, H3 K27M-mutant\". In the 2021 WHO update, DMGs were incorporated into the newly defined category of primarily pediatric-type diffuse high-grade gliomas, and nomenclature was changed to \"DMG, H3 K27-altered\" to encompass additional molecular drivers beyond the canonical H3 K27M mutation. Clinically, DMGs arise as expansile, infiltrating tumors within midline structures and may present as non-enhancing or enhancing lesions on imaging. Diagnosis is based on neuroimaging and molecular confirmation by immunohistochemistry or sequencing when tissue is available. DMGs are categorized as WHO grade 4 malignant tumors due to their aggressive biology leading to rapid and infiltrative growth. Owing to their deep and midline location, surgical resection is typically not feasible. Radiation therapy is the backbone of treatment, but there is no standard regimen of chemotherapy that has demonstrated durable efficacy. Recent progress in therapeutic approaches has led to a major breakthrough on 6 August 2025 when the U.S. Food and Drug Administration granted the accelerated approval of dordaviprone (ONC201), marking it as the first systemic therapy for progressive DMG harboring H3 K27M mutation. Other novel approaches, including chimeric antigen receptor (CAR) T-cell directed therapies and convection-enhanced delivery, are actively under investigation. We aim to comprehensively review DMGs, including the recent insights into their biology, the evolving therapeutic landscape, and the opportunities to fuel this new momentum against one of the most formidable gliomas.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}