Biomedicines最新文献

{"title":"The Interactive Effects of Fruit Intake Frequency and Serum miR-484 Levels as Biomarkers for Incident Type 2 Diabetes in a Prospective Cohort of the Spanish Adult Population: The Di@bet.es Study.","authors":"Ana Lago-Sampedro, Wasima Oualla-Bachiri, Cristina Maldonado-Araque, Sergio Valdés, Inmaculada González-Molero, Viyey Doulatram-Gamgaram, Elias Delgado, Felipe J Chaves, Luis Castaño, Alfonso Calle-Pascual, Josep Franch-Nadal, Gemma Rojo-Martínez, Sara García-Serrano, Eva García-Escobar","doi":"10.3390/biomedicines13010160","DOIUrl":"10.3390/biomedicines13010160","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Although evidence suggests that miR-484 and several fruit components are involved in glucose metabolism and insulin resistance metabolic pathways, the relationship between serum miR-484 levels and fruit consumption in relation to the risk of Type 2 diabetes (T2DM) remains elusive. The aim of this study was to evaluate the possible association between serum miR-484 levels and fruit intake frequency with the risk of T2DM in the Spanish adult population. <b>Methods</b>: 2234 subjects from the Di@bet.es cohort study without T2DM at baseline were studied. Socio-demographic, anthropometric and clinical data were recorded, as well as responses to a questionnaire on habits, including frequency of fruit consumption (daily vs. occasional). T2DM was diagnosed at baseline and after 7.5 years of follow-up. Baseline serum miR-484 levels were measured using real-time qPCR and categorized based on the 25th percentile. Association analyses were performed using logistic regression models adjusted for potential confounders. Interaction effects were evaluated on the multiplicative and additive scales. <b>Results</b>: There was no association between miR-484 levels and fruit intake frequency. Categorized miR-484 levels and fruit consumption were inversely and independently associated with the likelihood of incident T2DM. Analysis of the interaction effect suggests the presence of both positive multiplicative and additive interactions between miR-484 categories and fruit consumption frequency. <b>Conclusions</b>: Our study demonstrates a protective effect of daily fruit intake and high miR-484 levels regarding the risk of T2DM and supports the nutritional recommendations advocating daily fruit consumption. This study also suggests that the combined effect of low miR-484 levels and occasional fruit intake may increase the risk of T2DM beyond their independent effects.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036312","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":"Potential Modulatory Role of Phoenixin-14 in Epithelial-Mesenchymal Transition of Endometriotic 12Z Cells.","authors":"Karolina Iwona Kulinska, Magdalena Wierzbicka, Anna Dera-Szymanowska, Krzysztof Szymanowski, Mirosław Andrusiewicz, Maria Wołuń-Cholewa","doi":"10.3390/biomedicines13010158","DOIUrl":"10.3390/biomedicines13010158","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Endometriosis is a painful chronic condition in which the endometrium grows outside the uterus. The epithelial-mesenchymal transition (EMT) is critical to endometriosis progression, where cells lose epithelial traits and gain invasiveness. <b>Methods</b>: This study investigates the effects of phoenixin-14 (PNX-14), a neuropeptide found at reduced levels in endometriosis patients, on the expression of two molecular EMT markers, CDH1 (E-cadherin) and THBS2 (thrombospondin 2), as well as cell viability in the endometriosis-derived 12Z cell line. Cells were treated with physiological (0.2 nM) and endometriosis-relevant (0.05 nM) concentrations of PNX-14. Gene expression was analyzed using RT-qPCR, while protein localization was assessed by immunocytochemistry. Cell viability was measured using an XTT assay. <b>Results</b>: <i>THBS2</i> gene expression was significantly decreased, and <i>CDH1</i> remained unchanged in cells stimulated by 0.05 nM PNX-14. Immunolocalization indicates a weaker THBS2 and CDH1 protein immunosignal reaction for 0.05 nM PNX-14. PNX-14 treatment also exhibited a biphasic effect on cell viability. Lower concentration initially decreased viability at 48 h but then significantly increased it at 72 h. This increase coincided with the decrease in <i>THBS2</i> expression, suggesting a potential link between PNX-14, <i>THBS2</i>, and cell viability. <b>Conclusions</b>: A negative correlation between cell viability and the expression of both EMT markers further highlights their possible involvement in the survival and adaptability of ectopic epithelial cells. Our findings suggest a complex interplay between PNX-14, EMT markers, and cell viability in ectopic epithelial cells. PNX-14's ability to modulate these factors warrants further investigation to elucidate its role in endometriosis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036506","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":"Differential Role of NKG2A/HLA-E Interaction in the Outcomes of Bladder Cancer Patients Treated with <i>M. bovis</i> BCG or Other Therapies.","authors":"Inmaculada Ruiz-Lorente, Lourdes Gimeno, Alicia López-Abad, Pedro López Cubillana, Tomás Fernández Aparicio, Lucas Jesús Asensio Egea, Juan Moreno Avilés, Gloria Doñate Iñiguez, Pablo Luis Guzmán Martínez-Valls, Gerardo Server, Belén Ferri, José Antonio Campillo, María Victoria Martínez-Sánchez, Alfredo Minguela","doi":"10.3390/biomedicines13010156","DOIUrl":"10.3390/biomedicines13010156","url":null,"abstract":"<p><p><b>Background</b>: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette-Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. <b>Methods</b>: We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls. The proliferation and production of cytokines and cytotoxicity were evaluated in peripheral blood mononuclear cells, stimulated in vitro with anti-CD3/CD28 or BCG, from selected patients based on HLA-B -21M/T dimorphism (NKG2A ligands). <b>Results</b>: The HLA-B -21M/T genotype showed opposing results in BC patients treated with BCG or other therapies. The MM genotype, compared to MT and TT, was associated with a longer 75th-percentile overall survival (not reached vs. 68.0 ± 13.7 and 52.0 ± 8.3 months, <i>p</i> = 0.034) in BCG, but a shorter (8.0 ± 2.4 vs. 21.0 ± 3.4 and 19.0 ± 4.9 months, <i>p</i> = 0.131) survival in other treatments. The HLA-B -21M/T genotype was an independent predictive parameter of the progression-free survival (HR = 2.08, <i>p</i> = 0.01) and the OS (HR = 2.059, <i>p</i> = 0.039) of BC patients treated with BCG, together with age and tumor histopathologic characteristics. The MM genotype was associated with higher counts of circulating CD56^bright, fewer KIR2DL1/L2⁺ NK cells, and lower NKG2A expression, but not with differential in vitro NK cell functionality. <b>Conclusions</b>: The HLA-B -21M/T is independently associated with BC patient outcomes and can help to optimize the use of new immunotherapies in these patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036249","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":"Role of Epidural Electrode Stimulation in Three Patients with Incomplete AIS D Spinal Cord Injury.","authors":"Yu-Chen Chen, Xiang-Ling Huang, Hung-Yu Cheng, Ciou-Chan Wu, Ming-Yung Wu, Lian-Cing Yan, Shin-Yuan Chen, Sheng-Tzung Tsai, Shinn-Zong Lin","doi":"10.3390/biomedicines13010155","DOIUrl":"10.3390/biomedicines13010155","url":null,"abstract":"<p><p><b>Background/Objectives</b>: To determine whether epidural electrical stimulation (EES) improves sensory recovery and walking function in patients with chronic spinal cord injury (SCI) with a grade on the American Spinal Cord Injury Association impairment scale (AIS) of C or D at the cervical level. <b>Methods</b>: Three individuals with cervical-level chronic AIS D SCI were enrolled in the study. The mean injury duration and age were 4.8 ± 4.5 (range: 1.5-10) and 56.7 ± 9 years, respectively. The participants received personalized electrical stimulation for 36 weeks and were evaluated for their SCI characteristics, the result of an AIS assessment according to the lower extremity sensorimotor scale, their muscle activity, and preoperative walking ability parameters, initially as well as at weeks 8 and 36 of the EES intervention. <b>Results</b>: Participants receiving EES significantly increased the muscle activity in most lower limb muscles. Regarding the AIS assessment of the lower extremities, one participant fully regained a light touch sensation, while two fully recovered their pinprick sensation (AIS sensory scores increased from 14 to 28). One participant achieved a full motor score, whereas the others' scores increased by 19 and 7 points. Compared with preoperative gait parameters, two participants showed improvements in their walking speed and cadence. Walking symmetry, an important parameter for assessing walking function, improved by 68.7%, 88%, and 77% in the three participants, significantly improving the symmetry index (<i>p</i> = 0.003). <b>Conclusions</b>: Thus, EES may be an effective strategy for sensory impairment recovery, as well as muscular activity and strength improvement. These findings may facilitate stable walking in subjects with chronic incomplete SCI, but larger clinical trials are warranted. <b>Clinical</b> trial: NCT05433064.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036574","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":"TLR7: A Key Prognostic Biomarker and Immunotherapeutic Target in Lung Adenocarcinoma.","authors":"Feiming Hu, Chenchen Hu, Yuanli He, Yuanjie Sun, Chenying Han, Xiyang Zhang, Lingying Yu, Daimei Shi, Yubo Sun, Junqi Zhang, Dongbo Jiang, Shuya Yang, Kun Yang","doi":"10.3390/biomedicines13010151","DOIUrl":"10.3390/biomedicines13010151","url":null,"abstract":"<p><p><b>Background:</b> The tumor microenvironment (TME) plays a crucial role in the progression of lung adenocarcinoma (LUAD). However, understanding its dynamic immune and stromal modulation remains a complex challenge. <b>Methods:</b> We utilized the ESTIMATE algorithm to evaluate the immune and stromal components of the LUAD TME from the TCGA database. Correlations between these components and clinical characteristics and patient prognosis were analyzed. Toll-like receptor 7 (TLR7) was identified as a key prognostic biomarker through PPI network and COX regression analysis. Validation of TLR7 expression was conducted using GEO data, qPCR, WB, and IHC. A prognostic model was developed using a nomogram, incorporating TLR7 expression. Enrichment analysis, the Tumor Immune Estimation Resource database, and single-sample gene set enrichment analysis were used to explore TLR7's potential function. The response of the TLR7 subgroup to immunotherapy and drug sensitivity was observed. <b>Results:</b> We found significant associations between the immune and stromal components of LUAD TME and clinical features and prognosis. Specifically, TLR7 was identified as a prognostic biomarker, where lower expression in tumor tissues was linked to worse outcomes. This finding was further confirmed by comparing TLR7 expression in LUAD cells to normal bronchial epithelial cells, revealing lower expression in the tumor cells. Incorporating TLR7 into a nomogram prognostic model resulted in a good predictor of patient survival. Additionally, TLR7 was associated with immune function and positively correlated with various immune cells. Importantly, patients with high TLR7 expression were more likely to benefit from anti-PD-1 checkpoint blockade therapy. We also identified four treatment candidates for patients with high TLR7 expression. <b>Conclusion:</b> TLR7 is a powerful clinical feature that predicts patient prognosis, immunotherapeutic response, and drug candidates, providing additional insights for the treatment of LUAD.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036522","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":"Role of Vitamin D Status and Alterations in Gut Microbiota Metabolism in Fibromyalgia-Associated Chronic Inflammatory Pain.","authors":"Caterina Saija, Maria Paola Bertuccio, Alberto Scoglio, Vincenzo Macaione, Francesco Cacciola, Giuseppe Micalizzi, Daniela Caccamo, Carolina Muscoli, Monica Currò","doi":"10.3390/biomedicines13010139","DOIUrl":"10.3390/biomedicines13010139","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. <b>Methods</b>: Blood samples were collected from sixty-eight female FM patients (49.9 ± 12.35 years). Pain intensity was assessed by FIQ-R. The serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17, IFN-γ, as well as those of vitamin D (25(OH)D3) and the kynurenine/tryptophan ratio (Kyn/Trp) were determined by ELISA and HPLC, respectively. The plasma levels of the SCFAs acetate, butyrate, and propionate were detected by GC-MS. <b>Results</b>: A mean FIQ-R score indicated that the patients could be classified as having moderate FM. The mean levels of all cytokines, but IL-6 and IL-1β, were higher than the normal reference values. The highest concentrations of cytokines were observed in patients showing the highest FIQ-R scores and the lowest 25(OH)D3 levels. Deficient levels of acetate were found paralleled by an increase in Kyn/Trp. The highest acetate concentrations were detected in patients with the lowest FIQ-R scores and 25(OH)D3 levels. Significantly negative correlations were found between 25(OH)D3 concentrations and FIQ-R scores (<i>p</i> = 0.007) as well as IL-17 levels (<i>p</i> = 0.002) and between acetate and TNF-α (<i>p</i> = 0.040) as well as FIQ-R scores (<i>p</i> = 0.028), while significantly positive correlations were observed between Kyn/Trp and IL-17 (<i>p</i> = 0.027) as well as IFN-γ (<i>p</i> = 0.003). <b>Conclusions</b>: Our preliminary data suggest that the vitamin D status along with altered gut microbiota metabolism plays a major role in FM-related inflammatory pain. Replication of these findings in a larger cohort is required to provide additional insights.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036587","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":"Successful Pregnancy Outcome in a Patient Treated with Pembrolizumab and Exposed to Fluoro-Deoxyglucose (¹⁸F-FDG) PET/CT: Case Report and Review of Literature.","authors":"Anna Lucia Mastricci, Felice Sorrentino, Elisa Giansiracusa, Erika Zanzarelli, Graziana Silvana De Lucia, Vincenza Fernanda Fesce, Luigi Nappi, Lorenzo Vasciaveo","doi":"10.3390/biomedicines13010140","DOIUrl":"10.3390/biomedicines13010140","url":null,"abstract":"<p><p><b>Background:</b> Hodgkin lymphoma (HL) is a common malignancy among women of reproductive age. Some pregnancies occur during oncological treatments or diagnostic follow-ups, often involving contraindicated procedures. HL is fluorodeoxyglucose-avid; therefore, its staging is generally performed with ¹⁸F-FDG PET/CT, a diagnostic method contraindicated during pregnancy. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are innovative therapies for relapsed HL (rHL) with significant efficacy. However, ICIs can impair immune tolerance, potentially increasing immune-related adverse events. The PD-1/PD-L1 pathway, targeted by pembrolizumab, plays a critical role in maternal-fetal immune adaptation, raising concerns about its safety during pregnancy. <b>Case Report:</b> We report the case of a 36-year-old woman diagnosed with rHL who unknowingly became pregnant during treatment with pembrolizumab and ¹⁸F-FDG PET/CT scans. The pregnancy was diagnosed at 24 weeks, after five cycles of pembrolizumab during the first two trimesters and an ¹⁸F-FDG PET/CT scan in the first trimester. Following multidisciplinary counseling, the pregnancy was closely monitored, culminating in the delivery of a healthy male infant at 37.5 weeks. <b>Conclusions</b>: This case highlights a favorable maternal-fetal outcome despite exposure to pembrolizumab and ¹⁸F-FDG PET/CT during pregnancy. Given the limited data on such exposures, case reports like this are essential for improving counseling and management strategies. Further research and registries are crucial to provide robust evidence for clinical decision-making in these complex scenarios.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036608","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":"Early Identification of the Non-Transplanted Functional High-Risk Multiple Myeloma: Insights from a Predictive Nomogram.","authors":"Yanjuan Li, Lifen Kuang, Beihui Huang, Junru Liu, Meilan Chen, Xiaozhe Li, Jingli Gu, Tongyong Yu, Juan Li","doi":"10.3390/biomedicines13010145","DOIUrl":"10.3390/biomedicines13010145","url":null,"abstract":"<p><p><b>Background</b>: Patients with multiple myeloma (MM) who have a suboptimal response to induction therapy or early relapse are classified as functional high-risk (FHR) patients and have been shown to have a dismal prognosis. The aim of this study was to establish a predictive nomogram for patients with non-transplanted FHR MM. <b>Materials and Methods</b>: The group comprised 215 patients in our center between 1 January 2006 and 1 March 2024. To identify independent risk factors, univariate and multivariate logistic regression analyses were performed, and a nomogram was constructed to predict non-transplant FHR MM. To evaluate the nomogram's predictive accuracy, we utilized bias-corrected AUC, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). <b>Results</b>: Multivariate logistic regression demonstrated that younger age at onset, a higher proportion of LDH (more than 220 U/L), pattern A + C of M protein decline patterns, a lower proportion of patients with induction treatment efficacy than VGPR, and those undergoing maintenance therapies were independent risk factors for patients with non-transplanted FHR MM. The AUC scores for the training and internal validation groups were 0.940 (95% CI 0.893-0.986) and 0.978 (95% CI 0.930-1.000). DCA and CIC curves were utilized to further verify the clinical efficacy of the nomogram. <b>Conclusions</b>: We developed a nomogram that enables early prediction of non-transplant FHR MM patients. Younger age at onset, LDH ≥ 220 U/L, an A + C pattern of M-protein decline, and induction therapy efficacy not reaching VGPR are more likely to be FHR MM patients. Patients who do not undergo maintenance therapy are prone to early progression or relapse.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036392","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":"Increased Phenotype Severity Associated with Splice-Site Variants in a Hungarian Pediatric Neurofibromatosis 1 Cohort: A Retrospective Study.","authors":"Klára Veres, Benedek Nagy, Zsófia Ember, Judit Bene, Kinga Hadzsiev, Márta Medvecz, László Szabó, Zsuzsanna Zsófia Szalai","doi":"10.3390/biomedicines13010146","DOIUrl":"10.3390/biomedicines13010146","url":null,"abstract":"<p><p><b>Background:</b> Neurofibromatosis type 1 (NF1) is a complex neurocutaneous disorder caused by pathogenic variants in the <i>NF1</i> gene. Although genotype-phenotype correlation studies are increasing, robust clinically relevant correlations have remained limited. <b>Methods:</b> We conducted a retrospective analysis of data obtained from a cohort of 204 Hungarian individuals, with a mean age of 16 years (age range: 1-33 years). The data were collected over 15 years. <b>Results:</b> Among the cohort of 204 patients, 148 subjects fulfilled ≥2 criteria established by the National Health Institute. Genetic testing was performed in 70 patients, with an 82.8% detection rate, of which 13 patients were excluded. Among the remaining 45 pathogenic variants, 17 (37.7%) frameshift, 11 (24.4%) nonsense, 8 (17.8%) splice-site, 4 (8.9%) missense mutations, and 5 (11.11%) copy number variations (CNVs) were detected. Café-au-lait macules were present in all patients (100%). Intracranial malformations were the second most common feature (55.6%), followed by Lisch nodules (35.6%), neurofibromas (33.3%), and skeletal abnormalities (31.1%). <b>Conclusions:</b> In our cohort, patients with splice-site variants (8/45, 17.8%) demonstrated a notably more severe phenotype compared to findings reported in other studies, with a high prevalence of plexiform neurofibromas (37.5%), intracranial findings (62.5%), skeletal abnormalities (50%), Lisch nodules (50%), and even pseudarthrosis (25%). Correlating with the literature, missense variants represented a mild phenotype, while patients with microdeletion syndrome revealed a more severe phenotype.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036395","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":"Liver Elastography for Liver Fibrosis Stratification: A Comparison of Three Techniques in a Biopsy-Controlled MASLD Cohort.","authors":"Antonio Liguori, Giorgio Esposto, Maria Elena Ainora, Irene Mignini, Raffaele Borriello, Linda Galasso, Mattia Paratore, Maria Cristina Giustiniani, Laura Riccardi, Matteo Garcovich, Antonio Gasbarrini, Luca Miele, Maria Assunta Zocco","doi":"10.3390/biomedicines13010138","DOIUrl":"10.3390/biomedicines13010138","url":null,"abstract":"<p><p><b>Background:</b> The aim of this study was to investigate the accuracy in fibrosis staging of a novel shear wave elastography (SWE) device (S-Shearwave Imaging by Samsung) and a previously validated 2D-SWE by Supersonic Imagine (SSI) in patients with biopsy proven metabolic dysfunction-associated steatotic liver disease (MASLD). <b>Methods:</b> This prospective study included 75 consecutive patients with MASLD who underwent liver biopsy for suspected MASH. All patients underwent S-Shearwave Imaging by Samsung and 2D-SWE with SSI on the same day of liver biopsy. Fibrosis was histologically assessed using the METAVIR classification system. Agreement between the equipment was assessed with the Pearson coefficient. A receiver operator characteristic curve (ROC) analysis with the Youden index was used to establish thresholds for fibrosis staging. <b>Results:</b> A good correlation was found between S-Shearwave Imaging by Samsung and 2D-SWE with SSI (Pearson's R = 0.68; <i>p</i> < 0.01). At multivariate regression analysis, S-Shearwave Imaging was associated with advanced fibrosis (≥F3) independently from age, diabetes and platelets (OR 2.94, CI 1.69-5.11, <i>p</i> < 0.01). The fibrosis diagnostic accuracy of both S-Shearwave Imaging and 2D-SWE was good to optimal with AUROCs of 0.81 and 0.70 for significant fibrosis (≥F2), 0.94 and 0.91 for severe fibrosis (≥F3), respectively. The accuracy of S-Shearwave is not significantly different from Fibroscan and Agile3+ (DeLong test <i>p</i> value 0.16 and 0.15, respectively) while is slightly better than 2D-SWE, FIB4 and NFS (DeLong test <i>p</i> value < 0.05). For S-Shearwave Imaging by Samsung, the best cut-off values for diagnosing fibrosis ≥F2, ≥F3 were, respectively, 7.9 kPa (Sens 74.4%, Spec 87.5%) and 8.1 kPa (Sens 95.6%, Spec 78.8%). For 2D-SWE by SSI, the best cut-off values for diagnosing fibrosis ≥F2, ≥F3 were, respectively, 7.2 kPa (Sens 55.8%, Spec 84.4%) and 7.6 kPa (Sens 82.6%, Spec 84.6%). <b>Conclusion:</b> S-Shearwave Imaging is a useful and reliable non-invasive technique for staging liver fibrosis in patients with MASLD. Its diagnostic accuracy is non-inferior to other shear wave elastography techniques (TE and 2D-SWE by SSI).</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036497","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}