Diseases (Basel, Switzerland)最新文献

{"title":"Biochemical Markers in Pleural Fluid for the Diagnosis of Tuberculous Pleural Effusion: A Retrospective Study.","authors":"Natalia Zaporojan, Ramona Hodișan, Claudiu Zaporojan, Andreea Atena Zaha, Andrei Nicolae Csep, Dana Carmen Zaha","doi":"10.3390/diseases14090327","DOIUrl":"10.3390/diseases14090327","url":null,"abstract":"<p><strong>Background/objectives: </strong>The rapid diagnosis of tuberculous pleural effusion (TPE) presents significant challenges for clinicians due to its paucibacillary nature. Routine biochemical markers may complement microbiological and molecular tests, especially in resource-limited settings. The objective of this study was to evaluate the diagnostic performance of pleural fluid adenosine deaminase (ADA), lactate dehydrogenase (LDH), total protein (TP), and the ADA/LDH and ADA/TP ratios for tuberculous pleural effusion, using Löwenstein-Jensen culture and Xpert MTB/RIF as microbiological reference standards Methods: We conducted a retrospective study (2016-2024) including 325 consecutive patients investigated for suspected TPE in a tertiary hospital. ADA, TP and LDH were measured, and additional ratio-based indices (ADA/TP, ADA/LDH) were calculated for 325 pleural fluid (PF) samples. Löwenstein-Jensen (LJ) culture (with MPT64 confirmation) and GeneXpert MTB/RIF (Xpert MTB/RIF) were used as separate microbiological reference standards. Sensitivity (Se), specificity (Sp), and areas under the ROC curve (AUC) were estimated, and optimal thresholds were determined using the Youden index.</p><p><strong>Results: </strong>Among 325 pleural fluid samples, 23 (7.1%) were culture-positive. Xpert MTB/RIF was performed in 73/325 patients (22.5%), with <i>Mycobacterium tuberculosis</i> detected in 19/73 (26.0%) tested samples. In PF, ADA provided the best performance against culture, with Se of 100%. Correlation analysis in PF showed a moderate positive association between TP and LDH (<i>p</i> < 0.0001).</p><p><strong>Conclusions: </strong>Among routine biochemical markers, PF ADA shows high NPV. Integrating these rapid, low-cost tests alongside LJ culture and Xpert MTB/RIF may streamline the diagnostic pathway for TPE.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pallidal Volumetry and Neutrophil-to-Lymphocyte Ratio in Differentiating Progressive Supranuclear Palsy from Parkinson's Disease.","authors":"Bartosz Migda, Michał Kutyłowski, Natalia Madetko-Alster, Anna Migda, Karol Kutyłowski, Piotr Alster","doi":"10.3390/diseases14090330","DOIUrl":"10.3390/diseases14090330","url":null,"abstract":"<p><strong>Background: </strong>Progressive supranuclear palsy (PSP) and Parkinson's disease (PD) frequently present with overlapping clinical features, creating diagnostic challenges, particularly during the early stages of disease. Structural MRI and peripheral inflammatory biomarkers may provide complementary information for differential diagnosis.</p><p><strong>Objective: </strong>To evaluate the diagnostic performance of automated pallidal volumetry and the neutrophil-to-lymphocyte ratio (NLR), individually and in combination, for distinguishing PSP from PD.</p><p><strong>Methods: </strong>This retrospective case-control study included 12 patients with PSP and 12 patients with PD. Automated brain volumetry was performed using the volBrain 2.0 platform. Total pallidal volume was selected as the primary imaging biomarker based on its established involvement in PSP pathology. NLR was calculated from routine blood counts. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis. A combined MRI-blood model was constructed using binary logistic regression.</p><p><strong>Results: </strong>Patients with PSP demonstrated lower normalized pallidal volumes than patients with PD. Pallidal volume showed high diagnostic performance for differentiating PSP from PD (AUC = 0.885), whereas NLR demonstrated only modest discriminatory ability (AUC = 0.715). The combined pallidal volume-NLR model achieved an AUC of 0.903 compared with 0.885 for pallidal volumetry alone, but this difference was not statistically significant (DeLong <i>p</i> = 0.732), and sensitivity, specificity and overall accuracy remained unchanged.</p><p><strong>Conclusions: </strong>Automated pallidal volumetry provided substantially better discrimination between PSP and PD than NLR alone. Although the combined model showed a small numerical increase in AUC, this improvement was not statistically significant and did not alter sensitivity, specificity or overall accuracy. These findings do not demonstrate incremental diagnostic value of NLR beyond pallidal volumetry in this cohort. Larger prospective studies are needed to determine the clinical utility of combined MRI-blood biomarker approaches in PSP.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etiology and Clinical Manifestations of Acute Respiratory Infections in Pediatric Patients: A Retrospective Study in Moscow, Russia.","authors":"Diana A Grigoryan, Maria A Gordukova, Elena V Galeeva, Irina E Turina, Ekaterina V Ligskaya, Oleg B Kovalev, Alina D Matsvay","doi":"10.3390/diseases14090326","DOIUrl":"10.3390/diseases14090326","url":null,"abstract":"<p><strong>Background/objectives: </strong>Acute respiratory viral infections (ARVIs) are the leading cause of pediatric morbidity and exhibit considerable clinical heterogeneity. The analysis of clinical and etiological associations, as well as the identification of factors linked to severe ARVI cases, is essential for effective epidemiological surveillance.</p><p><strong>Methods: </strong>A retrospective, single-center observational study was conducted including 1362 non-COVID-19 pediatric cases of acute respiratory infections (ARIs), registered between 2021 and 2024. Viral pathogens were detected using real-time PCR for broad-spectrum screening of respiratory viruses.</p><p><strong>Results: </strong>Viral etiology was established in approximately 50% of cases. The most frequently detected pathogen was Human rhinovirus (HRV) (35.6%), followed by Respiratory syncytial virus (RSV) and Human adenovirus (HAdV). Despite its predominance, HRV did not demonstrate nosological specificity. The strongest associations with lower respiratory tract infections were identified for RSV (OR = 3.2) and Human bocavirus (HBoV; OR = 2.4), predominantly within the pneumonia category. RSV was also associated with bronchitis/bronchiolitis (OR = 1.8). Significant associations with upper respiratory tract infections were established for Influenza viruses (OR = 10.4) and HAdV, including nasopharyngitis (OR = 3.88) and acute tonsillitis (OR = 3.9). HAdV additionally demonstrated an association with otitis media (OR = 5.1). Severe disease was registered in 52.3% of all clinical observations and occurred most frequently among young children, particularly in cases associated with respiratory syncytial virus (RSV >80%), as well as with human bocavirus (HBoV) and Human metapneumovirus (HMPV) (~55-59%). Co-infections were not associated with increased disease severity compared with monoinfections (OR = 1.1).</p><p><strong>Conclusions: </strong>The obtained results highlight the contribution of specific etiological agents to severe respiratory infections in children. These findings support the prioritization of such pathogens in clinical diagnostics, including the design of diagnostic algorithms and the selection of patient management strategies in pediatric populations.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Spectrum of Human Herpesvirus 8/Epstein-Barr Virus-Co-Positive Lymphoproliferations and Lymphomas.","authors":"Epameinondas Koumpis, Maria Nasiou, Georgios Monastiriotis, Dimitrios Leonardos, Vasileios Georgoulis, Elisavet Apostolidou, Alexandra Papoudou-Bai, Panagiotis Kanavaros, Eleftheria Hatzimichael","doi":"10.3390/diseases14090323","DOIUrl":"10.3390/diseases14090323","url":null,"abstract":"<p><strong>Background/objectives: </strong>Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is a gamma-2 herpesvirus implicated in a distinctive group of lymphoproliferative disorders (LPDs) and lymphomas. In some of these entities, lesional cells are concurrently infected with Epstein-Barr virus (EBV), a gamma-1 herpesvirus, raising important questions regarding viral cooperation in lymphomagenesis. This narrative review summarizes the clinicopathological spectrum and biological significance of HHV-8/EBV co-positive lymphoproliferations.</p><p><strong>Methods: </strong>We provide a narrative synthesis of the biology of HHV-8 and EBV, including latent, abortive lytic, and productive lytic infection programmes and viral mechanisms involved in cell-cycle deregulation, apoptosis inhibition, immune evasion, and B-cell transformation. Major HHV-8-associated lymphoproliferative entities are reviewed within the current WHO-HAEM5 and International Consensus Classification frameworks, with particular attention to patterns of EBV co-infection and diagnostically atypical or overlapping lesions.</p><p><strong>Results: </strong>Primary effusion lymphoma, including its extracavitary presentation, is frequently EBV-positive, whereas HHV-8-positive germinotropic lymphoproliferative disorder is characteristically HHV-8/EBV dual-positive. In contrast, HHV-8-positive lesional cells in multicentric Castleman disease and HHV-8-positive diffuse large B-cell lymphoma are typically EBV-negative. True dual positivity requires demonstration of HHV-8 latency-associated nuclear antigen and EBV-encoded RNA within the same morphologically defined lesional cell population. Rare atypical cases show overlapping clinicopathological features among established entities.</p><p><strong>Conclusions: </strong>HHV-8/EBV co-positive lymphoproliferations comprise a biologically and diagnostically heterogeneous group. Although unusual overlapping cases suggest potential relationships among HHV-8-associated disorders, current evidence does not support a single continuous disease spectrum or a uniform mechanism of HHV-8/EBV cooperation.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Cyclin E1 Expression in Uterine Leiomyosarcomas and Leiomyomas.","authors":"Aleksandar Rakić, Lazar Nejković, Dejan Oprić, Ana Đorđević, Marija Rakić, Aleksandar Jurišić, Danilo Obradović","doi":"10.3390/diseases14090324","DOIUrl":"10.3390/diseases14090324","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Uterine leiomyosarcoma (uLMS) shares clinical and radiological similarities with benign uterine leiomyoma (LM), while validated discriminatory markers remain scarce. We compared cyclin E1 (CCNE1) expression in uLMS and LM tissue samples. <b>Methods:</b> This retrospective case-control study included 61 patients (16 uLMS, 45 LM) treated at a single institution (2017-2023). Of 22 eligible uLMS cases, six were excluded because suitable tissue was unavailable and they had significantly higher FIGO stages than the included cases. CCNE1 immunoreactivity was assessed using an adapted Allred score in five non-overlapping high-power fields selected from regions of highest expression. Two blinded pathologists independently scored each field, and the patient-level median was used for primary analysis. <b>Results:</b> The median CCNE1 Allred score was 6 (IQR 5-6) in uLMS versus 2 (IQR 0-3) in LM (<i>p</i> < 0.001), with excellent interobserver agreement (ICC 0.94). The AUC was 0.941 (95% CI 0.875-0.990). A data-derived cut-off ≥4 yielded 93.8% sensitivity and 84.4% specificity. A conservative minimum-expression analysis yielded an AUC of 0.882. Postmenopausal status was strongly associated with uLMS but was nearly completely confounded with the diagnostic group (12/16 uLMS vs. 0/45 LM). A premenopausal-only analysis was directionally consistent but underpowered. Clinical symptoms and tumor size did not differ between the groups. <b>Conclusions:</b> CCNE1 immunoexpression was substantially higher in uLMS than LM, with excellent reproducibility. Diagnostic-performance estimates remain exploratory and were influenced by tumor-region sampling, menopausal imbalance, and under-representation of advanced-stage uLMS. Independent multicenter validation, particularly in premenopausal and advanced-stage disease, is required before clinical application.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Anti-TNF Pharmacokinetics, Immunogenicity, and Therapeutic Response in Iraqi Patients with Inflammatory Bowel Disease: A Real-World Therapeutic Drug Monitoring Study.","authors":"Ban AbdulWahid Kanna, Suha Saeed Azeez","doi":"10.3390/diseases14090325","DOIUrl":"10.3390/diseases14090325","url":null,"abstract":"<p><p><b>Background</b>: Therapeutic drug monitoring (TDM) has emerged as an important strategy for optimizing anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD). However, data regarding anti-TNF pharmacokinetics and immunogenicity from Middle Eastern populations remain limited. This study evaluated the associations between serum anti-TNF trough concentrations, anti-drug antibody (ADAb) levels, and therapeutic response among Iraqi patients with IBD receiving infliximab or adalimumab therapy. <b>Methods</b>: This cross-sectional observational study included 80 patients with Crohn's disease or ulcerative colitis receiving maintenance infliximab or adalimumab therapy at a tertiary Gastroenterology Center in Iraq. Patients were categorized as responders or non-responders according to clinical disease activity indices and biochemical assessment. Serum trough levels of infliximab and adalimumab, as well as ADAb concentrations, were measured using an enzyme-linked immunosorbent assay (ELISA). <b>Results</b>: Responders had significantly higher serum trough concentrations than non-responders for both infliximab [3.75 µg/mL (IQR: 3.40-4.15) vs. 1.05 µg/mL (IQR: 0.92-1.12), <i>p</i> < 0.001] and adalimumab [6.32 µg/mL (IQR: 5.67-7.15) vs. 3.30 µg/mL (IQR: 2.70-4.26), <i>p</i> < 0.001]. Adalimumab-treated non-responders had significantly higher ADAb levels compared with responders (<i>p</i> = 0.047). <b>Conclusions</b>: Favorable therapeutic outcomes in Iraqi IBD patients treated with anti-TNF agents were associated with adequate serum trough levels and low ADAb levels. Reactive therapeutic drug monitoring may provide clinically valuable pharmacokinetic information capable of guiding individualized treatment optimization and identifying mechanisms of treatment failure in patients receiving infliximab or adalimumab therapy.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Functional Side of Multiple Endocrine Neoplasia Type 1-Associated Adrenal Disease: Mild Autonomous Cortisol Secretion.","authors":"Roberta Modica, Michele Coletta, Elio Benevento, Alessia Liccardi, Roberto Minotta, Gianfranco Di Iasi, Massimo Di Nola, Roberta Pia Bertenni, Annamaria Colao","doi":"10.3390/diseases14090322","DOIUrl":"10.3390/diseases14090322","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome characterized by primary hyperparathyroidism, duodeno-pancreatic and pituitary neuroendocrine tumors. Adrenal lesions are acknowledged manifestations of MEN1, but their functional characterization remains limited. Mild autonomous cortisol secretion (MACS) is associated with cardiometabolic risk and skeletal involvement in sporadic adrenal incidentaloma, significantly impacting patient morbidity, but data in MEN1 are lacking. The aims of the study were to estimate the prevalence of MACS in adult patients with MEN1 and radiological evidence of adrenal involvement, and to evaluate the associated biochemical, cardiometabolic, and skeletal features. <b>Methods:</b> This retrospective single-center observational study included adult patients with clinical, familial, or genetic MEN1 and adrenal involvement. MACS was defined as serum cortisol >1.8 µg/dL after a 1 mg overnight dexamethasone suppression test in the absence of overt Cushing syndrome. Cardiometabolic and skeletal characteristics were compared according to MACS status. <b>Results:</b> Among 101 MEN1 patients, 38 had adrenal involvement and 22 underwent complete hormonal evaluation. MACS was identified in 15 of the 22 patients (68.2%). Patients with MACS had significantly lower baseline ACTH concentrations and showed a trend toward a higher prevalence of metabolic syndrome. No significant differences were observed in osteoporosis or fracture prevalence. <b>Conclusions:</b> This is the first study specifically evaluating the prevalence of MACS in MEN1 patients with adrenal lesions. MACS appears to be more common than in sporadic adrenal incidentalomas and may represent an important factor for improving clinical characterization and tailoring patient management. Larger prospective studies are needed to define the optimal follow-up strategy.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Effectiveness of Subcutaneous Immunotherapy with an Undiluted Glutaraldehyde-Polymerized Pollen Extract Mixture in Adults and Children with Allergic Rhinitis with or Without Asthma Due to Olive and Grass Pollen.","authors":"Paula López-González, María Antonia Padial Vilchez, María Teresa Palomeque Rodríguez, María Galicia Dávila-Fernández, Virginia Bellido Linares, Emilio Funes Vera, Conchita Cordobés Durán, Ana Montoro Ferrer, Estefanía Moreno Mata, Victoria Villalobos Violán, Laura Ortega-Martín, Aída Gómez-Cardenosa","doi":"10.3390/diseases14090321","DOIUrl":"10.3390/diseases14090321","url":null,"abstract":"<p><strong>Background/objectives: </strong>To evaluate the tolerability and effectiveness of subcutaneous immunotherapy (SCIT) with a glutaraldehyde-polymerized undiluted mixture of grass and olive pollen in adults and children with allergic respiratory disease in routine clinical practice.</p><p><strong>Methods: </strong>Observational, ambispective, controlled multicenter study including patients ≥ 5 years with allergic rhinitis/rhinoconjunctivitis +/- asthma due to olive and grass pollen. Patients initiating SCIT with <i>Olea europaea</i>/grass pollens undiluted mixtures were included in the O&G group, and those continuing symptomatic treatment in the untreated (UT) group. Safety (primary objective) was assessed as the incidence of adverse reactions. Effectiveness variables (symptoms, control, and medication use) were compared during the pollen season before and after AIT; patients and investigators reported perceived satisfaction.</p><p><strong>Results: </strong>We included 218 patients in the O&G group (children, 23.4%; adolescents, 13.8%; adults, 62.8%) with a mean (SD) age of 26.5 (15.6) years, and 94 in the UT group. At the time of evaluation, patients had received treatment for a mean (SD) of 10.6 (2.5) months. Seventeen patients (7.8%) experienced 18 adverse reactions in total, all local (12 in adults, 6 in children; mean overall rate: 0.8%). Rhinitis frequency shifted from predominantly persistent to intermittent (-64.6% in persistent) (<i>p</i> < 0.0001), with significantly improved intensity and control overall and across age groups in the O&G group but not in the UT group. Patients with asthma symptoms decreased by -46.6% (<i>p</i> < 0.0001), along with improved asthma classification, treatment steps, and control overall (O&G group), and across most age groups. Changes in conjunctivitis symptoms followed a similar trend. Symptomatic medication use significantly decreased overall (O&G group) and across specific age groups. Patients and investigators perceived decreased symptoms and medication use after AIT.</p><p><strong>Conclusions: </strong>SCIT with a glutaraldehyde-polymerized undiluted allergen mixture of olive/grass pollen extract demonstrated safety and effectiveness to treat allergic rhinitis and asthma in adults and children in a real-world setting.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic and miRNA-Target Pathway Analysis of the DLK1-DIO3 Imprinted microRNA Cluster in Chronic Lymphocytic Leukemia.","authors":"Georgios S Markopoulos, Yannis V Simos, Konstantinos I Tsamis, Lampros Lakkas, Eleftheria Hatzimichael, Eleni Kapsali, Dimitrios Peschos, Leonidas Benetatos","doi":"10.3390/diseases14090320","DOIUrl":"10.3390/diseases14090320","url":null,"abstract":"<p><strong>Background/objectives: </strong>Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell malignancy in which B-cell receptor signaling, microenvironmental interactions, genomic lesions, and epigenetic deregulation cooperate to shape disease behavior. The imprinted DLK1-DIO3 locus at chromosome 14q32 contains the largest human miRNA cluster and has been implicated in cancer-related regulatory networks; however, its contribution to CLL remains incompletely defined.</p><p><strong>Methods: </strong>In the present study, we investigated the potential involvement of DLK1-DIO3 miRNAs in CLL biology by integrating public transcriptomic datasets with miRNA-centered pathway analysis. GSE70830 was used as a discovery dataset and GSE66117 as a supportive validation cohort to identify genes consistently downregulated in CLL compared with normal B cells.</p><p><strong>Results: </strong>The analyses identified 1236 and 2145 downregulated genes, respectively, and their intersection yielded a 345-gene consensus set. The overlap was significantly greater than expected by chance (odds ratio 2.33; <i>p</i> = 1.55 × 10^-31). This set was used as gene-filter input for DIANA-miRPath v3.0 analysis of the DLK1-DIO3 miRNA cluster, identifying eight KEGG pathways mainly involving B-cell receptor/NF-κB signaling, cell adhesion, leukocyte transendothelial migration, and glycan-related processes. DIANA-miRPath v4.0 provided pathway-centered refinement. GSE216258 miRNA analysis did not show generalized locus-wide upregulation, while a GSE12366 sensitivity analysis showed that 32 of the 345 genes overlapped the strongest naïve-memory B-cell differentiation signatures. The absence of uniform locus-wide upregulation suggests that these data do not establish a direct link between DLK1-DIO3 activation and generalized repression of the 345-gene set. Future studies are needed to identify gene- and pathway-specific effects.</p><p><strong>Conclusions: </strong>Overall, our findings support an association between DLK1-DIO3 miRNA target/pathway annotations and CLL-relevant transcriptional programs, providing a hypothesis-generating framework that warrants further experimental validation.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequential Application of Time-Stratified Demographic, Vital, Clinical-Laboratory, and Microbiology Variables for Accurate and Rapid Identification of Sepsis.","authors":"Krupa Arun Navalkar, José Garnacho-Montero, María Luisa Cantón-Bulnes, José Luís García-Garmendia, Ángel Estella, Adela Fernández-Galilea, Isidro Blanco, Maria Antonia Estecha-Foncea, Marina Gordillo-Resina, Jorge Rodríguez-Gómez, Juan Jesús Pineda-Capitán, Carmen Martínez-Fernández, Ana Escoresca-Ortega, Rosario Amaya-Villar, Juan Mora-Ordóñez, Sara González-Soto, Antonio Gutierrez-Pizarraya, Robert Balk, Russell R Miller, John P Burke, Gourang Patel, Jorge P Parada, Marcus J Schultz, Brendon P Scicluna, Emily Blodget, Santhi Kumar, Dayle Sampson, Thomas D Yager, Roy F Davis, Silvia Cermelli, Richard B Brandon","doi":"10.3390/diseases14090319","DOIUrl":"10.3390/diseases14090319","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Accurate early identification of sepsis remains a major clinical challenge due to its heterogeneous presentation and overlap of clinical signs with the non-infectious systemic inflammatory response syndrome (SIRS). Timely differentiation is crucial for improving patient outcomes, meeting sepsis bundle requirements and reducing inappropriate antimicrobial use. We hypothesized that clinical-laboratory data available within the first three hours of patient presentation could be used to identify patients with sepsis at a clinically useful level of diagnostic accuracy, in lieu of traditional microbiology results which would not become available until at least 12-24 h. Data from two independent studies were used to quantify the diagnostic value of demographic, vital, clinical-laboratory, and microbiological data available at three time points for distinguishing retrospectively diagnosed critically ill patients with either sepsis or non-infectious SIRS. A particular focus of this work was an assessment of the utility of SeptiCyte RAPID (Immunexpress Inc., Seattle, WA, USA) as an aid to sepsis diagnosis, producing actionable data within one hour.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Data from two independent study cohorts were analyzed. The \"510(k) cohort\" consisted of 419 adult patients in intensive care (ICU) (MARS, VENUS, and NEPTUNE studies). The \"Andalusian cohort\" consisted of 353 ICU patients from the PANGEA study. Logistic regression models, selected by a greedy search algorithm and validated by repeated cross-validation, were used to determine the contributions of different variables to diagnostic accuracy. Diagnostic performance was quantified by the area under the receiver operating characteristic curve (AUC).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;For the 510(k) cohort, a baseline AUC of 0.69-0.73 was observed using five to seven vital and demographic variables assessed immediately upon presentation (time T1). The addition of clinical-laboratory variables, in particular SeptiCyte RAPID, within one to three hours post-presentation (time T2) increased the AUC to 0.85-0.86. Finally, the addition of microbiological data 12-24 h post-presentation (time T3) further improved the AUC to 0.90-0.91. Similar results were obtained for the Andalusian cohort. AUC values at the three time points were as follows: At time T1, AUC = 0.67 based solely on vital signs and demographics; at time T2, AUC = 0.87 based on vitals + demographics + SeptiCyte RAPID ± other clinical-laboratory data; at time T3, AUC = 0.93 based on vitals + demographics + SeptiCyte RAPID ± other clinical-laboratory data + microbiology results. For both cohorts, the most significant variables included temperature, mean arterial pressure, respiratory rate, suspected infection site, SeptiCyte RAPID, procalcitonin, confirmed bacterial infection and positive blood culture confirmation. In summary, the AUC for diagnosing sepsis rose progressively from T1 (510(k) 0.69-0.73; And","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"14 9","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}