علوم آزمایشگاهی پزشکی
مقالهها، منابع و پژوهشهای تازه حوزه علوم آزمایشگاهی پزشکی
ورود به زیرشاخهتشخیص آزمایشگاهی، تصویربرداری و فناوریهای تشخیصی
برای رسیدن به فهرست متمرکزتر، یک مسیر تخصصی را انتخاب کنید.
مقالهها، منابع و پژوهشهای تازه حوزه علوم آزمایشگاهی پزشکی
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه بیوشیمی بالینی
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه هماتولوژی آزمایشگاهی
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه میکروبشناسی آزمایشگاهی
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه تشخیص مولکولی
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه رادیولوژی و تصویربرداری
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه پزشکی هستهای
ورود به زیرشاخهمقالهها، منابع و پژوهشهای تازه حوزه پاتوبیولوژی
ورود به زیرشاخهINTRODUCTION: Horseshoe kidney is an uncommon congenital fusion anomaly that can make renal tumor surgery especially challenging because of altered rotation, limited mobility, variable vascular supply, and an unpredictable collecting system (1-7). This video presents a robot-assisted partial nephrectomy for a high-complexity renal tumor in this setting. CASE PRESENTATION: A 33-year-old man, with ECOG 0 and no relevant comorbidities, was diagnosed with a 7.5-cm solid renal mass in the central posterior portion of the left moiety of a horseshoe kidney. The lesion had a RENAL score of 10p. Contrast-enhanced computed tomography and three-dimensional reconstruction were used to understand the relationship between the tumor, aberrant vessels, renal hilum, and collecting system, supporting the decision to attempt nephron-sparing surgery (5, 8). Surgical technique and results: The procedure was performed through a transperitoneal robotic approach with the patient in right lateral decubitus using the Da Vinci Si platform. Port placement followed a standard renal robotic configuration, with a paramedian supraumbilical camera port, three robotic working ports along a craniocaudal lateral axis, a caudal fourth-arm port, and two medial assistant ports for suction, exposure, and support during renorrhaphy. After exposure of the horseshoe kidney and left hilar dissection, two arterial branches and one renal vein were identified. Tumor excision was performed under vascular control, with 20 minutes of warm ischemia and no collecting system opening, followed by two-layer absorbable renorrhaphy with adjunctive hemostatic agents. The operative time was 150 minutes. No transfusion, conversion, drain placement, or relevant immediate complication occurred. The urinary catheter was removed after 24 hours, and the patient was discharged 72 hours after surgery. Pathology showed clear cell renal cell carcinoma, Fuhrman grade 3, pT2N0M0, with negative surgical margins. During 12 months of oncologic follow-up, renal function remained stable and semiannual imaging showed no evidence of recurrence. Contemporary video reports have also emphasized the feasibility of advanced robotic renal surgery and complex partial nephrectomy strategies in selected patients (9, 10). CONCLUSION: In a carefully selected patient, robot-assisted partial nephrectomy supported by three-dimensional planning was feasible for a complex renal tumor in a horseshoe kidney, with negative surgical margins, preserved renal function, and no recurrence during 12 months of follow-up.
BACKGROUND: Adolescent diabetic kidney disease (DKD) represents an early-onset microvascular complication characterized by prolonged metabolic exposure and accelerated renal decline. Elevated serum creatinine and blood urea nitrogen (BUN) are key biochemical indicators of impaired renal function. OBJECTIVES: This scoping review aims to systematically map and evaluate pharmacological strategies for slowing the rise of creatinine and BUN in adolescents (aged 10-19 years) with DKD, with emphasis on renoprotective mechanisms, therapeutic sequencing and the potential applicability of these therapies to adolescent populations. METHODS: A scoping review was conducted in accordance with PRISMA-ScR guidelines. A comprehensive literature search was performed using PubMed, Scopus and Google Scholar for studies published between 2020 and 2025. Eligible studies included clinical trials, observational studies, clinical guidelines and relevant reviews focusing on pharmacological interventions in adolescents (10-19 years) with diabetic kidney disease. Study selection was based on predefined inclusion and exclusion criteria. RESULTS: A total of 35 studies and guideline-based references were included in the final synthesis. Intensive glycemic control (insulin for type 1 diabetes; metformin ± insulin for type 2 diabetes) was associated with improved metabolic control and favorable renal outcomes. Renin-angiotensin system blockers consistently reduced albuminuria and induced an acute hemodynamic reduction but stabilized the long-term decline in estimated glomerular filtration rate (eGFR). Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated additional renoprotective effects in type 2 diabetes; risks (euglycemic DKA) limit use in type 1. In adult studies, finerenone attenuated inflammatory and fibrotic pathways; no adolescent data exist. Glucagon-like peptide-1 receptor agonists improved metabolic control and reduced obesity-associated renal stress. However, pediatric-specific evidence remains limited, and much of the available evidence is derived from adult studies. CONCLUSION: Adult data suggest potential benefits of early multi-target pharmacotherapy, but adolescent-specific evidence is needed to confirm a critical role in delaying renal deterioration. Whether integration of conventional and novel agents improves long-term renal outcomes in adolescents requires direct investigation. Further pediatric-focused research is required to establish safety, efficacy and optimal therapeutic strategies.
OBJECTIVE: To conduct blood group identification and genetic analysis on a pregnant woman suspected for having ABO blood group chimerism, and to explore the blood group identification methods and formation mechanisms of her chimerism. METHODS: A pregnant woman with mixed-field (MF) agglutination reactions in ABO forward typing detected at the Department of Transfusion, Zhongshan Hospital, Xiamen University on May 10, 2025 was selected as study subject. Blood grouping was carried out using a microcolumn gel method and saline method. The two populations of red blood cells (RBCs) from the proband, including those agglutinated and non-agglutinated with anti-A reagent, were separated for repeated blood grouping. Flow cytometry was used to quantitatively analyze the proportion of the two RBC populations. ABO genotyping was conducted via direct sequencing and PacBio long-read single-molecule real-time (SMRT) sequencing. Short tandem repeat (STR) analysis was performed on the proband's blood, buccal swabs, hair follicle samples, and the blood samples of her parents. Genetic analysis was carried out using multiplex PCR testing for Y-chromosome microdeletions, chromosomal karyotyping, and fluorescence in situ hybridization (FISH). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: xmzsyyky 2025-070). RESULTS: The proband's RBCs showed 4+ MF agglutination with anti-A, anti-A1, and anti-AB antibodies. After separation, agglutinated RBCs presented the A1 phenotype and non-agglutinated RBCs presented the O phenotype. Phenotyping for 14 additional RBC antigens showed no MF reaction. Flow cytometry showed that A-phenotype RBCs have accounted for 31.6%, and O-phenotype RBCs have accounted for 69.4%. Direct sequencing of the ABO gene revealed that the proband had an A1.02/O.01.01 genotype. SMRT sequencing results confirmed the presence of three distinct ABO allelic haplotypes: O.01.01 (containing the IVS4+102C>A variant), O.01.01, and A1.02. STR analysis showed that the TH01 and Penta E loci in the proband's multiple tissue samples all exhibited dual paternal and maternal DNA contributions, and a characteristic Y-chromosome peak was detected at the AMEL locus. Multiplex PCR for Y-chromosome microdeletions confirmed that the proband carried the AZFa/b/c, SRY and ZFY genes. G-banded karyotype analysis showed that the proband has a karyotype of 46,XY[1]/46,XX[99]. FISH revealed that the proportion of XY-karyotype cells in cultured peripheral blood was significantly lower than uncultured specimens. CONCLUSION: The proband is an ABO blood group chimera and a tetragametic chimera with a 46,XY/46,XX karyotype distributed throughout the body. This chimerism has originated from the fusion of male and female dizygotic twin embryos during early development.
Prostate-specific membrane antigen (PSMA) PET has transformed prostate cancer (PCa) imaging. Nevertheless, major diagnostic pitfalls remain as PSMA expression is not exclusive to PCa and may also occur in physiologic tissues and a range of benign and malignant conditions. These conditions may mimic PCa metastases, leading to potential misinterpretation. Accurate risk assessment of suspected lesions using PSMA PET/CT requires the integration of uptake intensity, lesion location, corresponding anatomic imaging findings, and clinical context. The authors outline common and diagnostically challenging mimics of PCa metastases seen at PSMA PET/CT and present a structured risk-assessment approach that incorporates current standardized scoring systems. ©RSNA, 2026 Supplemental material is available for this article.
Analytical performance in anti-doping science continues to evolve through the identification of novel metabolites, improved detection sensitivity, and the use of alternative biological matrices. In recent years, dried blood spots (DBS) have gained increasing attention in doping control due to advantages such as improved analyte stability and simplified, cost-effective sample collection, shipment, and storage. However, DBS sampling is inherently limited by the small sample volume and the restricted number of spots available for analysis. Therefore, sensitive and comprehensive analytical strategies are required to maximize the information obtained from a single DBS or Tasso M20 devices. This study aimed to develop and validate a two-step analytical workflow enabling the detection of 91 target compounds, including selected non-threshold substances (NTS) and anabolic steroid esters (ASE), in two dried blood matrices: cellulose-based DBS cards and volumetric absorptive microsampling devices (Tasso M20 pebbles). The protocol comprises extraction with a methanol-acetonitrile mixture (4:1, v/v), followed by LC-MS/MS analysis for NTS. Subsequently, the extract is evaporated, derivatized with Girard P reagent, and analyzed by LC-MS/MS for ASE detection. The validated method proved suitable for qualitative detection of the selected prohibited substances.
BACKGROUND: Owl monkeys (Aotus spp.) are a nocturnal nonhuman primate (NHP) native to central and South America that are used as infectious disease research models for human diseases, such as malaria and human immunodeficiency virus. Natural and infectious diseases may cause alterations in the hematology and serum biochemistry values, which necessitate the availability of reliable reference intervals for healthy animals. METHODS: In this study, hematology and serum chemistry reference intervals for Aotus nancymae were calculated from 191 healthy animals (95 female, 96 male) and were generated based on age class (juvenile, adult, geriatric), sex (adults only), and across the entire sample. RESULTS: Significant differences were observed in multiple parameters as a function of sex and age, some of which are inconsistent with existing data from Aotus spp. and other NHPs. CONCLUSIONS: The availability of age and sex specific reference intervals will be a valuable resource for monitoring the clinical health and effects of research interventions in owl monkeys.
Tucatinib (Irbinitinib, ARRY-380), a potent oral, selective HER2 kinase inhibitor that the FDA, has approved for the treatment of HER2-positive metastatic breast cancer and colorectal cancer. Tucatinib provides a powerful, targeted therapy for HER2-positive cancers, showing substantial benefits in survival and disease control, especially for patients with difficult-to-treat brain metastases, extending options beyond standard chemotherapy. This research aimed to create and validate a new rapid, sensitive, and specific LC-MS/MS technique for measuring tucatinib in dried blood spots (DBS) from mice, with afatinib serving as an internal standard (IS) following regulatory guidelines in the linearity range from 0.178 to 1009 ng/mL (r > 0.990). The chromatographic separation of tucatinib and IS was achieved using the Acquity BEH C18 column with an isocratic mobile phase at a flow rate of 0.6 mL/min within 1.15 min total run time and 2 μL injection volume. Detection and quantification of tucatinib and the IS was done by using a triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode. Tucatinib remained stable under various storage conditions. Comparison of DBS versus plasma samples concentrations showed a strong correlation, suggesting that DBS can serve as a valid alternative to plasma for pharmacokinetic evaluation.
Acquired von Willebrand disease (AvWD) in myeloproliferative neoplasms with extreme thrombocytosis causes paradoxical bleeding due to the mechanism of adsorption and ADAMTS13-mediated proteolysis of high-molecular-weight von Willebrand factor (vWF) multimers. When first-line cytoreductive therapy fails due to intolerance or nonadherence, rapid alternatives are limited. We describe a 74-year-old woman with JAK2V617F-mutated myeloproliferative neoplasm and hydroxyurea intolerance who presented with active mucosal bleeding and a platelet count of 952 000/μL. vWF antigen (vWF:Ag) was 0.37 IU/mL (reference range: 0.50-2.00 IU/mL), and vWF Ristocetin Cofactor activity (vWF:RCo) was 0.21 IU/mL (activity/antigen ratio 0.57; reference range 0.7-1.3), consistent with AvWD. A single thrombocytapheresis session on the Fresenius COM.TEC platform reduced the platelet count to 277 000/μL, with prompt cessation of bleeding. Repeat testing at 24 h showed improvement in vWF:RCo to 0.48 IU/mL (ratio 0.68), which likely reflects restoration of functional high-molecular-weight multimers. In this single case, thrombocytapheresis provided rapid and effective platelet reduction for AvWD secondary to myeloproliferative neoplasms when pharmacological cytoreduction is inadequate.
BACKGROUND AND AIMS: Bleeding risk in cirrhotic patients undergoing invasive procedures is traditionally assessed using conventional coagulation tests, which poorly reflect the rebalanced haemostatic state of cirrhosis and often lead to unnecessary transfusions. Viscoelastic testing (VET) provides a global assessment of coagulation and may enable more rational transfusion strategies. We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of VET-guided transfusion strategies in this setting. METHODS: We systematically searched PubMed, Embase and Scopus from inception to 10 April 2026. RCTs comparing VET-guided versus standard-of-care transfusion strategies in cirrhotic patients undergoing invasive procedures were included. Primary outcome was procedure-related bleeding; secondary outcomes included transfusion requirements. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using the Mantel-Haenszel method. RESULTS: Six RCTs including 296 patients were analysed. Procedure-related bleeding was rare and did not differ between groups (RR 0.74, 95% CI 0.24-2.31; I2 = 0%). In contrast, VET-guided strategies significantly reduced transfusion requirements, including any blood product transfusion (RR 0.33, 95% CI 0.26-0.44; I2 = 56%), platelet transfusion (RR 0.20, 95% CI 0.13-0.32; I2 = 40%), any fresh frozen plasma (FFP) exposure (RR 0.40, 95% CI 0.28-0.57; I2 = 63%) and FFP-only transfusion (RR 0.22, 95% CI 0.10-0.46; I2 = 81%). CONCLUSIONS: VET-guided transfusion strategies significantly reduce blood product utilisation without increasing bleeding risk in cirrhotic patients undergoing invasive procedures. These findings support a shift towards a physiology-based approach to haemostasis, with potential benefits for patient safety and resource optimisation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: CRD420261382437.
This study evaluated the effects of alpaca variety (Huacaya vs. Suri) and period on physiological parameters and stress indicators in late pregnancy, grazed on high-altitude cultivated pastures in Cusco, Peru (4,141 m.a.s.l). Eight Huacaya and six Suri alpacas were monitored in two experimental periods Transition (gestation months 8‒9) and Wet (gestation months 10-11), this last coinciding with the beginning of the rainy season. Data were analysed using a repeated measures model and Pearson correlations were established among selected variables. Regardless of variety, alpacas lost liveweight during the Transition period despite increased feed intake. Suri females displayed lower body temperatures (36.1 vs. 37.5 °C), and heart rates (60 vs. 65 beats/min) compared to Huacaya. No differences were associated either with variety or period in adrenocorticotropic hormone (ACTH) or cortisol in blood serum. The albumin-to-globulin ratio was lower in Suris and increased in Wet period. Differences in pasture crude protein contents between periods may explain increases blood urea nitrogen (BUN; + 1.25 mg/dL) in Wet period, whereas creatinine (CREA) was responsive to both variety and period. Distinct stress responses in Huacaya and Suri alpacas were evidenced by cortisol-ACTH correlations. Huacaya exhibit a stable hormonal feedback loop, whereas Suri are more influenced by period. Both alpaca varieties displayed unexpected negative cortisol-glucose correlations and differed in cortisol-protein metabolism associations. Despite physiological differences, kidney function remained consistent for both varieties. These findings highlight unique metabolic adaptations in alpacas and underscore the need for further research.
The present study was conducted to compare the hematological responses of Sahiwal and Hardhenu calves to different levels of thermal stress, expressed as Temperature-Humidity Index (THI), during the first 90 days of life. Blood samples were collected monthly in the morning (09:00-10:00 h) from 102 female calves, comprising a crossbred strain (Hardhenu, n = 54) and an indigenous breed (Sahiwal, n = 48), maintained at the Cattle Breeding Farm, LUVAS, Hisar, India, from July 2020 to June 2021. Calves were categorized into neonatal (≤ 30 days) and post-neonatal (31-90 days) groups. THI was classified as < 55, 55-75 and ≥ 75. Data were analyzed using a linear mixed model, with breed and THI as fixed effects and animal as a random effect. Estimated marginal means (± SE) were used to evaluate differences among groups. The results indicated that both breed and THI influenced several hematological parameters, with variations observed across age groups. Indigenous Sahiwal calves showed relatively higher erythrocytic indices (RBC, Hct and MCV) and neutrophil (NEU) percentages, suggesting better adaptability to thermal stress. In contrast, crossbred Hardhenu calves exhibited higher leukocyte (WBC) and lymphocyte (LYM) responses, indicating greater sensitivity to environmental conditions.Moderate THI (55-75) was generally associated with more stable hematological profiles, whereas higher THI (≥ 75) was linked with increased variability and changes in several parameters, reflecting heat stress effects. The study revealed significant effects of breed and THI on several hematological traits in calves, indicating breed-related differences in hematological responses under varying thermal environments. These findings may help in developing management strategies for dairy calves under tropical conditions. However, further studies with larger datasets and direct indicators of heat stress are required to validate their application in selection and management programmes under changing climatic conditions.
INTRODUCTION: Vitiligo is an acquired depigmenting disorder characterized by white macules resulting from the loss of functional melanocytes. MATERIAL AND METHODS: This multicenter, real-life observational study evaluated the efficacy of topical Ruxolitinib (15 mg/g) in 100 patients with non-segmental facial vitiligo treated twice daily for three months, combining clinical scales and noninvasive imaging techniques. Assessments at baseline, 30 days, and 90 days included Facial Vitiligo Area Scoring Index (F-VASI), Facial Vitiligo Extent Score - Body Surface Area (F-VES BSA), Vitiligo Extent Score (VES) grade, Physician's and Patient's Global Vitiligo Assessments, and Dermatology Life Quality Index. RESULTS: Significant improvements were observed across most clinical indices, with marked reductions in disease extent and severity scores (p < 0.0001). Quality of life also improved substantially, as reflected by DLQI reduction. Although F-VASI showed a smaller mean change, it remained statistically significant. DISCUSSION: Instrumental evaluation, including VISIA imaging, Wood's lamp examination, reflectance confocal microscopy, and LC-OCT, confirmed clinical findings by demonstrating repigmentation and a reduction in affected areas. Overall, topical Ruxolitinib proved effective in reducing facial vitiligo lesions and improving patient-reported outcomes. CONCLUSIONS: These findings support the therapeutic potential of JAK inhibitors, although further controlled studies are warranted to confirm long-term efficacy and safety.
Candida auris is a major public health concern worldwide due to its efficient transmission, environmental persistence, and broad resistance to approved antifungal classes. This review consolidates recent pharmacological developments in this regard, focusing on mechanistic insights and late-stage therapeutics. Novel agents demonstrate activity against multidrug- and pan-resistant isolates via distinct mechanisms of action and enhanced specific binding to CYP51. Repositioned drugs, host-defense peptides, and quorum-sensing modulators also expand the treatable spectrum, particularly for biofilm-associated and device-related infections. Concurrently, artificial intelligence (AI)-guided discovery, nanocarrier-enabled delivery, and multi-omics profiling are greatly accelerating target identification and enhancing the drug metabolism of small-molecule fragments. The emerging combined approaches mark a transition towards mechanism-based antifungal development to combat the increasing clinical burden posed by C. auris. Ongoing integration of precision diagnostics, pharmacodynamic optimization, and novel discovery platforms will be key to translating these advances into durable, real-world therapeutic solutions.
PURPOSE: Biliary atresia (BA) often requires liver transplantation despite Kasai portoenterostomy (KPE). The prognostic role of hepatobiliary scintigraphy remains unclear. METHODS: Twenty-three infants undergoing KPE between 2017 and 2024 were retrospectively analyzed. Patients without 6-h bowel activity on technetium-99 m PMT hepatobiliary scintigraphy underwent 24-h delayed imaging. The primary endpoint was jaundice clearance (total bilirubin < 2 mg/dL within 3 months). Ancillary analyses included an internally validated receiver operating characteristic (ROC) cutoff and correlation of the 24-h porta hepatis-to-hepatic surface (PH/HS) ratio with 1-year bilirubin, native liver survival (NLS), and portal plate bile duct diameter. RESULTS: Sixteen infants achieved jaundice clearance, and their 24-h PH/HS ratio was higher (1.20 vs. 1.11, p = 0.049). ROC analysis identified an exploratory cutoff of 1.15 (apparent area under the curve [AUC], 0.768; internally validated AUC, 0.670). Excluding patients transplanted within 1 year, the PH/HS ratio correlated inversely with 1-year bilirubin (r = - 0.720). NLS did not differ significantly between groups, and the association with portal plate bile duct diameter was weak. CONCLUSIONS: The 24-h PH/HS ratio was associated with post-KPE jaundice clearance. However, these findings remain preliminary and hypothesis-generating. As a noninvasive preoperative parameter beyond routine laboratory testing, the PH/HS ratio warrants prospective multicenter validation.
Gallbladder carcinoma (GBC) is an aggressive malignancy characterized by late-stage presentation, poor prognosis, and limited therapeutic options. Gallstones (GS) represent a major risk factor and are implicated in the majority of GBC cases; however, the molecular distinctions between GS-associated GBC (GBCGS) and GS-independent/de novo GBC (dnGBC) remain poorly defined. To date, no GBC subtype-specific molecular biomarkers have been established. In this study, we employed an integrative transcriptomic and systems biology framework to delineate coding and non-coding RNA signatures underlying GBC pathogenesis. Transcriptomic profiling was performed on tumor tissues representing dnGBC and GBCGS subtypes, followed by comprehensive computational analyses including differential expression analysis, protein-protein interaction (PPI) networks construction, lncRNA-mRNA correlation networks, and competing endogenous RNA (ceRNA) network integration to identify key regulatory nodes. Systems-level analysis revealed distinct pathway enrichments between the two subtypes, indicating molecular heterogeneity in their pathobiology. In dnGBC, lncRNA DIO3OS and a novel transcript MSTRG.16633.1 were identified as highly connected candidate regulatory lncRNAs associated with genes involved in cell adhesion molecule (CAM) pathways. In contrast, GBCGS was characterized by lncRNA LINC00852 and novel transcript MSTRG.53675.1, which were associated with hub mRNAs enriched in the oncogenic signaling pathway. Expression of candidate mRNAs and lncRNAs identified from network analyses were validated by quantitative RT-PCR. This pilot study highlights the complex molecular heterogeneity within the two GBC subtypes and identifies potential RNA signatures involved in dnGBC and GBCGS pathogenesis that may contribute to improved understanding of molecular stratification and targeted therapeutic development.
Trichodermin, a sesquiterpene antibiotic from Trichoderma species, shows anticancer potential. In this study, anti-glioblastoma activity was evaluated by (3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay, colony formation, lactate dehydrogenase (LDH) release assay, flow cytometry, wound-healing, transwell invasion, adhesion, Western blot, combination-index analysis, and an orthotopic luciferase glioblastoma mouse model. Trichodermin reduced viability and clonogenicity and increased LDH release of T98G and A172 cells. Trichodermin induced G2/M arrest with p53 activation and downregulation of cyclin B, cyclin A, and cyclin-dependent kinase 1 (CDK1). In addition, trichodermin induced caspase-dependent apoptosis. Invasion, wound healing, and adhesion were suppressed with modulation of epithelial-mesenchymal transition (EMT)-related proteins. Combination index analysis demonstrated a synergistic interaction between trichodermin and temozolomide, possibly due to increased apoptosis. In the mouse model, intraperitoneal trichodermin inhibited intracranial tumour growth and prolonged survival, and increased cleaved caspase-3 expression in tumour tissues. These findings indicate that trichodermin exerts anti-glioblastoma activity and warrants further preclinical evaluation as a potential adjunct to temozolomide therapy.
Attention-deficit/hyperactivity disorder (ADHD) affects 2.5% of adults and is associated with cognitive decline and dementia. The neurobiological mechanisms contributing to adverse outcomes in ADHD are poorly understood. ADHD-related brain alterations may persist into later life and interact with ageing-related processes, potentially increasing susceptibility to neuropathology. This preregistered systematic review synthesised neuroimaging findings in adults aged 35 years and older with clinical, symptomatic, or genetic risk for ADHD, and summarised cognitive and clinical correlates. A search of five databases produced 13 included studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Most studies (11/13) had low risk of bias. Compared to controls, ADHD groups exhibited alterations in fronto-striatal, fronto-parietal, and limbic systems implicated in executive control and attention. Middle-aged adults with clinical ADHD showed more widespread cortical structural differences, whereas older adults demonstrated abnormalities primarily in frontal regions, possibly reflecting attenuation of differences through ageing. Two functional studies in those with clinical ADHD reported frontal hypoactivation alongside parietal hyperactivation, consistent with compensatory recruitment. Among undiagnosed samples, there were interactions between genetic risk for ADHD and Alzheimer's disease-related pathology affecting brain and cognitive outcomes. Overall, ADHD-associated neurobiological alterations appear to persist into older age. Longitudinal investigations are needed to clarify these relationships.
BACKGROUND: Epidemiological studies link long-term air pollution to an increased risk of hepatocellular carcinoma (HCC), but the underlying toxicological targets remain poorly understood. We used an integrative computational framework to identify and prioritize candidate molecular mediators potentially linking pollutant-associated gene signatures with hepatocarcinogenesis. METHODS: We retrieved pollutant-responsive genes associated with seven toxicants from the Comparative Toxicogenomics Database and intersected them with HCC-associated genes. We used protein-protein interaction (PPI) network analysis to identify hub nodes. An optimized machine learning pipeline (glmBoost and Ridge regression) was trained on GSE36376 and validated in three independent cohorts. We mapped gene program activity within the tumor microenvironment using single-cell RNA sequencing (scRNA-seq) and modeled perturbations with scTenifoldKnk. Finally, we assessed structural compatibility between pollutants and protein targets. RESULTS: We identified 240 genes at the intersection of pollutant and HCC sets. Enrichment analysis highlighted innate immune signaling and chronic inflammation, specifically the IL-17, TNF, and NF-κB pathways. Hub nodes included IL6, TNF, MMP9, and AKT1. The machine learning model prioritized five candidate transcriptomic markers: FOS (AUC = 0.944), PARP1 (AUC = 0.929), MMP9 (AUC = 0.813), CCL5 (AUC = 0.747), and JUN (AUC = 0.733), all validated across cohorts. scRNA-seq module scoring showed the highest activity in T cells, monocytes, and macrophages. However, these data lack individual-level pollutant exposure documentation. In silico MMP9 knockout perturbed genes involved in angiogenesis and the extracellular matrix. Molecular docking suggested preliminary structural compatibility between toluene and MMP9 (-5.2 kcal/mol). CONCLUSION: This analysis outlines a potential "pollutant-immune/inflammation-HCC" framework and identifies five transcriptomic signatures for further validation. These findings support a hypothesis that air pollutant-associated molecular programs may be linked to HCC pathobiology and warrant experimental validation.
BACKGROUND & AIMS: Antibiotic resistance is a major determinant of the efficacy of Helicobacter pylori (H. pylori) eradication treatment. Our objective was to evaluate the prevalence and geographical distribution of primary antibiotic resistance in patients infected with H. pylori across Europe over the last four decades. METHODS: Bibliographical searches were conducted from 1990 to 2024 in the PubMed database with no language restrictions. Selected studies evaluated the primary resistance of H. pylori to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline and rifampicin in adults. Data were grouped by country and time intervals (1990-1999, 2000-2009, 2010-2019, 2020-2024) to identify potential trends. High resistance thresholds were defined as ≥15% for clarithromycin and levofloxacin, and ≥30% for metronidazole. RESULTS: A total of 216 studies were included: 188 with information on clarithromycin resistant strains (86,917 patients), 138 on metronidazole (83,995 patients), and 77 on levofloxacin (40,619 patients). The overall prevalence of primary resistance to clarithromycin, levofloxacin, and metronidazole was 16% (95% confidence interval, 7-24%), 18% (10-21%), and 33% (29-36%), respectively. Primary resistance to clarithromycin and levofloxacin increased steadily across all periods, reaching 24% and 21%, respectively, in the most recent period. Primary resistance to amoxicillin, tetracycline, and rifampicin remained low, at 2.3%, 1%, and 4%, respectively. Overall, Southern European countries had higher resistance rates than Northern European countries. CONCLUSIONS: In Europe, the prevalence of primary H. pylori resistance to clarithromycin and levofloxacin has increased over time and is high in recent years. Variability exists between countries, with Southern European regions showing higher rates.
BACKGROUND: Tuberculosis infection (TBI) diagnosis in BCG-vaccinated, high-burden settings remains challenging. RESEARCH QUESTION: We aimed to assess the sensitivity, specificity, and safety of the C-tuberculin skin test (C-TST), compared with PPD RT-23, for tuberculosis infection in BCG-vaccinated adults. STUDY DESIGN AND METHODS: Randomised, double-blind clinical trial in Brazil. Adults with pulmonary tuberculosis (PTB) and asymptomatic controls without known TB exposure or prior TB/TPT underwent C-TST, PPD RT-23, and QuantiFERON-TB Gold Plus (QFT-Plus). Skin tests were read by two strategies: (a) induration only or (b) induration or erythema, at a ≥5-mm cut-off. Sensitivity was assessed in PTB; specificity for C-TST and PPD RT-23 was estimated against QFT-Plus. Adverse events were monitored. RESULTS: Among 446 participants (141 PTB; 305 controls), at the 5-mm cut-off, C-TST showed lower sensitivity but higher specificity than PPD RT-23. With strategy (a) and (b), C-TST sensitivity was 0.67 and 0.68, specificity was 0.92 and 0.9, compared to 0.74 sensitivity and 0.78 specificity for PPD RT-23. Adverse events were more frequent in PTB: 12.1% (C-TST) and 6.4% (PPD RT-23); none were serious. CONCLUSION: In BCG‑vaccinated adults, C-TST showed a trade-off of higher specificity and lower sensitivity than PPD RT-23 at the 5-mm cut-off; and a favourable safety profile. Adding erythema to readings did not improve accuracy, suggesting that C-TST may be a useful alternative for programmatic TBI screening in high-burden settings. TRIAL REGISTRATION: Trial registry number RBR-7tn2ysw (https://ensaiosclinicos.gov.br/ registered on 25 January 2021).
Acute gastroenteritis (AGE) is a common cause of pediatric emergency department (ED) visits and is frequently associated with dehydration and metabolic disturbances. Rapid assessment of electrolytes and glucose is essential in clinical management. Although venous blood gas analysis provides faster results, its agreement with standard serum biochemistry in pediatric AGE remains unclear. This retrospective observational study included children aged 1 month to 18 years who presented to the pediatric ED with AGE between January 1, 2024, and December 31, 2025, and underwent paired venous BGA and serum biochemical testing during the same visit. A total of 1853 paired measurements were obtained from 1191 patients, as some children contributed multiple paired measurements during repeated testing. Method comparison was performed according to Clinical and Laboratory Standards Institute (CLSI) EP09-A3 guidelines using intraclass correlation coefficients (ICC), paired comparisons, Pearson correlation, and Bland-Altman analysis. Both analyzers demonstrated acceptable intra-device reliability (ICC > 0.70). However, agreement between venous blood gas and serum biochemistry was poor for sodium, potassium, chloride, and glucose, with all inter-method ICC values below 0.70. Mean values differed significantly between methods for all parameters (P < .01). Bland-Altman analysis demonstrated wide limits of agreement (LOA) between the 2 methods; for example, glucose measurements showed a mean difference of 2.1 mg/dL with LOA ranging from -64.3 to 68.5 mg/dL. Venous blood gas electrolyte and glucose measurements are not interchangeable with serum biochemistry in children with acute gastroenteritis. While blood gas analysis may be useful for rapid screening or trend monitoring in urgent settings, confirmatory serum biochemical testing remains necessary for clinical decision-making in pediatric AGE.
Although pulse oximetry (SpO2) is useful for real-time monitoring of oxygen saturation, it may not predict which patients will subsequently develop hypoxemia and require oxygen therapy. Laboratory biomarkers collected at admission may therefore facilitate earlier risk stratification and guide clinical decision-making. This study aimed to evaluate the association between the lactate dehydrogenase-to-albumin ratio (LAR) and oxygen therapy requirement in hospitalized patients with COVID-19. This retrospective study included hospitalized patients with COVID-19 admitted to the ICU of the Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February and March 2020. Patients were categorized into a non-oxygen therapy group (n = 40) and a group requiring oxygen therapy (n = 21) according to the requirement for supplemental oxygen therapy (SpO2 < 93%). Univariate and multivariate logistic regression analyses were performed to identify factors associated with oxygen therapy requirement. Receiver operating characteristic (ROC) curves were used to assess the predictive performance of the identified factors. Sixty-one hospitalized patients with COVID-19 (mean age 63.18 ± 11.01 years; 22 males [36.07%]) were included, among whom 21 required oxygen therapy. Multivariable logistic regression analysis showed that the lactate dehydrogenase-to-albumin ratio (LAR; OR = 2.06, 95% CI: 1.00-4.21, P = .049) was independently associated with oxygen therapy requirement. ROC analysis demonstrated that LAR had an area under the curve (AUC) of 0.762 with 81.0% sensitivity and 72.5% specificity at an optimal cutoff value of 5.240. A combined model incorporating LAR, lymphocyte count, cough, d-dimer, bilateral lung involvement, chest tightness, and shortness of breath achieved an AUC of 0.818 with 76.2% sensitivity and 80.0% specificity. LAR was independently associated with oxygen therapy requirement in hospitalized patients with COVID-19 and may help clinicians identify patients at higher risk of requiring oxygen therapy, thereby supporting early triage and optimal allocation of medical resources.
BACKGROUND: Cognitive impairment is a relatively prevalent comorbidity in chronic obstructive pulmonary disease (COPD), yet its neuropathological mechanism remains poorly understood. METHODS: We enrolled 48 stable COPD patients, categorized into cognitively normal (CogN, n = 22) and impaired (Cog, n = 26) groups based on Montreal Cognitive Assessment (MoCA) scores, along with 34 matched healthy controls. All participants underwent 3T MRI with quantitative susceptibility mapping (QSM) to quantify regional brain iron content. Group comparisons of whole-brain and region-of-interest susceptibility were performed. Mediation analysis was then used to test whether specific brain iron deposition mediates the relationship of both COPD status and peripheral inflammatory markers with cognitive performance. RESULTS: Cog patients showed increased total iron in the right cerebellum crus I, while CogN patients exhibited higher paramagnetic susceptibility (χpara) in the left orbitofrontal cortex (OFC), right precentral gyrus, and right brainstem. χpara in the left OFC and right brainstem were positively correlated with total MoCA, abstraction, and orientation scores. Mediation analysis demonstrated that χpara of the left OFC mediated the effects of both COPD status and systemic neutrophil counts on impaired abstraction. Additionally, right brainstem χpara mediated the relationship between COPD and deficits in orientation. CONCLUSIONS: COPD patients with cognitive impairment exhibited distinct patterns of brain iron deposition. Importantly, deposition in several key regions served as a potential mediator, linking both COPD and systemic inflammation to specific cognitive deficits. These preliminary findings suggest a possible association between brain iron accumulation and cognitive impairment in COPD, offering candidate neuroimaging markers for early identification. .
BACKGROUND: Androgenetic alopecia (AGA) is the most common type of hair loss in men. Finasteride and dutasteride are oral 5-alpha-reductase inhibitors. This study compared their efficacy and safety in Iranian men with moderate to severe AGA. METHODS: This randomized single-blind clinical trial included 46 men aged 20-50 years. Patients received finasteride 1 mg daily or dutasteride 0.5 mg daily for 24 weeks. Hair density and thickness were measured by trichoscopy and photographs. Satisfaction was recorded with a visual analog scale (VAS). Adverse effects were documented. RESULTS: Both groups improved in hair growth after 24 weeks with no significant difference. Serum PSA fell in the dutasteride group from 0.63 ± 0.18 to 0.42 ± 0.22 (p < 0.001). No significant change appeared in the finasteride group. Dutasteride produced greater PSA reduction than finasteride (B = 0.17, p < 0.01). Age had no effect on PSA (p = 0.58). VAS scores showed no difference. Safety profiles were similar. Sexual side effects were most common, with erectile dysfunction more frequent in the finasteride group. No serious events occurred. CONCLUSION: Finasteride and dutasteride improved hair density with similar safety. Dutasteride caused stronger PSA reduction, suggesting more potent 5-alpha-reductase inhibition.
BACKGROUND: Ovarian steroid cell tumors-not otherwise specified (SCT-NOS) is a rare category of sex cord-stromal tumor, however, its pathophysiology is unclear. A comprehensive cellular atlas of ovarian SCT-NOS remains lacking. METHODS: We reported a case of a 41-year-old woman with hyperandrogenism for whom histopathological analysis confirmed the presence of ovarian SCT-NOS. This study utilized single-cell RNA sequencing in a case of ovarian SCT-NOS. RESULTS: Seven cell types, including four keratin 19 (KRT19)⁺ steroidogenic cell subtypes, were identified in the tumor microenvironment. We detected aberrant gene expression across various cell types in ovarian SCT-NOS. KRT19⁺ steroidogenic cells were enriched in genes involved in ovarian steroidogenesis and steroid biosynthesis pathways, which was consistent with the pathobiology of hyperandrogenism. Moreover, we revealed distinct immune cell types in the tumor microenvironment. Five immune cell types within the tumor microenvironment were identified, among which tumor-associated macrophage (TAM) and dendritic cell (DC) were the predominant immune cells. CONCLUSIONS: This transcriptomic analysis revealed distinct cell types and key genes within the tumor microenvironment, offering insights into the cellular heterogeneity and molecular mechanisms of ovarian SCT-NOS, thereby enhancing the understanding and encouraging further investigations into ovarian SCT-NOS.
Rapid diagnosis of viral diseases in pepper (Capsicum annuum L.) is crucial for preventing pathogen spread, reducing yield losses, and supporting the green and sustainable development of the pepper industry. Here, we present an integrated, low-cost centrifugal microfluidic chip that simultaneously detects nucleic acids from six pepper viruses. All reagents are pre-stored on-chip as dried powders and are used to perform real-time fluorescence reverse transcription loop-mediated isothermal amplification (RT-LAMP). The developed assay showed strong agreement with conventional diagnostic methods of polymerase chain reaction (PCR). This platform offers a practical approach for rapid nucleic acid-based diagnostics and epidemiological monitoring of pepper viral diseases.
BACKGROUND: Given the established association between chronic kidney disease (CKD) and systemic inflammation, this study examined the relationships between complete blood count (CBC)-derived inflammatory markers and prevalent CKD. METHODS: Two data sets (Chinese clinical data, n = 4,518; NHANES 2017-2020, n = 7,724) are analyzed. Seven CBC‑derived inflammatory indices were calculated: SII, SIRI, NLR, dNLR, NMLR, MLR, and PLR. Each index was categorized into quartiles (Q1-Q4). Weighted logistic regression (for NHANES) and unweighted logistic regression (for the Chinese clinical data) were applied to estimate associations with CKD, with sequential adjustment for demographics, body mass index, and comorbidities. To control for multiple comparisons, false discovery rate (FDR) correction was applied. Furthermore, subgroup analysis, restricted cubic spline analysis and sensitivity analysis were also performed in this study. RESULTS: In the two fully adjusted models, the highest quartile (Q4) of SIRI, NLR, and NMLR was significantly associated with higher odds of prevalent CKD compared with Q1. After FDR correction, these associations remained significant in both cohorts: in the Chinese cohort, all padj < 0.001; in NHANES, padj = 0.028 for SIRI, 0.040 for NLR, and 0.041 for NMLR. Sensitivity analyses consistently supported the primary findings: excluding outliers, log2 transformation, and the alternative CKD definition yielded similar effect directions and significance levels. Heterogeneity was observed across subgroups, and restricted cubic splines revealed nonlinear dose‑response relationships (p for nonlinearity <0.05). CONCLUSIONS: Elevated SIRI, NLR, and NMLR are associated with prevalent CKD, suggesting systemic inflammation may play a role, yet prospective studies are required to establish temporality and causality.
BACKGROUND AND OBJECTIVE: Accurate nodal staging in intermediate- to high-risk prostate cancer (PCa) is crucial for treatment decisions. While extended pelvic lymph node dissection (ePLND) is the standard, it is invasive and has a low diagnostic yield. A 2019 analysis suggested that non-invasive imaging such as PSMA-PET/CT and ferumoxtran-enhanced macrophage-MRI (m-MRI) is cost-effective, but at the possible expense of a small QALY loss compared to ePLND, based on limited evidence. Recent Phase 3 trials have provided new data, prompting a reevaluation. Therefore, the aim of this article is to update a model with recent trial data to assess the cost-effectiveness of m-MRI and PSMA-PET/CT versus ePLND in Germany. MATERIAL AND METHODS: We adapted a Markov model to simulate lifetime outcomes for men with intermediate- to high-risk PCa from a German insurer's perspective, with costs updated to 2025 level. Diagnostic accuracy data were derived from recent multicenter trials. Costs and QALYs were calculated using a 3% discount rate. Sensitivity analyses tested uncertainties. A practical interactive online-tool is provided for clinical decision-making and research purposes, which can incorporate various input data (https://macrophage-mri.app). RESULTS: Both imaging options were dominant over ePLND (€37,855; 18.11 QALYs). PSMA-PET/CT was €7,869 cheaper and gained 0.800 QALYs; m-MRI was €9,985 cheaper and gained 0.990 QALYs. m-MRI was superior, saving €2,116 and gaining 0.19 QALYs over PSMA-PET/CT. The probabilistic analysis showed that m-MRI was optimal over 95% of the time at an €80,000/QALY threshold; the probability of PSMA-PET/CT being optimal was less than 5%. CONCLUSIONS: An imaging-first approach outperforms routine ePLND, with m-MRI as a cost-effective option. PSMA-PET/CT's low sensitivity limits its usefulness, though it is still cheaper than ePLND. These results support including m-MRI in guidelines for initial staging.
Rapid identification of bacteria and their virulence factors is essential for global public health. Isothermal amplification has become a cornerstone of point-of-care diagnostics, enabling genetic testing to be faster, simpler, and more accessible than culturing or polymerase chain reaction (PCR). This review examines recent advances in some of the most commonly used isothermal amplification methods for bacterial detection: SDA, LAMP, HDA, RPA, RCA, and NASBA. The integration of isothermal amplification with the CRISPR/Cas system or microfluidic devices is also highlighted as an advanced gene detection technology. We present various readout methods used to detect gene amplification products or processes, including colorimetric, fluorescent, electrochemical, and quartz microbalance techniques. These integrated approaches can detect very small amounts of bacterial DNA, in under an hour, providing rapid, sensitive, versatile, and portable tools for health control.
Bacterial diseases of banana are a growing global threat, causing yield losses and increased management costs. Major diseases include Moko, banana blood disease (BBD), and banana Xanthomonas wilt (BXW), caused by Ralstonia solanacearum, Ralstonia syzygii subsp. celebesensis, and Xanthomonas vasicola pv. musacearum, respectively. Effective surveillance requires point-of-care diagnostics such as loop-mediated isothermal amplification (LAMP) for on-site use. We aimed to develop three LAMP assays to specifically detect the bacteria responsible for Moko, BBD and BXW, directly from banana tissues, using a simplified DNA extraction protocol. The BBD - and BXW-LAMP assays demonstrated 100% specificity, yielding negative results for a broad range of non-target bacteria, including closely related species as well as pathogenic and endophytic strains associated with banana, and positive results for all the tested target strains. For Moko disease, a duplex-LAMP assay was developed to detect all strains from the four globally most relevant sequevars: IIB-3, IIB-4, IIA-6, and IIA-24. The duplex-LAMP successfully detected all target strains, except one that was shown to be non-pathogenic to Cavendish bananas. All non-target strains tested negative, with the exception of a delayed signal for one strain belonging to Ralstonia thomasi, not associated with banana environment (hospital strain). These results were supported by an extensive in silico analysis conducted on 9,668 Burkholderiaceae and 7,483 Xanthomonadaceae genomes. Detection limits ranged from 0.1 pg/µl to 1 pg/µl DNA, and from 104 to 105 CFU/ml on banana tissues spiked with calibrated bacterial suspensions, depending on the assay. The LAMP assays prove highly effective for detecting target pathogens in both artificially inoculated banana plants and field samples, offering a promising tool for improving disease management strategies.