BioMed Research International

Objective: To critically evaluate the influence of extracellular matrix stiffness on tumor progression, prognosis, and clinical implications in patients with oral squamous cell carcinoma. Design: This systematic review followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and the protocol was registered in PROSPERO (CRD420251156429). Five databases (PubMed, Scopus, Embase, Web of Science, and OATD) were searched without restrictions on publication year or language. Human studies that evaluated extracellular matrix stiffness in oral squamous cell carcinoma, either as an assessment method or as a prognostic factor, were included; in vitro and animal studies were excluded. Results: Eight human studies involving 436 patients were included. Elastography was the most frequent measurement method, employed in four studies. Mean tumor thickness was reported in three studies and ranged from 3.0 to 4.4 mm. Extracellular matrix stiffness was expressed in various units (e.g., 37.7 gf, 23.5 kPa) and was consistently higher in tumor tissue than in normal mucosa in all studies. Three studies demonstrated a significant positive correlation between stiffness and tumor thickness. One study identified predictive cut-off values for lymph node metastasis and reported that high matrix stiffness was an independent predictor of worse overall survival (HR = 4.022; 95% CI: 1.294-12.495; p = 0.016) and recurrence-free survival (HR = 5.680; 95% CI: 1.146-28.143; p = 0.033). A meta-analysis of five studies (307 patients) showed a significantly higher standardized stiffness in oral squamous cell carcinoma compared with normal oral mucosa (standardized mean difference = 5.28; 95% CI: 2.61-7.94; p < 0.001), with substantial heterogeneity (I2= 98.6%). Conclusions: Extracellular matrix stiffness is elevated in oral squamous cell carcinoma and is associated with greater tumor thickness, lymph node metastasis and, in one study, worse survival. These findings support extracellular matrix stiffness as a potential biomechanical marker, pending further validation in standardized prospective studies.

Background: Chronic kidney disease (CKD) may progress to stage 5 CKD (end-stage renal disease, ESRD), but stage-associated molecular alterations remain incompletely characterized. This study aimed to identify candidate biomarkers associated with CKD and ESRD. Methods: Two discovery datasets comparing CKD or ESRD with healthy controls were analyzed using differential expression analysis and weighted gene co-expression network analysis. Candidate genes were identified by intersecting differentially expressed genes with key co-expression modules, followed by protein-protein interaction network analysis using Degree, Closeness, and Maximal Clique Centrality algorithms. Candidate genes were evaluated in independent GEO validation datasets and further examined by quantitative real-time PCR and western blotting using clinical blood samples. Results: Ten hub genes were identified, among which EPB42, KLF1, and H3F3A were prioritized for further evaluation. EPB42 showed decreased expression in CKD but increased expression in ESRD, indicating an opposite-direction pattern between the two disease states. KLF1 showed no significant difference between healthy controls and CKD but was increased in ESRD, whereas H3F3A was increased in CKD and further increased in ESRD. Functional enrichment analysis highlighted processes related to oxygen transport, mitochondrial function, muscle-associated processes, and inflammation, suggesting possible involvement of hypoxia-associated oxidative injury and ferroptosis-related processes. Conclusions: Integrated transcriptomic and experimental analyses identified EPB42, KLF1, and H3F3A as candidate stage-associated biomarkers in CKD and ESRD. In particular, the opposite-direction expression pattern of EPB42 may provide additional molecular information for distinguishing CKD from ESRD.

Background/Aims: In medical practice, the rising prevalence of infections in kidney transplant recipients (KTRs) is a notable concern. However, understanding the incidence and risk factors associated with infections in KTRs remains limited. This study aims to assess the incidence and factors associated infection among KTRs. Additionally, we also investigate the median time of each infection among KTRs. Methods: A retrospective cohort study was conducted from 1 January 2018- 31 December 2022 at Thailand's tertiary hospital. We performed univariable and multivariable logistic regression analyses to identify potential risk factors related infection and investigated for the incidence and median time of each infection among KTRs. Results: A total of 179 participants were included in this study. Our findings reveal the kidney from living donor was protective factor for infection among KTRs (aOR 0.063, 95% CI 0.005-0.792; p = 0.032). Urinary tract infections (UTIs)showed as the predominant pathogenic manifestation among KTRs (43%). The median time of UTIs, cytomegalovirus (CMV) infection and pneumocystis pneumonia (PCP) were 16, 57 and 94.5 days, respectively. Conclusions: Our study establishes that receiving a kidney from a living donor is a protective factor against post-kidney transplant infections. Particularly urinary tract infections were most common of infection. Monitoring urinary tract infections post-transplantation is recommended. Moreover, awareness of UTI, CMV infection and PCP should be concerned during 2-3 months after transplantation. However, due to a small sample size; we recommend to increase the number of particular participants in further investigations.

Objective Based on the bioinformatics method of multi-database integration, this study systematically analyzes the expression characteristics, clinical pathological correlation, prognostic value, potential molecular mechanisms, and immune infiltration patterns of hepatocyte growth factor receptor (MET) in gastric cancer. Methods The UALCAN and GEPIA databases were employed to examine the differential expression of MET between gastric cancer and normal gastric mucosal tissues, as well as its associations with clinicopathological features. Kaplan-Meier Plotter was utilized to evaluate the impact of MET expression on overall survival (OS) and progression-free survival (PFS). Protein-protein interaction (PPI) network was constructed via LinkedOmics, followed by Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of co-expressed genes. Four algorithms, TIMER, CIBERSORT, EPIC, and MCPcounter, were used to cross evaluate the correlation between MET expression and immune cell infiltration; Further validate the cell type specific expression of MET using the gastric cancer single-cell sequencing queues (GSE134520, GSE167297) built into the TISCH database. Results MET expression was significantly elevated in gastric cancer tissues compared with normal gastric mucosa (P < .05), and its expression level was significantly correlated with tumor grade and TNM stage. Patients with high MET expression exhibited significantly poorer OS and PFS than those with low MET expression (P < .05). The PPI network revealed that MET could interact with 20 key proteins, including EGFR, ERBB2, HGF, STAT3, and GRB2 etc. GO enrichment analysis suggests that differentially expressed genes are significantly enriched in functions such as the ERBB signaling pathway, cadherin binding, and DNA repair complexes; KEGG enrichment analysis showed that MET related genes were significantly enriched in pathways such as homologous recombination, nuclear cytoplasmic transport, mismatch repair, and oxidative phosphorylation. Immune infiltration analysis showed that the negative association between MET and B cells infiltration has cross algorithm robustness, while the association with neutrophils, CD8+ T cells, CD4+ T cells, and macrophages exhibits algorithmic heterogeneity or insignificance; There is no significant correlation between MET and common immune checkpoint molecules such as PD-1, PD-L1, CTLA4, etc. Single cell validation further confirmed that MET is mainly enriched in malignant epithelial cells and endothelial cells, and is almost not expressed in immune cells. Conclusions Multidimensional bioinformatic analyses demonstrate that elevated MET expression serves as an independent risk factor for unfavorable prognosis in gastric cancer. MET may mediate dual drug resistance in gastric cancer via crosstalk with multiple signaling molecules (including EGFR, ERBB2, HGF, STAT3 and GRB2) and dysregulation of the homologous recombination repair pathway. Results from multiple-algorithm immune infiltration analysis, single-cell dataset analysis and immune checkpoint correlation analysis indicate that MET exerts only modest direct regulatory effects on the gastric cancer immune microenvironment. This exploratory study offers systematic bioinformatic evidence supporting MET as a candidate prognostic biomarker and potential therapeutic target for gastric cancer. Further functional experiments and prospective cohort studies are required to validate its molecular mechanisms and clinical utility.

Background Pediatric nephrotic syndrome (NS) significantly increases cardiovascular risk, primarily through activation of the renin-angiotensin-aldosterone system (RAAS) and chronic inflammation. This study aimed to evaluate the relationship between serum aldosterone and interleukin 6 (IL-6) levels with carotid intima-media thickness (CIMT) in children with steroid-sensitive (SSNS) and steroid-resistant NS (SRNS), both before and after combined treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). Materials and methods A prospective cohort study enrolled 32 children aged 2-18 years with idiopathic NS at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia (May-June 2024). Participants received lisinopril (ACEI) or valsartan (ARB) for 12 weeks. Serum aldosterone was quantified via liquid chromatography-tandem mass spectrometry, IL-6 via electrochemiluminescence immunoassay, and CIMT via high-resolution B-mode Doppler ultrasound. Data were analyzed using SPSS version 26.0, including Shapiro Wilk normality testing, Pearson/Spearman correlations, and multivariate linear regression (enter method, R2=0.022), with statistical significance set at p<0.05. Results CIMT decreased significantly post-treatment (0.13{+/-}0.04 cm to 0.06{+/-}0.01 cm; p<0.001). Serum aldosterone remained stable (5.15 to 4.0 ng/dL; p=0.933), as did IL-6 (3.5 pg/mL; p=0.156). Univariate analyses revealed weak correlations (aldosterone-CIMT: R2=0.075; IL-6-CIMT: R2=0.215). Multivariate regression (R2=0.022) identified SRNS as positively associated with CIMT change (p=0.047), while aldosterone and IL-6 showed no significant independent effects. Conclusion This study highlights that ACEI and ARB therapy improved CIMT regardless of steroid sensitivity, suggesting vascular benefits may occur through pathways independent of aldosterone and IL-6 modulation.

Hard-tissue surgery requires precise spatial control, while conventional computer-assisted navigation presents guidance separately from the operative field. Augmented reality can bring navigation information closer to the surgeon, but how best to translate this information into intuitive intraoperative guidance remains underexplored. We therefore developed an augmented reality navigation system (ANS) that translates real-time deviations from the planned trajectory into co-located holographic action cues. Evaluation comprised typodont and ex vivo porcine experiments, a randomized crossover study in 40 dental trainees, and eight clinical cases. In porcine mandibles, ANS showed lower angular deviation than static and dynamic navigation (1.78 vs 6.42 and 4.02 degrees). Among trainees, accuracy was comparable with dynamic navigation, while workload was lower (29.18 vs 33.15), usability higher (73.13 vs 68.88), and visual-focus ratings improved (3.55 vs 2.28). Clinical cases supported feasibility. These findings support co-located action guidance as an alternative interface paradigm for surgical navigation.

Objective Describe the profile of consumers utilising Emergency Departments (ED) across Victorian hospitals for dental conditions between financial year 2018-19 to 2022-23. Methods Dental conditions were grouped according to the diagnosis categories using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM). Presentations for non-dental conditions were classified as 'Other'. Dependent variables included age, sex, Aboriginal and Torres Strait Islander (Aboriginal) background, language other than English, interpreter required, remoteness, and socio-economic disadvantage according to the Index of Relative Socio-economic Disadvantage (IRSD). The primary outcome evaluated is the relative risk ratio (RRR) of having a hospital ED presentation for a dental condition compared to a non-dental condition and age-specific rates per 100,000 population. Multinomial logistic regression was performed following the backwards elimination method. Results Over the years 2018-19 to 2022-23, 0.55% (n=44,382) of ED presentations across Victorian hospitals by Victorian residents were due to dental conditions. Patients aged 20-44 years have the highest RRR compared to other age groups for dental-related ED presentations. Patients experiencing social inequity in terms of demographic factors such as Aboriginal background, requiring an interpreter, not living in a major city and living in areas of greater disadvantage (IRSD) have statistically significant increased RRR for dental-related ED presentations. Conclusion Patient characteristics were useful for identifying the relative risk of dental-related ED presentations between socio-economic and demographic groups to inform relevant public policy design focus on preventing dental-related ED.

Hypertriglyceridemia is commonly managed with lipid-lowering drugs such as statins; however, adverse effects, dose intolerance, and financial barriers may limit their use. Therefore, affordable and potentially safer plant-derived alternatives warrant investigation. This study evaluated the lipid-lowering effects of ethanol extracts of Fucus vesiculosus and Phytolacca berry, administered individually or in combination, in mice fed a butter-enriched diet for 12 weeks. Forty-eight mice were randomly assigned to six groups: normal control (Group 1), butter control (Group 2), statin control (Group 3), Fucus vesiculosus extract (Ext-1; Group 4), Phytolacca berry extract (Ext-2; Group 5), and the combined extracts (Group 6). Body weight, organ-to-body-weight ratios, serum lipid parameters, and histopathological changes were assessed. Group 3 showed the lowest final body weight, while Group 6 demonstrated a comparable body-weight trajectory. Organ-to-body-weight ratios varied among groups, with Group 3 generally showing the highest values and Group 6 comparatively lower ratios for several organs. Group 5 had the lowest total cholesterol concentration, followed by Group 3, whereas Group 6 showed cholesterol levels comparable to the normal control and statin groups. Notably, Group 6 exhibited the lowest serum triglyceride concentration (129.9 mg/dL). Histopathological examination revealed relatively mild hepatic alterations and limited vascular plaque formation in Group 6. The combined extracts demonstrated favorable effects on body-weight gain and serum lipid profiles, particularly triglycerides, with comparatively mild histopathological changes. Further mechanistic, dose-response, toxicity, and long-term studies are warranted before clinical application can be considered.

Background In Kenya, stroke is one of the top five causes of mortality, with a high rate of inpatient mortality. The American Heart Association (AHA) and American Stroke Association (ASA) translated scientific evidence into evidence-based clinical practice guidelines aimed at reducing inpatient mortality and improving the quality of care for stroke patients. Despite the proven benefits of the ASA stroke guidelines in improving stroke care, translation of the guidelines in various settings remains a key challenge. This study aimed to quantify the gap between evidence-based recommendations and current stroke care practices in a peri-urban referral facility in Kiambu, Kenya. The study was conducted at xxxxxxxxxx Hospital, a peri-urban referral facility in Kiambu County, Kenya. Methods: We reviewed records of stroke patients attending xxxxxxxxxxx from January 1, 2020, to December 31, 2023. The study evaluated acute stroke management practices and secondary prevention against the 2019 American Heart Association/American Stroke Association (AHA/ASA) Guidelines for the Early Management of Acute Ischemic Stroke. Results: The median distance travelled by stroke patients to the facility was 47.8 kilometres; further, the median onset-to-presentation time was 24 hours. The study evaluated eight clinical practices against the ASA guidelines. The facility lacked a dedicated stroke unit. Remarkably, patients arriving within the therapeutic window for intravenous alteplase and thrombectomy did not receive these treatments. Secondary prevention measures, including discharge on an antiplatelet regimen, were moderately adhered to; among the 86 eligible ischemic stroke patients, 67 (77.9%) were correctly discharged on aspirin. Similarly, 84/123 (68.3%) of the patients were discharged on statin therapy. Conclusion: Evidence-based stroke care recommendations were minimally adhered to at this peri-urban referral facility in Kiambu, Kenya. Contribution: This study quantifies the gap between evidence-based stroke care recommendations and current clinical practice in a peri-urban referral facility in Kenya, providing context-specific evidence to inform quality improvement initiatives and guideline implementation efforts in similar resource-constrained settings.

Automated dental implant planning using artificial intelligence (AI) faces challenges in interpretability, safety assurance, and applicability beyond single-tooth cases. This paper presents a unified explainable framework for cone-beam computed tomography (CBCT) that handles both single-tooth and consecutive multiple missing teeth. The method combines nnU-Net-based anatomical segmentation with a transparent geometric optimization pipeline. Implant placement is formulated as a lexicographic multi-objective constrained optimization problem that enforces clinical safety margins while balancing bone engagement, mesiodistal spacing, and buccolingual position. For multi-tooth cases, a global coordination strategy ensures inter-implant parallelism, minimum spacing, and a common insertion path. The framework was validated on 20 single-tooth and 9 consecutive multi-tooth cases. The AI plans achieved a centroid distance of 1.60+/-1.05 mm for single-tooth cases and 1.22+/-0.32 mm for multi-tooth cases, with approximately 7 degrees axial angle difference. All plans achieved 100% compliance with predefined safety thresholds. In a Turing-style test, experts were unable to distinguish AI from human intelligence (HI) plans under blinded conditions. By decoupling perception from reasoning and embedding clinical knowledge as explicit constraints, the framework offers an interpretable and clinically trustworthy solution for computer-aided implant dentistry.

Invasive candidiasis has become more common in recent decades, particularly within ICUs. Identifying specific Candida spp., and testing their sensitivity to antifungal drugs is crucial for effective treatment that helps healthcare providers to detect potential treatment challenges early. This study aimed to identify Candida spp. at their spp. level present in blood, assess their susceptibility to antifungal agents, and apply a random forest classifier to predict the best antifungal drug for a given species. The isolates were classified at the species complex level through MALDI-TOF MS. The strains' susceptibility to antifungal agents such as AMB, FLZ, VOZ, ITZ, POZ, CAS, MFN, and ANF was assessed using CLSI guidelines. Out of the 354 Candida spp. isolated from blood, C. utilis was found to be the predominant species, followed by C. tropicalis, and C. albicans. This study demonstrated that MFN and ANF exhibited high potency, with an impressive MIC90 of 0.12 {micro}g/mL against all isolates, surpassing CAS, which had a slightly higher overall MIC90 of 0.25 {micro}g/mL. FLZ exhibited the highest MIC90 value among the azoles at 16 {micro}g/mL, while VOZ, ITZ, and POZ all had MIC90 values of 0.5 {micro}g/mL. AMB MIC90 values were 2 {micro}g/mL against all isolated Candida species. The Random Forest AI/ML model showed perfect overall prediction, with the actual and predicted best antifungal drugs matching for all fungal species. This study is particularly essential because rare Candida spp. becoming more common and exhibiting higher MICs to AMB and FLZ and required suitable remedies for controlling the infection.

This was a cohort study of 1,663 subjects (1196 women, 467 men; median age 48 years, IQR 37-57) with thyroid nodules recruited from 2020 to 2025 in five tertiary medical centers. Cytological/histopathological diagnoses were established by an independent review committee, and preoperative serum thyroid hormone metabolites (THMs) were tested using liquid chromatography tandem mass spectrometry. A diagnostic model on this serum THM test to distinguish between differentiated thyroid cancer (DTC) and benign thyroid nodule (BTN) was trained on 872 retrospective subjects (454 DTC and 418 BTN), followed, prospectively, by model validation on 392 subjects (195 DTC and 197 BTN) and a second validation on 399 subjects (300 DTC and 99 BTN). Following successful diagnostic model training, the model validation demonstrated a diagnostic specificity of 99.5% (196/197), sensitivity of 92.3% (180/195), positive predictive value (PPV) of 99.4%, negative predictive value (NPV) of 92.9%, and diagnostic accuracy of 95.9% (95% CI, 90.8 to 100.0%) for DTC. Combination of the two validation cohorts showed a diagnostic specificity of 99.7% (295/296), sensitivity of 92.1% (456/495), PPV of 99.8%, NPV of 88.3%, and diagnostic accuracy of 94.9% (95% CI, 91.5 to 98.0%) for DTC. The test on indeterminate Bethesda categories III-IV (139 DTC, 87 BTN) showed a diagnostic specificity of 100.0% (87/87), sensitivity of 93.5% (130/139), PPV of 100.0%, NPV of 90.6%, and diagnostic accuracy of 96.0% (95% CI, 89.2 to 100.0%) for DTC. This study develops a novel molecular blood test of serum THMs for preoperative diagnostic evaluation of thyroid nodules, which displays a high PPV and decent NPV with an excellent overall diagnostic accuracy for DTC.

Objective: Hyperthyroidism and hypothyroidism related to iodine deficiency are major public health concerns in Afghanistan. This study aimed to assess the frequency of thyroid dysfunction among male patients referred for thyroid testing and its association with age, and to examine monthly trends in thyroid dysfunction at Asia Med Laboratory in Herat, Afghanistan, from July 2021 to January 2022. Methods: A retrospective analysis was conducted on 250 male patients aged 0-69 years. We measured Serum TSH, total T4, and total T3 levels, and thyroid status was classified using age specific reference ranges. In addition, the frequency of thyroid dysfunction was analyzed across age groups with monthly trends of thyroid state. Results: Overall, the euthyroid state consisted of 69.2% of participants, 24.8% with overt hypothyroidism, 3.2% with overt hyperthyroidism, and 2.8% with subclinical hyperthyroidism. Thyroid status differed significantly by age (p = 0.0135), with hypothyroidism increasing in older age groups and reaching its highest proportion among men aged 60-69 years (55.6%). Euthyroidism predominated in patients aged 10-39 years, while hyperthyroidism across age groups remained relatively infrequent. After September 2021, a threefold increase was observed in the total number of male patients referred for thyroid testing. During this period, the proportion of hyperthyroidism increased slightly, whereas hypothyroidism cases declined. Conclusion: In conclusion, hypothyroidism was more frequent with older age. The rise in absolute case numbers after September 2021 likely reflects increased patient referrals, underscoring the need for ongoing monitoring of thyroid function. The study may assist in the early management of thyroid disorders and in reducing their complications.

Purpose: To compare the performance of three large language models (LLMs), ChatGPT-o1, Grok 3, and Gemini 2.0 Pro, on the American College of Prosthodontists' National Prosthodontic Resident Examination (NPRE). Materials and Methods: Official NPRE examinations from years 2015-2024 were retrieved from the American College of Prosthodontists website and used to prompt each LLM. Paid access tiers and advanced reasoning were enabled. Responses from LLMs were recorded and compared against the official answer keys for accuracy, variability across years, and consistency of responses. Duplicate questions were retained for the primary analysis and removed in a sensitivity analysis. Accuracy (percent correct) was compared using generalized estimating equations binary logistic regression (primary); Cochran's Q with Bonferroni-adjusted McNemar tests (sensitivity). Year-to-year variability (SD of annual accuracy) was compared using weighted Levene tests. Consistency across duplicate items was quantified as the percentage of perfect matches and compared using Cochran's Q with Bonferroni-adjusted McNemar tests. Results: Across 1,487 questions, overall accuracy differed among models (global P < 0.001). ChatGPT-o1 achieved 78.4% correct, Grok 3 76.4%, and Gemini 2.0 Pro 73.2%; ChatGPT-o1 and Grok 3's accuracy significantly exceeded Gemini 2.0 Pro (both P [&le;] 0.016), with no significant difference between ChatGPT-o1 and Grok 3 (P = 0.099). After removing duplicates (n = 1,200), results were similar: ChatGPT-o1, Grok 3, and Gemini 2.0 Pro were 77.1%, 76.6%, and 71.5% correct, respectively; ChatGPT-o1 and Grok 3's accuracy was significantly higher than Gemini 2.0 Pro (both P < 0.001). Variability across years did not differ significantly (P [&ge;] 0.097). Grok 3 showed significantly higher perfect-match consistency (79.2%) than ChatGPT-o1 (69.4%) and Gemini 2.0 Pro (64.5%) (P [&le;] 0.010). Conclusions: Contemporary LLMs showed 70-80% accuracy on postgraduate prosthodontic multiple-choice content. While promising for educational support, residual error and inconsistency warrant human oversight and transparent methods reporting before curricular adoption.

Purpose: Uveal melanoma (UM) is a rare but aggressive intraocular malignancy originating in the uvea (choroid, iris, and ciliary body). Despite primary treatment, 50% of UM patients develop metastases to the liver, lungs, bones, and skin. Topotecan, a topoisomerase I inhibitor, and SP141, an MDM2 inhibitor, have been studied in cancers, including retinoblastoma. This study explores a combined approach with these drugs in the 92-1 UM cell line. Methods: Primary choroidal melanoma-derived 92-1 cells were treated with topotecan and SP141 individually to determine IC50 values. Cell viability and proliferation were assessed using the MTT assay and the xCELLigence real-time monitoring system. The synergistic effects were analyzed quantitatively using the Loewe Additivity and Highest Single-Agent (HSA) models. Flow cytometry was employed to analyze cell cycle distribution, while cell death and apoptosis were monitored via high-throughput, real-time quantitative analysis using the IncuCyte live-cell kinetic imaging system. Results: Both Topotecan and SP141 induced significant cell death in 92-1 cells. xCELLigence showed dose- and time-dependent inhibition of proliferation. Combining sub-IC50 concentrations of topotecan and SP141 exhibited significant synergistic effects, markedly reducing growth. Cell cycle analysis revealed that topotecan causes a dose-dependent biphasic arrest in G2 and S phases, while SP141 causes G2/M arrest, leading to cell death. Cytotoxicity assays corroborated increased cell death following combination therapy, and the Caspase 3/7 assay indicated that apoptosis is the mechanism underlying cell death. Conclusions: The multi-targeted approach combining topotecan and SP141 drugs demonstrated synergistic therapeutic effects in 92-1 cells, suggesting a potential treatment strategy for managing UM.

Introduction: Thyroid diseases are major health problems and among the most common endocrine disorders worldwide, including in Ethiopia. They are characterized by alterations in hormone secretion, enlargement of the thyroid gland, or both. Fine needle aspiration cytology is an important initial screening tool, and histopathologic examination is essential for the definitive diagnosis of thyroid disease. This study aimed to compare the diagnostic accuracy of fine needle aspiration cytology with histopathology in identifying thyroid diseases. Methods: A cross-sectional study was conducted at three health facilities in Hawassa City, Ethiopia, involving 304 patients who underwent both thyroid fine needle aspiration cytology and histopathologic examination of the same site between 30th October 2024 and 29th October 2025. FNAC results were classified using the Bethesda system, with histopathology as the gold standard. Data were entered into Kobo Toolbox, exported to SPSS version 27, and analyzed using cross-tabulation and chi-square ({chi}{superscript 2}) tests to determine diagnostic accuracy. Result: 304 patient records were included in the study. The fine needle aspiration cytology was determinate/diagnostic in 81.6% of cases. The study revealed the sensitivity and specificity of fine needle aspiration cytology to be 88.2% (CI 77.6-95.1%) and 94.4% (CI 90.6-97.1%), respectively. The false negative and false positive rates in this study were 2.4% and 4.4%, respectively. The positive predictive value was 80.3% (CI 68.7-89.3%), and the negative predictive value was 96.8% (CI 93.8-98.7%). The accuracy of fine needle aspiration cytology in differentiating benign from malignant thyroid lesions was 93.1%. Conclusion: FNAC demonstrated strong agreement with histopathology and remains a reliable, cost-effective first-line diagnostic tool for thyroid disease, particularly in resource-limited settings. Strengthening sample handling, ultrasound guidance, and adherence to Bethesda criteria may further improve diagnostic precision

Preoperative anaemia is common in adults undergoing cardiac surgery and may identify patients at increased perioperative risk. This systematic review and meta-analysis synthesised contemporary observational evidence in accordance with PRISMA 2020. Five databases were searched for peer-reviewed English language studies published from 2017 to July 2026. Random effects meta-analyses used restricted maximum likelihood estimation with Hartung-Knapp confidence intervals; crude exact count estimates were synthesised primarily and adjusted estimates separately. Fourteen observational cohort studies involving 74,571 adults, including 17,349 (23.3%) with anaemia, were included. Preoperative anaemia was associated with red cell transfusion (OR, 3.66; 95% CI, 2.14-6.24), acute kidney injury or renal failure (OR, 2.43; 95% CI, 1.84-3.21), early mortality (OR, 2.11; 95% CI, 1.40-3.17), and postoperative infection (OR, 1.49; 95% CI, 1.21-1.82), but not postoperative stroke (OR, 1.16; 95% CI, 0.43-3.17). Certainty was low for renal outcomes and very low for the other outcomes. Preoperative anaemia is an important perioperative risk marker, particularly for transfusion and renal complications, although causality cannot be established.

BACKGROUND: The protein 4.1a/4.1b ratio is an intrinsic molecular marker of mean red blood cell (RBC) age resulting from progressive deamidation of protein 4.1b during RBC circulation. Despite its potential for estimating mean RBC age from a single blood sample, its application has been limited by labor-intensive RBC membrane preparation, and its interindividual variability has not been characterized in a large human population. METHODS: We developed a low-volume method for direct RBC membrane isolation from whole blood using saponin permeabilization and differential centrifugation without prior RBC washing. Membrane proteins were separated by SDS-PAGE, and protein 4.1a/4.1b ratios were determined by densitometric analysis with Gaussian peak fitting. Assay conditions, sample-volume requirements, membrane protein recovery, and analytical reproducibility were evaluated. The method was subsequently applied to 114 anonymized residual samples from routine diagnostic testing selected for complete blood count parameters within the corresponding laboratory reference intervals. RESULTS: The optimized procedure used 50 uL of whole blood, 0.06% saponin, and centrifugation at 9000 g, although protein 4.1a/4.1b remained measurable from starting volumes as low as 5 uL. Mean within-subject CVs were 3.90% for electrophoretic/densitometric determination and 5.39% for membrane protein recovery; whole-procedure CVs in 3 subjects were 1.40% to 3.50%. In the population analysis, the mean protein 4.1a/4.1b ratio was 1.428 (SD 0.146), with an observed range of 1.052 to1.799 and a central 95% interval of 1.151 to 1.695. Ratios did not differ significantly between females and males (P=0.246) or among females aged 18 to 50 years, females aged >50 years, and males (P=0.151). The ratio showed modest positive correlations with chronological age in females (Spearman p=0.26, P=0.047) and males (p=0.33, P=0.015), while substantial interindividual variability remained across the age range. CONCLUSIONS: Direct isolation of RBC membranes from small volumes of whole blood enables reproducible determination of the protein 4.1a/4.1b ratio using a simplified workflow. Application of the assay to a comparatively large human population revealed substantial interindividual variation in this molecular marker of mean RBC age that was not explained by sex or chronological age alone. The method provides a practical approach for investigating biological variation in mean RBC age and its potential contribution to laboratory measurements influenced by RBC survival.

Objective: Dendritic cells (DCs) are priming local immune responses, and their tissue-associated activity increases in inflammatory conditions. In patients with coronary artery disease (CAD), circulating dendritic cell precursors (DCPs) are reduced. This study investigates circulating DCPs and tissue densities of migrated DCs in CAD patients undergoing bypass surgery, focussing on patients with chronic kidney disease (CKD) as a risk factor for CAD and a condition of chronic vascular inflammation. Approach and Results: Circulating DCPs were measured in the peripheral blood (before surgery) using fluorescence-activated cell sorting (FACS) in n=59 patients and results were compared with an age-matched healthy control group (n=45). DCs were stained (Fascin) in circular sections of the internal thoracic artery taken during bypass surgery and mature (CD83+) and immature (CD209+) DCs were differentiated. Cell densities were obtained digitally. Descriptive statistics and correlation analysis generated hypotheses. Circulating myeloid DCPs were reduced (p<0.001), concomitant CKD added no further reduction. Immature DCs were predominantly detected in the adventitia, mature DCs dominated in the intima (p<0.001). In CKD, reduced circulating myeloid DCPs correlated with immature DCs in the vessel wall (r=0.87; p=0.002) and rather mature DCs were detectable; in patients without CKD immature DCs were dominating. C-reactive protein correlated with mature DCs (r=0.38; p=0.026). Conclusions: Quantities of DCPs and mature and immature DCs vary between the vessel wall layers. The dominance of immature myeloid DCs in the adventitia suggests activation of the vascular-associated lymphoid tissue (VALT). Intensified inflammation associated with CKD may have promoted the maturation of myeloic DCs.

Background: The systemic immune-inflammation index (SII) is a routinely available blood-derived marker with potential prognostic relevance after coronary artery bypass grafting (CABG). We evaluated associations between preoperative SII and postoperative outcomes. Methods: PubMed, Embase, Scopus and Web of Science were searched to 1 October 2026, with supplementary searches through 14 October 2026. Peer-reviewed observational studies evaluating preoperative SII in adults undergoing CABG were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale. Compatible categorical associations and exploratory adjusted continuous mortality effects were pooled separately using restricted maximum-likelihood random-effects models; other findings were summarized descriptively. Results: Thirty-one reports were included, with an aggregate sample of 30,976 and possible cohort overlap; five contributed to meta-analysis. Two off-pump cohorts comprising 1,378 patients and 180 atrial-fibrillation events yielded an imprecise crude association with postoperative atrial fibrillation (OR 1.60, 95%CI 0.53-4.82; I2=68%). An exploratory crude synthesis indicated greater intra-aortic balloon pump use with higher SII (OR 2.45, 95%CI 1.16-5.18; I2=51%). Two cohorts with differing follow-up yielded an exploratory adjusted mortality HR of 1.11 (95% Wald CI 1.05-1.18) per study-specific SD increase in log-SII. In one 624-patient cohort, high SII was associated with postoperative acute kidney injury after adjustment (OR 3.35, 95% CI 2.25-4.97).Apparent atrial-fibrillation discrimination varied (AUC 0.587-0.946). Conclusions: Preoperative SII showed associations with selected adverse outcomes after CABG, supporting further evaluation as an accessible prognostic marker. Its incremental value beyond established clinical risk models requires validation. Keywords: Systemic immune-inflammation index; Coronary artery bypass grafting; Atrial fibrillation; Prognosis; Systematic review