Bosnian Journal of Basic Medical Sciences (BJBMS)
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Gastrointestinal diffuse large B-cell lymphoma: Clinical characteristics and prognostic analysis from SEER database
Full text linkThis study systematically analyzed the clinicopathological characteristics and prognostic factors of gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) patients using the SEER database. The Kaplan-Meier method was used to survival analysis, while LASSO regression analysis was utilized to further filter variables. The Pi for interaction was applied to verify the interactions in the multivariate analysis, and total survival risks were distinguished using hierarchical survival curves. Multivariate Cox regression analysis revealed that hazard ratio (HR) values indicated that age over 60 years (HR = 2.85), Ann Arbor stage (stage II: HR = 1.22; stage III: HR = 1.31; stage IV: HR = 1.85), and being widowed (HR = 1.40) were independent poor prognostic factors. In contrast, chemotherapy (HR = 0.37), radiotherapy (HR = 0.84), surgery (HR = 0.86), and lymph node resection (HR = 0.79) were associated with significant survival benefits. Additionally, an intestinal primary site (HR = 0.89), white race (HR = 0.78), and other races (HR = 0.65) were correlated with better prognosis. The nomogram model constructed from these independent prognostic factors demonstrated excellent predictive performance in both the training and validation cohorts, achieving a C-index of 0.71, significantly outperforming the traditional Ann Arbor staging system, which had a C-index of 0.56. Receiver operating characteristic (ROC) curve analysis indicated high discriminative ability for predicting 3-year, 5-year, and 10-year survival rates, with area under curve (AUC) values of 0.746, 0.756, and 0.756, respectively. Decision curve analysis (DCA) further confirmed the model\u27s significant clinical net benefit across a wide range of threshold probabilities. The nomogram model developed in this study, based on extensive SEER database data, effectively predicts the prognosis of GI-DLBCL patients and provides a quantitative tool for individualized treatment
Ending nuclear weapons, before they end us
Full text linkThis May, the World Health Assembly (WHA) will vote on re-establishing a mandate for the World Health Organization (WHO) to address the health consequences of nuclear weapons and war (1). Health professionals and their associations should urge their governments to support such a mandate and support the new UN comprehensive study on the effects of nuclear war.
Read more in the PDF https://www.bjbms.org/ojs/index.php/bjbms/article/view/12736/3911
Predictive biomarkers for post-neonatal necrotizing enterocolitis intestinal stenosis: Role of JMJD3, CRP, and PCT
Full text linkNecrotizing enterocolitis (NEC) is a severe, often life-threatening gastrointestinal disease in neonates, predominantly affecting preterm infants, and is frequently complicated by intestinal stenosis—a condition whose nonspecific clinical manifestations make early diagnosis and timely intervention particularly challenging. We aimed to investigate the clinical characteristics of NEC intestinal stenosis and its correlation with the histone demethylase Jumonji domain-containing protein 3 (JMJD3). A total of 310 children with NEC treated between February 2021 and June 2024 were retrospectively enrolled, categorizing them into an NEC group (n=265) and a post-NEC intestinal stenosis group (n=45). General data and laboratory indicators were collected, and analyses were performed to identify factors influencing the development of post-NEC intestinal stenosis. Spearman correlation analysis was utilized to assess relationships between JMJD3 and clinical parameters. Results indicated that the post-NEC intestinal stenosis group exhibited significantly lower platelet counts (PLT) and elevated levels of serum C-reactive protein (CRP), procalcitonin (PCT), and JMJD3 in intestinal tissues (p<0.05). JMJD3 was significantly associated with the development of post-NEC intestinal stenosis (p<0.001), presenting a 3.114-fold increased risk. Furthermore, JMJD3 levels were negatively correlated with PLT levels and positively correlated with CRP and PCT levels (p<0.001). Receiver operating characteristic curve analysis demonstrated that the combination of CRP, PCT, and JMJD3 provided the highest predictive efficiency, with an area under the curve of 0.918, sensitivity of 86.67%, specificity of 86.42%, and a Youden index of 0.731 (p<0.05), all surpassing the performance of individual markers. In conclusion, levels of CRP, PCT, and JMJD3 were significantly elevated in NEC children with intestinal stenosis. Their combined assessment presents a highly effective approach for the early diagnosis of post-NEC intestinal stenosis
Diabetes-induced redistribution of mast cells to the adventitia in ascending aortic aneurysms
Full text linkMast cells (MCs) are inflammatory cells that reside mainly in the intima of healthy and early- atherosclerotic abdominal aortas but migrate to the adventitia in advanced atherosclerosis and abdominal aortic aneurysms. We compared MC infiltration in the intima, media, and adventitia of ascending aortic aneurysms from patients with diabetes mellitus (DM) or arterial hypertension (AH). Fifty-one patients (36–81 years) undergoing surgical repair were enrolled and allocated to a DM group without AH (n = 9) or an AH group without DM (n = 42). Aortic specimens were stained with hematoxylin–eosin and immunohistochemically labeled with anti-CD117 to detect MCs and anti-vWF to visualize blood vessels. Compared with the AH group, the DM group had fewer MCs in the intima and more in the adventitia (Mann–Whitney test, p < 0.05). In both groups, intact MCs outnumbered degranulated MCs in the adventitia, whereas no such difference was observed in the intima or media (p < 0.05). Medial vascular density did not differ between groups (p < 0.05). In the AH group, medial vascularization correlated positively with intact, degranulated, and total MC counts, whereas in the DM group it correlated only with degranulated MCs (Spearman, p < 0.05). These findings suggest that DM-associated aneurysms exhibit a distinct MC distribution and vascular response, indicating a pathogenesis that differs from that of AH-associated aneurysms
Vitamin D deficiency and uterine leiomyoma in unexplained infertility
Full text linkUterine leiomyomas are the most common benign tumors of the female genital tract, and alongside hormonal and genetic factors, emerging evidence implicates vitamin D deficiency in their pathogenesis. We investigated the association between serum 25-hydroxyvitamin D [25(OH)D] and the presence of uterine leiomyomas in women with unexplained infertility. In this retrospective case–control study, 148 women aged 18–45 years presenting to the Infertility Clinic of Ankara Bilkent City Hospital between July 2019 and February 2024 were included: 74 had imaging-confirmed leiomyomas (non-submucosal; FIGO types 4–6) and 74 infertile controls had no leiomyomas. Serum 25(OH)D was measured and demographic/clinical data were analyzed with appropriate parametric and non-parametric tests; correlations used Spearman’s rho, and an ANCOVA adjusted for body mass index (BMI) and season assessed group differences. Groups were comparable in age and BMI (e.g., age 35.08 ± 5.79 vs 33.30 ± 5.57 years; p = 0.062). Mean serum 25(OH)D was significantly lower in women with leiomyomas than in controls (41.4 ± 23.7 vs 62.0 ± 34.2 nmol/L; p < 0.001), and this difference remained significant after adjustment for BMI and season (ANCOVA F = 10.7, p = 0.001). Vitamin D levels did not differ by leiomyoma number (single vs multiple: 44.1 ± 21.6 vs 38.5 ± 25.83 nmol/L; p = 0.32) or location (intramural vs subserosal: 40.7 ± 24.9 vs 43.1 ± 21.1 nmol/L; p = 0.69), and were not correlated with leiomyoma size (Spearman r = −0.04; p = 0.70). Among women with unexplained infertility, uterine leiomyomas are thus associated with significantly lower serum 25(OH)D levels, independent of BMI and season, whereas vitamin D status is unrelated to leiomyoma number, size, or location. These findings support a potential role of vitamin D deficiency in leiomyoma pathogenesis and underscore the need for larger, multicenter prospective studies to clarify causality and clinical implications
KDM3A drives NSCLC proliferation and metastasis via H3K9 demethylation, EMT activation and MMP-9 upregulation
Full text linkHistone methylation dysregulation is a crucial epigenetic driver of lung carcinogenesis; however, the role of lysine-specific demethylase 3A (KDM3A) in non-small cell lung cancer (NSCLC) remains inadequately understood. In this study, we established NSCLC cell models with both KDM3A overexpression and knockdown to investigate its functional impact. In vitro assays demonstrated that KDM3A depletion increased histone H3 lysine 9 dimethylation (H3K9me2), suppressed cell proliferation, and impaired migration and invasion by attenuating epithelial-mesenchymal transition (EMT) and the expression of matrix metalloproteinase-9 (MMP-9). Conversely, KDM3A overexpression led to reduced H3K9me2 levels, activated EMT, and enhanced metastatic potential. Mechanistically, KDM3A decreased H3K9me2 occupancy at the promoters of VIM and MMP-9, thus upregulating their expression. Additionally, KDM3A downregulated E-cadherin by activating the p-STAT3 pathway. In vivo, KDM3A knockdown significantly inhibited tumor growth in xenograft models. Clinical analyses revealed elevated KDM3A expression in metastatic NSCLC tissues, with a negative correlation between KDM3A and H3K9me2, and a positive association between KDM3A and FOXP3. These findings establish KDM3A as an epigenetic modulator of NSCLC progression through H3K9me2-dependent regulation of EMT and metastatic pathways, highlighting its therapeutic potential for NSCLC treatment
Vitamin D and calcium status in preeclampsia and pregnancy-induced hypertension
Full text linkHypertensive disorders of pregnancy are major causes of maternal and perinatal morbidity and mortality, and nutritional factors such as vitamin D and calcium have been proposed as modifiable risks; therefore, we investigated the association between maternal vitamin D and calcium status and pregnancy-induced hypertension (PIH) and pre-eclampsia (PE) and explored the relation with supplementation. In this observational cross-sectional study, 84 third-trimester women were enrolled from two hospitals in Lublin, Poland (41 PIH/PE, 43 controls). Serum total and ionised calcium, 25-hydroxyvitamin D [25(OH)D], and 1,25-dihydroxyvitamin D₃ were measured using standardised immunoassays, and group differences, correlations, and multivariable logistic regression were applied with adjustment for body mass index (BMI), maternal age, gestational age, calcium fractions, and gestational diabetes. PIH/PE cases had lower 25(OH)D than controls (27.8 vs 35.7 ng/mL; p = 0.012) and higher BMI (33.0 vs 27.5 kg/m²; p < 0.001), while total and ionised calcium and 1,25-dihydroxyvitamin D₃ were similar (all p ≥ 0.40); supplement use was more frequent among controls (84% vs 73%). In adjusted models, higher BMI increased the odds of PIH/PE (OR 1.19 per kg/m²) and higher 25(OH)D was protective (OR 0.92 per ng/mL); discrimination was fair (AUC 0.78). These findings support an association between vitamin D insufficiency and obesity with hypertensive pregnancy disorders and suggest preserved calcium homeostasis, but given the cross-sectional design, third-trimester sampling, small sample size, and non-standardised supplementation, causal inference and preventive recommendations cannot be made; larger prospective studies beginning in early pregnancy are warranted to test whether optimising vitamin D and calcium can reduce hypertensive complications
Exosomes in cancer metabolism and drug resistance: A review
Full text linkThe transfer of molecular cargo in exosomes plays a crucial role in cancer progression, influencing metabolic processes, angiogenesis, immune interactions, and invasive capabilities. This review synthesizes current evidence on how exosomes modulate tumor metabolism and drive drug resistance, and outlines therapeutic opportunities. We searched PubMed, Scopus, Web of Science, and Google Scholar for English-language studies using terms related to exosomes/extracellular vesicles, glycolysis, oxidative phosphorylation (OXPHOS), lipid metabolism, and drug resistance/chemoresistance, and integrated the literature qualitatively. Evidence indicates that exosomes reprogram tumor and stromal metabolism by delivering enzymes and non-coding RNAs that boost glycolysis and dampen OXPHOS, activate cancer-associated fibroblasts and extracellular matrix (ECM) remodeling, and modulate ferroptosis. They stimulate angiogenesis (e.g., via vascular endothelial growth factor (VEGF)/Wnt pathways) and promote immune escape through programmed death-ligand 1 (PD-L1), transforming growth factor beta (TGF-β), and macrophage reprogramming. Exosomal integrins and proteases contribute to epithelial–mesenchymal transition (EMT), organotropism, and pre-metastatic niche formation. Critically, exosomes propagate chemoresistance by exporting drugs and spreading determinants—including P-gp/BCRP/MRP-1, anti-apoptotic proteins, and regulatory RNAs—to previously sensitive cells; adipose-derived vesicles and lipid cargos further reinforce metabolic plasticity and therapy resistance. Given their stability, nanoscale dimensions, and ability to cross the blood–brain barrier, exosomes are promising vectors for targeted delivery; engineered vesicles can enhance chemotherapy responsiveness and counteract resistance, particularly alongside immunotherapy. In summary, interventions that disrupt exosome biogenesis, cargo loading, or uptake—paired with engineered exosomes for precision delivery—could mitigate drug resistance, metastasis, and immune evasion and advance more effective cancer treatment
CARWL score as a predictor of radiation-induced periodontitis in locally advanced head and neck cancer undergoing concurrent chemoradiotherapy
Full text linkAlthough concurrent chemoradiotherapy (CCRT) has improved outcomes in locally advanced head and neck cancer (LA-HNC), radiation-induced periodontitis (RIP) remains an under-recognized oral toxicity with significant consequences, including tooth loss and osteoradionecrosis. This study evaluates the utility of the novel CARWL score—a combined index of the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL)—for stratifying the risk of RIP in LA-HNC patients without baseline periodontitis undergoing CCRT. We conducted a retrospective analysis of 67 LA-HNC patients who underwent CCRT and received detailed oral examinations before and after treatment; none had periodontitis at the initiation of CCRT. Receiver operating characteristic (ROC) curve analysis identified an optimal pretreatment CAR cutoff of 3.07, with SWL defined as greater than 5% body weight loss in the preceding six months. Based on CAR (≥3.07 vs. <3.07) and SWL (present vs. absent), patients were categorized into three CARWL groups. The primary endpoint was the association between the baseline CARWL group and the rates of RIP following CCRT. RIP was diagnosed in 17 patients (25.4%) during follow-up, with incidences increasing progressively across CARWL-0, CARWL-1, and CARWL-2 groups (11.8% vs. 20.8% vs. 38.5%; p = 0.007). In multivariable Cox proportional-hazards analysis, a higher CARWL score emerged as an independent predictor of increased RIP risk (adjusted HR = 3.64; 95% CI 1.41–9.37; p = 0.007), and supplementary logistic regression sensitivity analysis corroborated these findings (adjusted OR = 3.58; 95% CI 1.35–9.45). These findings demonstrate that the pretreatment CARWL score serves as a straightforward and readily available biomarker that effectively stratifies the risk of radiation-induced periodontitis in LA-HNC patients treated with CCRT
Tubular functional capacity and maladaptive parathyroid hormone response in early-stage chronic kidney disease
Full text linkClinical data regarding the interaction between tubular functional capacity (TFC) and maladaptive parathyroid gland response in early-stage chronic kidney disease (CKD) are limited. This study aimed to evaluate the association between parathyroid gland response, measured as intact parathyroid hormone (iPTH) serum concentration (pg/mL) using chemiluminescent microparticle immunoassay, and the dissociation between the decline in glomerular filtration rate (GFR) and TFC, assessed through radionuclide clearances. TFC was evaluated by measuring effective renal plasma flow (mERPF, ml/min/1.73m²) using (131I) Hippurate (131I-H) clearance, while GFR was measured using (99m) Tc-DTPA (mGFR, ml/min/1.73m²). Consecutive participants with preexisting CKD (N=111, female 44%, male 56%) were enrolled and stratified into four groups based on CKD stages (1, 2, 3a, and 3b). Median serum iPTH concentrations significantly differed between Stage 1 [23 (20.4-25.5) pg/mL] and Stage 2 [23.6 (20.5-26.8) pg/mL] compared to Stage 3a [38.1 (34.1-41.9) pg/mL] and Stage 3b [45.8 (39.7-51.9) pg/mL] (p=0.01). In Stage 1, there was a significant positive association between iPTH and mERPF (p=0.003). Conversely, in Stage 3b, iPTH was significantly negatively associated with both mGFR and mERPF (p<0.05 for both). Regression models that included the interaction between CKD stage and either mGFR or mERPF, alongside other predictors (age, CKD stage, body mass index, ionized calcium, and 25-hydroxyvitamin D), revealed significant associations with iPTH (p<0.05 for all variables). The assessment of TFC using 131I-H plasma clearance does not enhance the detection of maladaptive parathyroid gland responses compared to evaluating CKD stage and its relationship with declining glomerular and tubular clearances in early-stage CKD patients