Education Training And Research

This reply addresses the comments by You et al. regarding our article entitled "The effect of supervised aerobic exercise on adipokine and myokine biomarkers in patients with cancer during systemic chemotherapy." We appreciate their constructive remarks concerning study design, sample composition, and biomarker assessment timing. In this correspondence, we clarify that these aspects were explicitly acknowledged as limitations in our original paper and further elaborate on the methodological and ethical considerations underlying our approach. We agree that future randomized and multicenter studies with standardized biomarker protocols are needed to deepen the understanding of exercise-oncology interactions. Such academic exchanges contribute meaningfully to refining research quality and promoting the integration of exercise as an essential component of supportive cancer care.

The aim of this study was to investigate the factors affecting the development of pulmonary hypertension (PH) in patients with progressive massive fibrosis (PMF) and to determine the relationship between PH development and life expectancy. In this retrospective study, 181 patients with PMF were recruited over a 9-year period and 96 were eligible for analysis. We used echocardiography (ECHO) findings to estimate the likelihood of developing PH. We used Bernoulli's equation with tricuspid regurgitation velocity measurement and calculated systolic pulmonary artery pressure (sPAP) by adding the estimated right atrial pressure. We accepted sPAP values of 37 and 50 mm Hg as criteria for moderate and high probability PH. The prevalence of moderate or high probability PH (PH group) was 29.1% in patients with PMF. Older age (OR:1.059, p=0.036) and presence of C opacity (OR:4.607, p=0.024) were found to be risk factors for PH in patients with PMF. The survival rate (39.2%) and mean survival time (65.20±9.94 months) were significantly lower in the PH group compared to the non-PH group (p=0.002). PH development was primarily associated with fibrotic disease burden rather than coexisting airflow obstruction. The development of PH and the increase in the degree of PH have a negative effect on the mean survival time. Preventing the development of PMF, which has a poor prognosis, by taking necessary precautions is the most effective option in treatment.

Inherited kidney diseases represent a genetically and clinically heterogeneous group of disorders affecting both pediatric and adult populations. Advances in next-generation sequencing (NGS) have improved diagnostic precision; however, genotype-phenotype correlations and diagnostic yield vary substantially across disease entities. We retrospectively evaluated 165 patients referred for genetic testing due to suspected inherited kidney disease. Patients were classified into three clinical groups: polycystic kidney disease, Alport syndrome, and other syndromic patients with inherited kidney diseases. Genetic analysis was performed using NGS with Human Phenotype Ontology-based gene filtering and included evaluation of both single-nucleotide variants and copy number variations. Overall diagnostic yield differed markedly between groups. A molecular diagnosis was achieved in 71.4% of Alport patients, 41.0% of PKD patients, and 70.2% of patients in the Other syndromic group. In the Alport group, variants were identified exclusively in COL4A3, COL4A4, and COL4A5, with pathogenicity and gene involvement correlating with disease severity and the presence of extrarenal manifestations. The PKD group showed predominant involvement of PKD1, followed by PKHD1 and PKD2, while a substantial proportion of patients remained genetically negative, reflecting technical and biological complexity. The Other group exhibited pronounced genetic heterogeneity, with variants distributed across multiple genes involved in tubular, glomerular, metabolic, and ciliopathy-related pathways. Computational assessments demonstrated that several variants of uncertain significance (VUS) were located in functionally critical domains and were predicted to disrupt protein stability, intermolecular interactions, or conserved structural motifs, thereby supporting the biological plausibility of their potential pathogenic impact. Phenotype-driven NGS enables effective molecular diagnosis across diverse inherited kidney diseases while revealing disease-specific differences in diagnostic yield and genotype-phenotype correlations. Systematic inclusion of variants of uncertain significance and careful integration of genetic and clinical data are essential for accurate interpretation and long-term patient management. Collectively, this study enhances understanding of inherited kidney diseases and underscores the value of integrating comprehensive genomic and computational approaches into routine nephrogenetic practice.

Introduction & Objective: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), with limited treatment options for steroid-resistant cases. Ruxolitinib, a JAK1/2 inhibitor, has shown promise in treating steroid-resistant acute (aGVHD), chronic (cGVHD), and overlap GVHD (oGVHD), but real-world data remain limited. This study evaluated the real-world efficacy and safety of ruxolitinib in allo-HSCT patients with steroid-resistant GVHD. Materials & Methods: This retrospective, multicenter study included adult patients treated with ruxolitinib for Grade II or higher aGVHD or moderate-to-severe cGVHD at nine centers in Turkey (2017-2024). Clinical characteristics, treatment responses, and adverse events were recorded. Primary outcomes were overall response rate (ORR) and overall survival (OS). Results: Among 80 patients (mean age: 39.3 ± 13.3 years; 60 males), 39 had aGVHD, 68 cGVHD, and 15 oGVHD. The ORR was 72 of 80 patients (90.0%) (complete response: 37 of 80 [46.3%], partial response: 35 of 80 [43.8%]). The 1-year and 2-year OS rates were 91.3% and 82.5%. Severe cGVHD (p < 0.001) and lack of response to ruxolitinib (p = 0.018) were associated with reduced OS. Adverse events included infections in 40 of 80 patients (50.0%), cytopenias in 23 of 80 (28.7%), and cytomegalovirus reactivation in 20 of 80 (25.0%). Conclusion: In this retrospective multicenter cohort, ruxolitinib was associated with high response rates in steroid-refractory GVHD, while disease severity remained a key determinant of survival, and findings should be interpreted as exploratory.

Responsiveness and minimal clinically important difference (MCID) are among the psychometric properties necessary for interpreting results. However, responsiveness and MCID of the Falls Efficacy Scale-International (FES-I) and the Biodex Balance System (Biodex-BS) in individuals with Parkinson's disease (PD) have not yet been determined. The objective of this study is to establish the responsiveness and MCID of FES-I and Biodex-BS, as well as Berg Balance Scale, Time up and Go (TUG) test, Tinetti Gait and Balance Scale (TGBS), and Mini-Balance Evaluation Systems Test in PD. In this prospective observational cohort study, 86 individuals with PD were assessed. Responsiveness was evaluated utilizing 11 predefined hypotheses. MCID was calculated using anchor and distribution-based methods. In this study, the Global Rating of Change-Patient (GRC-P) and Global Rating of Change-Therapist (GRC-T) and the Activity-Specific Balance Confidence Scale (ABC) were used as anchors. ROC analysis was utilized in the anchor-based method. The Fall Risk Test-Overall Stability Index (FRT-OSI), one of the Biodex-BS parameters, showed the highest responsiveness. TUG and FES-I indicated a substantial responsiveness, while the TGBS demonstrated the lowest responsiveness. MCID of FRT-OSI, which had the highest responsiveness, had 0.78 with the distribution-based method. In the anchor-based method, MCID with GRC-P, GRC-T, and ABC anchors were 0.54, 0.95, and 0.54, respectively. FRT-OSI demonstrated the highest responsiveness in PD. TUG and FES-I may be used as alternatives when a Biodex-BS is inaccessible. TGBS clinical utility may be limited. MCIDs determined in this study may help interpret the clinical importance of the results.

Bisphenol A (BPA), a synthetic compound widely used in plastic manufacturing, has been shown to cause testicular damage and disrupt spermatogenesis. This study aimed to investigate the potential protective effects of astaxanthin (AST) against BPA-induced testicular injury. Four experimental groups of Wistar Albino rats were established (n=8 per group): Control, Sham, BPA, and BPA+AST. At the conclusion of the study, serum samples were analyzed for total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI) [OSI=TOS/TAC], and CRP. Histopathological evaluations included measurements of tubule diameter, Johnsen scoring, and Masson's trichrome staining. The expression levels of anti-B-cell lymphoma 2 (Bcl-2) and anti-Bcl-2-associated X protein (Bax) were assessed using immunofluorescence (IF) staining and RT-qPCR in testicular tissues. Additionally, tissue collagen (COL1A1, COL3A1) expressions were quantified via RT-qPCR.Results indicated significant increases in TOS, OSI, and CRP levels in the BPA group (p<0.001, p<0.001, and p=0.042, respectively), while TAC levels remained unchanged (p=0.119). AST administration did not significantly alter these biochemical parameters. Histopathological analysis revealed decreased Johnsen scores and tubule diameters in the BPA group; however, these metrics improved in the BPA+AST group. IF analysis confirmed that AST restored the pro-apoptotic Bax/Bcl-2 imbalance induced by BPA (p<0.001), although RT-qPCR results indicated that AST normalized only Bax expression (p<0.001) while Bcl-2 levels remained unchanged (p=0.487). Moreover, COL1A1 and COL3A1 were significantly upregulated in the BPA group (p<0.001 for both), and Masson's trichrome staining corroborated the presence of fibrosis in this group. AST treatment mitigated these fibrotic changes, as evidenced by reductions in gene expression (p=0.001 for COL1A1 and p=0.005 for COL3A1) and improvements in Masson's trichrome staining.In conclusion, this study suggests that AST may confer a protective effect against BPA-induced testicular damage by reducing apoptosis and fibrosis; however, changes in oxidative stress markers did not achieve statistical significance. Furthermore, AST may enhance spermatogenesis.

Prostate cancer predominantly affects older men and generally has a favorable early-stage prognosis, yet the prognostic significance of nutritional and inflammatory status remains uncertain. This study evaluated the prognostic value of the Prognostic Nutritional Index (PNI) and Geriatric Nutritional Risk Index (GNRI) in elderly patients with localized prostate cancer. This single-center retrospective cohort study included 205 patients aged ≥65 years with early-stage prostate cancer treated between 2018 and 2024. Nutritional status was assessed at baseline using serum albumin, lymphocyte count, and body weight to calculate the PNI and GNRI. Overall survival was analyzed using standard survival analysis methods. All statistical analyses were performed using SPSS software version 26.0. The median patient age was 72 years. Of all patients, 41% were 75 years or older. Survival analysis showed that patients with low PNI had a median OS of 78 months. Those with high PNI had a median OS of 115 months (p = 0.008). Low GNRI was linked to a median survival of 74 months. High GNRI was linked to 120 months (p = 0.009). Higher Gleason score (≥8), higher PSA (≥10 ng/mL), older age (≥75 years), and clinical T2 disease were associated with worse outcomes. By contrast, radiotherapy improved survival (122 vs. 94 months, p = 0.008). In multivariate analysis, low PNI, low GNRI, high Gleason score, and high PSA remained independent predictors. The PNI and GNRI serve as practical and accessible indicators of nutritional status and inflammation, thereby improving prognostic assessment and risk stratification in older patients with early-stage prostate cancer.

Isolated coronary artery ectasia (CAE) is a less common form of CAE. The clinical significance of isolated CAE has not been elucidated yet. We aimed to compare the patients with myocardial infarction (MI) due to isolated CAE with the patients without CAE. We retrospectively included patients who underwent coronary angiography with a diagnosis of first MI caused by isolated CAE. We excluded patients with >20% stenosis in any vessel other than the lesion responsible for the MI. A second group of patients with MI without CAE was selected as the control group. The primary outcome was the composite of all-cause death and nonfatal recurrent MI occurring after index hospitalization. A total of 404 patients were included. Overall, 63.9% of MIs were ST-elevation MI. Almost all patients in the isolated CAE group had multivessel diffuse ectasia, with 71.3% classified as Markis I, and 26.7% as Markis II. Death or MI recurrence occurred in 54 (26.7%) patients in the isolated CAE group and 33 (16.3%) patients in the control group (P=0.011). Death occurred in 8 (4.0%) patients in the isolated CAE group versus 6 (3.0%) patients in the control group; recurrent MI in 46 (22.8%) versus 27 (13.4%) patients, respectively. Stent thrombosis was more common in the CAE group compared with the control group (8.9% versus 1.5%; P<0.001). In multiple variable analysis, the presence of CAE was associated with death/recurrent MI (hazard ratio, 1.84 [95% CI, 1.11-3.05]; P=0.017), and recurrent MI (hazard ratio, 2.07 [95% CI, 1.08-3.96]; P=0.029). The patients with MI due to isolated CAE had a higher risk of recurrent MI and stent thrombosis compared with the patients without CAE. In this study, the rate of recurrent MI from the index infarct artery was also higher in the patients with CAE.

Objective: This study aimed to compare fetal adrenal gland volume (AGV), fetal zone (FZ) depth, and middle adrenal artery pulsatility index (MAA-PI) between pregnancies presenting with preterm labor and gestational age-matched asymptomatic controls, and to evaluate size-adjusted adrenal metrics (corrected AGV [cAGV] and fetal zone-total gland depth ratio) in relation to gestational age at delivery and neonatal outcomes. Methods: This prospective analytical cross-sectional (case-control) study included 60 singleton pregnancies (30 with preterm labor and 30 asymptomatic controls) evaluated at a tertiary perinatology unit between 24 + 0 and 36 + 6 weeks' gestation. Transvaginal cervical length and transabdominal fetal adrenal measurements (AGV, FZ depth, and MAA-PI) were obtained at enrollment. Estimated fetal weight (EFW) at the index scan was retrieved, and corrected AGV (cAGV = AGV/EFW) and fetal zone-total gland depth ratio were calculated. Outcomes were gestational age at delivery, birthweight, Apgar scores, and neonatal intensive care unit (NICU) admission. Nonparametric group comparisons and Spearman correlations were used. Results: Gestational age at ultrasound was identical between groups (median 31 + 6 weeks). Compared with controls, the preterm labor group had shorter cervical length (12.5 vs. 33.5 mm, p < 0.001), higher AGV (1.53 vs. 1.08 cm3, p < 0.001) and FZ depth (7.45 vs. 5.30 mm, p < 0.001), and lower MAA-PI (1.11 vs. 1.46, p < 0.001). EFW at the index scan did not differ between groups (p = 0.900). Corrected AGV (cAGV) was higher in the preterm labor group (0.87 (0.76-1.06) vs. 0.59 (0.51-0.70), p < 0.001), and the fetal zone-total gland depth ratio was higher (0.328 (0.312-0.346) vs. 0.263 (0.241-0.278), p < 0.001). The preterm labor group delivered earlier (33 + 0 vs. 36 + 2 weeks, p < 0.001), had lower birthweight (1875 vs. 3188 g, p < 0.001), and more frequent NICU admission (50.0% vs. 6.7%; odds ratio 14.0, 95% CI 2.82-69.56; p < 0.001). Within the preterm labor group, gestational age at delivery correlated positively with cervical length (ρ = 0.900) and MAA-PI (ρ = 0.770) and negatively with AGV (ρ = -0.770) and FZ depth (ρ = -0.733), all p < 0.001; correlations were stronger for cAGV (ρ = -0.953, p < 0.001). Conclusions: Enlarged fetal adrenal gland volume and fetal zone depth together with reduced middle adrenal artery pulsatility index are associated with preterm labor and earlier delivery. Size-adjusted adrenal metrics (cAGV and fetal zone-total gland depth ratio) remained significantly different between groups, supporting these measures as potential adjuncts for risk stratification at presentation.

<title>Abstract</title> Despite recent advances in bladder cancer treatment, therapeutic resistance remains a critical challenge, necessitating the identification of novel molecular targets. This study used an integrative in silico approach to evaluate the prognostic value and molecular landscape of the immune regulatory molecule CD276 (B7-H3). Analyses of TCGA and GTEx datasets showed that CD276 is significantly upregulated in tumor tissues compared with normal controls, with higher expression in Stage 2 and beyond relative to normal and Stage 1. Kaplan Meier and univariate Cox regression analyses indicated that high CD276 expression is associated with poorer overall survival. Mechanistically, CD276 expression was associated with PI3K–Akt pathway enrichment and a myeloid/macrophage enriched immune contexture, including M2 like macrophage signatures. Finally, pancancer pharmacogenomic profiling across large cancer cell line panels suggested a broad resistance-associated pattern in CD276 high models, with reduced sensitivity (higher IC50) to PI3K/mTOR inhibitors and several cytotoxic agents used in urothelial cancer regimens (e.g., gemcitabine and methotrexate). Collectively, these findings support CD276 as a candidate biomarker linked to aggressive biology and motivate experimental and clinical validation of CD276 directed strategies in advanced bladder cancer.