İstanbul Sağlık ve Teknoloji Üniversitesi Kurumsal Akademik Arşivi
DSpace@İSTÜN, Üniversite mensupları tarafından doğrudan ve dolaylı olarak yayınlanan; kitap, makale, tez, bildiri, rapor, araştırma verisi gibi tüm akademik kaynakları uluslararası standartlarda dijital ortamda depolar, Üniversitenin akademik performansını izlemeye aracılık eder, kaynakları uzun süreli saklar ve telif haklarına uygun olarak Açık Erişime sunar.
Güncel Gönderiler
Utilization patterns and clinical outcomes following oocyte cryopreservation in Turkey: A multicenter cohort study within a nationally regulated setting
(Galenos Publishing House, 2026) Aydın, Gerçek; Tavuz, Aziz İhsan; Uzelli Şimşek, Hayal; Simavlı, Serap; Doğer, Emek
Purpose: To analyse the utilization patterns, patient characteristics, and reproductive outcomes of oocyte cryopreservation (OC) performed under the current fertility preservation (FP) framework in Turkey. Methods: This retrospective multicenter cohort study analyzed data from Ministry of Health-accredited FP programs across Turkey between 2005 and 2026. The study included women who underwent OC for approved medical indications, predominantly diminished ovarian reserve and FP before gonadotoxic treatment. Primary outcomes were oocyte utilization rates and reproductive outcomes among women who returned to use their cryopreserved oocytes. Secondary outcomes included socio-demographic profiling and cycle-level characteristics. Results: A total of 1,582 women were included. Mean age at cryopreservation was 33.5±7.2 years. Most women underwent OC for diminished ovarian reserve (92.3%), while 7.6% underwent FP before treatment for malignant disease. Most participants were university-educated (63.9%) and employed (65.7%), with obstetrics and gynecology specialists being the primary source of awareness (53.3%). Mean anti-Müllerian hormone was 0.6±0.6 ng/mL, and a mean of 3.6±3.0 mature oocytes were cryopreserved per cycle. During the observation period, only 39 women (2.4%) returned to utilize their cryopreserved oocytes. Among thaw cycles, the clinical pregnancy rate per transfer was 15.6%, and the implantation rate was 12.7%. Conclusion: In this large multicenter cohort, OC was predominantly performed in women with diminished ovarian reserve, resulting in relatively limited oocyte yield and low observed utilization during the available follow-up period. These findings provide real-world data on the characteristics, utilization patterns, and reproductive outcomes of FP programs in Turkey and may help inform future clinical practice and policy discussions.
Novel 1-benzyl-oxindole indole hybrids targeting PDGFR-β, SRC, and c-MET signaling and inducing caspase-3-dependent apoptosis in pancreatic cancer cells
(Elsevier, 2026) Cinek, Tuğçe; Yıldırım, Merve; Cihan-Üstündağ, Gökçe; Genç Akar, Öyküm; Sancar, Serap; Erol-Bozkurt, Ayşe; Özen-Eroğlu, Güneş; Küçüker, Begüm; Öztay, Füsun; Kuruca, Serap; Bolkent, Şehnaz; Karalı, Nilgün
As part of our ongoing efforts to develop N-benzylated oxindole derivatives as multi-target anticancer agents, novel N-benzyl oxindole indoles (4a–z) were designed, synthesized and structurally characterized. Their cytotoxic activities were evaluated against HCT-116, HT-29, A549, MIA PaCa-2, A498, CAKI-1, MDA-MB-231, and MCF-7 cancer cells, as well as Beas2b noncancerous cells. Most compounds exhibited significantly stronger cytotoxicity and selectivity than the reference drug sunitinib malate. Mechanistic studies were performed on compounds 4a, 4b, 4d, 4g, 4i, 4q, and 4y, which displayed submicromolar cytotoxic effects (IC50 = 0.27- 0.97 μM) and high selectivity indices (SI = 91.3->370.4). Among these, compounds 4a, 4b, and, 4i, which exhibited stronger cytotoxic effects than sunitinib malate, significantly induced apoptosis and markedly suppressed general tyrosine kinase (TK) activity. Compounds 4a (IC50 = 0.27 μM, SI = 167.8) and 4b (IC50 = 0.48 μM; SI = 91.2) markedly reduced PDGFR-β and SRC signaling, and inhibited ERK signaling more potently than sunitinib malate (IC50 = 4.03 μM, SI = 3.2) in MIA PaCa-2 cells. Notably, compound 4a also exhibited stronger reduction c-MET signaling than sunitinib malate, whereas compound 4b was less effective against this target. Overall, compound 4a displayed the most potent multi-target inhibitory profile and was identified as lead candidate. Molecular docking studies further supported its stable binding within the ATPbinding pockets of PDGFR-β, SRC, and c-MET kinases, consistent with its observed inhibitory activity. Further mechanistic studies demonstrated that compound 4a induces caspase-3-mediated apoptosis through a Bax/Bcl-2- independent pathway, accompanied by increased levels of cytochrome c and p53. Collectively, these findings identify compound 4a as a potent, selective, and multi-target lead candidate for further development against pancreatic cancer.
Neural approximation of fuzzy gain-scheduled PID control for a dual-crank strandbeest walking mechanism
(IEEE, 2026) Coşkun, Yusuf; Özyılmaz, Lale
This study presents a simulation-based comparison of PID, Fuzzy-PID, and artificial neural network (ANN)-assisted gain-scheduled PID controllers for a modular dual-motor Strandbeest walking mechanism. The mechanism was designed in SolidWorks and transferred to MATLAB/Simscape Multibody, where each leg group is driven by an independent crank and the crank angle is controlled through a joint torque actuator. The ANN is not used as a stand-alone controller; instead, it provides a smooth approximation of the fuzzy gain-scheduling map used in the Fuzzy-PID controller. The controllers are evaluated under step, sinusoidal, disturbance-rejection, and square-wave reference scenarios. The ANN approximated the fuzzy gain map with coefficients of determination of 0.99, 0.92, and 0.83 for the proportional, integral, and derivative gains, respectively. The ANN-assisted controller reduced tracking error in the sinusoidal, square-wave, and disturbance cases, while the Fuzzy-PID controller achieved the lowest stepresponse overshoot. The results show that neural approximation can provide a computationally simple and smooth gain-scheduling structure for simulation-based crank-angle control, although it should not be interpreted as an exact closed-loop reproduction of the original Fuzzy-PID controller.
A 12-week randomized controlled trial of the dietary approaches to stop hypertension (DASH) diet in seropositive rheumatoid arthritis: Effects on disease activity and outcomes
(Elsevier, 2026) Özüpek, Gökçen; Altay, İkbal Süheyla; Kalyoncu Atasoy, Zeynep Begüm; Torun, Ege Sinan
Background & aims: Dietary interventions may improve rheumatoid arthritis (RA) outcomes through anti-inflammatory and metabolic pathways. This study aimed to evaluate the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on disease activity and treatment outcomes in patients with seropositive RA. Methods: In this 12-week parallel-group randomized controlled trial, 82 patients with seropositive RA were randomly assigned to a DASH diet intervention (n = 40) or a control group maintaining their usual diet (n = 42). The primary outcome was change in disease activity assessed using the Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS-28 E SR). Secondary outcomes included change in DAS-28 based on C-reactive protein (DAS-28 CRP), as well as tender and swollen joint counts, ESR, CRP, visual analogue scale (VAS) scores for pain and general health, the Health Assessment Questionnaire (HAQ), and the Short Form-36 (SF-36). Adherence to the intervention was evaluated using the DASH diet score. Assessments were performed at baseline and at weeks 4, 8, and 12. Data were analyzed according to the intention-to-treat principle. Repeated clinical outcomes were analyzed using robust mixed ANOVA or generalized estimating equations (GEE), as appropriate. Results: Of the 82 randomized patients, 49 completed the 12-week study. Adherence to the DASH diet increased significantly in the intervention group compared with the control group (p < 0.001). From baseline to Week 12, DAS-28 ESR decreased by 0.92 points in the DASH group versus 0.17 points in the control group, corresponding to a 0.75-point greater reduction (group × time interaction, p = 0.001). Significant between-group differences in change were also observed for DAS-28 CRP (− 0.62), ESR (− 3.90 mm/h), VAS-pain (− 2.19), VAS-general health (− 2.12), and HAQ (− 0.38) (all group × time p˂0.05). For SF-36, significant between-group differences in change were observed for physical functioning (+10.15), role-physical (+47.30), bodily pain (+22.17), vitality (+18.52), role-emotional (+38.61), and mental health (+12.06) (all group × time p < 0.05). CRP, tender and swollen joint counts did not show significant group × time interactions (p > 0.05). Furthermore, in the intervention group, improvements in DASH diet adherence were negatively correlated with changes in DAS-28 ESR and DAS-28 CRP scores (both p < 0.05). Conclusions: A 12-week DASH dietary intervention may provide clinically meaningful improvements in disease activity and patient-reported outcomes in patients with seropositive RA. These findings support the potential role of the DASH dietary pattern as a promising dietary approach to complement the management of RA. However, the relatively high attrition rate should be considered when interpreting the findings. Trial registration: This trial is registered with Clinicaltrials.gov (ID: NCT07170033). https://clinicaltrials.gov/study/NCT07170033
Optimization of diclofenac sodium-loaded alginate microparticles: Chitosan-assisted encapsulation and ph-dependent release
(MDPI Publishing, 2026) Asgarova, Kamala; Toprakçı, İrem; Bozkurt, Rabia Nur; Kurtulbaş, Ebru; Çağatay, Barış; Şahin, Selin
Alginate microparticles offer a simple approach for drug encapsulation. However, their performance depends on formulation conditions. Diclofenac sodium (DCF) was encapsulated in alginate microparticles by ionic gelation. Sodium alginate concentration, CaCl2 concentration and hardening time were optimized by Response Surface Method (RSM) using Box–Behnken design (RSM-BBD). Encapsulation efficiency (EE) varied considerably with the formulation conditions. The model showed a good fit (R2 = 0.9685), while CaCl2 concentration was the main factor affecting EE. The optimum conditions were 1.91% (w/v) sodium alginate, 4.99% (w/v) CaCl2 and 23.4 min hardening time. The experimental EE was 80.34%, close to the predicted value of 80.41%. Chitosan was added to the optimized formulation at concentrations of 0.10–0.20% (w/v). EE increased with chitosan concentration and reached 93.85% at 0.20%. Drug release was studied in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The release data were evaluated using zero-order, first-order, Higuchi and Korsmeyer–Peppas models. Characterization revealed a transition from a predominantly lamellar and fissured surface in the optimized alginate formulation to a more granular and highly textured architecture following chitosan incorporation, while the released fractions exhibited distinct hydrodynamic and electrokinetic characteristics. The addition of a low amount of chitosan therefore increased DCF encapsulation and changed its release behavior under gastrointestinal conditions.
