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Öğe Design and synthesis of novel caffeic acid phenethyl ester (CAPE) derivatives and their biological activity studies in glioblastoma multiforme (GBM) cancer cell lines(Elsevier Inc., 2022) Onur Sucu, Bilgesu; Koç, Elif Beyza; Şavluğ İpek, Özgecan; Mirat, Afranur; Almas, Furkan; Güzel, Melike Aybala; Doğan, Berna; Uludağ, Damla; Karakaş, Nihal; Durdağı, Serdar; Güzel, MustafaGlioblastoma Multiforme (GBM) is the most aggressive brain tumor and classified as one of the deadliest cancers. The current treatment plans for GBM remains to be ineffective because of its rapid progress and inability of the drugs used to cross the blood-brain barrier (BBB). Thus, developing more effective and potent medicines for GBM are needed. There have been several reports demonstrating that CAPE presents reasonably good anti-cancer activity in certain cancer cell lines and can penetrate the blood-brain barrier. Accordingly, in this study we synthesized several novel CAPE analogs with the addition of more druggable handles and solubilizing entities and subsequently evaluated their in vitro therapeutic efficacies in GBM cell lines (T98G and LN229). The most potent compound was then examined extensively and results showed that the 50 ?M novel CAPE analog (compound 10) significantly decreases the viability of both T98G and LN229 GBM cells as compared to CAPE itself. Moreover, the compound 10 was not cytotoxic to healthy human cells (fibroblast-like mesenchymal stem cells) at the same concentration. Apoptotic (32.8%, and 44.6%) cell populations were detected in the compound 10 treated groups for LN229 and T98G, respectively. As an indication of apotosis, significantly increased PARP cleavage was detected in compound 10 versus CAPE treated LN229. In addition, we conducted molecular docking and molecular dynamics (MD) simulations studies on certain targets playing roles on GBM disease pathway such as NF-?B, EGFR, TNF-?, ERK2, PAPR1, hCA IX and hCA XII. Our findings demonstrated that designed CAPE analogs have anti-cancer activity on GBM cells and in silico studies also demonstrate the inhibitory ability of suggested compounds via interactions with critical residues in binding pockets of studied targets. Here, we suggest the novel CAPE analog to study further against GBM. Therefore, identification of the compound related molecular signature may provide more to understand the mechanism of action.Öğe Determinants of brain drain among physicians in Turkey: Findings from a national exploratory study(2025) Bener, Abdulbari; Ventriglio, Antonio; Almas, Furkan; Bhugra, DineshBackground: The shortage of physicians in Turkey is a highly critical emergency. In fact, physicians’ migration to developing or high-income countries, defined as brain drain, threatens the sustainability of the national healthcare system. Aims: This study explored the driving factors associated with Turkish Physicians’ brain drain, including high-economic inflation, social-politics, poor-living, equity, violence, and the desire to practice medical activity abroad. Methods: A cross-sectional survey of 1,861 Turkish physicians aged 25 to 65 years old was conducted employing the Brain Drain questionnaire, the Depression Anxiety Stress Scale (DASS-21), the Patient Health Questionnaire 9 (PHQ-9), and the Fatigue Assessment Scale (FAS). Results: Significant differences were observed among physicians staying in Turkey versus considering migration to Western countries, regarding their age, gender, marital status, educational level, occupational status, work years, hospital night shifts, income, and cigarette/nargileh smoking habits (all p ⩽.018). The main reasons for brain drain included transport problems, harassment, low salary, malpractice, bad environment, job insecurity, workload, burnout, treating difficult patients, inadequate postgraduate systems, peer-pressure, health safety concerns, and favoritism in the workplace, as well as stress and depression caused by work overload. In fact, depression, anxiety, stress, fatigue, and burnout varied significantly among the different groups of physicians (all p ⩽.013). Additionally, key predictors of brain drain were better job opportunities, poor hospital management (in Turkey), job-related stress, dealing with difficult patients, research deficiencies, workload, burnout, transportation issues, short consultation time, low salary, and fatigue. Among the general factors contributing to the brain drain in the Turkish Health System, we identified significant issues related to research deficiencies, compulsory working duties, poor quality of postgraduate, inadequate medical-schools, poor hospital management, and shortage of consultants. Conclusion: Physicians’ migration is a major global public health concern, leading to substantial risks for healthcare services, especially in Turkey. Many physicians decide to migrate to work in Western countries.Öğe Generatect: text-conditional generation of 3d chest ct volumes(2025) Hamamcı, İbrahim Ethem; Er, Sezgin; Tezcan, Alperen; Şimşek, Ayşe Gülnihan; Esirgün, Şevval Nil; Almas, Furkan; Doğan, İrem; Daşdelen, Muhammed Furkan; Menze, BjoernText-conditional medical image generation is vital for radiology, augmenting small datasets, preserving data privacy, and enabling patient-specific modeling. However, its applications in 3D medical imaging, such as CT and MRI, which are crucial for critical care, remain unexplored. In this paper, we introduce GenerateCT, the first approach to generating 3D medical imaging conditioned on free-form medical text prompts. GenerateCT incorporates a text encoder and three key components: a novel causal vision transformer for encoding 3D CT volumes, a text-image transformer for aligning CT and text tokens, and a text-conditional super-resolution diffusion model. Without directly comparable methods in 3D medical imaging, we benchmarked GenerateCT against cutting-edge methods, demonstrating its superiority across all key metrics. Importantly, we explored GenerateCT’s clinical applications by evaluating its utility in a multi-abnormality classification task. First, we established a baseline by training a multi-abnormality classifier on our real dataset. To further assess the model’s generalization to external datasets and its performance with unseen prompts in a zero-shot scenario, we employed an external dataset to train the classifier, setting an additional benchmark. We conducted two experiments in which we doubled the training datasets by synthesizing an equal number of volumes for each set using GenerateCT. The first experiment demonstrated an 11% improvement in the AP score when training the classifier jointly on real and generated volumes. The second experiment showed a 7% improvement when training on both real and generated volumes based on unseen prompts. Moreover, GenerateCT enables the scaling of synthetic training datasets to arbitrary sizes. As an example, we generated 100,000 3D CT volumes, fivefold the number in our real dataset, and trained the classifier exclusively on these synthetic volumes. Impressively, this classifier surpassed the performance of the one trained on all available real data by a margin of 8%. Lastly, domain experts evaluated the generated volumes, confirming a high degree of alignment with the text prompts. Access our code, model weights, training data, and generated data at https://github.com/ibrahimethemhamamci/GenerateCT.Öğe Reassessing normal voiding standards: A cross-sectional study based on medical professionals’ evaluations with portable uroflowmetry and IPSS(2024) Almas, Furkan; Daşdelen, Muhammed Furkan; Seyhan, Züleyha; Sargolzaeimoghaddam, Maral; Sarg, Arya; Ünlü, Ömer; Horuz, Rahim; Albayrak, Selami; Koçak, Mehmet; del Pilar Laguna Pes, Maria; de la Rosette, Jean J. M. C. H.Background/Objectives: LUTS and voiding dysfunctions are prevalent in urology clinics, with uroflowmetry and IPSS as the prevailing diagnostic methods. Nevertheless, objective assessment can be constrained by age, gender, and variability in the test conditions. Portable (home) uroflowmetry addresses these limitations, allowing for more natural urinary flow recordings beyond clinic confines. This study aims to characterize spontaneous voiding patterns in healthcare professionals, exploring gender differences, variability in repeated measurements, and correlations among voiding parameters, IPSS, age, and BMI. Methods: This cross-sectional study was conducted during the SIU 43rd Congress in Istanbul using smart uroflow devices such as the Oruba Oruflow Uroflow Recorder, which were installed in public toilets. A total of 431 healthcare professionals participated by providing demographic information and completing the IPSS questionnaire. The data analysis included uroflowmetric parameters such as maximum flow rate (Qmax), average flow rate (Qave), and voided volume (VV), in addition to IPSS and demographic data to assess the possible associations with IPSS, age, BMI, and gender differences. Results: Of the participants, 76% were male and 24% female, with a higher prevalence of LUTS in women. Despite no significant gender difference in voided volume, men with lower volumes demonstrated more severe LUTS. Notably, women exhibited higher Qmax and Qave rates irrespective of their IPSS scores, contrasting with men whose flow rates declined with age and LUTS severity. In men, the total IPSS score was inversely associated with uroflowmetric performance, particularly impacting voiding symptoms over storage symptoms. Repeated measurements revealed noteworthy variability in Qmax and VV, without any influence from gender, BMI, age, or symptom severity. Conclusions: Our findings highlight the importance of gender-specific considerations in evaluating voiding complaints through uroflowmetry and IPSS. The significant variability observed in repeated uroflowmetry studies underlines the need for multiple measurements. Overall, this research emphasizes the significance of portable (home) uroflowmetry and calls for a reassessment of normal voiding standards in (non) clinical settings.Öğe The relationship between urinary incontinence, osteoarthritis, and musculoskeletal system disorders(2024) Çelik, Nursanem; Çelik, Süleyman; Seyhan, Züleyha; Daşdelen, Muhammed Furkan; Almas, Furkan; Albayrak, Selami; Horuz, Rahim; del Pilar Laguna Pes, Maria; de la Rosette, Jean J. M. C. H.; Koçak, MehmetBackground/Objectives: Urinary incontinence diminishes quality of life, and its severity can be worsened by mobility impairments. This study explored the link between urinary incontinence, osteoarthritis, and back musculoskeletal system disorders, considering pain, mobility issues, and daily activity difficulties. Methods: This cross-sectional study included respondents aged ? 15 years from the 2008 Turkish Health Studies Survey (n = 13,976). We assessed self-reported urinary incontinence, daily activity, mobility impairment, pain, osteoarthritis, and musculoskeletal disorders to explore their association with urinary incontinence. Gender-specific logistic regression models included chronic conditions related to urinary incontinence. Results: The prevalence of urinary incontinence was higher in the participants with osteoarthritis and back musculoskeletal system problems. Among the patients with osteoarthritis, the prevalence was 25.84% in the mobility-impaired group and 10.03% in the non-impaired group. Similarly, 33.02% of those with activities of daily living (ADL) difficulties and 12.93% of those without difficulties had incontinence. The frequency of urinary incontinence increased with pain severity. According to the multivariable logistic regression analyses, the adjusted odds ratio (95% confidence interval) of urinary incontinence for osteoarthritis was 1.58 (95% CI 1.23–2.02, p < 0.01) for females and 2.38 (95% CI 1.62–3.49, p < 0.01) for males. Conclusions: Urinary incontinence was more common in females, increased with age, and was found to be associated with osteoarthritis and back musculoskeletal system disorders. Among the patients with osteoarthritis and back musculoskeletal system disorders, those with mobility impairment and daily activity difficulties had a higher prevalence of urinary incontinence. The patients with more severe pain had a higher frequency of urinary incontinence.Öğe When bladder and brain collide: Is there a gender difference in the relationship between urinary incontinence, chronic depression, and anxiety?(Multidisciplinary Digital Publishing Institute (MDPI), 2023) Daşdelen, Muhammed Furkan; Almas, Furkan; Çelik, Süleyman; Çelik, Nursanem; Seyhan, Züleyha; del Pilar Laguna Pes, Maria; Albayrak, Selami; Horuz, Rahim; Koçak, Mehmet; de la Rosette, Jean J. M. C. H.In longitudinal and cross-sectional studies, depression and anxiety have been associated with urinary incontinence (UI) in women. However, this association has not been studied in men. Utilizing data from the 2008 Turkish Health Studies Survey conducted by the Turkish Statistical Institute, we analyzed 13,830 participants aged 15 years and above. We investigated the association of UI with psychological discomfort in both sexes using multivariable logistic regression. High psychological discomfort significantly correlated with UI in males (OR 2.30, 95% CI 1.43–3.71) and females (OR 2.78, 95% CI 1.80–4.29). Anxiety increased UI likelihood in females (OR 2.36, 95% CI 1.61–3.46) and males (OR 2.37, 95% CI 1.10–5.13). Depression related significantly to UI in females (OR 2.54, 95% CI 1.81–3.58) but not males (OR 1.63, 95% CI 0.71–3.76). Antidepressant and anxiolytic use was not significantly related to UI in either gender. Anxiety and psychological discomfort contribute to UI in both genders. While depression significantly correlates with UI in females, it does not show the same magnitude and significance in males. Antidepressant and anxiolytic use did not significantly influence the association. These findings underscore the psychological distress-UI link, advocating a holistic approach for managing UI in individuals with mental health conditions.
