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Item Metadata only Survival outcomes of patients with oligometastatic non-small cell lung cancer who were treated with radical therapy: a multicenter analysis(Turkiye Klinikleri, 2023) 0000-0002-1273-1674; Açikgöz, Özgür; Bilici, Ahmet; Tataroğlu Özyükseler, Deniz; Göktaş Aydin, Sabin; Rzazade, Rashad; Ölmez, Ömer Fatih; Başak Çağlar, Hale; N/A; Selçukbiricik, Fatih; Faculty Member; School of Medicine; 202015Background/aim: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. Materials and methods: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. Results: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5–48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. Conclusion: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2. © TÜBİTAK.Item Metadata only Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer(Future Medicine Ltd, 2023) 0000-0002-1273-1674; Kahraman, Seda; Erul, Enes; Seyyar, Mustafa; Gumusay, Ozge; Bayram, Ertugrul; Demirel, Burcin Cakan; Acar, Omer; Aksoy, Sercan; Baytemur, Naziyet Kose; Sahin, Elif; Cabuk, Devrim; Basaran, Gul; Paydas, Semra; Yaren, Arzu; Guven, Deniz Can; Erdogan, Atike Pinar; Demirci, Umut; Yasar, Alper; Bayoglu, Ibrahim Vedat; Hizal, Mutlu; Gulbagci, Burcu; Paksoy, Nail; Davarci, Sena Ece; Yilmaz, Funda; Dogan, Ozlem; Orhan, Sibel Oyucu; Kayikcioglu, Erkan; Aytac, Ali; Keskinkilic, Merve; Mocan, Eda Eylemer; Unal, Olcun Umit; Aydin, Esra; Yucel, Hakan; Isik, Deniz; Eren, Onder; Uluc, Basak Oyan; Ozcelik, Melike; Hacibekiroglu, Ilhan; Aydiner, Adnan; Demir, Hacer; Oksuzoglu, Berna; Cilbir, Ebru; Cubukcu, Erdem; Cetin, Bulent; Oktay, Esin; Erol, Cihan; Okutur, Sadi Kerem; Yildirim, Nilgun; Alkan, Ali; Aksoy, Asude; Karakas, Yusuf; Ozkanli, Gulhan; Duman, Berna Bozkurt; Aydin, Dincer; Dulgar, Ozgecan; Er, Muhammed Muhiddin; Teker, Fatih; Yavuzsen, Tugba; Aykan, Musa Baris; Inal, Ali; Iriagac, Yakup; Kalkan, Nurhan Onal; Keser, Murat; Sakalar, Teoman; Menekse, Serkan; Kut, Engin; Bilgin, Burak; Karaoglanoglu, Muge; Sunar, Veli; Ozdemir, Ozlem; Turhal, Nazim Serdar; Karadurmus, Nuri; Yalcin, Bulent; Sendur, Mehmet Ali Nahit; N/A; Selçukbiricik, Fatih; Faculty Member; School of Medicine; 202015Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.Item Metadata only Five-year outcome and safety in patients treated with ımmune checkpoint blockade therapies for urothelial carcinoma: experience from real-world clinical practice(CIG Media Group, Lp, 2023) 0000-0002-1273-1674; Tural, Deniz; Arslan, Cagatay; Olmez, Omer Fatih; Akar, Emre; Erman, Mustafa; Urun, Yuksel; Erdem, Dilek; Karadurmus, Nuri; Kilickap, Saadettin; N/A; Selçukbiricik, Fatih; Faculty Member; School of Medicine; 202015This 5-year analysis of real-world data confirms the durable response and long-term survival with ICTs in a broader range of patients with metastatic urothelial carcinoma. After 24 months, PFS and OS curves remained nearly flat. The safety profile was consistent with previous reports, and no new safety signals were observed. Background: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). Patients and Methods: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. Results: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. Conclusion: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients.Item Metadata only Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy(BMC, 2023) 0000-0002-1273-1674; Karacin, Cengiz; Oksuzoglu, Berna; Demirci, Ayse; Keskinkilic, Merve; Baytemur, Naziyet Kose; Yilmaz, Funda; Selvi, Oguzhan; Erdem, Dilek; Avsar, Esin; Paksoy, Nail; Demir, Necla; Goksu, Sema Sezgin; Turker, Sema; Bayram, Ertugrul; Celebi, Abduessamet; Yilmaz, Hatice; Kuzu, Omer Faruk; Kahraman, Seda; Gokmen, Ivo; Sakin, Abdullah; Alkan, Ali; Nayir, Erdinc; Ugrakli, Muzaffer; Acar, Omer; Erturk, Ismail; Demir, Hacer; Aslan, Ferit; Sonmez, Ozlem; Korkmaz, Taner; Celayir, Ozde Melisa; Karadag, Ibrahim; Kayikcioglu, Erkan; Sakalar, Teoman; Oktem, Ilker Nihat; Eren, Tulay; Urul, Enes; Mocan, Eda Eylemer; Kalkan, Ziya; Yildirim, Nilgun; Ergun, Yakup; Akagunduz, Baran; Karakaya, Serdar; Kut, Engin; Teker, Fatih; Demirel, Burcin Cakan; Karaboyun, Kubilay; Almuradova, Elvina; Unal, Olcun Umit; Oyman, Abdilkerim; Isik, Deniz; Okutur, Kerem; Oztosun, Bugra; Gulbagci, Burcu Belen; Kalender, Mehmet Emin; Sahin, Elif; Seyyar, Mustafa; Ozdemir, Ozlem; Kanitez, Metin; Dede, Isa; Gumus, Mahmut; Gokmen, Erhan; Yaren, Arzu; Menekse, Serkan; Ebinc, Senar; Aksoy, Sercan; Imamoglu, Goksen Inanc; Altinbas, Mustafa; Cetin, Bulent; Uluc, Basak Oyan; Er, Ozlem; Karadurmus, Nuri; Erdogan, Atike Pinar; Artac, Mehmet; Tanriverdi, Ozgur; Cicin, Irfan; Sendur, Mehmet Ali Nahit; Oktay, Esin; Bayoglu, Ibrahim Vedat; Paydas, Semra; Aydiner, Adnan; Salim, Derya Kivrak; Geredeli, Caglayan; Yavuzsen, Tugba; Dogan, Mutlu; Hacibekiroglu, Ilhan; N/A; Selçukbiricik, Fatih; Faculty Member; School of Medicine; 202015Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.Item Metadata only The role of socioeconomic adversity and armed conflict in executive function, theory of mind and empathy in children(Springer Nature, 2023) 0000-0001-9992-5174; Kara, B; Department of Psychology; Selçuk, Bilge; Faculty Member; College of Social Sciences and Humanities; 52913This study investigates the role of socioeconomic adversity and armed conflict in executive function (EF), theory of mind (ToM) and empathy in a rarely studied group, children living in eastern Turkey. The data were collected from 115 children (60 girls) aged 39 to 95 months (M = 68.22, SD = 14.62). Results revealed that children’s performance was low in the EF and ToM tasks, and high in the empathy task. In path analysis, controlling for age, armed conflict experience predicted lower EF (β = − 0.15) and higher empathy (β = 0.21), and socioeconomic adversity predicted lower ToM (β = 0.20). These findings contribute to our knowledge on cognitive and emotional development of children who live in such disadvantaged contexts. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Metadata only Perivascular PDGFRB plus cells accompany lesion formation and clinical evolution differentially in two different EAE models(Elsevier Sci Ltd, 2023) 0000-0002-0860-8964; 0000-0003-3222-874X; 0000-0003-3413-0332; N/A; 0000-0003-3672-7343; 0000-0001-6783-4593; 0000-0001-6503-8665; 0000-0001-8882-0019; 0000-0002-4292-9761; 0000-0001-5948-8491; Ulusoy, Canan; Seyaj, Seddiq Zeybel, Mujdat; Tuncer, Asli; Karabudak, Rana; Kucukali, Cem Ismail; Tuzun, Erdem; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A; Özdemir, Yasemin Gürsoy; Vural, Atay; Çakmak, Özgür Öztop; Budan, Abdullah Salih; Uçar, Ege Anıl; Gökyüzü, Aysu Bilge; Özkan, Esra; Atak, Dila; Şekerdağ, Emine; Köseoğlu, Gülsüm Deniz; Faculty Member; Faculty Member; Faculty Member; Undergraduate Student; Undergraduate Student; PhD Student; Researcher; PhD Student; PhD Student; Master Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; N/A; Graduate School of Health Sciences; Graduate School of Health Sciences; Graduate School of Health Sciences; 170592; 182369; 299358; N/A; N/A; N/A; N/A; N/A; N/A; N/ABackground: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) that may lead to progressive disability. Here, we explored the behavioral pattern and the role of vasculature especially PDGFRB+ pericytes/ perivascular cells, in MS pathogenesis. Methods: We have evaluated vascular changes in two different experimental allergic encephalomyelitis (EAE) mice models (MOG and PLP-induced). PDGFRB+ cells demonstrated distinct and different behavioral patterns. In both models, fibrosis formation was detected via collagen, fibronectin, and extracellular matrix accumulation. Results: The PLP-induced animal model revealed that fibrosis predominantly occurs in perivascular locations and that PDGFRB+ cells are accumulated around vessels. Also, the expression of fibrotic genes and genes coding extracellular matrix (ECM) proteins are upregulated. Moreover, the perivascular thick wall structures in affected vessels of this model presented primarily increased PDGFRB+ cells but not NG2+ cells in the transgenic NG2DsRed transgenic animal model. On the other hand, in MOG induced model, PDGFRB+ perivascular cells were accumulated at the lesion sites. PDGFRB+ cells colocalized with ECM proteins (collagen, fibronectin, and lysyl oxidase L3). Nevertheless, both MOG and PLP-immunized mice showed increasing EAE severity, and disability parallel with enhanced perivascular cell accumulation as the disease progressed from earlier (day 15) to later (day 40). Conclusion: As a result, we have concluded that PDGFRB+ perivascular cells may be participating in lesion progression and as well as demonstrating different responses in different EAE models.Item Metadata only Using stable isotopes to measure the dietary responses of Costa Rican forest birds to agricultural countryside(Frontiers Media Sa, 2023) 0000-0003-3193-0377; Fullwood, Melissa J.; Cerling, Thure E.; Brenes, Federico Oviedo; Daily, Gretchen C.; Ehrlich, Paul R.; Chamberlain, Page; Newsome, Seth D.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of Sciences; 327589How human modification of native habitats changes the feeding patterns and nutritional ecology of tropical birds is critical to conserving avian biodiversity, but tropical bird diets are laborious to investigate using the traditional methods of diet analysis. Stable isotope analysis provides a cost-effective and efficient proxy to identify general foraging patterns, especially when dietary shifts spanning multiple trophic levels have occurred due to ecosystem disturbance or transformation. To characterize the diets of forest bird species that persist in tropical agricultural countryside, we compared feather carbon (delta C-13) and nitrogen (delta N-15) isotope values of four species caught and radio-tracked in a 270 hectare forest reserve, smaller forest remnants (including mature forest, secondary forest, and riparian strips), and coffee plantations in mid-elevation (ca. 800-1,400 m) southern Costa Rica. Bird habitat choice had a significant effect on diet composition as revealed by delta C-13 and delta N-15 values. Three of the four species studied showed evidence of significantly reduced consumption of invertebrates in coffee plantations, with the isotope values of two species (Tangara icterocephala and Mionectes oleaginous) indicating, by comparison, nearly a doubling of invertebrate consumption in forest remnants. Our results suggest that coffee plantations are deficient in invertebrates preferred by forest generalist birds that forage in both native forest remnants and coffee plantations. In this region, typical of mountainous American tropics, small forest remnants and a larger forest reserve provide critical dietary resources for native forest birds that utilize the agricultural countryside.Item Metadata only Assessing genetic diversity patterns at neutral and adaptive loci to inform population reinforcement of an endangered migratory vulture(Springer Heidelberg, 2023) 0000-0003-3193-0377; Bounas, Anastasios; Saravia-Mullin, Victoria; Mendez, Maria; Arkumarev, Volen; Aghajanyan, Lusine; Ararat, Korsh; Buechley, Evan; Dobrev, Vladimir; Dobrev, Dobromir; Efrat, Ron; Klisurov, Ivaylo; Kret, Elzbieta; Skartsi, Theodora; Oppel, Steffen; Petrov, Rusko; Sekercioglu, Cagan H.; Vaidl, Anton; Donazar, Jose A.; Nikolov, Stoyan C.; Sotiropoulos, Konstantinos; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of Sciences; 327589One of the primary goals of conservation translocation programs should be the maintenance of both population demographic stability and genetic diversity. Here, we provide genetic management recommendations to inform a population reinforcement of the declining Egyptian Vulture population in the Balkans. Specifically, we examined whether the number of released individuals is sufficient to prevent genetic diversity loss due to random genetic drift and what the origin of the individuals should be that comprise the captive breeding pool. To this aim, we estimated and assessed genetic diversity levels and genetic structure of Egyptian Vulture populations across much of the species' range using both neutral and non-neutral candidate loci involved in migration. We then evaluated the effects of the currently proposed population management scheme and candidate source populations on retaining allelic diversity. Our results show low differentiation values among populations and absence of genetic structure which point to past high gene flow. Furthermore, there was no predicted significant impact of different source populations on the genetic diversity of the recipient Balkan population. We also found that the declining Egyptian Vulture population in the Balkans still retains high levels of genetic diversity and therefore genetic diversity restoration is not currently needed. However, without any management, diversity is likely to decrease fast because of increased genetic drift as the population size continues to decline. Population reinforcement with nine birds per year for 20 years would provide sufficient demographic support for the population to retain > 85% of rare allelic diversity. Birds originating from the Balkans would ensure ecological and behavioral similarity and thus would be the best option for reinforcement. Nevertheless, our results demonstrate that to prevent further population contraction and loss of adaptive alleles, releasing individuals of different origin would also be appropriate.Item Metadata only Editorial: avian biodiversity collapse in the Anthropocene: drivers and consequences(Frontiers Media Sa, 2023) 0000-0003-3193-0377; Sutherland, William J.; Buechley, Evan R.; Li, Binbin V.; Ocampo-Penuela, Natalia; Mahamued, Bruktawit Abdu; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; College of Sciences; 327589Item Metadata only Mid-nineteenth-century Gemlik and its environs: a survey of a West Anatolian region and its long-term economic and demographic development(Routledge Journals, Taylor and Francis Ltd, 2023) 0000-0003-3206-0190; 0000-0002-7858-2691; 0000-0002-1391-5643; Department of History; N/A; N/A; Kabadayı, Mustafa Erdem; Sefer, Akın; Erünal, Efe; Faculty Member; Researcher; PhD Student; College of Social Sciences and Humanities; Graduate School of Social Sciences and Humanities; Graduate School of Social Sciences and Humanities; 33267; 180375; N/AThis paper discusses the interrelations between migration, agricultural production, class, and cultural belonging, focusing on the economic and demographic transformation of Gemlik, an Ottoman district that underwent substantial change over the course of the nineteenth century. Based on the mid-nineteenth-century population and tax registers of the town of Gemlik and of two villages in the district, Kursunlu and Kumla-i Sagir, we demonstrate that the agricultural economy in the district was heavily shaped by commodity production in the context of the district's increasing integration into global markets. By tracing specific patterns of mobility and settlement over time, we show that the process of global integration was entangled with class and cultural differentiation in the region.