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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access DNA methylation profiling identifies novel markers of progression in hepatitis B-related chronic liver disease(BioMed Central, 2016) Vatansever, Sezgin; Hardy, Timothy; Sarı, Aysegül Akder; Çakalağaoğlu, Fulya; Avcı, Arzu; Zeybel, Gemma Louise; Bashton, Matthew; Mathers, John C.; Ünsal, Belkis; Mann, Jelena; N/A; Department of Molecular Biology and Genetics; Zeybel, Müjdat; Karahüseyinoğlu, Serçin; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; School of Medicine; 214694; 110772Background: Chronic hepatitis B infection is characterized by hepatic immune and inflammatory response with considerable variation in the rates of progression to cirrhosis. Genetic variants and environmental cues influence predisposition to the development of chronic liver disease; however, it remains unknown if aberrant DNA methylation is associated with fibrosis progression in chronic hepatitis B. Results: To identify epigenetic marks associated with inflammatory and fibrotic processes of the hepatitis B-induced chronic liver disease, we carried out hepatic genome-wide methylation profiling using Illumina Infinium beadarrays comparing mild and severe fibrotic disease in a discovery cohort of 29 patients. We obtained 310 differentially methylated regions and selected four loci comprising three genes from the top differentially methylated regions: hypermethylation of HOXA2 and HDAC4 along with hypomethylation of PPP1R18 were significantly linked to severe fibrosis. We replicated the prominent methylation marks in an independent cohort of 102 patients by bisulfite modification and pyrosequencing. The timing and causal relationship of epigenetic modifications with disease severity was further investigated using a cohort of patients with serial biopsies. Conclusions: Our findings suggest a linkage of widespread epigenetic dysregulation with disease progression in chronic hepatitis B infection. Cpg methylation at novel genes sheds light on new molecular pathways, which can be potentially exploited as a biomarker or targeted to attenuate inflammation and fibrosis.Publication Open Access Effectiveness of posterior structures in the development of proximal junctional kyphosis following posterior instrumentation: a biomechanical study in a sheep spine model(Elsevier, 2019) Akgül, Turgut; Sarıyılmaz, Kerim; Özkunt, Okan; Dikici, Fatih; Yazıcıoğlu, Önder; N/A; Korkmaz, Murat; Doctor; School of MedicineIntroduction: proximal junctional kyphosis – PJK has been defined by a 10 or greater increase in kyphosis at the proximal junction as measured by the Cobb angle from the caudal endplate of the uppermost instrumented vertebrae (UIV) to the cephalad endplate of the vertebrae 1 segments cranial to the UIV. In this biomechanical study, it is aimed to evaluate effects of interspinosus ligament complex distruption and facet joint degeneration on PJK development. Materials and methods: posterior instrumentation applied between T2 – T7 vertebrae using pedicle screws to randomly selected 21 sheeps, divided into 3 groups. First group selected as control group (CG), of which posterior soft tissue and facet joints are protected. In second group (spinosus group, SG) interspinosus ligament complex which 1 segment cranial to UIV has been transected, and third group (faset group-FG) was applied facet joint excision. 25 N, 50 N, 100 N, 150 N and 200 N forces applied at frequency of 5 Hertz as 100 cycles axial to the samples. Then, 250 N, 275 N and 300 N forces applied static axially. Interspinosus distance, kyphosis angle and discus heights was measured in radiological evaluation. Abnormal PJK was defined by a proximal junctional angle greater than 100 and at least 100 greater than the corresponding preoperative measurement. Results: in CG group, average interspinosus distance was 6,6 ± 1.54 mm and kyphosis angle was 2,2 ± 0.46° before biomechanical testing, and they were measured as 9,4 ± 1.21 mm and 3,3 ±0.44° respectively after forces applied to samples. In SG group, average interspinosus distance was 6,2 ± 1.72 mm and kyphosis angle was 2,7 ± 1.01° before experiment, and they were measured as 20,8 ± 5.66 mm and 15,1 ± 2.34° respectively after forces applied to samples. In FG group, average interspinosus distance was 4,8 ± 1.15 mm and kyphosis angle was −1 ± 4.14° before experiment, and they were measured as 11,1 ±1.96mm and 11 ± 2.87° respectively after forces applied to samples. In comparison to group CG, statistically significant junctional kyphosis was seen on both FG and SG group after statistical analysis. (p < 0.05). PJK was seen statistically significant more on SG group than FG group. (p < 0.05). Not any statistically significant difference was seen on measurement of disk distances among three groups. (p > 0.05) Conclusions: protecting interspinosus ligament complex and facet joint unity during posterior surgical treatment for spine deformation is vital to prevent PJK development. Based on our literature review, this is the first biomechanical study that reveals interspinosus ligament complex are more effective on preventing PJK development than facet joints.Publication Open Access Isolated omental metastasis of renal cell carcinoma after extraperitoneal open partial nephrectomy : a case report(Elsevier, 2016) Sağlıcan, Yeşim; N/A; N/A; N/A; N/A; Acar, Ömer; Sağ, Alan Alper; Falay, Fikri Okan; Selçukbiricik, Fatih; Tabak, Levent; Esen, Tarık; Faculty Member; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; Faculty Member; School of Medicine; 237530; N/A; N/A; N/A; N/A; N/A; 50536INTRODUCTION: Metachronous metastatic spread of clinically localized renal cell carcinoma (RCC) affects almost 1/3 of the patients. They occur most frequently in lung, liver, bone and brain. Isolated omental metastasis of RCC has not been reported so far. CASE PRESENTATION: A 62-year-old patient previously diagnosed and treated due to pulmonary sarcoidosis has developed an omental metastatic lesion 13 years after having undergone open extraperitoneal partial nephrectomy for T1 clear-cell RCC. Constitutional symptoms and imaging findings that were attributed to the presence of a sarcomatoid paraneoplastic syndrome triggered by the development this metastatic focus complicated the diagnostic work-up. Biopsy of the [18F]-fluorodeoxyglucose (+) lesions confirmed the diagnosis of metastatic RCC and the patient was managed by the resection of the omental mass via near-total omentectomy followed by targeted therapy with a tyrosine kinase inhibitor. DISCUSSION: Late recurrence of RCC has been reported to occur in 10-20% of the patients within 20 years. Therefore lifelong follow up of RCC has been advocated by some authors. Diffuse peritoneal metastases have been reported in certain RCC subtypes with adverse histopathological features. However, isolated omental metastasis without any sign of peritoneal involvement is an extremely rare condition. CONCLUSION: To our knowledge, this is the first reported case of metachronously developed, isolated omental metastasis of an initially T1 clear-cell RCC. Constitutional symptoms, despite a long interval since nephrectomy, should raise the possibility of a paraneoplastic syndrome being associated with metastatic RCC. Morphological and molecular imaging studies together with histopathological documentation will be diagnosticPublication Open Access Fear of happiness among college students: the role of gender, childhood psychological trauma, and dissociation(Medknow Publications, 2019) Türk, Tuğba; Öztürk, Erdinç; N/A; Şar, Vedat; Faculty Member; School of Medicine; 8542Aims: this study aimed to evaluate the fear of happiness among college students and its relationship to gender, childhood psychological trauma, and dissociation. Setting and Design: College students were addressed as study population, and a relational screening method was implemented. Materials and Methods: among 184 participants, 93 (50.5%) were women. The Fear of Happiness Scale (FHS), the Childhood Trauma Questionnaire (CTQ), and the Dissociative Experiences Scale (DES) were administered to all participants. Statistical Analysis Used: MannuWhitney-U and Student's t-tests were implemented for comparison of groups. Pearson correlation and stepwise multiple regression analyses were conducted to identify associations between variables. Results: there were no differences on DES, FHS, and CTQ total scores between genders. DES was associated with CTQ total scores in both genders. Women had higher scores than men on childhood emotional abuse and fear of "cheerfulness ends up with bad faith." Compared to nonmembers, female dissociative taxon members had higher scores on all childhood trauma types except sexual abuse, and on all types of fear of happiness except "good fortune ends up with disaster" which was the only type of fear significantly elevated among male dissociative taxon members. A stepwise regression analysis revealed that depersonalization, childhood emotional neglect, and physical abuse predicted fear of happiness among women which was predicted by absorption among men. Conclusions: there is a relationship between childhood psychological trauma, dissociation, and fear of happiness. Women seem to be more vulnerable in this path of obsessional thinking which affects different realms in male and female genders.Publication Open Access Appropriate use of tocilizumab in COVID-19 infection(Elsevier, 2020) Keske, Şiran; Sait, Bilgin; Çimen, Cansu; Çelebi, İrfan; Palaoğlu, Erhan; N/A; Tekin, Süda; İrkören, Pelin; Kapmaz, Mahir; Ergönül, Önder; Uğur, Semra; Şentürk, Evren; Çakar, Nahit; Çağlayan, Benan Niku; Tabak, Levent; Bakır, Veli Oğuzalp; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Faculty Member; School of Medicine; Graduate School of Sciences and Engineering; N/A; N/A; N/A; 110398; N/A; 48359; N/A; 230719; N/A; N/AObjective: this study aimed to describe the effectiveness and optimum use of tocilizumab (TCZ) treatment by the support of clinical, laboratory and radiologic observations. Methods: all patients were followed up in the hospital with daily interleukin-6 (IL-6), C-reactive protein (CRP), ferritin, D-dimer, full blood count, and procalcitonin. Thoracic computed tomography (CT) was performed on admission, when oxygen support was necessary, and seven days after TCZ started. Disease course of the patients was grouped as severe or critical, according to their clinical, laboratory and radiologic evaluations. Results: forty-three patients were included: 70% were male; the median age was 64 years (minimum– maximum: 27–94); and six (14%) patients died. The median duration of oxygen support before the onset of TCZ was shorter among the severe patient group than the critical patient group (1 vs. 4 days, p < 0.001). Three cases of 21 (14%) who received TCZ in the ward were transferred to ICU, and none of them died. The levels of IL-6, CRP, ferritin, D-dimer, and procalcitonin were significantly lower in the severe cases group than the critical cases group (p = 0.025, p = 0.002, p = 0.008, p = 0.002, and p = 0.001, respectively). Radiological improvement was observed in severe cases on the seventh day of TCZ. Secondary bacterial infection was detected in 41% of critical cases, but none of the severe ones. Conclusion: earlier use of TCZ in COVID-19 infection was beneficial for survival, length of hospitalization and duration of oxygen support. The recommendation for administration of TCZ was based on an increase in requirement of oxygen support, progression in thoracic CT, and elevation of inflammation markers, including IL-6, CRP, ferritin, and D-dimer, and decrease in % lymphocytes.Publication Open Access Does resection of heterotopic ossification of the elbow result in satisfactory functional outcomes?(Galenos Yayınevi, 2019) Kapıcıoğlu, Mehmet; Sağlam, Yavuz; Ersen, Ali; Atalar, Ata, Can; Durmaz, Hayati; N/A; Demirhan, Mehmet; Faculty Member; School of Medicine; 9882Objective: heterotopic ossification (HO) is a common cause of elbow stiffness following surgical treatment of elbow trauma. In this study, our aim was to evaluate the mid-term functional outcomes of open surgical procedures for HO. Methods: in this retrospective study approved by the institutional review board (IRB), all patients who were diagnosed as having stiff elbow due to HO and underwent surgical resection at a single institution from 2006 to 2013 were included. Intrinsic (inside the joint) pathologies were excluded. Range of motion (ROM) in sagittal and coronal planes, complications, functional scores such as Quick Disabilities of the Arm, Shoulder and Hand Score (Q-DASH), and Mayo Elbow Performance Score (MEPS) were evaluated before and after surgery. Results: there were 19 patients (16 males, 3 females) with a mean age of 38.6 (range 15-69) years. At an average follow-up of 36 +/- 8 months, the mean flexion-extension arc was improved from 27.4 degrees to 99.2 degrees (p<0.001) and mean supination-pronation arc was improved from 48.9 degrees to 102.3 degrees (p<0.001). The mean Q-DASH score was decreased from 68.2 to 17.1 (p<0.001) and mean MEPS was improved from 37.5 to 85.6 (p<0.001). Conclusion: excision of heterotopic bone and releasing contracted tissues around elbow can provide a substantial increase in range of motion and improvement in clinical scores.Publication Open Access Views of Turkish people on oocyte and sperm donation(Çukurova Üniversitesi, 2019) Şenol, Derya Kaya; Yılmaz, Sema Dereli; Bal, Meltem Demirgöz; Beji, Nezihe Kızılkaya; Çalışkan, Seval; N/A; Urman, Cumhur Bülent; Faculty Member; School of Medicine; 12147Purpose: the aim of the study is to determine the views of the Turkish people on oocyte/sperm donation. Materials and methods: following informed consent, a questionnaire was given to women and their spouses who presented to obstetrics and gynecology outpatient clinics of a university hospital. The data collection form consists of 35 questions about the demographics of the participants and their thoughts about oocyte/sperm donation. A total of 428 women, including 323 women and 105 men, agreed to participate in the sampling study. Results: sixty-four-point three percent of the women and 71.4% of males found use of donated oocytes/sperms in infertile couples unacceptable. Sixty-three-point one percent of the participants said that both couples receiving, and those donating oocytes/sperms should get counseling. Twenty-one point-five percent of the participants approved of infertile couples' receiving oocytes/sperms donated by their relatives (e.g. sister) and friends and 31,8% agreed about getting them from strangers. Eighty-eight-point seven percent of the primary school graduates, 73.4% of the university graduates and postgraduates, 76.7% of the employed participants, 86.2% of the participants with an income lower than their expenses and 85.1% of the participants with live children reported to unaccept donated sperms if their spouses had a problem preventing them from having a child. Conclusion: more than half of the participants declared that it was not appropriate to have children through infertile-donated oocyte/sperm. / Amaç: bu çalışmanın amacı, Türk halkının oosit / sperm bağışı hakkındaki görüşlerini belirlemektir. Gereç ve Yöntem: tanımlayıcı kesitsel tipteki bu çalışma bir üniversite hastanesinin kadın hastalıkları ve doğum polikliniğine, kadınlar ve eşlerine veri toplama formu uygulanarak yürütüldü. Veri toplama formu katılımcıların demografik özelliklerine ve oosit/sperm bağışı hakkındaki düşüncelerine ilişkin 35 sorudan oluşmaktadır. Örnekleme çalışmaya katılmayı kabul eden 323'ü kadın, 105'i erkek toplam 428 kişi dahil edildi. Bulgular: kadınların %64.3’ü, erkeklerin %71.4’ü infertile çiftlerde bağışlanmış oosit/sperm kullanımını uygun bulmadığını belirtti. Katılımcıların %63.0’ü, oositler/sperm bağışçılarının ve bağışı kabul edenlerin danışmanlık alması gerektiğini söyledi. Uygun bulan kişilerin %21.5’i akraba (örneğin kızkardeşi) ve arkadaş tarafından yapılan oosit/sperm bağışını uygun bulurken, %31.8'i yabancılardan almayı uygun bulmaktadır. İlkokul mezunlarının %88.7’si, üniversite ve üzeri düzeyde mezunların %73.4'ü, çalışanların %76.7'si, gelirleri giderlerinden daha düşük olanların%86.2'si ve yaşayan çocuğu olanların %77,1'i eşlerinde çocuk sahibi olmayı engelleyen bir problem varlığında bağışlanan oosit/sperm yoluyla çocuk sahibi olmayı kabul etmeyeceklerini belirttiler. Sonuç: katılımcıların yarıdan fazlası, infertilitede bağışlanmış oosit/sperm yoluyla çocuk sahibi olmasını uygun bulmadığını beyan etmiştir.Publication Open Access Extensive androgen receptor enhancer heterogeneity in primary prostate cancers underlies transcriptional diversity and metastatic potential(Nature Portfolio, 2022) Kneppers, J.; Severson, T.M.; Siefert, J.C.; Schol, P.; Joosten, S.E.P.; Yu, I.P.L.; Huang, C.F.; Morova, T.; Giambartolomei, C.; Seo, J.H.; Baca, S.C.; Carneiro, I.; Emberly, E.; Pasaniuc, B.; Jerónimo, C.; Henrique, R.; Freedman, M.L.; Wessels, L.F.A.; Bergman, A.M.; Zwart, W.; N/A; Lack, Nathan Alan; Altıntaş, Umut Berkay; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Sciences and Engineering; 120842; N/AAndrogen receptor (AR) drives prostate cancer (PCa) development and progression. AR chromatin binding profiles are highly plastic and form recurrent programmatic changes that differentiate disease stages, subtypes and patient outcomes. While prior studies focused on concordance between patient subgroups, inter-tumor heterogeneity of AR enhancer selectivity remains unexplored. Here we report high levels of AR chromatin binding heterogeneity in human primary prostate tumors, that overlap with heterogeneity observed in healthy prostate epithelium. Such heterogeneity has functional consequences, as somatic mutations converge on commonly-shared AR sites in primary over metastatic tissues. In contrast, less-frequently shared AR sites associate strongly with AR-driven gene expression, while such heterogeneous AR enhancer usage also distinguishes patients’ outcome. These findings indicate that epigenetic heterogeneity in primary disease is directly informative for risk of biochemical relapse. Cumulatively, our results illustrate a high level of AR enhancer heterogeneity in primary PCa driving differential expression and clinical impact.Publication Open Access Evidence-based medical oncology and interventional radiology paradigms for liver-dominant colorectal cancer metastases(Baishideng Publishing Group (BPG), 2016) N/A; N/A; Sağ, Alan Alper; Selçukbiricik, Fatih; Mandel, Nil Molinas; Faculty Member; Faculty Member; Faculty Member; School of MedicineColorectal cancer metastasizes predictably, with liver predominance in most cases. Because liver involvement has been shown to be a major determinant of survival in this population, liver-directed therapies are increasingly considered even in cases where there is (limited) extrahepatic disease. Unfortunately, these patients carry a known risk of recurrence in the liver regardless of initial therapy choice. Therefore, there is a demand for minimally invasive, non-surgical, personalized cancer treatments to preserve quality of life in the induction, consolidation, and maintenance phases of cancer therapy. This report aims to review evidence-based conceptual, pharma cological, and technological paradigm shifts in parenteral and percutaneous treatment strategies as well as forthcoming evidence regarding next-generation systemic, locoregional, and local treatment approaches for this patient population.Publication Open Access Al2O3 micro- and nanostructures affect vascular cell response(Royal Society of Chemistry (RSC), 2016) Kiefer, Karin; Akpınar, Gürler; Haidar, Ayman; Ikier, Tuba; Akkan, Çağrı Kaan; Akman, Erhan; Lee, Juseok; Miro, Marina Martinez; Kaçar, Elif; Demir, Arif; Veith, Michael; Kasap, Murat; Kesmez, Mehmet; Abdul-Khaliq, Hashim; Aktaş, Cenk; N/A; Ural, Dilek; Faculty Member; School of Medicine; 1057In-stent restenosis (ISR) is one of the most common and serious complications observed after stent implantation. ISR is characterized by the inordinate proliferation of smooth muscle cells (SMC) that leads to narrowing of the blood vessels. To achieve a healthy endothelium, it is critical to selectively enhance the growth of endothelial cells (EC) while suppressing the growth of smooth muscle cells, which is still a major challenge and yet to be achieved. In this study, novel surfaces have been developed to support the selective growth of endothelial cells. Micro-and nanostructured Al2O3 surfaces with unique topographical features were fabricated and tested. Surface characterization and cellular response of endothelial cells (HUVEC) as well as smooth muscle cells (HUVSMC) has been investigated at cellular and molecular levels. A topography driven selective cell response of ECs over SMCs was demonstrated successfully. This selective response of ECs was also analyzed at protein levels in order to understand the basic mechanism.