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Publication Metadata only 18F-FDG PET/CT imaging in a patient with a rare diagnosis of sarcomatoid malignant peritoneal mesothelioina(Lippincott Williams & Wilkins, 2013) Tokmak, Handan; Demirkol, Onur M.; Kaban, Kerim; N/A; Mandel, Nil Molinas; Dilege, Şükrü; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 194197; 122573Malignant peritoneal mesothelioma is an uncommon but deadly disease arising from serosal surfaces of the peritoneum. Asbestos exposure is the most recognized risk factor. We report a case of diffuse, sarcomatoid malignant peritoneal mesothelioma who presented to the hospital with abdominal pain. The patient had an abdominal MRI scan as initial scanning which demonstrated nonspecific findings suspected of peritoneal carcinomatosis. The patient was admitted to our department for the metabolic characterization of the lesions with F-18-FDG PET/CT imaging and the diagnosis of the primary malignancy. F-18-FDG PET/CT imaging revealed diffusely increased metabolic activity throughout the peritoneum and the histopathological features were compatible with sarcomatoid malignant peritoneal mesothelioma.Publication Metadata only 32 novel pathogenic sequence variants in 253 DMD/BMD patients from Turkey(Nature Publishing Group, 2018) Toksoy, G.; Aghayev, A.; Bagirova, G.; Tekce, H. Durmus; Avci, S.; Altunolu, U.; Parman, Y.; Oflazer, P.; Yapici, Z.; N/A; Kayserili, Hülya; Faculty Member; School of Medicine; 7945N/APublication Metadata only 3D ultrasound assessment of effect of controlled ovarian stimulation on endometrioma volume(Oxford University Press (OUP), 2016) Seyhan, A.; Balaban, B.; Urman, Cumhur Bülent; Ata, Mustafa Barış; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 12147; 232576N/APublication Metadata only 423.11: Long-term compromised immune regulation after rituximab induction in blood group incompatible living-donor renal transplantation-5 year results of a prospective pilot study(Lippincott Williams & Wilkins, 2022) Weimer, Rolf; Karakizlis, Hristos; Renner, Fabrice; Dietrich, Hartmut; Daniel, Volker; Schüttler, Christian; Kämper, Daniel; Leicht, Dominik; Wörlen, Michael; Renner, Lene; Milchsack, Katrin; Padberg, Winfried; Opelz, Gerhard; Süsal, Caner; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 351800Background: An increased frequency of severe infectious diseases and BK viremia has been described after ABOi renal transplantation. As rituximab induction may alter immunoregulation in these patients, we analyzed clinically relevant immune parameters in a prospective renal transplant study up to 5 years posttransplant. Materials and Methods: Mononuclear cell subsets (peripheral blood; lymph nodes taken during transplant surgery), intracellular cytokine responses, CD4 helper function and in-vitro B cell responses were assessed pretransplant and up to 5 years posttransplant in 85 renal transplant recipients (living donation: n=25 ABO incompatible (ABOi) and n=30 ABO compatible (ABOc); deceased donation (DD): n=30, all ABO compatible). Results: Severe infectious diseases occurred more often in ABOi than ABOc recipients within 2 years posttransplant (11/24 (46%) versus 6/30 (20%), P=0.042) but not beyond. The incidence of BK viremia was significantly enhanced in rituximab versus non-rituximab treated patients (1 year: 9/29 (31%) versus 4/54 (7%), P=0.009; 5 years: 10/30 (33%) versus 7/53 (13%), P=0.029). After rituximab induction in ABOi recipients, counts of peripheral blood B cell subsets were profoundly downregulated even 3 years posttransplant and reached the level of non-ABOi recipients after 4 years (memory B cells after 5 years). T-dependent and T-independent B cell responses were significantly impaired in ABOi patients up to 2 years posttransplant (P=0.010 and P=0.053, respectively) whereas CD4 helper activity was not compromised. CD4+ T cell counts were significantly lower in ABOi compared to ABOc recipients at 3 and 6 months (P=0.025 and P=0.046, respectively), but showed no differences in the percentage of Tregs. In regional lymph nodes of ABOi patients, we found a significant downregulation of CD20+ but not CD19+ B cells (P<0.0005), of naive B cells (P=0.031) and short lived plasma cells (P<0.0005) at the time of transplantation. Conclusion: An increased frequency of severe infectious diseases and BK viremia in rituximab treated ABOi renal transplant recipients may be explained by significantly downregulated CD4+ T cell counts up to 6 months and a profoundly delayed B cell repopulation, most pronounced with regard to memory B cells, together with compromised B cell responses up to 2 years posttransplant. IL-10, as a key player in chronic BK virus infection, was not upregulated in rituximab-treated ABOi transplant recipients.Publication Metadata only 5-HT causes venodilatation to reduce blood pressure in the rat(Karger, 2016) Seitz, Bridget M.; Krieger-Burke, Theresa; Darios, Emma S.; Thompson, Janice M.; Watts, Stephanie W.; N/A; Orer, Hakan S.; Faculty Member; School of Medicine; 53477N/APublication Metadata only A 5-year analysis of demographics, cycle characteristics and reproductive outcomes of 907 egg freezing cycles in patients with diminished ovarian reserve and age-related fertility decline(Elsevier Science Inc, 2019) Çil, Aylin P.; Abalı, Remzi; Boza, Ayşen; Karakış, Lale S.; Ceyhan, Mehmet; Aksakal, Ece; Bahçeci, Mustafa; Urman, Bülent; Keleş, İpek; Öktem, Özgür; Ata, Mustafa Barış; Doctor; Doctor; Faculty Member; School of Medicine; Koç University Hospital; N/A; 102627; 182910Publication Metadata only A case of secondary hemophagocytic lymphohistiocytosis (HLH) following incomplete kawasaki's disease (KD). Importance of distinguishing recurrent kd from HLH(2014) Kebudi, R.; Dindar, A.; Gürakan, F.; Devecioğlu, O.; Sözmen, Banu Oflaz; Faculty Member; School of Medicine; 198711N/APublication Metadata only A case with acute baked milk protein-induced enterocolitis syndrome(Wiley, 2019) N/A; N/A; N/A; Saçkesen, Cansın; Yılmaz, Özlem; Demirkol, Demet; Faculty Member; Doctor; Faculty Member; School of Medicine; School of Medicine; School of Medicine; 182537; 140706; 108964N/APublication Metadata only A case-control candidate gene study on base excision repair mechanism (BER) as a novel therapeutic target in bipolar disorder(Wiley, 2022) Ozerdem, Aysegul; Veldic, Marin; Singh, Balwinder; Frye, Mark; Schulze, Thomas; Biernacka, Joanna; Winham, Stacey J.; N/A; Ceylan, Deniz; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 137755N/APublication Metadata only A clinicopathological analysis of synchronously multifocal renal cell neoplasms(Springer, 2019) Gumrukcu, G.; Sayman, E.; Yuksel, O.; Aker, F.; N/A; Baydar, Dilek Ertoy; Faculty Member; School of Medicine; Koç University Hospital; 8025Publication Metadata only A combined clinical and computational approach to understand the sod1a4t-mediated pathogenesis of rapidly progressive familial amyotrophic lateral sclerosis(Wiley, 2019) Gelener, P.; Diker, S.; Ergoren, M. C.; Terali, K.; Tan, E.; N/A; Başak, Ayşe Nazlı; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 1512Here, we aim to provide a comprehensive clinical and biomolecular description of familial amyotrophic lateral sclerosis (fALS) in a 25-year-old female patient with respect to the SOD1A4T genotype. The clinical diagnosis of the disease was based on family history, neurological examination, electroneurophysiological studies, and revised El Escorial criteria. The heterozygous presence of the A4T mutation in the proband was confrmed by PCR coupled with Sanger sequencing of exon 1 of the SOD1 gene. The mutation was introduced in silico into the three-dimensional structure of the native protein. After energy minimization and quality assessment, non-covalent interactions around threonine-4 and changes in protein stability were calculated computationally. The patient difered widely in age at onset, initial neurological symptoms and fndings, and survival time from her kindred, in which several members are afected. SOD1A4T-linked fALS in this case had bulbar involvement at onset, a combination of lower and upper motor neuron signs and showed rapid progression. Unlike alanine-4, threonine-4 failed to engage in hydrophobic interactions with the vicinal non-polar amino acids. The overall fold of the modeled SOD1A4T mutant remained intact, but unfolding free energy estimations disclosed a decrease in the protein’s stability. We report a phenotypically distinct patient with fALS due to the SOD1A4T mutation and further expand the largest pedigree ever published for SOD1A4T-linked fALS. Genotype‒phenotype correlation in fALS is complex, and it demands detailed clinical investigation and advanced scientifc research. Awareness of the broadened phenotypic spectrum might potentially enhance the diagnosis and genetic counseling of fALS.Publication Metadata only A comperative molecular analysis of DNA damage response and apoptosis of malignant granulosa cells after exposure to gemcitabine and cisplatin(Bmj Publishing Group, 2019) Vatansever, Doğan; Bildik, Gamze; Taşkıran, Çağatay; Öktem, Özgür; Faculty Member; Teaching Faculty; Faculty Member; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; 193687; N/A; 134190; 102627Introduction/Background: We aimed to compare gemcitabine vs. cisplatin in terms of DNA damage response, viability/apoptosis of malignant granulosa cells. Methodology: Malignant granulosa tumour cell lines (COV434 and KGN) were used for the experiments. Cell viability, proliferation, DNA damage response and apoptosis were investigated using immunofluorescence staining and immunoblotting. Cell cycle analysis was carried out using flow cytometry. In vitro oestradiol and AMH productions were analysed by ECLIA method. Gemcitabine and cisplatin were used at four different concentrations corresponding to their therapeutic blood levels. Results: Gemcitabine treatment caused DNA damage, cellular stress, inhibited proliferation and activated cell cycle check-point sensors and induced apoptosis as shown by increased expression of g-histone H2AX, p-JNK, Chk-1/Chk-2, cleaved forms of PARP and caspase-3 in the asynchronous cells in a dose dependent manner. As a Result: the proliferation and in vitro AMH and oestrogen production of the cells were decreased at post-exposure 24h. In the cells synchronized at S phase gemcitabine significantly inhibited DNA synthesis and blocked their proliferation. Similar effects were also observed after cisplatin treatment. Exposure of the cells to gemcitabine at G2/M transition abolished the progression of mitosis, caused mitotic arrest and failure to exit mitosis as evidenced by the inhibition of Cyclin B degradation and absence of de-phosphorylation of cdc-2 at Tyr 15 residue. However, such an effect was not observed in the cells synchronized and treated with cisplatin at G2/M. Conclusion: These results may suggest that anti-metabolite chemotherapy drug gemcitabine might have anti-neoplastic actions on granulosa cell tumour.Publication Metadata only A comprehensive comparative transcriptional and translational analyses of the impact of ovarian response type, stimulation protocol and mode of trigger on the luteal function(Elsevier Science Inc, 2018) Seyhan, A; Yakın, Kayhan; Ata, Mustafa Barış; Öktem, Özgür; Bildik, Gamze; Urman, Cumhur Bülent; Faculty Member; Faculty Member; Faculty Member; Teaching Faculty; Faculty Member; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; 106822; 182910; 102627; N/A; 12147Objective: We aimed to compare molecular characteristics of the luteal granulosa cells between natural vs. stimulated IVF cycles in good and poor-responders. Design: Translational research study. Materials and Methods: Luteinized granulosa cells were obtained from good (n=154) and poor responder (n=64) IVF patients comparable for age, type and dose of gonadotropin and IVF etiology. Good-responders (4-15 oocytes) underwent natural (n=22), GnRH agonist (long protocol n=44) and antagonist IVF cycles triggered with rec-hCG (n=46) or GnRH agonist leuprolide acetate (n=42). Poor-responders fulfilling the Bologna criteria consisted of 64 patients undergoing GnRH antagonist protocol triggered with hCG (n=36) or hCG+GnRH agonist (n=28). Results: In the good-responders, natural cycle (NC) granulosa cells were significantly more viable (88%) compared to the stimulated IVF cycles (66%, 64% and 37% for agonist and antagonist cycles triggered with hCG and agonist respectively, p<0.05). The mRNA expression of steroidogenic enzymes (SCC, stAR, 3B-HSD, 17B-HSD and aromatase), LH receptor and VEGF and in vitro E2 and P productions were comparable between hCG-triggered agonist and antagonist cycles, but significantly higher than NC in the first days of culture. However, on the following days their hormone productions and viability began to decline very rapidly with the most drastic decrease being observed in the agonist triggered cycles. By contrast, NC granulosa cells maintained their viability and produced E 2 and P in increasing amounts in culture up to six days. The expression of anti-apoptotic genes (AKT-1, BCL2-L2) were significantly lower, and pro-apoptotic genes (BAD, BID, BAX, Cas3) were significantly higher in the stimulated cycles particularly in the agonist triggered ones compared to NC granulosa cells. Pulse exposure to cisplatin induced apoptosis only in a small fraction of the cells from the NCs whereas the same exposure caused massive apoptosis in the cells of the stimulated cycles (27% vs. 78% respectively, p<0.01). In the poor-responders both viability and steroidogenic activity of the cells were more severely reduced compared to the antagonist cycles of the good-responders. There were no significant differences between hCG and hCG+agonist triggered cycles in terms of viability, hormone production, VEGF and LH receptor expressions in the luteal granulosa cells. Conclusions Reduced survival and increased apoptosis of luteal granulosa cells leading to defective steroid production in stimulated cycles in comparison to natural ones may at least in part explain why luteal phase is defective and requires exogenous P supplementation for support in these cycles. Also dual trigger does not appear to improve luteal function in the poor-responders.Publication Metadata only A cross-language evaluation of the Kintsch and Van Dijk model of text comprehension(Psychology Press, 1996) Department of Psychology; Gülgöz, Sami; Faculty Member; Department of Psychology; College of Social Sciences and Humanities; 49200N/APublication Metadata only A deep breath for the mothers of dissabled children(Springer, 2016) N/A; N/A; Ocakçı, Ayşe Ferda; Faculty Member; School of Nursing; 1729N/APublication Metadata only A deleterious recessive mutation in NUAK2 causes absence of brain in humans(Elsevier Science Bv, 2017) Ghosh, Kakaly; Navaratnam, Naveenan; Chan, Puck Wee; Tan, Thong Teck; Ng, Alvin Yu Jin; Tohari, Sumanty; Pomp, Oz; Venkatesh, Byrappa; Altunoglu, Umut; Bonnard, Carine; N/A; Kayserili, Hülya; Reversade, Bruno; Faculty Member; Faculty Member; School of Medicine; School of Medicine; 7945; 274182N/APublication Metadata only A difficult diagnosis in a child with renal mass: desmoplastic small round cell tumour of the kidney(Springer, 2018) Aydin, Özkan; N/A; N/A; Armutlu, Ayşe; Baydar, Dilek Ertoy; Teaching Faculty; Faculty Member; School of Medicine; School of Medicine; 133567; 8025N/APublication Metadata only A drop in serum progesterone(p4) levels between 5th and 7th days of triggering ovulation is associated with lower ongoing pregnancy rate(opr) in intrauterine insemination cycles(Oxford Univ Press, 2022) Orhan, N.; Gunalp, G. S.; Yarali, H.; Mumusoglu, S.; N/A; Bozdağ, Gürkan; Faculty Member; School of Medicine; 55090N/APublication Metadata only A meta-analysis of anxiety disorder comorbidity in pediatric bipolar disorder(Elsevier Science Inc, 2016) Taşkıran, Ali Sarper; Eser, Hale Yapıcı; Mutluer, Tuba; Kılıç, Özge; Özcan, Aslıhan; Necef, Işıl; Yalçınay-İnan, Merve; Öngür, Dost; Other; Faculty Member; Faculty Member; Doctor; Other; Doctor; Doctor; N/A; School of Medicine; School of Medicine; School of Medicine; N/A; N/A; School of Medicine; N/A; N/A College of Engineering; School of Medicine; School of Medicine; N/A; N/A; School of Medicine; N/A; N/A; Koç University Hospital; 195168; 134359; 305311; N/A; N/A; N/A; N/A; N/AObjectives: AD are among the most prevalent comorbid conditions in pediatric bipolar disorder (PBD). There are conflicting results in the literature regarding prevalence of AD subtypes, and significant discrepancy with PBD course of illness (episodic or chronic) or diagnostic criteria (narrow or broad). Our aim in conducting meta-analysis is to investigate the prevalence of subtypes of comorbid anxiety disorders and its relations with the onset (childhood or adolescent) and course (episodic or chronic) of PBD. Methods: We have conducted a systematic research of Pubmed by using “bipolar disorder, affective psychosis, generalized anxiety disorder, panic, social phobia, obsessive compulsive disorder and anxiety disorder” as keywords to search in title/abstract until September 2015. Among 3202 articles, a total of 430 abstracts were found to be related; 82 were conducted in pediatric population, which were read in full text by at least two authors and data was extracted for outcome measures. Articles that include the data from the same population sample were excluded. Data was analyzed with random effects model using R statistical program package. Results: Data from 33 studies were included in the final analysis. The prevalence of any AD in PBD was 44 percent (95% CI 0.38–0.50), prevalence of AD subtypes were GAD 25 percent (95% CI 0.18–0.36); Separation Anxiety Disorder (SAD) 22 percent (95% CI 0.14–0.33); OCD 17 percent (95% CI 0.11–0.23); Social Phobia (SP) 15 percent (95% CI 0.08–0.27); Panic Disorder (PD) 10 percent (95% CI 0.05–0.19). When only episodic PBD were concerned, prevalence rates differed, with any AD 38 percent (95% CI 0.28–0.48); GAD 19 percent (95% CI 0.08–0.41); SAD 21 percent (95% CI 0.10–0.40); OCD 11 percent (95% CI 0.03–0.29); SP 11 percent (95% CI 0.04–0.27); PD 9 percent (95% CI 0.03–0.23). Prevalence of any AD (34% (95% CI 0.23-0.48), GAD and SAD were found as lower and OCD, SP and PD were slightly higher in adolescent onset compared to childhood onset PBD. Conclusions: Youth with BD are at increased risk of AD; nearly one in two has an AD. GAD and SAD are among the most prevalent comorbidities. AD are seen less with episodic and adolescent onset PBD. AD should be carefully investigated alongside the mood symptoms in PBD, as comorbidity may change course, treatment and subtyping of the disorder.Publication Metadata only A multicenter international study to evaluate different aspects of relationship between MS and pregnancy(Sage, 2019) Zakaria, M.; Alroughani, R.; Moghadasi, A. N.; Terzi, M.; Sen, S.; Koseoglu, M.; Efendi, H.; Soysal, A.; Gozubatik-Celik, G.; Ozturk, M.; Sahraian, M.; Akinci, Y.; Kaya, Z. E.; Saip, S.; Siva, A.; N/A; Department of Industrial Engineering; Altıntaş, Ayşe; Gönen, Mehmet; Faculty Member; Faculty Member; Department of Industrial Engineering; School of Medicine; College of Engineering; 11611; 237468N/A