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Publication Open Access Multifunctional alginate-based hydrogel with reversible crosslinking for controlled therapeutics delivery(Elsevier, 2020) Ekinci, Duygu; N/A; Department of Chemical and Biological Engineering; Batool, Syeda Rubab; Nazeer, Muhammad Anwaar; Kızılel, Seda; Şahin, Afsun; PhD Student; Faculty Member; Faculty Member; Department of Chemical and Biological Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; N/A; N/A; 28376; 171267Glycan-based alginate hydrogels have great potential in creating new vehicles with responsive behavior and tunable properties for biomedicine. However, precise control and tunability in properties present major barrier for clinical translation of these materials. Here, we report the synthesis of pH responsive anthracene modified glycan-based hydrogels for selective release of therapeutic molecules. Hydrogels were crosslinked through simultaneous photopolymerization of vinyl groups and photodimerization of anthracene. Incorporation of anthracene into these gels leads to reversible control on crosslinking and transition between gel/sol states through dimerization/dedimerization of anthracene groups. Chemotherapeutic drug doxorubicin-loaded hydrogels were then tested in a cancer mimetic microenvironment where 85% of the drug was released from anthracene-conjugated hydrogels at pH 2 for 6 days. Control on gelation with anthracene incorporation was observed through alterations in modulus, where storage modulus was increased two-fold with anthracene conjugation during photopolymerization and photodimerization. Furthermore, cell survival analysis revealed that anthracene conjugation could selectively compromise cancer cell viability without inducing significant toxicity on healthy fibroblasts. This study combines light-induced control of crosslink density due to anthracene and pH-triggered therapeutics delivery with alginate. The approach would be applicable for systems where multiple control is required with high precision.Publication Open Access Recommendations for clinical decision-making in children with type 1 diabetes and celiac disease: type 1 diabetes and celiac disease joint working group report(Galenos Yayınevi, 2022) Dalgıç, B.; Gökşen, D.; Aydoğdu, S.; Savaş, Erdeve Ş.; Kuloğu, Z.; Doğan, Y.; Aycan, Z.; Keser, A.; Beşer, Ö.F.; Özbek, M.N.; Bideci, A.; Ertem, D.; Evliyaoğlu, O.; Eliüz Tipici, B.; Gökçe, T.; Muradoğlu, S.; Koca, T.; Tütüncüler, F.; Baş, F.; Darendeliler, F.; Selimoğlu, M.A.; Hatun, Şükrü; Yeşiltepe Mutlu, Rahime Gül; Kızılkan, Nuray Uslu; Taşkın, Orhun Çığ; Faculty Member; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 153504; 153511; 221274; 166686It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients’ families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors’ own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.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 Liver transplantation in hepatic myelopathy(Kare Yayıncılık, 2022) Acar, Sencan; Dinçkan, Ayhan; Akyıldız, Murat; Faculty Member; School of Medicine; 123080Hepatic myelopathy (HMy) is a rare neurological complication of liver cirrhosis that involves spastic paraplegia caused by lateral cord demyelination especially due to the accumulation of some metabolites such as ammonia and manganese. We report a young adult woman presenting with spasticity and paraparesis in extremities after intrahepatic portosystemic shunting (TIPS) application and underwent deceased liver transplantation (LT). A 39-year-old woman underwent deceased LT because of cryptogenic liver cirrhosis. She underwent a TIPS procedure 5 years ago. After that, hepatic encephalopathy and spasticity appeared. She was on the waiting list for 3 years. Neurological findings after LT significantly decreased, but did not return to normal. After the emergence of neurological findings, the earlier LT can provide improvement in neurological findings.Publication Open Access Generation of transgene-free iPSC lines from three patients with Friedreich's ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene(Elsevier, 2021) Kelekçi, Simge; Uğurlu Çimen, Deniz; Demir, Ata Berk; Özçimen, Burcu; Yıldız, Abdullah Burak; Karakuş, Mehmet Batuhan; Börklü Yücel, Esra; Önder, Tamer Tevfik; PhD Student; Undergraduate Student; Other; Faculty Member; Graduate School of Health Sciences; School of Medicine; Koç University Hospital; N/A; N/A; N/A; N/A; N/A; N/A; N/A; 42946Friedreich's ataxia (FRDA) is a rare neurodegenerative disorder which is caused by triplet repeat expansion (GAA) in the first intron of FXN gene. In this present study, we generated induced pluripotent stem cells (iPSC) lines from fibroblasts of three unrelated FRDA patients using integration-free episomal vectors. All iPSC lines express the pluripotency markers such as OCT4 and SSEA4, display normal karyotypes and can differentiate into all three germ layers via in vivo teratoma formation assay.Publication Open Access Irritable bowel syndrome demographics: a Middle Eastern multinational cross-sectional study(Iranian Association of Gastroenterology and Hepatology, 2022) Alavinejad, Pezhman; Ghanavati, Parvin Mousavi; Alboraie, Mohamed; Emara, Mohamed; Baghaee, Siamak; Daryani, Naser Ebrahimi; Farsi, Farnaz; Hajiani, Eskandar; Hashemi, Seyed Jalal; Lak, Elena; Taheri, Yasaman; Dangi, Abhijit; Baran, Bülent; Faculty Member; School of Medicine; Koç University Hospital; 167583Background: irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal (GI) disorder. In this study, we aimed to evaluate the different aspects of IBS among Middle Eastern residents. Methods: during the study period, patients attending gastroenterology clinics of nine tertiary referral centers in four Middle Eastern couturiers (Iran, Egypt, Kuwait, and Turkey) were evaluated by Rome IV diagnostic criteria, and those who fulfilled the diagnostic criteria of IBS were asked to fill in a questionnaire covering different demographics and clinical aspects. Results: overall, during a 6-month period, 509 patients with IBS were included. 41.3% of the participants were male (210 patients), and 37.4% of them had academic education. 50% of the participants were Caucasian, and 34% were Arab, and originally, they were citizens of 18 countries. 77.4% of the participants were residents of subtropical areas, while 22.2% were living in temperate regions. The average age of the participants during the first presentation in subtropical and temperate areas were 38.4 ± 12.19 and 38.06 ± 12.18 years, respectively (P = 0.726). The most common subtypes of IBS in subtropical areas were unclassified (IBS-U, 44.4%), constipation dominant (IBS-C, 27.6%), mixed pattern (IBS-M, 21%), and diarrhea dominant (IBS-D, 6.8%) in descending order while in temperate areas the most common subtypes were IBS-U (43.3%), and IBS-D (22.1%), respectively (P < 0.001). Besides abdominal pain, the most common symptom of patients in each region was bloating (62.2% and 68.1%, respectively, P = 0.246). The rate of depression and anxiety were significantly higher among the residents of temperate areas in comparison with subtropical regions (41.6% vs. 16.5% and 80.5% vs. 58.4%, respectively, P < 0.001). Conclusion: although the average age of IBS presentation is the same in subtropical and temperate areas, it seems that in temperate areas, the rate of IBS-D is more prevalent than in subtropical regions. The rate of anxiety and depression are significantly higher among those who searched social media and the internet to get information about their problems.Publication Open Access What is the current role and what are the prospects of the robotic approach in liver surgery?(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Sijberden, J.P.; Hilal, M.A.; Bozkurt, Emre; Koç University HospitalRobotic liver surgery is being applied with increasing frequency. Comparable, and in specific settings superior, perioperative outcomes compared to laparoscopic liver surgery have been reported. In its current form, the most commonly mentioned advantage of robotic surgery is improved dexterity. Important obstacles to its wider implementation in daily clinical practice are the associated costs, technical difficulties, and a scarce amount of evidence. Robotic liver surgery will likely continue to evolve in parallel with technological developments that enhance the robots' abilities. In parallel with the historical development of minimally invasive surgery, the laparoscopic and robotic approaches are now frequently utilized to perform major abdominal surgical procedures. Nevertheless, the role of the robotic approach in liver surgery is still controversial, and a standardized, safe technique has not been defined yet. This review aims to summarize the currently available evidence and prospects of robotic liver surgery. Minimally invasive liver surgery has been extensively associated with benefits, in terms of less blood loss, and lower complication rates, including liver-specific complications such as clinically relevant bile leakage and post hepatectomy liver failure, when compared to open liver surgery. Furthermore, comparable R0 resection rates to open liver surgery have been reported, thus, demonstrating the safety and oncological efficiency of the minimally invasive approach. However, whether robotic liver surgery has merits over laparoscopic liver surgery is still a matter of debate. In the current literature, robotic liver surgery has mainly been associated with non-inferior outcomes compared to laparoscopy, although it is suggested that the robotic approach has a shorter learning curve, lower conversion rates, and less intraoperative blood loss. Robotic surgical systems offer a more realistic image with integrated 3D systems. In addition, the improved dexterity offered by robotic surgical systems can lead to improved intra and postoperative outcomes. In the future, integrated and improved haptic feedback mechanisms, artificial intelligence, and the introduction of more liver-specific dissectors will likely be implemented, further enhancing the robots' abilities.Publication Open Access Turk Cardiology Association completion report: COVID-19 pandemic and things to know about cardiovascular diseases (25 Mart 2020)(Turkish Society of Cardiology, 2020) Aktoz, Meryem; Altay, Hakan; Aslanger, Emre; Atalar, Enver; Baykan, Ahmet Oytun; Barçın, Cem; Barış, Nezihi; Boyacı, Asiye Ayça; Çavuşoğlu, Yüksel; Çelik, Ahmet; Cinier, Göksel; Değertekin, Muzaffer; Ertürk, Mehmet; Erol, M. Kemal; Görenek, Bülent; Gürsoy, Mustafa Ozan; Hunuk, Burak; Kahveci, Gökhan; Karabay, Can Yücel; Karaca, Ilgın; Kayıkcıoğlu, Meral; Keskin, Muhammed; Kılıç, Teoman; Kırma, Cevat; Kocabaş, Umut; Küçükoğlu, Serdar; Mutlu, Bülent; Nalbantgil, Sanem; Okuyan, Ertuğrul; Okyay, Kaan; Özen, Deniz Kaptan; Özgül, Sami; Özpelit, Ebru; Pirat, Bahar; Sert, Sena; Sinan, Ümit Yaşar; Şener, Yusuf Ziya; Tatlı, Ersan; Tekkesin, Ahmet İlker; Tutar, Eralp; Yıldırımtürk, Özlem; Aytekin, Vedat; Ural, Dilek; Ergönül, Önder; Faculty Member; Faculty Member; Faculty Member; School of Medicine; N/A; 1057; 110398In December 2019, in the city of Wuhan, in the Hubei province of China, treatment-resistant cases of pneumonia emerged and spread rapidly for reasons unknown. A new strain of coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) was identified and caused the first pandemic of the 21st century. The virus was officially detected in our country on March 11, 2020, and the number of cases increased rapidly; the virus was isolated in 670 patients within 10 days. The rapid increase in the number of patients has required our physicians to learn to protect both the public and themselves when treating patients with this highly infectious disease. The group most affected by the outbreak and with the highest mortality rate is elderly patients with known cardiovascular disease. Therefore, it is necessary for cardiology specialists to take an active role in combating the epidemic. The aim of this article is to make a brief assessment of current information regarding the management of cardiovascular patients affected by COVID-19 and to provide practical suggestions to cardiology specialists about problems and questions they have frequently encountered. / Aralık 2019’da, Çin’in Hubei eyaletindeki Wuhan şehrinde, nedeni bilinmeyen, tedaviye dirençli pnömoni olguları ile ortaya çıkan ve devamında hızla yayılarak XXI. yüzyılın ilk pandemisine neden olan yeni koronavirüsün (severe acute respiratory syndrome koranavirüs-2 [SARS-CoV-2]) 11 Mart 2020 tarihinde ülkemizde de resmi olarak saptanmasının ardından olgu sayısı hızla artmış ve 10 gün içerisinde 670 hastada virüs izole edilmiştir. Hasta sayısındaki hızlı artış, hekimlerimizin bir yandan etkilenen hastalara müdahale ederken diğer yandan toplumu ve kendilerini korumayı öğrenmelerini gerektirmektedir. Salgından en çok etkilenen ve ölüm oranı en yüksek seyreden grup, bilinen kalp ve damar hastalıkları olan yaşlılardır. Bu nedenle, kardiyoloji uzmanlarının salgınla mücadelede aktif görev almaları kaçınılmazdır. Bu makale, COVID-19’dan etkilenen kalp-damar hastalarının yönetiminde güncel bilgilerin kısa bir değerlendirmesini yapmayı ve kardiyoloji uzmanlarına sık karşılaştıkları sorunlar ve sorular hakkında pratik öneriler sunmayı amaçlamaktadır.Publication Open Access Thrombolysis in Myocardial Infarction Risk Index predicts one-year mortality in patients with heart failure: an analysis of the SELFIE-TR study(Karger Publishers, 2022) Güvenç, Rengin Çetin; Güvenç, Tolga Sinan; Çavusoğlu, Yüksel; Yılmaz, Mehmet Birhan; Ural, Dilek; Faculty Member; School of Medicine; 1057Objective: predicting outcomes is an essential part of evaluation in patients with heart failure (HF). While there are multiple individual laboratory and imaging variables, as well as risk scores available for this purpose, they are seldom useful during the initial evaluation. In this analysis, we aimed to understand predictive usefulness of Thrombosis in Myocardial Infarction Risk Index (TIMI-RI), a simple index that is calculated at bedside using three commonly available variables, using data from a multicenter HF registry. Subjects and Methods: a total of 728 patients from 23 centers were included to this analysis. Data on hospitalizations and mortality were collected by direct interviews, phone calls and electronic databases. TIMI-RI was calculated as defined before. Patients were divided into three equal tertiles to perform analyses. Results: rehospitalization for HF was significantly higher in patients within the 3rd tertile, and 33.5% of patients within the 3rd tertile were dead within one-year follow up as compared to 14.5% of patients within the 1st tertile and 15.6% patients within the 2nd tertile (p<0.001, log-rank p<0.001 for pairwise comparisons on survival analysis). A TIMI-RI higher than 33 had a negative predictive value of 84.8% and a positive predictive value of 33.8% for prediction of one-year mortality. This predictive usefulness was independent of other demographic, examination and clinical variables (OR:1.74, 95%CI:1.05-2.86, p=0.036). Conclusion: TIMI-RI is a simple index that predicts one-year mortality in patients with HF, and it could be useful for rapid evaluation and triage of HF patients at the time of initial contact.Publication Open Access Autophagy and cancer dormancy(Frontiers, 2021) Akçay, Arzu; Akkoç, Yunus; Peker, Nesibe; Gözüaçık, Devrim; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; 40248Metastasis and relapse account for the great majority of cancer-related deaths. Most metastatic lesions are micro metastases that have the capacity to remain in a non-dividing state called "dormancy" for months or even years. Commonly used anticancer drugs generally target actively dividing cancer cells. Therefore, cancer cells that remain in a dormant state evade conventional therapies and contribute to cancer recurrence. Cellular and molecular mechanisms of cancer dormancy are not fully understood. Recent studies indicate that a major cellular stress response mechanism, autophagy, plays an important role in the adaptation, survival and reactivation of dormant cells. In this review article, we will summarize accumulating knowledge about cellular and molecular mechanisms of cancer dormancy, and discuss the role and importance of autophagy in this context.