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Publication Open Access "Whole" vs "fragmented" approach to EAACI pollen season definitions: a multicenter study in six Southern European cities(Wiley, 2020) Hoffmann, Tara Maria; Şahin, Aydan Acar; Aggelidis, Xenophon; Arasi, Stefania; Barbalace, Andrea; Bourgoin, Anne; Bregu, Blerina; Brighetti, Maria Antonia; Caeiro, Elsa; Sozmen, Sule Caglayan; Caminiti, Lucia; Charpin, Denis; Couto, Mariana; Delgado, Luis; Businco, Andrea Di Rienzo; Dimier, Claire; Dimou, Maria, V; Fonseca, Joao A.; Göksel, Özlem; Güvensen, Aykut; Hernandez, Dolores; Jang, Dah Tay; Kalpaklıoğlu, Füsun; Lame, Blerta; Llusar, Ruth; Makris, Michael P.; Mazon, Angel; Mesonjesi, Eris; Nieto, Antonio; Pahus, Laurie; Pajno, Giovanni Battista; Panasiti, Ilenia; Panetta, Valentina; Papadopoulos, Nikolaos G.; Pellegrini, Elisabetta; Pelosi, Simone; Pereira, Ana Margarida; Pereira, Mariana; Pinar, Munevver; Pfaar, Oliver; Potapova, Ekaterina; Priftanji, Alfred; Psarros, Fotis; Sfika, Ifigenia; Suarez, Javier; Thibaudon, Michel; Travaglini, Alessandro; Tripodi, Salvatore; Verdier, Valentine; Villella, Valeria; Xepapadaki, Paraskevi; Matricardi, Paolo M.; Dramburg, Stephanie; Öztürk, Ayşe Bilge; Saçkesen, Cansın; Yazıcı, Duygu; Faculty Member; Faculty Member; PhD Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; Koç University Hospital; 147629; 182537; N/ABackground: the adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. Objective To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. Methods: as part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. Results: the analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). Conclusion: the Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.
Publication Metadata only 18F-FDG PET/CT mean suv and metabolic tumor volume for mean survival time in non-small cell lung cancer(Lippincott Williams and Wilkins, 2015) Kurtipek, Ercan; Çaycı, Mustafa; Düzgün, Nuri; Esme, Hıdır; Terzi, Yüksel; Bakdık, Süleyman; Ünlü, Yaşar; Burnik, Cengiz; Bekçi, Taha Tahir; N/A; Aygün, Murat Serhat; Teaching Faculty; School of Medicine; Koç University Hospital; 291692Objective: The study was designed to determine the relationship between survival time of standardized uptake value (SUVmax and SUVmean) and metabolic tumor volume (MTV) in patients with non-small cell lung cancer (NSCLC), and examine the impact of demographic, clinical, and radiological data of these patients on survival. Materials and Methods: We performed a retrospective analysis of the records of 79 patients with NSCLC who presented to our hospital between May 2010 and March 2013, received a final diagnosis, and underwent 18F-FDG PET/CT for staging. Clinical, radiological, and 18F-FDG PET/CT parameters with an impact on prognosis such as the SUVmax of the primary tumor as calculated by the volumetric region of interest in the 18F-FDG PET/CT scans during initial diagnosis, mean SUV of the tumor, and MTV obtained with a threshold of SUVmax greater than 2.5 were recorded and statistically analyzed. A statistical analysis was carried out based on the clinical, radiological, and PET/CT findings of the patients who were divided into 2 groups: survivors and nonsurvivors. Results: Seventy patients (88.6%) were men, and 9 (11.4%) were women. The mean age was 63.65 ± 11.51 years in the nonsurvivor group (n = 40) versus 62.74 ± 10.60 years in the survivor group (n = 39) (Table 1). The mean survival time from diagnosis was 7.9 ± 6.52 months in the nonsurvivor group versus 14.09 ± 7.41 months in the survivor group. The mean survival time was 12.9 ± 7.9 months for those aged 60 or younger, whereas it was 9.9 ± 7.2 years for those aged 60 or older. According to the Cox regression analysis, higher MTV [relative risk (RR), 1.006; P = 0.03] and mean SUVmax (mSUV) (RR, 1.302; P = 0.03) had a significant impact on shortening of the mean survival time. However, no statistical significance was reached for SUVmax measurements (RR, 0.970; P = 0.39). Furthermore, there was a significant relationship between increased tumor size (andlt;2 cm, 2-4 cm, and ≥4 cm) and shortened mean survival time (P = 0.03). Conclusion: The present study showed that MTV and mSUV of FDG PET/CT scans of the tumor, but not SUVmax, had a significant impact on survival time of patients with NSCLC. Based on this result, we believe that we might have more accurate information about the survival time of our patients if we also evaluate mSUV and MTV in combination with mSUV, which is frequently used for diagnosis and monitoring of patients with NSCLC during our daily practice. © 2015 Wolters Kluwer Health, Inc. All rights reserved.Publication Open Access A brand-new cardiorenal syndrome in the Coronavirus Disease- 2019 (COVID-19) setting(Oxford University Press (OUP), 2020) Apetrii, Mugurel; Enache, Stefana; Siriopol, Dimitrie; Burlacu, Alexandru; Kanbay, Asiye; Scripcariu, Dragos; Covic, Adrian; Kanbay, Mehmet; Faculty Member; School of Medicine; 110580Coronaviruses are a major pathogen for adults, causing up to one-third of community-acquired respiratory tract infections in adults during epidemics. Although the pandemic outbreak of coronavirus disease-2019 (COVID-19) targets preferentially patient’s lungs, recent data have documented that COVID-19 causes myocarditis, acute myocardial infarction, exacerbation of heart failure and acute kidney injury. Studies show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to its predecessor SARS-CoV, engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor. ACE2 is also expressed in the heart, providing a link between coronaviruses and the cardiovascular system.Publication Metadata only A common genetic variation of melanoma inhibitory activity-2 labels a subtype of pancreatic adenocarcinoma with high endoplasmic reticulum stress levels(Nature, 2015) Kong, Bo; Wu, Weiwei; Valkovska, Nataliya; Jäger, Carsten; Hong, Xin; Nitsche, Ulrich; Friess, Helmut; Esposito, Irene; Kleeff, Jörg; Michalski, Christoph W.; N/A; Erkan, Murat Mert; Faculty Member; School of Medicine; 214689HNF1 homeobox A (HNF1A)-mediated gene expression constitutes an essential component of the secretory pathway in the exocrine pancreas. Melanoma inhibitory activity 2 (MIA2), a protein facilitating protein secretion, is an HNF1A target. Protein secretion is precisely coordinated by the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) system. Here, we demonstrate that HNFA and MIA2 are expressed in a subset of human PDAC tissues and that HNF1A induced MIA2 in vitro. We identified a common germline variant of MIA2 (c.A617G: p.I141M) associated with a secretory defect of the MIA2 protein in PDAC cells. Patients carrying MIA2I141M survived longer after tumor resection but the survival benefit was restricted to those patients who received adjuvant chemotherapy. The MIA2I141M variant was associated with high expression of ER stress/UPR genes – in particular those of the ERN1/XBP arm – in human PDAC samples. Accordingly, PDAC cell lines expressing the MIA2I141M variant expressed high levels of ERN1 and were more sensitive to gemcitabine. These findings define an interaction between the common MIA2I141M variant and the ER stress/UPR system and specify a subgroup of PDAC patients who are more likely to benefit from adjuvant chemotherapy. © 2015, Nature Research. All rights reserved.Publication Metadata only A family from Turkey with congenital myasthenia and hereditary(Wiley, 2023) Tezen, D.; Gündüz, A.; Demirbilek, V.; Khojakulov, Zakhiriddin; Başak, Ayşe Nazlı; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicinePublication Metadata only A new option for the reconstruction of orbital floor defects with heterologous cortical bone(Churchill Livingstone, 2015) Ozel, Bora; Findikcioglu, Kemal; Guney, Kirdar; Barut, Ismail; Ozmen, Selahattin; N/A; Sezgin, Billur; Faculty Member; School of Medicine; 133762Background: The orbital floor is one of the most frequently injured areas of the maxillofacial skeleton during facial trauma. A retrospective analysis of patients who have undergone treatment of orbital floor fractures with heterologous cortical bone is presented. Methods: This retrospective study was carried out with 21 patients over a period of 4 years between 2010 and 2014. All patients with a traumatic orbital floor defect who underwent reconstruction with heterologous cortical bone were included. The operations were carried out under general anesthesia for all patients. A subciliary incision was used in 20 patients and an infraorbital approach was used in one patient. All patients underwent follow-up examinations clinically as well as radiologically, at 1, 3, 6 and 12 months postoperatively. Computed tomographic scans were taken at the postoperative 6th month, and at the first postoperative year if needed. Results: Preoperatively, the physical examination revealed diplopia in 17 patients (80.9%), gaze restriction in 14 patients (66.6%), enophthalmos in six patients (28.5%), and infraorbital nerve paresthesia in two patients (9.5%). None of the patients showed impaired visual acuity preoperatively or postoperatively. Diplopia and gaze restriction resolved postoperatively in all of the patients. All patients had a negative intraoperative forced duction test demonstrating free globe movement. Enophthalmos showed complete resolution in the postoperative period. In one of the two patients with preoperative infraorbital nerve paresthesia, this resolved at the postoperative fifth month. Scleral show appeared in six patients but resolved completely within 3-8 weeks with massage. There was no graft extrusion, resorption or displacement during the follow-up period. Conclusions: Tecnoss Semi Soft Lamina is a good alternative for the reconstruction of blowout fractures due to its plasticity and biocompatible structure. Without donor site morbidity, it is a safe and appropriate heterologous bone graft material for maxillofacial applications such as orbital floor reconstruction. We cannot recommend its use for near-total, wide orbital floor defects as it may not provide enough support in such circumstances.Publication Open Access A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe(Oxford University Press (OUP), 2020) ESHRE COVID-19 Working Group; Vermeulen, Nathalie; Gianaroli, Luca; Lundin, Kersti; Mocanu, Edgar; Rautakallio-Hokkanen, Satu; Tapanainen, Juha S.; Veiga, Anna; Ata, Mustafa Barış; Faculty Member; School of Medicine; 182910Study question: how did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? Summary answer: MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. What is known already: with the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. Study design size duration: a structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. Participants/materials setting methods: the information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. Main results and the role of chance: by aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. Large scale data: N/A. Limitations reasons for caution: data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. Wider implications of the findings: the current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations. Study funding/competing interests: there was no funding for the study, apart from technical support from ESHRE. The authors had no COI to disclose.Publication Metadata only A potential biomarker for individuals of chronic subjective tinnitus with normal hearing: serum prestin levels(Wiley, 2023) Bulut, Erdogan; Budak, Metin; Guven, Selis Gulsevin; Atilgan, Emre; Uzun, Cem; School of MedicinePublication Metadata only A proof-of-concept for epigenetic therapy of tissue fibrosis: inhibition of liver fibrosis progression by 3-Deazaneplanocin A(Cell Press, 2017) Luli, Saimir; Sabater, Laura; Hardy, Timothy; Oakley, Fiona; Leslie, Jack; Page, Agata; Salvador, Eva Moran; Sharkey, Victoria; Tsukamoto, Hidekazu; Chu, David C. K.; Singh, Uma Sharan; Ponzoni, Mirco; Perri, Patrizia; Di Paolo, Daniela; Mendivil, Edgar J.; Mann, Jelena; Mann, Derek A.; N/A; Zeybel, Müjdat; Faculty Member; School of Medicine; 214694The progression of fibrosis in chronic liver disease is dependent upon hepatic stellate cells (HSCs) transdifferentiating to a myofibroblast-like phenotype. This pivotal process is controlled by enzymes that regulate histone methylation and chromatin structure, which may be targets for developing anti-fibrotics. There is limited pre-clinical experimental support for the potential to therapeutically manipulate epigenetic regulators in fibrosis. In order to learn if epigenetic treatment can halt the progression of pre-established liver fibrosis, we treated mice with the histone methyltransferase inhibitor 3-deazaneplanocin A (DZNep) in a naked form or by selectively targeting HSC-derived myofibroblasts via an antibody-liposome-DZNep targeting vehicle. We discovered that DZNep treatment inhibited multiple histone methylation modifications, indicative of a broader specificity than previously reported. This broad epigenetic repression was associated with the suppression of fibrosis progression as assessed both histologically and biochemically. The anti-fibrotic effect of DZNep was reproduced when the drug was selectively targeted to HSC-derived myofibroblasts. Therefore, the in vivo modulation of HSC histone methylation is sufficient to halt progression of fibrosis in the context of continuous liver damage. This discovery and our novel HSC-targeting vehicle, which avoids the unwanted effects of epigenetic drugs on parenchymal liver cells, represents an important proof-of-concept for epigenetic treatment of liver fibrosis.Publication Metadata only A simplified grid method of camera-captured images may be a practical alternative if validated ai-assisted counting is inaccessible(Elsevier Science Inc, 2023) Adsay, David; Eren, Ozgur; Basturk, Olca; Department of Computer Engineering; Esmer, Rohat; Armutlu, Ayşe; Taşkın, Orhun Çığ; Koç, Soner; Tezcan, Nuray; Aktaş, Berk Kaan; Kulaç, İbrahim; Kapran, Yersu; Demir, Çiğdem Gündüz; Saka, Burcu; Department of Computer Engineering; School of Medicine; Graduate School of Sciences and Engineering; College of EngineeringN/A