İstanbul Sağlık ve Teknoloji Üniversitesi Kurumsal Akademik Arşivi
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    MAFLD: A comprehensive review of the link between metabolic dysfunction and cardiovascular risk

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    Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over 30% of the global population. It is a multisystem condition with a strong association with cardiovascular disease (CVD), the leading cause of mortality worldwide. Key shared mechanisms, including insulin resistance, systemic inflammation, oxidative stress, and genetic predisposition, couple MAFLD with increased risks of coronary artery disease, ischemic heart disease, and heart failure. Early detection via non-invasive imaging and biomarkers is crucial for effective risk stratification. Management strategies emphasize lifestyle modifications and the development of targeted pharmacotherapies addressing metabolic and inflammatory pathways. Understanding the interconnected pathogenic mechanisms facilitates personalized interventions to reduce morbidity and improve long-term outcomes. A multidisciplinary approach remains essential to prevent and manage the cardiovascular implications of MAFLD.ME is supported by a National Health and Medical Research Council of Australia (NHMRC) investigator and ideas grants (AAP2008983 and APP2001692). MLY is supported by the “Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung” from The Featured Areas Research Centre Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan, and Center for Liquid Biopsy and Cohort Research KMU-TC109B05, Kaohsiung Medical University. ME, Avustralya Ulusal Sağlık ve Tıbbi Araştırma Konseyi (NHMRC) araştırmacı ve fikir hibeleri (AAP2008983 ve APP2001692) tarafından desteklenmektedir. MLY ise Tayvan Eğitim Bakanlığı (MOE) tarafından yürütülen Yüksek Öğrenim Filiz Projesi kapsamındaki Öne Çıkan Alanlar Araştırma Merkezi Programı kapsamındaki "Metabolik İlişkili Yağlı Karaciğer Hastalığı Mükemmeliyet Merkezi, Kaohsiung Ulusal Sun Yat-sen Üniversitesi" ve Kaohsiung Tıp Üniversitesi Sıvı Biyopsi ve Kohort Araştırma Merkezi (KMU-TC109B05) tarafından desteklenmektedir

    SFNN: A secure and diverse recommender system through graph neural network and regularized variational autoencoder

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    Acknowledgments The authors acknowledge the financial assistance the Algerian Ministry (MESRS) provided for the PRFU Project (PhD Thesis), coded: C00L07UN360120230002. Teşekkür Yazarlar, PRFU Projesi (Doktora Tezi) için Cezayir Bakanlığı (MESRS) tarafından sağlanan mali desteği (kod: C00L07UN360120230002) kabul etmektedir.Recommender systems are frequently improved to filter information and provide users with the most relevant items. However, they face limitations in balancing appropriate and diverse recommendations while ensuring the security and integrity of user data. A new recommender system based on secure fusion neural network is pre sented in this paper. It guarantees data integrity and confidentiality while balancing accuracy and diversity. It integrates a graph neural network that models user-item interactions to improve accuracy, with a regularized variational autoencoder whose evidence lower bound loss function is enhanced by a diversity-promoting regu larization term that favors latent-space dispersion, thereby improving recommendation diversity. To optimize the combination of the two neural networks scores, an adaptive fusion mechanism is introduced to generate final predictions that consider diverse user preferences while maintaining relevance. Furthermore, our approach uses blockchain technology to encrypt and secure data storage, ensuring the integrity and confidentiality of users’ data. The experiments conducted on three datasets show that the proposed model can achieve an accuracy of 78.13 % with an intra-list diversity of 46.82 % for Retail Rocket dataset, an accuracy of 82.44 % with an intra-list diversity of 37.78 % for clothing dataset, and an accuracy of 86.16 % with an intra-list diversity of 47.65 % for MovieLens-1 M dataset

    Lisans hemşirelik öğrencilerinin öznel mutluluk ve akademik katılımları: Korelasyonel bir çalışma

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    Happiness constitutes a fundamental component influencing individuals’ lifelong attitudes and career trajectories. This study aimed to investigate the relationship between subjective happiness and academic engagement among undergraduate nursing students. Employing a descriptive, cross-sectional, and correlational design, the study was conducted with a sample of 350 students. Data were collected through the Subjective Happiness Scale (SHS) and the Utrecht Work Engagement Scale – Short Form for Students (UWES-S-9 ©) and analysed using PSPP version 1.6.2- g78a33a. The mean subjective happiness score was 5.00±1.17, and the mean academic engagement score was 3.75±1.42, indicating moderate levels. Students aged 30 years and older, as well as those with middle or upper-middle income levels, demonstrated significantly higher happiness scores compared to their counterparts aged 20–25 years and those with lower income levels. Furthermore, students who chose the nursing program out of genuine interest and those who indicated a willingness to choose it again exhibited higher scores in both happiness and academic engagement. A significant positive association was observed between subjective happiness and academic engagement. To enhance students’ well-being, implementing social and financial support initiatives, promoting peer mentoring programs, and facilitating experience sharing activities are recommended. Providing comprehensive information about nursing career pathways may also strengthen students’ connection to the profession.Mutluluk, bireylerin yaşam boyu tutumlarını ve kariyer eğilimlerini şekillendiren temel bir unsurdur. Bu araştırma, lisans hemşirelik öğrencilerinin öznel mutluluk düzeyleri ile akademik katılımları arasındaki ilişkiyi incelemeyi amaçlamıştır. Tanımlayıcı, kesitsel ve korelasyonel bir desenle yürütülen çalışma, 350 öğrenci ile gerçekleştirilmiştir. Veriler, Öznel Mutluluk Ölçeği (SHS) ve Utrecht İşe Katılım Ölçeği – Öğrenciler için Kısa Form (UWES-S 9 ©) kullanılarak toplanmış, PSPP 1.6.2-g78a33a sürümü aracılığıyla analiz edilmiştir. Katılımcıların öznel mutluluk ortalama puanı 5,00±1,17, akademik katılım ortalama puanı ise 3,75±1,42 olarak saptanmış; her iki değişken de orta düzeyde bulunmuştur. Yaşı 30 ve üzeri olanlar ile orta veya üst-orta gelir düzeyine sahip öğrenciler, 20–25 yaş aralığındaki ve düşük gelir düzeyindeki akranlarına kıyasla anlamlı düzeyde daha yüksek mutluluk puanları göstermiştir. Ayrıca, hemşirelik bölümünü isteyerek tercih eden ve tekrar seçme eğiliminde olan öğrenciler, hem mutluluk hem de akademik katılım açısından daha yüksek puanlar elde etmiştir. Öznel mutluluk ile akademik katılım arasında anlamlı ve pozitif bir ilişki belirlenmiştir. Öğrenci mutluluğunu desteklemek amacıyla sosyal ve finansal destek mekanizmalarının güçlendirilmesi, akran mentörlük programlarının teşvik edilmesi ve deneyim paylaşımına yönelik etkinliklerin artırılması önerilmektedir. Bunun yanı sıra, hemşirelik mesleğindeki kariyer olanaklarına ilişkin kapsamlı bilgi sağlanması, öğrencilerin mesleğe olan aidiyet duygusunu güçlendirebilir

    Design, synthesis and anti‐influenza virus activity of 4‐tert‐butyl‐n‐(3‐oxo‐1‐thia‐4‐azaspiro[4.5]dec‐4‐yl) benzamide derivatives that target hemagglutinin‐mediated fusion

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    Hemagglutinin (HA) is a viral glycoprotein that mediates influenza virus entry into the host cell and is considered a relevant viral target. We here report the identification of a class of 4‐tert‐butylphenyl‐substituted spirothiazolidinones as HA‐mediated fusion inhibitors with specific activity against influenza A/H3N2 virus. The novel spirocyclic compounds were achieved by using one‐pot cyclocondensation method and the chemical structures were characterized by IR, 1 H NMR, 13C NMR, and elemental analysis. Compound 2c, bearing methyl substitutions at positions 2‐ and 8‐ of the spiro ring displayed an EC50 value against influenza A/H3N2 virus of 1.3 μM and an antiviral selectivity index of 30. The fusion‐inhibiting effect of compound 2c was revealed in the polykaryon assay which is based on cell‐cell fusion when influenza virus H3 HA‐transfected cells are exposed to low pH. Computer‐aided docking was performed to predict the possible binding pocket in the H3 HA trimer. Resistance data and in silico studies indicated that compound 2c has an overlapping binding pocket in the stem region of H3 HA with the known fusion inhibitors TBHQ and arbidol.We would like to thank Professor Gültaze Çapan for sharing expertize in medicinal chemistry. L.N. wishes to thank the team of L. Persoons for dedicated technical assistance. This workstudy was supported by Scientific Research Projects Coordination Unit of Istanbul University (Grant Number: 32246)

    Can blastocyst formation rate play a role as a predictor of PGT-A cycle outcomes?

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    OBJECTIVE To investigate clinical and embryological parameters that may serve as predictors of pregnancy outcomes in preimplantation genetic testing for aneuploidy (PGT-A) cycles. MATERIALS AND METHODS A total of 98 PGT-A cycles at a private in-vitro fertilization (IVF) center between April 2022 and July 2025 were enrolled. Trophectoderm biopsy cases without any known uterine anomalies and endometrial factor are included. Ovulation induction with letrozole (n=29) or hormone replacement therapy (HRT) (n=69) were used for endometrium preparation. Clinical and embryological cycle characteristics are analysed. Blastocyst formation rate (BFR) was calculated as the number of blastocysts per MII, and the euploidy rate refers to euploid embryos per biopsied embryos. Statistical analysis included t-tests or Mann-Whitney U for continuous variables, and Chi-square test for categorical variables. To identify potential confounding factors subgroup analyses and multivariate logistic regression were performed. RESULTS Among the 98 patients, 62 (63.3%) achieved pregnancy and 36 (36.7%) did not. There were no significant differences between the groups regarding age, BMI, total gonadotropin dose, or stimulation duration. Recombinant FSH agents were the most frequently administered (n=38), followed by hMG (n=23), combination of both (n=15) and recombinant FSH+recombinant LH (n=22). Analyzing the pregnancy results, no statistically significance was observed regarding the agents used, (p>0,05). The BFR was significantly higher in the pregnant group (0.36 ± 0.28) compared to the non-pregnant group (0.27 ± 0.24, p = 0.045). The estradiol/oocyte ratio was slightly higher in the pregnant group (319 ± 180 pg/mL) than in the non-pregnant group (287 ± 148 pg/mL), although not statistically significant (p = 0.48). The euploidy rate per was 59.3% (89/150) in the pregnant group and 68.8% (66/96) in the non-pregnant group, being not statistically significant (p = 0.13). Regarding confounding factors (female or male aneuploidy, the type of gonadotropin, the type of endometrial preparation protocol), none of these demonstrated a statistically significant association with pregnancy outcome in either univariate or multivariate models. CONCLUSIONS Given our results, BFRs may predict pregnancy outcomes whereas euploidy rates do not, despite being higher in non-pregnant cases contrary to expectations. IMPACT STATEMENT BFR in PGT-A cycles may help clinicians both to counsel current patients and to shape more individualized management strategies for future cases

    Sex specific knee joint soft tissue mineralization with fibrillin-1 mutation in male tight skin mice

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    Articular soft tissue mineralization and ossification are clear pathological signs of osteoarthritis (OA) joints. However their molecular and cellular aetiologies remain largely unknown. Transforming growth factor beta (TGF-β) family members are known contributors to both pathological ossification and osteoarthritis development. In this study, we used a fibrillin-1 (Fbn1) mutant mouse, the tight skin (TSK) mouse, to define the detrimental effects of abnormal Fbn1 in TSK mice and known high TGF-β activity in joint pathology such as articular soft tissue mineralization and ossification. Methods: Knee joints of male and female TSK and wild-type (WT) littermates were analysed by micro-computed tomography (micro-CT) imaging and histology for articular soft tissue pathologies, as well as OA severity. Both aged (10, 26, 35 and 52 weeks) and following in vivo non-invasive repetitive joint overloading were used. Results: We find that male TSK mice develop spontaneous soft tissue ossification from 26 weeks of age, followed by increased osteoarthritis at 1 year-old. In addition, knee joint overloading induced ligament and meniscal mineralisation and ossification in both WT and TSK male mice, but were significantly more severe in TSK knees, including ossification of the patella ligament and synovial lining. In contrast, female TSK knees did not develop more severe soft tissue mineralisation compared to littermate WT mice in neither aged nor overloaded knees. Conclusions: We conclude that Fbn1 mutation, and possibly overactive TGF-β activity in TSK mice, induce articular soft tissue ossification and osteoarthritis in a sex-specific manner. Further studies are needed to confirm the specific signalling involved and the relative protection from female mice from such pathologies.This research was funded by Arthritis Research UK (20859), Versus Arthritis (22451), Chinese Scholarship Council, the Medical Research Council (MR/X021068/1), The MRC-Arthritis Research UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA), and the Institute of Aging and Chronic Disease (University of Liverpool). Bu araştırma, Arthritis Research UK (20859), Versus Arthritis (22451), Çin Burs Konseyi, Tıbbi Araştırma Konseyi (MR/X021068/1), MRC-Arthritis Research UK Entegre Kas-İskelet Sistemi Yaşlanması Araştırma Merkezi (CIMA) ve Yaşlanma ve Kronik Hastalıklar Enstitüsü (Liverpool Üniversitesi) tarafından finanse edilmiştir

    Dental travma sonucu üst santral dişte oluşan kök kırığının gecikmiş tedavisi: 12 aylık takip

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    AMAÇ Karma dişlenme döneminde dental travmalar oldukça sık görülmekte olup, kron kırıkları en sık karşılaşılan dental travma türüdür. Bu yaralanmalarda tedavi seçenekleri travmanın şiddeti, hastanın yaşı, başvuru süresi, kök gelişim seviyesi ve çevre dokuların durumu gibi çeşitli faktörlere bağlı olarak değişkenlik gösterir. Bu olgu bildiriminde travmatik yaralanma sonucu daimi üst santral dişte gelişen kök kırığının endodontik tedavisi ve 12 aylık takibi sunulmaktadır. OLGU9 yaşında erkek hasta, üst sol santral dişinden kaynaklanan ağrı ve intraoral şişlik nedeniyle kliniğimize başvurmuştur. Hastadan alınan anamnezde 3 ay önce travma nedeni ile üst santral dişlerde kron kırığı meydana geldiği, ancak şikayeti olmadığı için hekime başvurulmadığı, bir hafta önce palatina ve bukkal sulkusu içeren intraoral enfeksiyon gelişmesi sebebiyle devlet hastanesine başvurulduğu ve antibiyotik reçete edilerek bir çocuk diş hekimine yönlendirildiği öğrenilmiştir. Klinik muayenede sağ santral dişin vital olduğu, sol santral dişin ise devital olduğu, apeksi hizasında şişlik ve mobilite olduğu tespit edilmiştir. Radyografik muayenede sağ ve sol üst santral dişlerin kök gelişimini tamamlamadıkları ve sol santral dişin apeksi hizasında radyolüsensi gözlenmiştir. Lokal anestezi altında sol santral dişe endodontik giriş sağlanmasını takiben, kanallar %2,5 NaOCl ile irrige edilimiş ve kök kanalına kalsiyum hidroksit patı yerleştirilmiştir. Aynı seans sağ santral diş geçici olarak restore edilmiştir. 10 gün sonra dişin kök ucu hizasında tekrar intraoral apse görülmesi nedeniyle pansuman yapılmış, tekrar kalsiyum hidroksit patı yerleştirilmiş ve hastaya antibiyotik reçete edilmiştir. 1 hafta sonra şişliğin devam etmesi ve bukkalde 6-7 mm derinliğinde periodontal cep tespit edilmesi nedeniyle aynı seansta cep kürete edilmiş ve kök kırığı şüphesi ile hastadan tomografik görüntüleme talep edilmiştir. Alınan görüntülemede, servikalden kökün orta üçlüsüne uzanan oblik bir kök kırığı tespit edilmiştir. Kanal içindeki mevcut kalsiyum hidroksit uzaklaştırılarak, kök kanalına antibiyotik patı yerleştirilmiştir. 2 hafta sonra intraoral apsede gerileme ve yapışık dişetinde iyileşme gözlenmesi üzerine kök kanalı MTA (Mineral Trioxide Aggregate) ile doldurulmuş, giriş kavitesi kompozit rezinle restore edilmiştir. Bir ay sonra estetik restorasyonlar tamamlanmıştır. 9. ay kontrolünde sol santral dişte herhangi bir klinik ve radyografik patoloji gözlenmezken, sağ santral dişte intraoral apse ve radyografide periapikal bölgede radyolüsensi tespit edilmiştir. Aynı seans kanal tedavisine başlanmış, sonrasında kök kanallarına kalsiyum hidroksit patı yerleştirilmiştir. Bir ay sonra biyoseramik esaslı kanal dolgu patı ve tek kon gutta-perka ile doldurulmuştur. 12 aylık takip sonucunda, klinik semptom gözlenmemiş olup, periradiküler dokularda kemik trabekülasyonunun başladığı izlenmiştir. SONUÇ Dental travma sonrası erken dönemde diş hekimine başvurulmaması ve tedavinin gecikmesi, mevcut tedavi sürecini daha karmaşık hale getirebilir. Özellikle iyileşmeyen ya da tekrarlayan klinik semptomların varlığında, erken tanı ve uygun tedavi planlaması için ileri görüntüleme yöntemlerine başvurulması büyük önem taşımaktadır. Bu nedenle tedavi sonrası takip, tedavinin bir parçasıdır

    GWAS analysis of sudden cardiac death cases in a Turkish population

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    Objective: Sudden death is defined as death occurring within one hour of the onset of symptoms, with cardiovascular diseases being one of the leading causes. The most common genetic factors leading to sudden cardiac death are hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomy6 opathy. In some cases, autopsies may reveal no evidence of long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, or Brugada Syndrome. Materials and Methods: We collected samples from sudden cardiac death cases aged 5–40 years (arrhythmia as Group 1, hypertrophy as Group 2, and ischemic heart disease as Group 3), as well as from healthy athletes (control group as Group 4), and analyzed them using genome6wide association study (GWAS) with a DNA microchip containing 196,725 single nucleotide polymorphism (SNP) markers thought to be associated with sudden cardiac death or other cardiovascular diseases. Results: We detected any possible genetic variations or patterns that could elucidate the mechanisms underlying sudden cardiac death in a Turkish population. In our study group, two polymorphisms; rs2971851 and rs9609516, stood out as prominent variants compared with healthy elite athletes. Conclusion: We aimed to identify potential genetic variations or patterns that could shed light on the mechanisms underlying sudden cardiac death in the Turkish population. In our study group, two poly6 morphisms, rs2971851 and rs9609516, emerged as prominent variants when compared to healthy athletes.This work was financially supported by the Research Fund of Istanbul University (Project No.20852). Bu çalışma, İstanbul Üniversitesi Araştırma Fonu tarafından mali olarak desteklenmiştir (Proje No. 20852)

    Energy production from gas hydrates

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    Gas hydrates are a type of natural formation that contains large amounts of mostly methane, which is also known as natural gas, and water, in the form of ice. Methane hydrates are cages of water molecules that surround and trap methane molecules. Gas hydrate is geophysical, geologically and economically important for several reasons: Gas hydrates are good cap rocks for oil and natural gas. The methane hydrate itself is an important energy source. A volume of gas hydrate can store up to 164 times per volume of gas as zipped gas, and the fact that gas hydrate occurs almost all around the world. Methane seepage may indicate the existence of a deeper hydrocarbon reservoir, and the methane production and migration in the slope sediments may cause massive slope failure. Last but not least Methane gas has a minimum 22 times more global warm absorption capacity compared to carbon dioxide if it is released into the atmosphere. In other words, greenhouse gas is due to its contribution to climate change. Gas hydrates have drawn significant interest as a potential near future energy resource. Research in the production field of gas hydrates has focused on several key areas, including the feasibility of commercial production, the environmental impacts, and the technological improvements associated with the safe recovery of gas

    PRDM6 promoter methylation as a potential epigenetic biomarker in BRCA-associated ovarian cancer

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    Background: Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies, primarily due to late-stage diagnosis. Aberrant DNA methylation is critical in tumorigenesis and represents a promising avenue for biomarker development. We hypothesized that PR/SET domain 6 (PRDM6) methylation is associated with breast cancer gene (BRCA) mutation status in OC. Methods: Peripheral blood samples were collected from 387 patients with high-grade serous ovarian cancer, 50 individuals with benign ovarian conditions, and 100 healthy controls. DNA methylation was evaluated using methylation-sensitive restriction enzymes (MSREs) and subsequently analyzed by real-time polymerase chain reaction (PCR). Descriptive statistics were employed to summarize categorical and continuous variables. Associations between PRDM6 methylation and clinical parameters, including BRCA mutation status, cancer antigen 125 (CA-125) levels, and age, were statistically analyzed. Results: PRDM6 methylation was detected in 53.9% of OC patients, 60.0% of individuals with benign ovarian disease, and 37.0% of healthy controls. The methylation frequency in OC patients was significantly higher than in healthy controls (p = 0.005). PRDM6 promoter methylation was detected in 64.8% of BRCA-mutated OC patients compared to 50.3% of BRCA negative patients, indicating a significant association between BRCA mutation status and PRDM6 methylation (p = 0.016). No significant associations were found between PRDM6 methylation and age, menopausal status, or CA-125 levels. Conclusions: PRDM6 methylation may serve as a non-invasive biomarker for early detection in high risk populations, particularly in BRCA mutation carriers.This study was funded by the Scientific Research Projects Coordination Unit of Istanbul University (Project number: TYL-2021-38160 and TOA-2020-35780). Bu çalışma İstanbul Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından finanse edilmiştir (Proje numarası: TYL-2021-38160 ve TOA-2020-35780)

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