PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 1Citation - Scopus: 1A Pragmatic Grouping Model for Bone-Only De Novo Metastatic Breast Cancer (MetS Protocol MF22-03)(MDPI, 2025) Goktepe, Berk; Demirors, Berkay; Senol, Kazim; Ozbas, Serdar; Sezgin, Efe; Lucci, Anthony; Soran, AtillaDe novo metastatic breast cancer (dnMBC) accounts for 3-10% of newly diagnosed cases, with 20-40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1-131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25-45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0-3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39-104) for GrA patients and 44 months (28-72) for GrB patients (HR 0.57, 95% CI 0.41-0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259-0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334-0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS.Article Role of Long Non-Coding RNA X-Inactive Transcript (XIST) in Neuroinflammation and Myelination: Insights From Cerebral Organoids and Implications for Multiple Sclerosis(MDPI, 2025) Pepe, Nihan Aktas; Acar, Busra; Zararsiz, Gozde Erturk; Guner, Serife Ayaz; Sen, AlaattinBackground/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer's and Parkinson's diseases and may be a promising therapeutic target.Article Citation - WoS: 1Citation - Scopus: 1Calcium Indicators With Fluorescence Lifetime-Based Signal Readout: a Structure-Function Study(MDPI, 2024) Simonyan, Tatiana R.; Varfolomeeva, Larisa A.; Mamontova, Anastasia V.; Kotlobay, Alexey A.; Gorokhovatsky, Andrey Y.; Bogdanov, Alexey M.; Boyko, Konstantin M.The calcium cation is a crucial signaling molecule involved in numerous cellular pathways. Beyond its role as a messenger or modulator in intracellular cascades, calcium's function in excitable cells, including nerve impulse transmission, is remarkable. The central role of calcium in nervous activity has driven the rapid development of fluorescent techniques for monitoring this cation in living cells. Specifically, genetically encoded calcium indicators (GECIs) are the most in-demand molecular tools in their class. In this work, we address two issues of calcium imaging by designing indicators based on the successful GCaMP6 backbone and the fluorescent protein BrUSLEE. The first indicator variant (GCaMP6s-BrUS), with a reduced, calcium-insensitive fluorescence lifetime, has potential in monitoring calcium dynamics with a high temporal resolution in combination with advanced microscopy techniques, such as light beads microscopy, where the fluorescence lifetime limits acquisition speed. Conversely, the second variant (GCaMP6s-BrUS-145), with a flexible, calcium-sensitive fluorescence lifetime, is relevant for static measurements, particularly for determining absolute calcium concentration values using fluorescence lifetime imaging microscopy (FLIM). To identify the structural determinants of calcium sensitivity in these indicator variants, we determine their spatial structures. A comparative structural analysis allowed the optimization of the GCaMP6s-BrUS construct, resulting in an indicator variant combining calcium-sensitive behavior in the time domain and enhanced molecular brightness. Our data may serve as a starting point for further engineering efforts towards improved GECI variants with fine-tuned fluorescence lifetimes.Article Citation - WoS: 5Citation - Scopus: 6A Comparative Study of Metaheuristic Feature Selection Algorithms for Respiratory Disease Classification(MDPI, 2024) Gürkan Kuntalp, D.; Özcan, N.; Düzyel, Okan; Kababulut, F.Y.; Kuntalp, M.The correct diagnosis and early treatment of respiratory diseases can significantly improve the health status of patients, reduce healthcare expenses, and enhance quality of life. Therefore, there has been extensive interest in developing automatic respiratory disease detection systems. Most recent methods for detecting respiratory disease use machine and deep learning algorithms. The success of these machine learning methods depends heavily on the selection of proper features to be used in the classifier. Although metaheuristic-based feature selection methods have been successful in addressing difficulties presented by high-dimensional medical data in various biomedical classification tasks, there is not much research on the utilization of metaheuristic methods in respiratory disease classification. This paper aims to conduct a detailed and comparative analysis of six widely used metaheuristic optimization methods using eight different transfer functions in respiratory disease classification. For this purpose, two different classification cases were examined: binary and multi-class. The findings demonstrate that metaheuristic algorithms using correct transfer functions could effectively reduce data dimensionality while enhancing classification accuracy. © 2024 by the authors.Article Citation - WoS: 1Citation - Scopus: 1Light-Dark and Activity Rhythm Therapy (l-Dart) To Improve Sleep in People With Schizophrenia Spectrum Disorders: a Single-Group Mixed Methods Study of Feasibility, Acceptability and Adherence(MDPI, 2023) Faulkner, Sophie; Didikoğlu, Altuğ; Byrne, Rory; Drake, Richard; Bee, PennyPeople with a diagnosis of schizophrenia often have poor sleep, even when their psychotic symptoms are relatively well managed. This includes insomnia, sleep apnoea, hypersomnia, and irregular or non-24 h sleep-wake timing. Improving sleep would better support recovery, yet few evidence-based sleep treatments are offered to this group. This paper presents a mixed methods feasibility and acceptability study of Light-Dark and Activity Rhythm Therapy (L-DART). L-DART is delivered by an occupational therapist over 12 weeks. It is highly personalisable to sleep phenotypes and circumstances. Ten participants with schizophrenia spectrum diagnoses and sleep problems received L-DART; their sleep problems and therapy goals were diverse. We measured recruitment, attrition, session attendance, and adverse effects, and qualitatively explored acceptability, engagement, component delivery, adherence, activity patterns, dynamic light exposure, self-reported sleep, wellbeing, and functioning. Recruitment was ahead of target, there was no attrition, and all participants received the minimum 'dose' of sessions. Acceptability assessed via qualitative reports and satisfaction ratings was good. Adherence to individual intervention components varied, despite high participant motivation. All made some potentially helpful behaviour changes. Positive sleep and functioning outcomes were reported qualitatively as well as in outcome measures. The findings above support testing the intervention in a larger randomised trial ISRCTN11998005.Article Citation - WoS: 4Citation - Scopus: 4A New Shapley-Based Feature Selection Method in a Clinical Decision Support System for the Identification of Lung Diseases(MDPI, 2023) Kababulut, Fevzi Yasin; Kuntalp, Damla Gurkan; Düzyel, Okan; Özcan, Nermin; Kuntalp, MehmetThe aim of this study is to propose a new feature selection method based on the class-based contribution of Shapley values. For this purpose, a clinical decision support system was developed to assist doctors in their diagnosis of lung diseases from lung sounds. The developed systems, which are based on the Decision Tree Algorithm (DTA), create a classification for five different cases: healthy and disease (URTI, COPD, Pneumonia, and Bronchiolitis) states. The most important reason for using a Decision Tree Classifier instead of other high-performance classifiers such as CNN and RNN is that the class contributions of Shapley values can be seen with this classifier. The systems developed consist of either a single DTA classifier or five parallel DTA classifiers each of which is optimized to make a binary classification such as healthy vs. others, COPD vs. Others, etc. Feature sets based on Power Spectral Density (PSD), Mel Frequency Cepstral Coefficients (MFCC), and statistical characteristics extracted from lung sound recordings were used in these classifications. The results indicate that employing features selected based on the class-based contribution of Shapley values, along with utilizing an ensemble (parallel) system, leads to improved classification performance compared to performances using either raw features alone or traditional use of Shapley values.Article Citation - WoS: 15Citation - Scopus: 16Formulation of Gluten-Free Cookies Utilizing Chickpea, Carob, and Hazelnut Flours Through Mixture Design(MDPI, 2023) Doğruer, Ilgın; Başer, Filiz; Güleç, Şükrü; Tokatlı, Figen; Özen, BanuLegume flours, which offer high nutritional quality, present viable options for gluten-free bakery products. However, they may have an objectionable flavor and taste for some consumers. In this study, it was aimed to improve the gluten-free cookie formulation by incorporating carob and hazelnut flours to pre-cooked chickpea flour and to investigate the techno-functional properties of the formulated cookies. The flours used in the formulations were assessed for their chemical and physical properties. This study employed a mixture design (simplex-centroid) to obtain the proportions of the flours to be used in the cookie formulations. The rheological characteristics of the doughs and the technological attributes of the baked cookies were determined. The addition of the hazelnut and carob flours had the overall effect of reducing the rheological characteristics of the cookie doughs. Furthermore, the textural attribute of the hardness of the baked cookies decreased as the ratio of hazelnut flour in the formulations was raised. The analysed results and sensory evaluation pointed to a formulation consisting of 30% pre-cooked chickpea/30% carob/30% hazelnut flours, which exhibited improved taste and overall acceptability scores. A total of 16.82 g/100 g of rapidly digestible starch, 5.36 g/100 g of slowly digestible starch, and 8.30 g/100 g of resistant starch exist in this particular cookie. As a result, combinations of chickpea, hazelnut, and carob flours hold promise as good alternatives for gluten-free cookie ingredients and warrant further exploration in the development of similar products.Article Citation - WoS: 16Citation - Scopus: 17Techno-Functional and in Vitro Digestibility Properties of Gluten-Free Cookies Made From Raw, Pre-Cooked, and Germinated Chickpea Flours(MDPI, 2023) Doğruer, Ilgın; Çoban, Başak; Başer, Filiz; Güleç, Şükrü; Özen, BanuChickpea flour, which is produced in various forms, has high protein and fiber content; therefore, it can be a good ingredient for gluten-free cookies. The objective of this study was to investigate and compare the properties of cookies formulated using raw (RCF), cooked (CCF), and germinated (GCF) chickpea flours. The techno-functional properties of these flours were determined, and scanning electron microscope images and mid-infrared spectra were obtained. The rheological properties of cookie doughs were measured along with their mid-infrared spectra. Baked cookies were analyzed for their technological properties as well as their in vitro digestion properties. Sensory analysis was also performed for all the cookies. The most significant difference among the flours was observed in their water retention capacity, and CCF had 119.7% higher water retention capacity compared to RCF. The dough made with CCF had quite different rheological properties from the others. The cookies baked with GCF had the highest baking loss and spread ratio. The CCF-containing cookies had the hardest structure. The cookies made from RCF had a higher resistant starch content followed by the cookies with GCF. All the cookies had similar scores in all aspects tested in the sensory analysis. The use of three different forms of chickpea flour in cookie formulations resulted in products with very different properties; however, their overall acceptability levels were close.Article Citation - WoS: 2Citation - Scopus: 3High-Pressure Processing of Traditional Hardaliye Drink: Effect on Quality and Shelf-Life Extension(MDPI, 2023) Atmaca, Bahar; Demiray, Merve; Akdemir Evrendilek, Gülsün; Bulut, Nurullah; Uzuner, SibelHardaliye, as one of the oldest and lesser known traditional beverages, is produced using red grape pomace from wine production. This drink production is achieved through lactic acid fermentation, with the addition of sour cherry leaves and mustard seeds-either heat-treated, grinded, or whole-in various concentrations. Hardaliye has a very short shelf life; thus, efforts have recently been made to process hardaliye with novel processing technologies in order to achieve shelf-life extension. Therefore, the high-hydrostatic-pressure (HHP) processing of hardaliye was performed to determine its impact on important properties, including in microbial inactivation and shelf-life extension, with respect to a Box-Behnken experimental design. Maximum log reductions of 5.38 & PLUSMN; 0.6, 5.10 & PLUSMN; 0.0, 5.05 & PLUSMN; 0.2, and 4.21 & PLUSMN; 0.0 with HHP were obtained for Brettanomyces bruxellensis, total mesophilic aerobic bacteria, Lactobacillus brevis, and total mold and yeast, respectively. The processing parameters of 490 MPa and 29 & DEG;C for 15 min were found as the optimal conditions, with the response variables of an optical density at 520 nm and the inactivation of L. brevis. The samples processed at the optimal conditions were stored at both 4 and 22 & DEG;C for 228 d. While the non-treated control samples at 4 and 22 & DEG;C were spoiled at 15 and 3 d, the HHP-treated samples were spoiled after 228 and 108 d at 4 and 22 & DEG;C, respectively.Article Citation - WoS: 21Citation - Scopus: 22High-Dose Exposure To Polymer-Coated Iron Oxide Nanoparticles Elicits Autophagy-Dependent Ferroptosis in Susceptible Cancer Cells(MDPI, 2023) Lomphithak, Thanpisit; Helvacıoğlu, Selin; Armenia, Ilaria; Keshavan, Sandeep; Ovejero, Jesus G.; Baldi, Giovanni; Ravagli, Costanza; Grazú, Valeria; Fadeel, BengtFerroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (Fe2O3 and Fe2O3@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (Fe3O4-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 mu g/mL. However, when the cells were exposed to higher concentrations (200-400 mu g/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells.