WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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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: 1Tracing the Values of Fading Rural Architectural Heritage: the Case of Cold-Water Baths in Western Anatolia(MDPI, 2025) Guler, Selen; Ustuk, Ozan; Yuceer, HulyaThis research explores the underappreciated traditional cold-water baths of Western Anatolia, once integral to the region's agrarian culture. Due to waves of change, which had markedly begun by the pandemic in 2019 and the aftermath of the 2020 Samos earthquake, there has been a growing interest in living in peri-urban areas, resulting in the invasion of agricultural grounds by new construction, mainly including detached houses with gardens. Such a harsh growth not only threatens the fertile lands, but also the irreplaceable cultural heritage they embrace. In this regional frame, this study focuses on three surviving baths within the Karaburun Peninsula, casting light on their current precarious state as relics of a diminishing rural way of life and local heritage. The traditional cold-water baths, constructed amidst agricultural fields for seasonal use in select villages throughout & Idot;zmir, stand as unique exemplars of rural architecture. Characterised by their singular domed chambers and their reliance on water from adjacent wells, these structures today face abandonment and disrepair. Through a multi-disciplinary lens blending ethnography, oral history, and spatial analysis, this paper portrays these unassuming yet culturally impactful baths, elucidating their intrinsic value within the heritage domain. The inquiry contributes significantly to the heritage conservation discussion, highlighting the broad spectrum of values beyond mere historical interest. By articulating the symbiotic relationship between heritage and its community, this research underscores the pressing need to weave these baths into the fabric of current social structures, safeguarding their place within the collective memory.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.Review Citation - WoS: 19Citation - Scopus: 22Water Dams: From Ancient To Present Times and Into the Future(MDPI, 2024) Angelakis, Andreas N.; Baba, Alper; Valipour, Mohammad; Dietrich, Jorg; Fallah-Mehdipour, Elahe; Krasilnikoff, Jens; Ahmed, Abdelkader T.Since ancient times, dams have been built to store water, control rivers, and irrigate agricultural land to meet human needs. By the end of the 19th century, hydroelectric power stations arose and extended the purposes of dams. Today, dams can be seen as part of the renewable energy supply infrastructure. The word dam comes from French and is defined in dictionaries using words like strange, dike, and obstacle. In other words, a dam is a structure that stores water and directs it to the desired location, with a dam being built in front of river valleys. Dams built on rivers serve various purposes such as the supply of drinking water, agricultural irrigation, flood control, the supply of industrial water, power generation, recreation, the movement control of solids, and fisheries. Dams can also be built in a catchment area to capture and store the rainwater in arid and semi-arid areas. Dams can be built from concrete or natural materials such as earth and rock. There are various types of dams: embankment dams (earth-fill dams, rock-fill dams, and rock-fill dams with concrete faces) and rigid dams (gravity dams, rolled compacted concrete dams, arch dams, and buttress dams). A gravity dam is a straight wall of stone masonry or earthen material that can withstand the full force of the water pressure. In other words, the pressure of the water transfers the vertical compressive forces and horizontal shear forces to the foundations beneath the dam. The strength of a gravity dam ultimately depends on its weight and the strength of its foundations. Most dams built in ancient times were constructed as gravity dams. An arch dam, on the other hand, has a convex curved surface that faces the water. The forces generated by the water pressure are transferred to the sides of the structure by horizontal lines. The horizontal, normal, and shear forces resist the weight at the edges. When viewed in a horizontal section, an arch dam has a curved shape. This type of dam can also resist water pressure due to its particular shape that allows the transfer of the forces generated by the stored water to the rock foundations. This article takes a detailed look at hydraulic engineering in dams over the millennia. Lessons should be learned from the successful and unsuccessful applications and operations of dams. Water resource managers, policymakers, and stakeholders can use these lessons to achieve sustainable development goals in times of climate change and water crisis.Article Iron-Promoted 1,5-Substitution Reaction of Endocyclic Enyne Oxiranes With Memgbr: a Stereoselective Method for the Synthesis of Exocyclic 2,4,5-Trienol Derivatives(MDPI, 2023) Kuş, Melih; Omur, Cenk; Karaca, Sila; Artok, LeventThe iron-promoted 1,5-substitution reaction of endocyclic oxiranes with MeMgBr yields exocyclic 2,4,5-trienols with high diastereomeric ratios of up to 100:0. However, for the method's success, the oxirane ring must have a trans-configuration. The reactions exhibit strong stereoselectivity concerning the methylation mode and the configuration of the resulting exocyclic double bond. Enantiomerically pure enyne oxiranes can be synthesized through Sharpless asymmetric dihydroxylation and subsequent manipulations. With these reagents, it has been possible to produce exocyclic 2,4,5-trienols in enantiopure forms. Importantly, this process maintains chirality without degradation during the center-to-axis transfer of chirality.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: 3Atomic-Scale Insights Into Carbon Dioxide Hydrogenation Over Bimetallic Iron-Cobalt Catalysts: a Density Functional Theory Study(MDPI, 2023) Tuncer, Dilan; Kızılkaya, Ali CanThe conversion of carbon dioxide to fuels and chemicals is a promising long-term approach for mitigating CO2 emissions. Despite extensive experimental efforts, a fundamental understanding of the bimetallic catalytic structures that selectively produce the desired products is still lacking. Here, we report on a computational surface science approach into the effect of the Fe doping of Co(111) surfaces in relation to CO2 hydrogenation to C1 products. Our results indicate that Fe doping increases the binding strength of surface species but slightly decreases the overall catalytic activity due to an increase in the rate-limiting step of CO dissociation. FeCo(111) surfaces hinder hydrogenation reactions due to lower H coverages and higher activation energies. These effects are linked to the Lewis basic character of the Fe atoms in FeCo(111), leading to an increased charge on the adsorbates. The main effect of Fe doping is identified as the inhibition of oxygen removal from cobalt surfaces, which can be expected to lead to the formation of oxidic phases on bimetallic FeCo catalysts. Overall, our study provides comprehensive mechanistic insights related to the effect of Fe doping on the catalytic behavior and structural evolution of FeCo bimetallic catalysts, which can contribute to the rational design of bimetallic catalysts.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.