PubMed İndeksli Yayınlar Koleksiyonu
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Article High Carbohydrate Diet Decreases Microbial Diversity and Increases Il-1β Levels in Mice Colon(Korean Society Food Science & Technology-kosfost, 2024) Ulutas, Mehmet Sefa; Aydin, Erkin; Cebeci, AysunWestern diet is known to contribute to intestinal dysbiosis and the progression of inflammation. Although the Turkish diet has different macronutrient contents, the intestinal inflammatory disease incidences in T & uuml;rkiye are comparable to Western countries. Thus, we hypothesized that high carbohydrate diets also contribute to inflammation of the colon. We compared diets with different macronutrient compositions and investigated their effects on colonic microbiota, cytokine, histology, and tight junction protein levels. High carbohydrate diet caused the lowest microbial diversity and is accompanied by the highest expression of interleukin-1 beta and claudin-1. A low carbohydrate diet with zero fiber resulted in the lowest inflammatory markers as well as the lowest occludin and claudin levels. Overall, our results indicate that carbohydrate and fiber contents of the diets are important contributors to colon health.Article Citation - WoS: 9Citation - Scopus: 10An Answer to Colon Cancer Treatment by Mesenchymal Stem Cell Originated from Adipose Tissue(Mashhad Univ Med Sciences, 2018) Iplik, Elif Sinem; Ertugrul, Baris; Kozanoglu, Ilknur; Baran, Yusuf; Cakmakoglu, BediaObjective(s): Colon cancer is risen up with its complex mechanism that directly impacts on its treatment as well as its common prevalence. Mesenchymal stem cells (MSCs) have been considered as a therapeutic candidate for conventional disease including cancer. In this research, we have focused on apoptotic effects of adipose tissue-derived MSCs in colon cancer. Materials and Methods: MSCs were obtained from adipose tissue and characterized by Flowcytometer using suitable antibodies. MSCs, HT-29, HCT-116, RKO and healthy cell line MRC5 were cultured by different seeding procedure. After cell viability assay, changes in caspase 3 enzyme activity and the level of phosphatidylserine were measured. Results: For cell viability assay, a 48 hr incubation period was chosen to seed all cells together. There was a 1.36-fold decrease in caspase 3 enzyme activity by co-treatment of RKO and MSCs in addition to 2.02-fold decrease in HT-29 and MSCs co-treatment, and 1.103-fold increase in HCT-116 and MSCs. The results demonstrated that HCT-116 led to the highest rate of apoptotic cell death (7.5%) compared with other cells. Conclusion: We suggest that MSCs might remain a new treatment option for cancer by its differentiation and repair capacity.Article Citation - WoS: 21Citation - Scopus: 23Photonic-Lantern Coherent LIDAR System(Optical Soc Amer, 2015) Ozdur, Ibrahim; Toliver, Paul; Woodward, T. K.In this work, a photonic-lantern-based coherent LIDAR system is experimentally demonstrated and the voltage signal-to-noise ratio improvement is analyzed. A voltage signal-to-noise ratio (SNRV) improvement of 2.8 is demonstrated experimentally for photonic-lantern-based coherent receivers relative to single-mode coherent receivers. The voltage signal-to-noise ratio improvement is obtained when other parameters are kept constant. We have also analyzed the effect of random optical power distribution among the single-mode fibers. We found that the distribution does not significantly impact the SNRV improvement. The mean value of voltage signal-to-noise ratio improvement is found to be similar to 2.4. (C) 2015 Optical Society of AmericaArticle Citation - WoS: 31Citation - Scopus: 33Discovery of Adapalene and Dihydrotachysterol as Antiviral Agents for the Omicron Variant of SARS-CoV-2 Through Computational Drug Repurposing(Springer, 2023) Fidan, Ozkan; Mujwar, Somdutt; Kciuk, MateuszSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been significantly paralyzing the societies, economies and health care systems around the globe. The mutations on the genome of SARS-CoV-2 led to the emergence of new variants, some of which are classified as "variant of concern" due to their increased transmissibility and better viral fitness. The Omicron variant, as the latest variant of concern, dominated the current COVID-19 cases all around the world. Unlike the previous variants of concern, the Omicron variant has 15 mutations on the receptor-binding domain of spike protein and the changes in the key amino acid residues of S protein can enhance the binding ability of the virus to hACE2, resulting in a significant increase in the infectivity of the Omicron variant. Therefore, there is still an urgent need for treatment and prevention of variants of concern, particularly for the Omicron variant. In this study, an in silico drug repurposing was conducted through the molecular docking of 2890 FDA-approved drugs against the mutant S protein of SARS-CoV-2 for Omicron variant. We discovered promising drug candidates for the inhibition of alarming Omicron variant such as quinestrol, adapalene, tamibarotene, and dihydrotachysterol. The stability of ligands complexed with the mutant S protein was confirmed using MD simulations. The lead compounds were further evaluated for their potential use and side effects based on the current literature. Particularly, adapalene, dihydrotachysterol, levocabastine and bexarotene came into prominence due to their non-interference with the normal physiological processes. Therefore, this study suggests that these approved drugs can be considered as drug candidates for further in vitro and in vivo studies to develop new treatment options for the Omicron variant of SARS-CoV-2. [GRAPHICS] .Article Citation - WoS: 18Citation - Scopus: 20Optimization Study on Surface Roughness and Tribological Behavior of Recycled Cast Iron Reinforced Bronze MMCs Produced by Hot Pressing(MDPI, 2021) Gunes, Aydin; Sahin, Omer Sinan; Duzcukoglu, Hayrettin; Salur, Emin; Aslan, Abdullah; Kuntoglu, Mustafa; Pimenov, Danil YurievichSurface roughness reflects the quality of many operational parameters, namely service life, wear characteristics, working performance and tribological behavior of the produced part. Therefore, tribological performance is critical for the components used as tandem parts, especially for the MMCs (Metal Matrix Composites) which are a unique class of materials having extensive application areas such as aerospace, aeronautics, marine engineering and the defense industry. Current work covers the optimization study of production parameters for surface roughness and tribological indicators of newly produced cast iron reinforced bronze MMCs. In this context, two levels of temperature (400 and 450 degrees C), three levels of pressure (480, 640 and 820 MPa) and seven levels of reinforcement ratios (60/40, 70/30, 80/20, 90/10, 100/0 of GGG40/CuSn10, pure bronze-as received and pure cast iron-as received) are considered. According to the findings obtained by Taguchi's signal-to-noise ratios, the reinforcement ratio has a dominant effect on surface roughness parameters (Ra and Rz), the coefficient of friction and the weight loss in different levels. In addition, 100/0 reinforced GGG40/CuSn10 gives minimum surface roughness, pure cast iron provides the best weight loss and pure bronze offers the desired coefficient of friction. The results showed the importance of material ingredients on mechanical properties by comparing a wide range of samples from starting the production phase, which provides a perspective for manufacturers to meet the market supply as per human requirements.Article Citation - WoS: 2Citation - Scopus: 1Computational Prediction of MicroRNAs in Histoplasma Capsulatum(Academic Press Ltd- Elsevier Science Ltd, 2020) Demirci, Mueserref Duygu SagarMicroRNAs (miRNAs) are small and non-coding RNAs that regulate gene expression through post-transcriptional regulation. Although, the standard miRNA repository, MiRBase, lists more than 200 organisms having miRNA mediated regulation mechanism and thousands of miRNAs, there is not enough information about miRNAs of fungal species. Considering that there are various fungal pathogens causing disease phenotypes, it is important to search for miRNAs of those organisms. The leading cause of endemic mycosis in the USA is a fungal disease known as histoplasmosis, which is resulted by infection with a fungal intracellular parasite, Histoplasma capsulatum (H. capsulatum). In this work, genomes of H. capsulatum strains NAm1 and G217B were explored for potential miRNA like sequences and structures. Through a complex workflow involving miRNA detection and target prediction, several miRNA candidates of H. capsulatum and their possible targets in human were identified. The results presented here indicate that H. capsulatum might be one of the fungal pathogens having a miRNA based post-transcriptional gene regulation mechanism and it might have a miRNA mediated host - parasite interaction with human.Article Citation - WoS: 16Citation - Scopus: 18Recent Advances in Machine Learning for Network Automation in the O-RAN(MDPI, 2023) Hamdan, Mutasem Q.; Lee, Haeyoung; Triantafyllopoulou, Dionysia; Borralho, Ruben; Kose, Abdulkadir; Amiri, Esmaeil; Tafazolli, RahimThe evolution of network technologies has witnessed a paradigm shift toward open and intelligent networks, with the Open Radio Access Network (O-RAN) architecture emerging as a promising solution. O-RAN introduces disaggregation and virtualization, enabling network operators to deploy multi-vendor and interoperable solutions. However, managing and automating the complex O-RAN ecosystem presents numerous challenges. To address this, machine learning (ML) techniques have gained considerable attention in recent years, offering promising avenues for network automation in O-RAN. This paper presents a comprehensive survey of the current research efforts on network automation usingML in O-RAN.We begin by providing an overview of the O-RAN architecture and its key components, highlighting the need for automation. Subsequently, we delve into O-RAN support forML techniques. The survey then explores challenges in network automation usingML within the O-RAN environment, followed by the existing research studies discussing application of ML algorithms and frameworks for network automation in O-RAN. The survey further discusses the research opportunities by identifying important aspects whereML techniques can benefit.Article A Potential Hemostatic Chitosan/Gelatin Cryogel Impregnated with Verbascum Thapsus Leaf Extract for Noncompressible Hemorrhage Management(IOP Publishing Ltd, 2025) Uzuner, Hacernur; Yuruk, Adile; Isoglu, Ismail AlperIn this study, we prepared a series of chitosan/gelatin (CS/GEL) cryogels containing Verbascum thapsus (V. thapsus) leaf extract and identified a lead formulation for noncompressible hemorrhage (NCH). Cryogels with average pore diameters ranging from 225 to 478 mu m were fabricated through cryogelation at various CS/GEL ratios. C15 was chosen as the base scaffold due to its homogeneous pore distribution, with a pore size coefficient of variation (CV) of approximately 0.22. Extract loading was 1%, 5%, 10%, and 20% w/v. Functional porosity was reported by the relative accessible void index (RAVI). In PBS, the values relative to neat C15 were 1.00, 0.27, 0.20, 0.13, and 0.09 for concentrations of 0%, 1%, 5%, 10%, and 20% w/v, respectively. In citrated blood, the series was 1.00, 0.29, 0.12, 0.14, and 0.09. After loading, equilibrium swelling decreased and the compressive modulus increased, consistent with partial pore filling in a fixed network. The cryogels maintained an interconnected macroporous network and showed swelling from 300% to 3600% in blood and PBS. Antibacterial activity reached 89% inhibition, and cell viability remained above 80%. Hemolysis was low and within acceptance limits. Clotting improved in whole blood as the blood clotting index decreased from 11.9 to 6.5, and the clotting time was approximately 6 min. The 5% w/v group provided the optimal balance of clotting, antibacterial effects, and biocompatibility. This study presents a novel hemostatic CS/GEL cryogel containing V. thapsus leaf extract that holds strong potential for future applications in NCH management.Article Citation - WoS: 12Citation - Scopus: 144D-QSAR Investigation and Pharmacophore Identification of Pyrrolo[2,1-C][1,4]Benzodiazepines Using Electron Conformational-Genetic Algorithm Method(Taylor & Francis Ltd, 2016) Ozalp, A.; Yavuz, S. C.; Sabanci, N.; Copur, F.; Kokbudak, Z.; Saripinar, E.In this paper, we present the results of pharmacophore identification and bioactivity prediction for pyrrolo[2,1-c][1,4]benzodiazepine derivatives using the electron conformational-genetic algorithm (EC-GA) method as 4D-QSAR analysis. Using the data obtained from quantum chemical calculations at PM3/HF level, the electron conformational matrices of congruity (ECMC) were constructed by EMRE software. The ECMC of the lowest energy conformer of the compound with the highest activity was chosen as the template and compared with the ECMCs of the lowest energy conformer of the other compounds within given tolerances to reveal the electron conformational submatrix of activity (ECSA, i.e. pharmacophore) by ECSP software. A descriptor pool was generated taking into account the obtained pharmacophore. To predict the theoretical activity and select the best subset of variables affecting bioactivities, the nonlinear least square regression method and genetic algorithm were performed. For four types of activity including the GI(50), TGI, LC50 and IC50 of the pyrrolo[2,1-c][1,4] benzodiazepine series, the r(train)(2), r(test)(2) and q(2) values were 0.858, 0.810, 0.771; 0.853, 0.848, 0.787; 0.703, 0.787, 0.600; and 0.776, 0.722, 0.687, respectively.Article Neuroinflammatory Human Brain Organoids Enable Comprehensive Drug Screening Studies: Fingolimod and Its Analogues in Focus(Bentham Science Publishing Ltd, 2026) Acar, Busra; Pepe, Nihan Aktas; Zivkovic, Aleksandra; Stark, Holger; Sen, AlaattinIntroduction The absence of physiologically relevant models for neuroinflammatory brain disorders, such as multiple sclerosis (MS), highlights the need for improved drug screening platforms. To bridge this gap, this study aimed to develop a human brain organoid (hBO) model incorporating essential neural cell types, including astrocytes, microglia, and oligodendrocytes.Methods hBOs were generated from H9 stem cells, and neuroinflammatory characteristics were elicited by lipopolysaccharide (LPS). The expression of specific neuronal and inflammatory markers was assessed through qRT-PCR, immunofluorescence staining (IFS), and ELISA.Results IFS of mature hBOs with anti-SOX2, anti-SATB2, anti-MAPT, anti-GFAP, anti-MBP, and anti-IBA1 antibodies and images collected with the confocal microscope confirmed the differentiation of H9 cells into cortical neurons, astrocytes, microglia, and oligodendrocyte cell types. Elevated GFAP, IBA1, NF-kappa B, and IL-6 levels, along with reduced CNPase expression with LPS treatment, were considered reflective of MS-like pathology and were used to test fingolimod and its derivatives. Fingolimod and all its derivatives, specifically ST-1505, decreased MAPT (2.1-fold in ELISA, 1.7-fold in IFS), GFAP (1.8-fold in IFS), TNF alpha (5.4-fold in qRT-PCR), and FABP (1.5-fold in ELISA) levels, and increased IL-10 (11-fold in qRT-PCR) and MBP (2.9-fold in IFS) levels.Discussion The present data collectively showed LPS to evoke neuroinflammation in the hBO model, while fingolimod and its derivatives, particularly ST-1505, exhibited significant anti-inflammatory and neuroprotective properties by counteracting these evoked changes in the hBO model.Conclusion The findings supported the applicability of brain organoids as a model system for drug screening studies for neuroinflammatory brain diseases.Article Citation - Scopus: 1The Impact of Knitted Linked Seams on Comfort and Friction Perception(Taylor & Francis Ltd, 2024) Temel, Mevra; Scott, Eleanor; Cain, Rebecca; Johnson, Andrew A.Friction from knitted clothing can cause discomfort and skin issues, underscoring the importance of tactile comfort for wearers. Seamless knitted garments are assumed to be comfortable to wear, yet there is little understanding of their tactile comfort in comparison to linked seams - the most common form of knitted garment. This novel study examines the influence of a garments knitted structural architecture on clothing comfort and wearability by investigating skin friction and tactile perception across ten body regions in both male and female participants, using two commonly utilised materials and seam designs: cotton and merino wool with plain and linked seams. The impact of seam design and regional factors on skin friction and tactile perception was analysed, revealing varying levels across tested body regions. Removing seams exposed a greater surface area to skin contact, leading to higher perceived friction levels. As such, structural elements in knitted garments enhance wearer comfort. Seamless knitwear manufacturing offers a more environmentally conscious option compared to traditional cut-and-sew processes. This study investigated the impact of knitted garment material and structure on wearer comfort by analysing skin friction and tactile perception across ten upper body regions. Removing seams increased garment-to-skin contact leading to wearer discomfort.Article Citation - Scopus: 1Image Processing Methodology for Patient-Specific Instrument Design(Wiley, 2020) Mohammad Sadeghi, Majid; Kececi, Emin FarukBackground Patient-specific instrumentation (PSI) improves accuracy of surgical operations. PSI needs software for preoperative planning and instrument design. In this study, we explain the methodology of developing a software tool for PSI guide design and preoperative planning in reverse shoulder arthroplasty (RSA). Methods Approaches used to prepare input data, transform them into meaningful features and use of those features to create special guide geometries are explained by describing different algorithms and libraries. Results The developed software is tested on three different patients' data. Preoperative planning is performed and guides designed by software and the patients' bones are manufactured and tested for RSA. The method of building a software is presented to do the preoperative planning and designing specific guides for each patient are shown to be properly functional. Conclusions This study proves processes in the development of the PSI software and the design of a specific guide for RSA.Article Citation - WoS: 26Citation - Scopus: 31miRcorrNet: Machine Learning-Based Integration of miRNA and mRNA Expression Profiles, Combined with Feature Grouping and Ranking(PeerJ Inc., 2021) Yousef, M.; Göy, G.; Mitra, R.; Eischen, C.M.; Jabeer, A.; Bakir-Güngör, B.A better understanding of disease development and progression mechanisms at the molecular level is critical both for the diagnosis of a disease and for the development of therapeutic approaches. The advancements in high throughput technologies allowed to generate mRNA and microRNA (miRNA) expression profiles; and the integrative analysis of these profiles allowed to uncover the functional effects of RNA expression in complex diseases, such as cancer. Several researches attempt to integrate miRNA and mRNA expression profiles using statistical methods such as Pearson correlation, and then combine it with enrichment analysis. In this study, we developed a novel tool called miRcorrNet, which performs machine learning-based integration to analyze miRNA and mRNA gene expression profiles. miRcorrNet groups mRNAs based on their correlation to miRNA expression levels and hence it generates groups of target genes associated with each miRNA. Then, these groups are subject to a rank function for classification. We have evaluated our tool using miRNA and mRNA expression profiling data downloaded from The Cancer Genome Atlas (TCGA), and performed comparative evaluation with existing tools. In our experiments we show that miRcorrNet performs as good as other tools in terms of accuracy (reaching more than 95% AUC value). Additionally, miRcorrNet includes ranking steps to separate two classes, namely case and control, which is not available in other tools. We have also evaluated the performance of miRcorrNet using a completely independent dataset. Moreover, we conducted a comprehensive literature search to explore the biological functions of the identified miRNAs. We have validated our significantly identified miRNA groups against known databases, which yielded about 90% accuracy. Our results suggest that miRcorrNet is able to accurately prioritize pan-cancer regulating high-confidence miRNAs. miRcorrNet tool and all other supplementary files are available at https://github.com/ malikyousef/miRcorrNet. © 2021 Elsevier B.V., All rights reserved.Article Citation - WoS: 20Citation - Scopus: 24miRdisNET: Discovering MicroRNA Biomarkers That Are Associated With Diseases Utilizing Biological Knowledge-Based Machine Learning(Frontiers Media S.A., 2023) Jabeer, Amhar; Temiz, Mustafa; Bakir-Gungor, Burcu; Yousef, MalikDuring recent years, biological experiments and increasing evidence have shown that MicroRNAs play an important role in the diagnosis and treatment of human complex diseases. Therefore, to diagnose and treat human complex diseases, it is necessary to reveal the associations between a specific disease and related miRNAs. Although current computational models based on machine learning attempt to determine miRNA-disease associations, the accuracy of these models need to be improved, and candidate miRNA-disease relations need to be evaluated from a biological perspective. In this paper, we propose a computational model named miRdisNET to predict potential miRNA-disease associations. Specifically, miRdisNET requires two types of data, i.e., miRNA expression profiles and known disease-miRNA associations as input files. First, we generate subsets of specific diseases by applying the grouping component. These subsets contain miRNA expressions with class labels associated with each specific disease. Then, we assign an importance score to each group by using a machine learning method for classification. Finally, we apply a modeling component and obtain outputs. One of the most important outputs of miRdisNET is the performance of miRNA-disease prediction. Compared with the existing methods, miRdisNET obtained the highest AUC value of .9998. Another output of miRdisNET is a list of significant miRNAs for disease under study. The miRNAs identified by miRdisNET are validated via referring to the gold-standard databases which hold information on experimentally verified MicroRNA-disease associations. miRdisNET has been developed to predict candidate miRNAs for new diseases, where miRNA-disease relation is not yet known. In addition, miRdisNET presents candidate disease-disease associations based on shared miRNA knowledge. The miRdisNET tool and other supplementary files are publicly available at: .Article Citation - WoS: 8Citation - Scopus: 8Thermo-Responsive Complexes of c-Myc Antisense Oligonucleotide With Block Copolymer of Poly(OEGMA) and Quaternized Poly(4-Vinylpyridine)(Wiley-VCH Verlag GmbH, 2017) Topuzogullari, Murat; Elalmis, Yeliz Basaran; Isoglu, Sevil DincerSolution behavior of thermo-responsive polymers and their complexes with biological macromolecules may be affected by environmental conditions, such as the concentration of macromolecular components, pH, ion concentration, etc. Therefore, a thermo-responsive polymer and its complexes should be characterized in detail to observe their responses against possible environments under physiological conditions before biological applications. To briefly indicate this important issue, thermo-responsive block copolymer of quaternized poly(4-vinylpyridine) and poly(oligoethyleneglycol methyl ether methacrylate) as a potential nonviral vector has been synthesized. Polyelectrolyte complexes of this copolymer with the antisense oligonucleotide of c-Myc oncogene are also thermo-responsive but, have lower LCST (lower critical solution temperature) values compared to individual copolymer. LCST values of complexes decrease with molar ratio of macromolecular components and presence of salt. Dilution of solutions also affects solution behavior of complexes and causes a significant decrease in size and an increase in LCST, which indicates possible effects of severe dilutions in the blood stream.Article Citation - WoS: 16Citation - Scopus: 18Microfluidic Chip Based Direct Triple Antibody Immunoassay for Monitoring Patient Comparative Response to Leukemia Treatment(Springer, 2020) Icoz, Kutay; Akar, Unal; Unal, EkremWe report a time and cost-efficient microfluidic chip for screening the leukemia cells having three specific antigens. In this method, the target blast cells are double sorted with immunomagnetic beads and captured by the 3rd antibody immobilized on the gold surface in a microfluidic chip. The captured blast cells in the chip were imaged using a bright-field optical microscope and images were analyzed to quantify the cells. First sorting was performed with nano size immunomagnetic beads and followed by 2nd sorting where micron size immunomagnetic beads were used. The low-cost microfluidic platform is made of PMMA and glass including micro size gold pads. The developed microfluidic platform was optimized with cultured B type lymphoblast cells and tested with the samples of leukemia patients. The 8 bone marrow samples of 4 leukemia patients on the initial diagnosis and on the 15th day after the start of the chemotherapy treatment were tested both with the developed microfluidic platform and the flow cytometry. A 99% statistical agreement between the two methods shows that the microfluidic chip is able to monitor the decrease in the number of blast cells due to the chemotherapy. The experiments with the patient samples demonstrate that the developed system can perform relative measurements and have a potential to monitor the patient response to the applied therapy and to enable personalized dose adjustment.Article Citation - WoS: 30Citation - Scopus: 31Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches(Dove Medical Press Ltd, 2022) Tecik, Melisa; Adan, AysunFMS-like tyrosine kinase 3 (FLT3) is mutated in approximately 30% of acute myeloid leukemia (AML) patients. The presence of FLT3-ITD (internal tandem duplication, 20-25%) mutation and, to a lesser extent, FLT3-TKD (tyrosine kinase domain, 5- 10%) mutation is associated with poorer diagnosis and therapy response since the leukemic cells become hyperproliferative and resistant to apoptosis after continuous activation of FLT3 signaling. Targeting FLT3 has been the focus of many pre-clinical and clinical studies. Hence, many small-molecule FLT3 inhibitors (FLT3is) have been developed, some of which are approved such as midostaurin and gilteritinib to be used in different clinical settings, either in combination with chemotherapy or alone. However, many questions regarding the best treatment strategy remain to be answered. On the other hand, various FLT3-dependent and -independent resistance mechanisms could be evolved during FLT3i therapy which limit their clinical impact. Therefore, identifying molecular mechanisms of resistance and developing novel strategies to overcome this obstacle is a current interest in the field. In this review, recent studies of approved FLT3i and knowledge about major resistance mechanisms of clinically approved FLT3i's will be discussed together with novel treatment approaches such as designing novel FLT3i and dual FLT3i and combination strategies including approved FLT3i plus small-molecule agents targeting altered molecules in the resistant cells to abrogate resistance. Moreover, how to choose an appropriate FLT3i for the patients will be summarized based on what is currently known from available clinical data. In addition, strategies beyond FLT3i's including immunotherapeutics, small-molecule FLT3 degraders, and flavonoids will be summarized to highlight potential alternatives in FLT3-mutated AML therapy.Article The Need for Death Pedagogy: Academics' Opinions on the Place of Death in the Curricula(Routledge Journals, Taylor & Francis Ltd, 2025) Sonbul, Zeynep FundaThis paper seeks to explore the opinions of educational sciences academics on how death pedagogy should be integrated into curricula across preschool, primary, secondary, and high school levels. The sample comprises academics specializing in educational sciences, who have conducted at least two studies on death, loss, and bereavement, and are affiliated with various universities in T & uuml;rkiye. Seven academics responded to six open-ended questions, and their qualitative responses were analyzed. The results indicated unanimous support for including death pedagogy in the formal curriculum. Key implementation considerations include: (a) collaborating with experts to define the content, methods, and scope; (b) providing comprehensive training for all teachers on the subject and offering additional support for those grappling with their own mortality; (c) ensuring that school counselors play a central role in all phases of planning, implementation, and evaluation; and (d) highlighting the significance of death pedagogy in fostering students' psychological resilience.Article Citation - WoS: 53Citation - Scopus: 55Bond Energies of ThO+ and ThC+: A Guided Ion Beam and Quantum Chemical Investigation of the Reactions of Thorium Cation With O2 and CO(AIP Publishing, 2016) Cox, Richard M.; Citir, Murat; Armentrout, P. B.; Battey, Samuel R.; Peterson, Kirk A.Kinetic energy dependent reactions of Th+ with O-2 and CO are studied using a guided ion beam tandem mass spectrometer. The formation of ThO+ in the reaction of Th+ with O-2 is observed to be exothermic and barrierless with a reaction efficiency at low energies of k/k(LGS) = 1.21 +/- 0.24 similar to the efficiency observed in ion cyclotron resonance experiments. Formation of ThO+ and ThC+ in the reaction of Th+ with CO is endothermic in both cases. The kinetic energy dependent cross sections for formation of these product ions were evaluated to determine 0 K bond dissociation energies (BDEs) of D-0(Th+-O) = 8.57 +/- 0.14 eV and D-0(Th+-C) = 4.82 +/- 0.29 eV. The present value of D-0(Th+-O) is within experimental uncertainty of previously reported experimental values, whereas this is the first report of D-0(Th+-C). Both BDEs are observed to be larger than those of their transition metal congeners, TiL+, ZrL+, and HfL+ (L = O and C), believed to be a result of lanthanide contraction. Additionally, the reactions were explored by quantum chemical calculations, including a full Feller-Peterson-Dixon composite approach with correlation contributions up to coupled-cluster singles and doubles with iterative triples and quadruples (CCSDTQ) for ThC, ThC+, ThO, and ThO+, as well as more approximate CCSD with perturbative (triples) [CCSD(T)] calculations where a semi-empirical model was used to estimate spin-orbit energy contributions. Finally, the ThO+ BDE is compared to other actinide (An) oxide cation BDEs and a simple model utilizing An(+) promotion energies to the reactive state is used to estimate AnO(+) and AnC(+) BDEs. For AnO(+), this model yields predictions that are typically within experimental uncertainty and performs better than density functional theory calculations presented previously. Published by AIP Publishing.Article Citation - WoS: 6Citation - Scopus: 8Histone Deacetylase Inhibition and Autophagy Modulation Induces a Synergistic Antiproliferative Effect and Cell Death in Cholangiocarcinoma Cells(Amer Chemical Soc, 2023) Yenigul, Munevver; Akcok, Emel Basak GencerCholangiocarcinoma, also known as biliary tract cancer,is an aggressiveadenocarcinoma arising from epithelial cells lining the intra- andextrahepatic biliary system. The effects of autophagy modulators andhistone deacetylase (HDAC) inhibitors in cholangiocarcinoma are notfully known. It is essential to understand the molecular mechanismsand the effects of HDAC inhibitors in the context of cholangiocarcinoma.The antiproliferative effect of different HDAC inhibitors and autophagymodulation was investigated by the MTT cell viability assay in TFK-1and EGI-1 cholangiocarcinoma cell lines. Combination indexes werecalculated using CompuSyn software. Consequently, apoptosis was detectedby Annexin V/PI staining. The effect of the drugs on the cell cyclewas measured by the propidium iodide staining. The HDAC inhibitionwas confirmed via acetylated histone protein levels by western blotting.HDAC inhibitors, MS-275 and romidepsin, showed a better synergisticeffect with the nocodazole combination. The combination treatmentexerted its growth inhibitory effect by cell cycle arrest and inductionof apoptosis. The cell cycle analysis of the combination treatmentshowed that the S phase and G2/M phase were achieved. Moreover, thenecrotic and apoptotic cell population increased after single HDACinhibitors and combination treatment. The anti-cancer effect of HDACinhibitors is revealed by acetylation levels of histones. While acetylationlevels were increased in response to HDAC inhibitors and autophagymodulator combinations, the HDAC expression decreased. This studyhighlights the importance of the combination of HDAC inhibition andautophagy modulators and demonstrates a synergistic effect, whichcould be a promising therapy and novel treatment approach for cholangiocarcinoma.
