Browsing by Subject "Diagnosis"

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Open Access
Akut koroner sendromların otomatik ST/T sınıflandırıcısı ile erken tanısı
(IEEE, 2014-10) Terzi, M. Begüm; Arıkan, Orhan; Abacı, A.; Candemir, M.; Dedoğlu, Mehmet
In patients with acute coronary syndrome, temporary chest pains together with changes in ECG ST segment and T wave occur shortly before the start of myocardial infarction. In order to diagnose acute coronary syndromes early, a new technique which detects changes in ECG ST/T sections is developed. As a result of implementing the developed technique to real ECG recordings, it is shown that the proposed technique provides reliable detections. Therefore, the developed technique is expected to provide early diagnosis of acute coronary syndromes which will lead to a significant decrease in heart failure and mortality rates. © 2014 IEEE.
Open Access
All-fiber nanosecond laser system generating supercontinuum spectrum for photoacoustic imaging
(IEEE, 2013) Yavas, S.; Kipergil, E. A.; Akçaalan, Önder; Eldeniz, Y. Burak; Arabul, U.; Erkol H.; Unlu, M.B.; Ilday, F. Ömer
Photoacoustic microscopy (PAM) research, as an imaging modality, has shown promising results in imaging angiogenesis and cutaneous malignancies like melanoma, revealing systemic diseases including diabetes, hypertension, coronery artery, cardiovascular disease from their effect on the microvasculature, tracing drug efficiency and assessment of therapy, monitoring healing processes such as wound cicatrization, brain imaging and mapping, neuroscientific evaluations. Clinically, PAM can be used as a diagnostic and predictive medicine tool; even have a part in disease prevention[1]. © 2013 IEEE.
Open Access
Amphiphilic peptide coated superparamagnetic iron oxide nanoparticles for in vivo MR tumor imaging
(Royal Society of Chemistry, 2016) Ozdemir, A.; Ekiz, M. S.; Dilli, A.; Güler, Mustafa O.; Tekinay, A. B.
Magnetic resonance imaging (MRI) is a noninvasive imaging technique that provides high spatial resolution and depth with pronounced soft-tissue contrast for in vivo imaging. A broad variety of strategies have been employed to enhance the diagnostic value of MRI and detect tissue abnormalities at an earlier stage. Superparamagnetic iron oxide nanoparticles (SPIONs) are considered to be suitable candidates for effective imaging due to their small size, versatile functionality and better biocompatibility. Here, we demonstrate that coating SPIONs with proline-rich amphiphilic peptide molecules through noncovalent interactions leads to a water-dispersed hybrid system suitable as an MRI contrast agent. Cellular viability and uptake of amphiphilic peptide coated SPIONs (SPION/K-PA) were evaluated with human vascular endothelial cells (HUVEC) and estrogen receptor (ER) positive human breast adenocarcinoma (MCF-7) cells. The efficiency of SPION/K-PA as MRI contrast agents was analyzed in Sprague-Dawley rats with mammary gland tumors. MR imaging showed that SPION/K-PA effectively accumulated in tumor tissues, enhancing their imaging potential. Although nanoparticles were observed in reticuloendothelial system organs (RES) and especially in the liver and kidney immediately after administration, the MR signal intensity in these organs diminished after 1 h and nanoparticles were subsequently cleared from these organs within two weeks. Histological observations also validated the accumulation of nanoparticles in tumor tissue at 4 h and their bioelimination from the organs of both healthy and tumor-bearing rats after two weeks.
Open Access
Atomic force microscopy for the investigation of molecular and cellular behavior
(Elsevier, 2016-10) Ozkan A.D.; Topal, A. E.; Dana, A.; Güler, Mustafa O.; Tekinay, A. B.
The present review details the methods used for the measurement of cells and their exudates using atomic force microscopy (AFM) and outlines the general conclusions drawn by the mechanical characterization of biological materials through this method. AFM is a material characterization technique that can be operated in liquid conditions, allowing its use for the investigation of the mechanical properties of biological materials in their native environments. AFM has been used for the mechanical investigation of proteins, nucleic acids, biofilms, secretions, membrane bilayers, tissues and bacterial or eukaryotic cells; however, comparison between studies is difficult due to variances between tip sizes and morphologies, sample fixation and immobilization strategies, conditions of measurement and the mechanical parameters used for the quantification of biomaterial response. Although standard protocols for the AFM investigation of biological materials are limited and minor differences in measurement conditions may create large discrepancies, the method is nonetheless highly effective for comparatively evaluating the mechanical integrity of biomaterials and can be used for the real-time acquisition of elasticity data following the introduction of a chemical or mechanical stimulus. While it is currently of limited diagnostic value, the technique is also useful for basic research in cancer biology and the characterization of disease progression and wound healing processes.
Open Access
Demographics, treatment and outcomes of atrial fibrillation in a developing country: the population-based TuRkish Atrial Fibrillation (TRAF) cohort
(Oxford University Press, 2017) Yavuz, B.; Ata, N.; Oto, E.; Katircioglu-Öztürk, D.; Aytemir, K.; Evranos, B.; Koselerli, R.; Ertugay, E.; Burkan, A.; Ertugay, E.; Gale, C. P.; Camm, A. J.; Oto, A.
Aims: Although atrial fibrillation (AF) is increasingly common in developed countries, there is limited information regarding its demographics, co-morbidities, treatments and outcomes in the developing countries. We present the profile of the TuRkish Atrial Fibrillation (TRAF) cohort which provides real-life data about prevalence, incidence, comorbidities, treatment, healthcare utilization and outcomes associated with AF. Methods and results: The TRAF cohort was extracted from MEDULA, a health insurance database linking hospitals, general practitioners, pharmacies and outpatient clinics for almost 100% of the inhabitants of the country. The cohort includes 507 136 individuals with AF between 2008 and 2012 aged >18 years who survived the first 30 days following diagnosis. Of 507 136 subjects, there were 423 109 (83.4%) with non-valvular AF and 84 027 (16.6%) with valvular AF. The prevalence was 0.80% in non-valvular AF and 0.28% in valvular AF; in 2012 the incidence of non-valvular AF (0.17%) was higher than valvular AF (0.04%). All-cause mortality was 19.19% (97 368) and 11.47% (58 161) at 1-year after diagnosis of AF. There were 35 707 (7.04%) ischaemic stroke/TIA/thromboembolism at baseline and 34 871 (6.87%) during follow-up; 11 472 (2.26%) major haemorrhages at baseline and 10 183 (2.01%) during followup, and 44 116 (8.69%) hospitalizations during the follow-up. Conclusion: The TRAF cohort is the first population-based, whole-country cohort of AF epidemiology, quality of care and outcomes. It provides a unique opportunity to study the patterns, causes and impact of treatments on the incidence and outcomes of AF in a developing country. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.
Open Access
Development of methods for identification and characterization of autologous antibody responses in Small Cell Lung Cancer and Behcet’s Disease
(2016-08) Poyraz, Alper
Autologous antibodies are known to be elicited in Behçet’s Disease (BD) and Small Cell Lung Cancer (SCLC). SCLC consists 15-20% of all lung cancer cases. It is follows a most aggressive course and generally patients are diagnosed at later stages. The median survival of patients is 9-12 months. Diagnostic methods such as CT and PET are somewhat useful in the diagnosis of lung cancer but not so much for SCLC as the doubling time of this tumor is very rapid. Therefore, new diagnostic tools are needed for early diagnosis and to increase median survival of patients. Behçet’s Disease is autoimmune disease and the prevalence of BD in Turkey is the highest in the world. Also autologous antibodies against various antigens associated with BD have been discovered in BD. BD has vascular, oral, cutaneous and neuronal subtypes and autologous antibodies correlating with each subtype have been reported. However, for BD, there does not exist a diagnostic or prognostic test as none have been developed yet. However autoantibodies can be utilized for the diagnosis and follow-up of SCLC and BD because it is known that autoantibodies are expressed well in advance of disease symptoms. The first aim of this study was to determine a correlation between antigen expression levels in tumor tissues and the presence of autologous antibodies. The second aim of this study was to extend earlier experiments related to the characterization of autologous antibodies against known and novel antigens in SCLC and BD, utilizing high-density protein arrays (PA). The third and major aim of this study was to develop a reliable and sensitive method that could be used to evaluate protein array screening results and lastly, to validate these results by performing optimized ELISA and Western Blot experiments. Previously, PAs were screened with 50 SCLC, 50 BD and 50 healthy serums in our laboratory, and evaluated visually utilizing no automation. Sensitivity and specificity values were calculated using custom-generated antigen panels which included 180 antigens. ELISA experiments were performed to validate antigens thus discovered. However, largely discrepant PA and ELISA results, together with inconsistent ELISA results required us to optimize ELISA conditions, as well as to generate an automated PA evaluation method that would generate numeric data. We modified ELISA by altering various parameters until we were able to obtain consistent results. We also generated a reliable method by which we could produce numeric data corresponding to antibody presence as determined from PA screening results. The method is based on the calculation of pixel intensities of sero-reactive clones on the array which are converted to numeric data, and the subsequent determination of proper cut-offs by which sensitivity and specificity of antibody responses can be generated by comparing values obtained from healthy to those obtained from diseased serum. We call this the “Digital Spot Evaluation” (DSE) tool. DSE was performed utilizing Adobe Photoshop CS6 and parameters of the test were optimized using five replicate screens of a given serum. Pearson’s r correlation values of repeated experiments after optimization were close to 1. Also, when protein arrays are screened using DSE on different days by different researchers, results are highly concordant. We evaluated protein array screening data obtained for SCLC and healthy sera by DSE. In particular, antibody intensities against SOX2, p53 and POLB proteins were calculated and sensitivity/specificity values were determined. With DSE based evaluation of protein arrays, we reached 44%, 6% and 20% sensitivity at 100% specificity for SOX2, p53 and POLB proteins respectively. On the other hand if we evaluate 3 proteins together as a panel, our sensitivity increases to 56% at 100% specificity, and 66% sensitivity at 96% specificity. However, even after optimization, ELISA results showed 32%, 4% and 4% sensitivity at 100% specificity for SOX2, p53 and POLB proteins respectively, demonstrating that DSE is significantly more sensitive than ELISA. We are planning to use DSE to evaluate PA data generated from many other types of tumors in the future and to and possibly to develop a kit based on this method to be utilized for the diagnosis and follow-up of SCLC and BD.
Open Access
Diagnosis of gastric carcinoma by classification on feature projections
(Elsevier, 2004) Güvenir, H. A.; Emeksiz, N.; İkizler, N.; Örmeci, N.
A new classification algorithm, called benefit maximizing classifier on feature projections (BCFP), is developed and applied to the problem of diagnosis of gastric carcinoma. The domain contains records of patients with known diagnosis through gastroscopy results. Given a training set of such records, the BCFP classifier learns how to differentiate a new case in the domain. BCFP represents a concept in the form of feature projections on each feature dimension separately. Classification in the BCFP algorithm is based on a voting among the individual predictions made on each feature. In the gastric carcinoma domain, a lesion can be an indicator of one of nine different levels of gastric carcinoma, from early to late stages. The benefit of correct classification of early levels is much more than that of late cases. Also, the costs of wrong classifications are not symmetric. In the training phase, the BCFP algorithm learns classification rules that maximize the benefit of classification. In the querying phase, using these rules, the BCFP algorithm tries to make a prediction maximizing the benefit. A genetic algorithm is applied to select the relevant features. The performance of the BCFP algorithm is evaluated in terms of accuracy and running time. The rules induced are verified by experts of the domain. © 2004 Elsevier B.V. All rights reserved.
Open Access
Environmental effect and genetic influence: A regional cancer predisposition survey in the Zonguldak region of Northwest Turkey
(Springer-Verlag, 2008) Kadir, S.; Önen-Hall, A. P.; Aydin, S. N.; Yakicier, C.; Akarsu, N.; Tuncer, M.
The Cretaceous-Eocene volcano-sedimentary units of the Zonguldak region of the western Black Sea consist of subalkaline andesite and tuff, and sandstone dominated by smectite, kaolinite, accessory chlorite, illite, mordenite, and analcime associated with feldspar, quartz, opal-CT, amphibole, and calcite. Kaolinization, chloritization, sericitization, albitization, Fe-Ti-oxidation, and the presence of zeolite, epidote, and illite in andesitic rocks and tuffaceous materials developed as a result of the degradation of a glass shards matrix, enclosed feldspar, and clinopyroxene-type phenocrysts, due to alteration processes. The association of feldspar and glass with smectite and kaolinite, and the suborientation of feldspar-edged, subparallel kaolinite plates to fracture axes may exhibit an authigenic smectite or kaolinite. Increased alteration degree upward in which Al, Fe, and Ti are gained, and Si, Na, K, and Ca are depleted, is due to the alteration following possible diagenesis and hydrothermal activities. Micromorphologically, fibrous mordenite in the altered units and the presence of needle-type chrysotile in the residential buildings in which cancer cases lived were detected. In addition, the segregation pattern of cancer susceptibility in the region strongly suggested an environmental effect and a genetic influence on the increased cancer incidence in the region. The most likely diagnosis was Li-Fraumeni syndrome, which is one of the hereditary cancer predisposition syndromes; however, no mutations were observed in the p53 gene, which is the major cause of Li-Fraumeni syndrome. The micromorphology observed in the altered units in which cancer cases were detected may have a role in the expression of an unidentified gene, but does not explain alone the occurrence of cancer as a primary cause in the region. © 2007 Springer-Verlag.
Open Access
Evaluation of TAGLN as a diagnostic marker in breast cancer
(2018-08) Köseer, Ayşe Sedef
Silecing of tumor suppressor genes via CpG hypermethylation in promoter regions is one of the frequent events occurring in different types of cancers. These genes have the potential as a diagnostic or a prognostic biomarker. Liquid biopsy is a relatively less invasive technique that is used for early diagnosis, therapy response prediction, minimal residual disease detection and real-time monitoring of tumor progression. In this study, a 402 bp region (-286 bp to -80 bp for Section 1, -102 bp to +115 bp for Section 2) located in TAGLN promoter containing 22 CpGs was analyzed in breast cancer patients and healthy donors to evaluate the biomarker potential of TAGLN promoter methylation levels in breast cancer. TAGLN promoter region was significantly hypermethylated in breast cancer patients (77.3%) compared to healthy donors (68.2%). Among differentially methylated CpGs, 6 out of 22 were hypermethylated and one was hypomethylated in breast cancer patients. We also analyzed the relationship between TAGLN promoter methylation levels and the patient's clinicopathological parameters. Analyses revealed that TAGLN promoter is highly methylated in breast cancer patients over 50 years of age compared to the healthy donors in the same age group. TAGLN promoter methylation did not differ as related to various clinicopathological parameters of breast cancer patients. TAGLN promoter methylation levels diagnosed breast cancer patients with 74.45% specificity and 57.58% sensitivity. Additionally, independent of the age group breast cancer patients (131.6 ng) exhibited higher levels of total cfDNA compared to healthy donors (56.4 ng). Pre- and postmenopausal breast cancer patients possessed higher total cfDNA levels compared to pre- and postmenopausal healthy donors. Total cfDNA levels did not differ in various clinicopathological parameters of breast cancer patients; however, total cfDNA levels diagnosed breast cancer patients with 73.33% specificity and 56.72% sensitivity. In summary, breast cancer patient sera can be used to identify the tumor profile, and TAGLN promoter hypermethylation and total cfDNA levels could serve as a diagnostic biomarker in breast cancer.
Open Access
Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine
(American Chemical Society, 2016-03) Fais, S.; O'Driscoll, L.; Borras, F. E.; Buzas, E.; Camussi, G.; Cappello, F.; Carvalho, J.; Cordeiro Da Silva, A.; Del Portillo, H.; El Andaloussi, S.; Ficko Trček, T.; Furlan, R.; Hendrix, A.; Gursel, I.; Kralj-Iglic, V.; Kaeffer, B.; Kosanovic, M.; Lekka, M. E.; Lipps, G.; Logozzi, M.; Marcilla, A.; Sammar, M.; Llorente, A.; Nazarenko, I.; Oliveira, C.; Pocsfalvi, G.; Rajendran, L.; Raposo, G.; Rohde, E.; Siljander, P.; Van, N. G.; Vasconcelos, M. H.; Yáñez-Mó, M.; Yliperttula, M. L.; Zarovni, N.; Zavec, A. B.; Giebel, B.
Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.
Open Access
Exosomes: Natural nanovesicle candidates used in the diagnosis and treatment
(Turkish Society of Immunology, 2013) Kahraman, T.; Gíiçlíiler G.; Gürsel I.
Exosomes are nano-vesicles released by all known cells. Although they were called as residual cells acting as a cleaner of undesired molecules out of cell during the first discovery in 1980s, recent studies have revealed critical physiological tasks of these vesicles over the past 20 years. These vesicles which can be produced by all body fluids play an important role in many biological activities including intracellular communication, signal conduction, genetic material transfer, and regulation of immune response. Due to their several tasks, exosomes play a crucial role in the disease pathogenesis. Considering all these tasks, exosomes can be considered in both diagnosis and treatment. Exosomes originating from distinct cells have immunosuppressive and immunostimulatory features and, thereby, therapeutic attempts which regulate immune function in case of autoimmune and immunosuppression. In addition, thanks to being natural nano-carriers, exosomes may pave the way for the development of new-generation vaccines containing both adjuvant and antigen. Besides therapeutic applications, there are evidences indicating that exosomes can be used in the diagnosis of several cancer forms including prostate cancer, glioblastoma, squamous-cell lung carcinoma and hepatocellular carcinoma, as they play a role in the disease pathogenesis. © 2014 Turkish Journal of Immunology.
Open Access
Femtosecond laser fabrication of fiber based optofluidic platform for flow cytometry applications
(SPIE, 2017) Serhatlioglu, Murat; Elbuken, Çağlar; Ortac, Bülend; Solmaz, Mehmet E.
Miniaturized optofluidic platforms play an important role in bio-analysis, detection and diagnostic applications. The advantages of such miniaturized devices are extremely low sample requirement, low cost development and rapid analysis capabilities. Fused silica is advantageous for optofluidic systems due to properties such as being chemically inert, mechanically stable, and optically transparent to a wide spectrum of light. As a three dimensional manufacturing method, femtosecond laser scanning followed by chemical etching shows great potential to fabricate glass based optofluidic chips. In this study, we demonstrate fabrication of all-fiber based, optofluidic flow cytometer in fused silica glass by femtosecond laser machining. 3D particle focusing was achieved through a straightforward planar chip design with two separately fabricated fused silica glass slides thermally bonded together. Bioparticles in a fluid stream encounter with optical interrogation region specifically designed to allocate 405nm single mode fiber laser source and two multi-mode collection fibers for forward scattering (FSC) and side scattering (SSC) signals detection. Detected signal data collected with oscilloscope and post processed with MATLAB script file. We were able to count number of events over 4000events/sec, and achieve size distribution for 5.95μm monodisperse polystyrene beads using FSC and SSC signals. Our platform shows promise for optical and fluidic miniaturization of flow cytometry systems. © 2017 SPIE.
Open Access
Graphene and carbon nanotubes interfaced electrochemical nanobiosensors for the detection of SARS-CoV-2 (COVID-19) and other respiratory viral infections: A review
(Elsevier BV, 2021-10) Özmen, E. N.; Kartal, Enise; Turan, Mehmet Bora; Yazıcıoğlu, A.; Niazi, J. H.; Qureshi, A.
Recent COVID-19 pandemic has claimed millions of lives due to lack of a rapid diagnostic tool. Global scientific community is now making joint efforts on developing rapid and accurate diagnostic tools for early detection of viral infections to preventing future outbreaks. Conventional diagnostic methods for virus detection are expensive and time consuming. There is an immediate requirement for a sensitive, reliable, rapid and easy-to-use Point-of-Care (PoC) diagnostic technology. Electrochemical biosensors have the potential to fulfill these requirements, but they are less sensitive for sensing viruses/viral infections. However, sensitivity and performance of these electrochemical platforms can be improved by integrating carbon nanostructure, such as graphene and carbon nanotubes (CNTs). These nanostructures offer excellent electrical property, biocompatibility, chemical stability, mechanical strength and, large surface area that are most desired in developing PoC diagnostic tools for detecting viral infections with speed, sensitivity, and cost-effectiveness. This review summarizes recent advancements made toward integrating graphene/CNTs nanostructures and their surface modifications useful for developing new generation of electrochemical nanobiosensors for detecting viral infections. The review also provides prospects and considerations for extending the graphene/CNTs based electrochemical transducers into portable and wearable PoC tools that can be useful in preventing future outbreaks and pandemics.
Open Access
Identification and utilization of autologous anti-tumor antibodies for the diagnosis and prognosis of cancer
(2015-12) Atakan, Şükrü
Lung cancer is the leading cause of cancer related death worldwide. Current diagnostic methods have limited power and unable to extend patient life significantly. SCLC; the most aggressive subtype of lung cancer is an immunogenic cancer type and able to elicit an immune response of which autologous antibodies are a measurable component. These antibodies are elicited even when the tumor is microscobic and impossible to be diagnosed clinically by the current methods of diagnosis thus antibodies can be utilized for early diagnosis. We aimed to develop a method to identify novel autologous antibodies, identify these antibodies for SCLC, Colorectal, Gastric and Ovarian cancers and validate these antibodies for SCLC diagnosis and prognosis and investigate their utility for autoimmune disease. We have developed and optimized PA screening for novel autologous antibody discovery. We have screened PA with serum pools of cancer patients (SCLC, Colorectal, Gastric and Ovarian), BD and healthy controls since PAs have many advantages compared to other discovery methods like SEREX. We have also performed sensitivity and specificity evaluations by screening custom PAs by individual sera. Image analysis softwares developed by collaboration utilized for evaluation of the screenings. The filtered valuable clones were ordered from the PA manufacturer and HisTagged protein expression and purification was performed with these clones. Pure proteins were screened with 3 independent SCLC and 2 Healthy control cohorts by an iterative ELISA approach for validation of these antibodies as valuable biomarkers. ELISA results were also confirmed by Western blotting. Monte Carlo, SVM and PC were utilized for cut-off determination, panel formation and ROC plotting. AUC was compared for evaluation of diagnostic power. Kaplan-Meier, UCR and MCR analysis was performed for prognostic analysis of the valuable antibodies. Seperately protein expression and autologous antibody presence correlation was evaluated by comparison of IHC and ELISA. The same autologous antibody identification strategy was utilized as a collaborative support for an independent study for identification of NBD specific biomarkers.We have identified 23 distinct autologous antibody biomarkers for SCLC after evaluation of PA and custom PA screenings. For 8 of these antibodies we have completed ELISA screening for all 3 SCLC and 2 healthy control cohorts. 6 of these autologous antibodies were shown to be valuable as a panel for SCLC diagnosis both by MC and SVM. Utilization of 4 of these antibodies; SOX2, p53, POLB and C11orf20, as a panel resulted in superior AUC thus high sensitivity and specificity values (55% sensitivity, 90% specificity). PC method resulted in higher AUC even only by combination of SOX2 and p53 (82% sensitivity, 90% specificity). Although individual correlations were identified, we were unable to show a significant correlation of seropositivity with survival for any of the antibodies which is common to all cohorts. We have identified a significant correlation between SOX2 antigen expression intensity and autologous antibody presence. Mtch1 was identified as a NBD specific autologous antibody by the utilization of our autologous antibody discovery and validation methodology. We were able to identify a panel of 4 antibodies; SOX2, p53, POLB and C11orf20, which resulted in 55% sensitivity at 90% specificity for SCLC. 2 of these antibodies were identified by this study as novel biomarkers; POLB and C11orf20. The panel is capable of exceeding the diagnostic power of the only commercially available diagnostic kit; EarlyCDT-Lung. PC method is very promising since a sensitivity value of 82% was reached at 90% specificity which is a diagnostic power comparable that of low-dose CT. As a future perspective we are planning to apply PC method to all the PA data and develop a kit based on this method to be utilized for SCLC diagnosis.
Open Access
Implantable microelectromechanical sensors for diagnostic monitoring and post-surgical prediction of bone fracture healing
(John Wiley and Sons Inc., 2015) McGilvray, K. C.; Ünal, E.; Troyer, K. L.; Santoni, B. G.; Palmer, R. H.; Easley, J. T.; Demir, Hilmi Volkan; Puttlitz, C. M.
The relationship between modern clinical diagnostic data, such as from radiographs or computed tomography, and the temporal biomechanical integrity of bone fracture healing has not been well-established. A diagnostic tool that could quantitatively describe the biomechanical stability of the fracture site in order to predict the course of healing would represent a paradigm shift in the way fracture healing is evaluated. This paper describes the development and evaluation of a wireless, biocompatible, implantable, microelectromechanical system (bioMEMS) sensor, and its implementation in a large animal (ovine) model, that utilized both normal and delayed healing variants. The in vivo data indicated that the bioMEMS sensor was capable of detecting statistically significant differences (p-value <0.04) between the two fracture healing groups as early as 21 days post-fracture. In addition, post-sacrifice micro-computed tomography, and histology data demonstrated that the two model variants represented significantly different fracture healing outcomes, providing explicit supporting evidence that the sensor has the ability to predict differential healing cascades. These data verify that the bioMEMS sensor can be used as a diagnostic tool for detecting the in vivo course of fracture healing in the acute post-treatment period. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Open Access
Kanser tanısı için kolon bezlerinin matematiksel analizi
(IEEE, 2009-04) Çığır, Celal; Sökmensüer, C.; Gündüz-Demir, Çiğdem
Neoplastic diseases including cancer cause organizational changes in tissues. Histopathological examination, which is routinely used for the diagnosis and grading of these diseases, relies on pathologists to identify such tissue changes under a microscope. However, as this examination mainly relies on the visual interpretation of pathologists, it may lead to a considerable amount of subjectivity. To reduce the subjectivity level, it is proposed to use computational methods that provide objective measures. These methods quantify the tissue changes associated with disease by defining features on tissue images. In this paper, colon glands are mathematically analyzed making use of different feature extraction approaches. In this analysis, morphological, intensity-based, and textural features are investigated and glands are classified using these features. Working on the images of 108 colon tissues of 36 patients, our experiments demonstrate that this classification leads to promising results for differentiating normal glands from the cancerous ones. ©2009 IEEE.
Open Access
Localization of diagnostically relevant regions of interest in whole slide images: a comparative study
(Springer New York LLC, 2016-08) Mercan, E.; Aksoy, S.; Shapiro, L. G.; Weaver, D. L.; Brunyé, T. T.; Elmore, J. G.
Whole slide digital imaging technology enables researchers to study pathologists’ interpretive behavior as they view digital slides and gain new understanding of the diagnostic medical decision-making process. In this study, we propose a simple yet important analysis to extract diagnostically relevant regions of interest (ROIs) from tracking records using only pathologists’ actions as they viewed biopsy specimens in the whole slide digital imaging format (zooming, panning, and fixating). We use these extracted regions in a visual bag-of-words model based on color and texture features to predict diagnostically relevant ROIs on whole slide images. Using a logistic regression classifier in a cross-validation setting on 240 digital breast biopsy slides and viewport tracking logs of three expert pathologists, we produce probability maps that show 74 % overlap with the actual regions at which pathologists looked. We compare different bag-of-words models by changing dictionary size, visual word definition (patches vs. superpixels), and training data (automatically extracted ROIs vs. manually marked ROIs). This study is a first step in understanding the scanning behaviors of pathologists and the underlying reasons for diagnostic errors. © 2016, Society for Imaging Informatics in Medicine.
Open Access
Mirna based identification of prostate cancer by investigation of urinary exosomes
(2020-08) Bozbeyoğlu, Naz
Prostate cancer is one of the most incident cancer subtypes with high mortality rate. Currently, diagnosis of prostate cancer is based on rectal examination, Prostate Specific Antigen (PSA) testing and biopsy. Normal range of PSA is defined as 0-4 ng/ml and individuals with higher PSA levels are considered as potential prostate cancer patients. However, PSA fluctuates as a result of many factors and it is shown to increase with age. Thus, PSA testing causes significantly high false positive results and many healthy men have biopsy unnecessarily due to high PSA levels or they even get overtreated. This situation has huge psychological as well as financial effects on these people. Herein, we investigated the diagnostic potential of urinary exosomal microRNAs (miRNA) in prostate cancer. Rather than investigation of cellular miRNAs, we focused on exosomal miRNAs because of high integrity of exosomes and their abundance in many biofluids including urine. Development of a sensitive diagnostic method from urine would be advantageous because accurate diagnosis of prostate cancer would be possible by a non-invasive procedure. miRNAs are the small non-coding RNAs and they suppress expression of target genes via degradation of mRNA or post-translational regulation. miRNAs have high potential as cancer biomarkers because they can act as tumor suppressor and repress oncogenic gene expression or function as oncogenic miRNA and suppress tumor suppressor gene expression. For this reason, we identified several candidate exosomal tumor suppressor and oncogenic miRNAs and continued our study with the most potent ones. At the beginning of the study, we validated that we efficiently isolated exosomes via several techniques such as flow cytometry, Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and Transmission Electron Microscopy (TEM). Then, we studied differential expression of candidate miRNAs in prostate cancer PC-3 cell line. Similar to our literature search findings, we found that expression levels of miR-107, miR-139, miR-145 and miR-204 were significantly lower in PC-3 exosomes in comparison to healthy urinary exosomes. On the other hand, oncomiRs; miR-21-5p, miR-375-5p and miR-574 3p were upregulated in PC-3 cell line exosomes. Of note, expression of another candidate miRNA; miR-30a was almost the same in PC-3 exosomes with healthy controls. We used these results as preliminary data and collected urine specimens from 17 prostate cancer patients. We firstly analyzed their PSA level-age and PSA Level- Gleason Score correlations. Our analyses revealed that PSA level was increasing with age and PSA was not correlated with Gleason Score. We concluded that PSA was being affected by several reasons in addition to tumor formation and it was not correlated with disease progression. Again, this was a finding which supported that a more sensitive diagnosis method than PSA testing was necessary for prostate cancer. When we detected expression levels of candidate miRNAs in urinary exosomes of prostate cancer patients and healthy controls, we observed that miR-107, miR-139, miR-145 and miR-204 were downregulated whereas miR-375-5p was upregulated in patients’ urinary exosomes. For miR-21, there was a very slight upregulation and miR-30a-5p and miR-574-3p levels were almost the same with healthy controls. Further, we wondered the diagnostic potential of these miRNAs in our patient cohort and we performed Receiver Operator Characteristic (ROC) Curve analysis for them. When they were used as combination, our miRNAs had 77% (AUC=0.7731) accuracy in distinguishing patients from healthy controls. After that, we examined miRNA dysregulations in patients with different PSA levels with the hypothesis that they may have different miRNA expression profiles. We saw that expression of miRNAs in exosomes patients with PSA<10 ng/ml and PSA=10-15 ng/ml were very similar with our expectations; downregulation of tumor suppressor and upregulation in oncogenic miRNAs whereas patients with PSA>15 ng/ml had a unique profile and all miRNAs were downregulated. Due to sample size limitations, we only tested diagnostic potential of candidate miRNAs in exosomes of patients with PSA<10 ng/ml and observed that AUC was 0.8500 so we could discriminate patients and healthy controls with 85% accuracy by using our candidate miRNA panel in testing. Taken together, our findings indicated that candidate urinary exosomal tumor suppressor and oncogenic miRNAs which we suggested in thesis are very potent in diagnosis of prostate cancer with differential expressions in prostate cancer patients with different PSA levels and this study opens the way for development of a noninvasive prostate cancer diagnosis method.
Open Access
Multi-objective contextual bandits with a dominant objective
(IEEE, 2017) Tekin, Cem; Turgay, Eralp
In this paper, we propose a new contextual bandit problem with two objectives, where one of the objectives dominates the other objective. Unlike single-objective bandit problems in which the learner obtains a random scalar reward for each arm it selects, in the proposed problem, the learner obtains a random reward vector, where each component of the reward vector corresponds to one of the objectives. The goal of the learner is to maximize its total reward in the non-dominant objective while ensuring that it maximizes its reward in the dominant objective. In this case, the optimal arm given a context is the one that maximizes the expected reward in the non-dominant objective among all arms that maximize the expected reward in the dominant objective. For this problem, we propose the multi-objective contextual multi-armed bandit algorithm (MOC-MAB), and prove that it achieves sublinear regret with respect to the optimal context dependent policy. Then, we compare the performance of the proposed algorithm with other state-of-the-art bandit algorithms. The proposed contextual bandit model and the algorithm have a wide range of real-world applications that involve multiple and possibly conflicting objectives ranging from wireless communication to medical diagnosis and recommender systems.
Open Access
Pap smear test görüntülerinde hücre çekirdeklerinin bölütlenmesi
(IEEE, 2009-04) Kale, Aslı; Aksoy, Selim; Önder, S.
Cervical cancer is a preventable disease and the dysplasia it causes can be scanned by using a pap smear test. It can be beneficial to develop a computer-assisted diagnosis system to make the pap smear test robust and widespread. The most fundamental part of such a system is the segmentation of nuclei and cytoplasm in cervical cell images. The aim of this study is to segment the nuclei in such images. First, markers on the nuclei are found by using mathematical morphology operations. Based on the obtained markers, marker-based watershed segmentation and balloon snake model are applied to find the nuclei contours in a data set consisting of cervical cell images. The data set is composed of six classes ranging according to the dysplasia degree of the cells. The results are evaluated according to the relative distance error measure, and the strengths and weakness of the methods are discussed. ©2009 IEEE.