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Publication Open Access 25-hydroxyvitamin D levels are low but not associated with disease activity in chronic spontaneous urticaria and depression(AEPress, 2020) Vurgun, Eren; Güntaş, Gürkan; Kocatürk Göncü, Özgür Emek; Memet, Bachar; Doctor; School of Medicine; Koç University Hospital; 217219; N/AAim: to evaluate vitamin D levels in patients with chronic spontaneous urticaria (CSU), depression and both of them, thus to fi nd out whether vitamin D may be a common causative factor of CSU and depression. Methods: thirty patients with CSU, 30 patients with depression, 30 patients with both CSU and depression and 30 healthy volunteers as control group were involved in the study. Serum 25-hydroxyvitamin D (25(OH) D) levels of these groups were measured and compared. Correlations between 25(OH)D levels and the activity of CSU and depression were analyzed. Results: healthy controls' 25(OH)D levels (17.2±8.8 ng/mL) were higher than patients with CSU (9.1±5.1 ng/mL), depression (8.9±6.1 ng/mL) and CSU with depression (7.7±4.7 ng/mL) (p<0.001, p<0.001 and p<0.001, respectively). There were no differences in 25(OH)D levels between CSU patients with and without depression, between depression patients and CSU patients with and without depression (p=0.43, p=0.82 and p=0.92, respectively). There were no correlations between 25(OH)D levels and the activity of CSU or depression (p=0.99 and p=0.76, respectively). Conclusion: Lower 25(OH)D levels in CSU and/or depression may appear as a secondary phenomenon, which means being result of these diseases rather than the cause (Tab. 1, Fig. 2, Ref. 41).Publication Open Access 3D engineered neural co-culture model and neurovascular effects of marine fungi-derived citreohybridonol(American Institute of Physics (AIP) Publishing, 2022) Polat, İrem; Özkaya, Ferhat Can; El-Neketi, Mona; Ebrahim, Weaam; Şengül, Gülgün; Department of Mechanical Engineering; Sokullu, Emel; Sarabi, Misagh Rezapour; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); School of Medicine; Graduate School of Sciences and Engineering; College of Engineering; 163024; N/A; 291971Marine-based biomolecules are emerging metabolites that have gained attention for developing novel biomaterials, drugs, and pharmaceutical in vitro platforms. Here, we developed a 3D engineered neural co-culture model via a 3D prototyped sliding frame-platform for multi-step UV lithography and investigated the neurovascular potential of citreohybridonol in neuroblastoma treatment. Citreohybridonol was isolated from a sponge-derived fungus Penicillium atrovenetum. The model was characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy analysis. Human umbilical cord vein endothelial cells (HUVECs) and neuroblastoma (SH-SY5Y) cell lines were encapsulated in gelatin methacrylate (GelMA) with and without citreohybridonol. The effect of citreohybridonol on the proliferation capacity of cells was assessed via cell viability and immunostaining assays. GelMA and 3D culture characterization indicated that the cells were successfully encapsulated as axenic and mixed with/without citreohybridonol. The cytotoxic test confirmed that the 3D microenvironment was non-toxic for cultural experiments, and it showed the inhibitory effects of citreohybridonol on SH-SY5Y cells and induced the proliferation of HUVECs. Finally, immunohistochemical staining demonstrated that citreohybridonol suppressed SH-SY5Y cells and induced vascularization of HUVECs in mixed 3D cell culture.Publication Open Access 3D microprinting of iron platinum nanoparticle-based magnetic mobile microrobots(Wiley, 2021) Giltinan, Joshua; Sridhar, Varun; Bozüyük, Uğur; Sheehan, Devin; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of Engineering; 297104Wireless magnetic microrobots are envisioned to revolutionize minimally invasive medicine. While many promising medical magnetic microrobots are proposed, the ones using hard magnetic materials are not mostly biocompatible, and the ones using biocompatible soft magnetic nanoparticles are magnetically very weak and, therefore, difficult to actuate. Thus, biocompatible hard magnetic micro/nanomaterials are essential toward easy-to-actuate and clinically viable 3D medical microrobots. To fill such crucial gap, this study proposes ferromagnetic and biocompatible iron platinum (FePt) nanoparticle-based 3D microprinting of microrobots using the two-photon polymerization technique. A modified one-pot synthesis method is presented for producing FePt nanoparticles in large volumes and 3D printing of helical microswimmers made from biocompatible trimethylolpropane ethoxylate triacrylate (PETA) polymer with embedded FePt nanoparticles. The 30 mu m long helical magnetic microswimmers are able to swim at speeds of over five body lengths per second at 200Hz, making them the fastest helical swimmer in the tens of micrometer length scale at the corresponding low-magnitude actuation fields of 5-10mT. It is also experimentally in vitro verified that the synthesized FePt nanoparticles are biocompatible. Thus, such 3D-printed microrobots are biocompatible and easy to actuate toward creating clinically viable future medical microrobots.Publication Open Access 3D printed microneedles for point of care biosensing applications(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Department of Mechanical Engineering; Sarabi, Misagh Rezapour; Nakhjavani, Sattar Akbar; Taşoğlu, Savaş; Faculty Member; Department of Mechanical Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 291971Microneedles (MNs) are an emerging technology for user-friendly and minimally invasive injection, offering less pain and lower tissue damage in comparison to conventional needles. With their ability to extract body fluids, MNs are among the convenient candidates for developing biosensing setups, where target molecules/biomarkers are detected by the biosensor using the sample collected with the MNs. Herein, we discuss the 3D printing of microneedle arrays (MNAs) toward enabling point-of-care (POC) biosensing applications.Publication Open Access 3D printed personalized magnetic micromachines from patient blood-derived biomaterials(American Association for the Advancement of Science (AAAS), 2021) Ceylan, Hakan; Doğan, Nihal Olcay; Yaşa, İmmihan Ceren; Department of Mechanical Engineering; Sitti, Metin; Musaoğlu, Miraç Nur; Kulalı, Zeynep Umut; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104; N/A; N/AWhile recent wireless micromachines have shown increasing potential for medical use, their potential safety risks concerning biocompatibility need to be mitigated. They are typically constructed from materials that are not intrinsically compatible with physiological environments. Here, we propose a personalized approach by using patient blood-derivable biomaterials as the main construction fabric of wireless medical micromachines to alleviate safety risks from biocompatibility. We demonstrate 3D printed multiresponsive microswimmers and microrollers made from magnetic nanocomposites of blood plasma, serum albumin protein, and platelet lysate. These micro-machines respond to time-variant magnetic fields for torque-driven steerable motion and exhibit multiple cycles of pH-responsive two-way shape memory behavior for controlled cargo delivery and release applications. Their proteinaceous fabrics enable enzymatic degradability with proteinases, thereby lowering risks of long-term toxicity. The personalized micromachine fabrication strategy we conceptualize here can affect various future medical robots and devices made of autologous biomaterials to improve biocompatibility and smart functionality.Publication Open Access 3D printing of elastomeric bioinspired complex adhesive microstructures(Wiley, 2021) Dayan, Cem Balda; Chun, Sungwoo; Krishna Subbaiah, Nagaraj; Drotlef, Dirk Michael; Akolpoğlu, Mükrime Birgül; Department of Mechanical Engineering; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; College of Engineering; School of Medicine; 297104Bioinspired elastomeric structural adhesives can provide reversible and controllable adhesion on dry/wet and synthetic/biological surfaces for a broad range of commercial applications. Shape complexity and performance of the existing structural adhesives are limited by the used specific fabrication technique, such as molding. To overcome these limitations by proposing complex 3D microstructured adhesive designs, a 3D elastomeric microstructure fabrication approach is implemented using two-photon-polymerization-based 3D printing. A custom aliphatic urethane-acrylate-based elastomer is used as the 3D printing material. Two designs are demonstrated with two combined biological inspirations to show the advanced capabilities enabled by the proposed fabrication approach and custom elastomer. The first design focuses on springtail- and gecko-inspired hybrid microfiber adhesive, which has the multifunctionalities of side-surface liquid super-repellency, top-surface liquid super-repellency, and strong reversible adhesion features in a single fiber array. The second design primarily centers on octopus- and gecko-inspired hybrid adhesive, which exhibits the benefits of both octopus- and gecko-inspired microstructured adhesives for strong reversible adhesion on both wet and dry surfaces, such as skin. This fabrication approach could be used to produce many other 3D complex elastomeric structural adhesives for future real-world applications.Publication Open Access 3D spatial organization and network-guided comparison of mutation profiles in Glioblastoma reveals similarities across patients(Public Library of Science, 2019) Dinçer, Cansu; Kaya, Tuğba; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; Department of Computer Engineering; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; 26605; 8745Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor. Molecular heterogeneity is a hallmark of GBM tumors that is a barrier in developing treatment strategies. In this study, we used the nonsynonymous mutations of GBM tumors deposited in The Cancer Genome Atlas (TCGA) and applied a systems level approach based on biophysical characteristics of mutations and their organization in patient-specific subnetworks to reduce inter-patient heterogeneity and to gain potential clinically relevant insights. Approximately 10% of the mutations are located in "patches" which are defined as the set of residues spatially in close proximity that are mutated across multiple patients. Grouping mutations as 3D patches reduces the heterogeneity across patients. There are multiple patches that are relatively small in oncogenes, whereas there are a small number of very large patches in tumor suppressors. Additionally, different patches in the same protein are often located at different domains that can mediate different functions. We stratified the patients into five groups based on their potentially affected pathways, revealed from the patient-specific subnetworks. These subnetworks were constructed by integrating mutation profiles of the patients with the interactome data. Network-guided clustering showed significant association between each group and patient survival (P-value = 0.0408). Also, each group carries a set of signature 3D mutation patches that affect predominant pathways. We integrated drug sensitivity data of GBM cell lines with the mutation patches and the patient groups to analyze the therapeutic outcome of these patches. We found that Pazopanib might be effective in Group 3 by targeting CSF1R. Additionally, inhibiting ATM that is a mediator of PTEN phosphorylation may be ineffective in Group 2. We believe that from mutations to networks and eventually to clinical and therapeutic data, this study provides a novel perspective in the network-guided precision medicine.Publication Open Access 3D-printed multi-stimuli-responsive mobile micromachines(American Chemical Society (ACS), 2020) Lee, Yun-Woo; Ceylan, Hakan; Yasa, İmmihan Ceren; Department of Mechanical Engineering; Kılıç, Uğur; Sitti, Metin; Faculty Member; Department of Mechanical Engineering; School of Medicine; College of EngineeringMagnetically actuated and controlled mobile micromachines have the potential to be a key enabler for various wireless lab-on-a-chip manipulations and minimally invasive targeted therapies. However, their embodied, or physical, task execution capabilities that rely on magnetic programming and control alone can curtail their projected performance and functional diversity. Integration of stimuli-responsive materials with mobile magnetic micromachines can enhance their design toolbox, enabling independently controlled new functional capabilities to be defined. To this end, here, we show three-dimensional (3D) printed size-controllable hydrogel magnetic microscrews and microrollers that respond to changes in magnetic fields, temperature, pH, and divalent cations. We show two-way size-controllable microscrews that can reversibly swell and shrink with temperature, pH, and divalent cations for multiple cycles. We present the spatial adaptation of these microrollers for penetration through narrow channels and their potential for controlled occlusion of small capillaries (30 μm diameter). We further demonstrate one-way size-controllable microscrews that can swell with temperature up to 65% of their initial length. These hydrogel microscrews, once swollen, however, can only be degraded enzymatically for removal. Our results can inspire future applications of 3D- and 4D-printed multifunctional mobile microrobots for precisely targeted obstructive interventions (e.g., embolization) and lab- and organ-on-a-chip manipulations.Publication Open Access A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells(Nature Publishing Group (NPG), 2018) Seferoğlu, Ayşe Bengisu; Department of Molecular Biology and Genetics; Dunn, Cory David; Keskin, Abdurrahman; Akdoğan, Emel; Lutfullahoglu-Bal, Guleycan; Department of Molecular Biology and Genetics; College of SciencesProkaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential in the era of eukaryogenesis. Since eukaryotes are highly compartmentalized, it is worthwhile to consider the mechanisms by which newly transferred proteins might reach diverse organellar destinations. Toward this goal, we have focused our attention upon the behavior of bacteria-derived tail anchors (TAs) expressed in the eukaryote Saccharomyces cerevisiae. In this study, we report that a predicted membrane-associated domain of the Escherichia coli YgiM protein is specifically trafficked to peroxisomes in budding yeast, can be found at a pre-peroxisomal compartment (PPC) upon disruption of peroxisomal biogenesis, and can functionally replace an endogenous, peroxisome-directed TA. Furthermore, the YgiM(TA) can localize to peroxisomes in mammalian cells. Since the YgiM(TA) plays no endogenous role in peroxisomal function or assembly, this domain is likely to serve as an excellent tool allowing further illumination of the mechanisms by which TAs can travel to peroxisomes. Moreover, our findings emphasize the ease with which bacteria-derived sequences might target to organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.Publication Open Access A broken gauge approach to gravitational mass and charge(Springer, 2002) Tucker, R. W.; Department of Physics; Dereli, Tekin; Faculty Member; Department of Physics; College of Sciences; 201358We argue that a spontaneous breakdown of local Weyl invariance offers a mechanism in which gravitational interactions contribute to the generation of particle masses and their electric charge. The theory is formulated in terms of a spacetime geometry whose natural connection has both dynamic torsion and non-metricity. Its structure illuminates the role of dynamic scales used to determine measurable aspects of particle interactions and it predicts an additional neutral vector boson with electroweak properties. © SISSA/ISAS 2002.Publication Open Access A cartridge based sensor array platform for multiple coagulation measurements from plasma(Royal Society of Chemistry (RSC), 2015) Bulut, Serpil; Yaralioglu, G. G.; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Çakmak, Onur; Ermek, Erhan; Kılınç, Necmettin; Barış, İbrahim; Kavaklı, İbrahim Halil; Ürey, Hakan; PhD Student; Other; Researcher; Teaching Faculty; Faculty Member; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; 109991; N/A; 111629; 40319; 8579This paper proposes a MEMS-based sensor array enabling multiple clot-time tests for plasma in one disposable microfluidic cartridge. The versatile LoC (Lab-on-Chip) platform technology is demonstrated here for real-time coagulation tests (activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)). The system has a reader unit and a disposable cartridge. The reader has no electrical connections to the cartridge. This enables simple and low-cost cartridge designs and avoids reliability problems associated with electrical connections. The cartridge consists of microfluidic channels and MEMS microcantilevers placed in each channel. The microcantilevers are made of electroplated nickel. They are actuated remotely using an external electro-coil and the read-out is also conducted remotely using a laser. The phase difference between the cantilever oscillation and the coil drive is monitored in real time. During coagulation, the viscosity of the blood plasma increases resulting in a change in the phase read-out. The proposed assay was tested on human and control plasma samples for PT and aPTT measurements. PT and aPTT measurements from control plasma samples are comparable with the manufacturer's datasheet and the commercial reference device. The measurement system has an overall 7.28% and 6.33% CV for PT and aPTT, respectively. For further implementation, the microfluidic channels of the cartridge were functionalized for PT and aPTT tests by drying specific reagents in each channel. Since simultaneous PT and aPTT measurements are needed in order to properly evaluate the coagulation system, one of the most prominent features of the proposed assay is enabling parallel measurement of different coagulation parameters. Additionally, the design of the cartridge and the read-out system as well as the obtained reproducible results with 10 mu l of the plasma samples suggest an opportunity for a possible point-of-care application.Publication Open Access A case of radiologically isolated syndrome developing Balo's concentric sclerosis lesions on long-term follow-up(Elsevier, 2022) Danyeli, Ayça Ersen; Altıntaş, Ayşe; Çalışkan, İlay; Peker, Selçuk; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Graduate School of Health Sciences; Koç University Hospital; 11611; N/A; N/A; 11480Background; Radiologically Isolated Syndrome (RIS) depicts a clinical scenario with multiple sclerosis (MS)-like magnetic resonance imaging (MRI) findings in individuals without clinical features of a demyelinating bout. Balo’s concentric sclerosis (BCS) on the other hand, is a variant of MS characterized by concentrically layered white mater demyelinating lesions. Case presentation: a 49-year-old male with an incidental brain lesion on MRI underwent a stereotactic biopsy and diagnosed as a demyelinating process. He remained asymptomatic throughout the long term clinical and radiological follow-up. However, the patient developed new demyelinating lesions with some showing concentric layers of BCS. Conclusion:this is the first reported case; to our knowledge, whereby a pathologically verified RIS patient developed characteristic BCS lesions. Our case highlights the heterogeneity of RIS as a clinico-radiological entity, requiring further sub-classification of the spectrum for improved managementPublication Open Access A characterization of the extended serial correspondence(Elsevier, 2015) Heo, Eun Jeong; Department of Economics; Yılmaz, Özgür; Faculty Member; Department of Economics; College of Administrative Sciences and Economics; 108638We study the problem of assigning objects to a group of agents. We focus on probabilistic methods that take agents' ordinal preferences over the objects. Importantly, we allow for indifferences among objects. Katta and Sethuraman (2006) propose the extended serial correspondence to solve this problem. Our main result is a characterization of the extended serial correspondence in welfare terms by means of stochastic dominance efficiency, stochastic dominance no-envy and "limited invariance," a requirement we adapt from Heo (2014a). We also prove that an assignment matrix is selected by the extended serial correspondence if and only if it satisfies "non-wastefulness" and "ordinal fairness," which we adapt from Kesten et al.Publication Open Access A class of Banach algebras whose duals have the Schur property(TÜBİTAK, 1999) Mustafayev, H.; Department of Mathematics; Ülger, Ali; Faculty Member; Department of Mathematics; College of SciencesCall a commutative Banach algebra A a γ-algebra if it contains a bounded group Λ such that aco(Λ) contains a multiple of the unit ball of A. In this paper, first by exhibiting several concrete examples, we show that the class of γ-algebras is quite rich. Then, for a γ-algebra A, we prove that A* has the Schur property iff the Gelfand spectrum Σ of A is scattered iff A* = ap(A) iff A* = Span(Σ).Publication Open Access A clinical comparison of home-based and hospital-based exercise programs following arthroscopic capsulolabral repair for anterior shoulder instability(Human Kinetics, 2020) Atalar, Ata Can; Eren, Şule Meral; Uçak, Ayla; Çerezci, Önder; Eren, İlker; Canbulat, Nazan; Demirhan, Mehmet; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 168021; 58534; 9882Context: ideal rehabilitation method following arthroscopic capsulolabral repair surgery for anterior shoulder instability has not been proven yet. Although rapid or slow protocols were compared previously, home- or hospital-based protocols were not questioned before. Objective: the aim of this prospective unrandomized controlled clinical trial is to compare the clinical outcomes of home-based and hospital-based rehabilitation programs following arthroscopic Bankart repair. Design: non-randomized controlled trial. Setting: orthopedics and physical therapy units of a single institution. Patients: fifty-four patients (49 males and 5 females) with an average age of 30.5 (9.1) years, who underwent arthroscopic capsulolabral repair and met the inclusion criteria, with at least 1-year follow-up were allocated into 2 groups: home-based (n = 33) and hospital-based (n = 21) groups. Interventions: both groups received identical rehabilitation programs. Patients in the home-based group were called for follow-up every 3 weeks. Patients in the hospital-based group admitted for therapy every other day for a total of 6 to 8 weeks. Both groups were followed identically after the eighth week and the rehabilitation program continued for 6 months. Main Outcome Measures: Clinical outcomes were assessed using Disabilities of Arm Shoulder Hand, Constant, and Rowe scores. Mann-Whitney U test was used to compare the results in both groups. Wilcoxon test was used for determining the progress in each group. Results: groups were age and gender matched (P =.61, P =.69). Average number of treatment sessions was 13.8 (7.3) for patients in the hospital-based group. Preoperative Disabilities of Arm Shoulder Hand (27.46 [11.81] vs 32.53 [16.42], P =.22), Constant (58.23 [14.23] vs 54.17 [10.46], P =.13), and Rowe (51.72 [15.36] vs 43.81 [19.16], P =.12) scores were similar between groups. Postoperative scores at sixth month were significantly improved in each group (P =.001, P =.001, and P =.001). No significant difference was observed between 2 groups regarding clinical scores in any time point. Conclusions: we have, therefore, concluded that a controlled home-based exercise program is as effective as hospital-based rehabilitation following arthroscopic capsulolabral repair for anterior shoulder instability.Publication Open Access A clinical scoring system to predict the development of bronchopulmonary dysplasia(Thieme Medical Publishers, 2015) Hayran, Mutlu; Derin, Hatice; Ovalı, Fahri; N/A; Gürsoy, Tuğba; Faculty Member; School of Medicine; 214691Objective: This study aims to develop a scoring system for the prediction of bronchopulmonary dysplasia (BPD). Methods: Medical records of 652 infants whose gestational age and birth weight were below 32 weeks and 1,500g, respectively, and who survived beyond 28th postnatal day were reviewed retrospectively. Logistic regression methods were used to determine the clinical and demographic risk factors within the first 72 hours of life associated with BPD, as well as the weights of these factors on developing BPD. Predictive accuracy of the scoring system was tested prospectively at the same unit. ResultsBirth weight, gestational age, gender, presence of respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, hypotension were the most important risk factors for BPD. Therefore, a scoring system (BPD-TM score) ranging from 0 to 13 and grouped in four tiers (0-3: low, 4-6: low intermediate, 7-9: high intermediate, and 10-13: high risk) was developed based on these factors. Below the score of 4, 4.1% of infants (18/436), above the score of 9, 100% (29/29) of the infants developed BPD. The score was validated successfully in 172 infants. Conclusion: With this easy to use scoring system, one can predict the neonate at risk for BPD at 72 hours of life and direct preventive measures toward these infants.Publication Open Access A combined diagnosis and treatment algorithm for spine infection management: a single-center experience(Springer Nature, 2022) Başak, Ahmet Tulgar; Hekimoğlu, Mehdi; Çerezci, Önder; Çakıcı, Nazlı; Özbek, Muhammet; Ateş, Özkan; Öktenoğlu, Bekir Tunç; Sasani, Mehdi; Özer, Ali Fahir; Faculty Member; Faculty Member; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; N/A; 220898; N/A; 1022Background and objective: Spinal infection (SI) is an infectious disease affecting the vertebral column, spinal cord, and adjacent structures. The infection can occur following interventions or spontaneously. The aim of this study was to highlight the importance of employing a methodological approach for the accurate and rapid diagnosis of SI and to share information on the most effective treatment method, which involves using a diagnostictreatment algorithm that can help with SI management. Methodology: this study included 50 patients diagnosed with SI between 2016 and 2020. The treatment follow-up period was limited to six months, and the study was conducted as a retrospective cohort analysis. The sample consisted of 22 female patients and 28 male patients, and the mean age of the patients was 50.2 years. All patients received diagnosis and treatment according to the algorithm described in this article. Results: in the study group, 60% of patients had an infection in the lumbar spine, 4% in the thoracal spine, 12% in the cervical spine, and 8% in the sacral spine. Previously operated patients were diagnosed on the 30.16th day on average. A total of 19 patients (38%) had no history of undergoing surgery. Radiologically, the most common finding was spondylodiscitis/discitis (32%). Osteomyelitis was detected in one (2%) patient. Methicillin-sensitive Staphylococcus aureus (MSSA) was the most commonly isolated organism in culture results and was detected in 13 patients (26%). The culture results of 12 patients (24%) were negative. The number of patients with active SI who were unstable and stabilized at the time of diagnosis was 11 (22%), and stabilization materials were removed in two patients (4%). In the 6th month of control, the patients did not have any complaints, signs of an infection, or unstable vertebral column. Conclusions: we conclude that the combined algorithm we recommend for the diagnosis and treatment of patients with SI can prevent negative deviation and is an effective treatment for this condition.Publication Open Access A combined VBM and DTI study of schizophrenia: bilateral decreased insula volume and cerebral white matter disintegrity corresponding to subinsular white matter projections unlinked to clinical symptomatology(Aves, 2017) Ulaşoğlu-Yıldız, Çiğdem; Aslan, Selçuk; Talı, Erhan Turgut; N/A; N/A; Onay, Aslıhan; Eser, Hale Yapıcı; Faculty Member; School of Medicine; N/A; 134359PURPOSE: Grey matter and white matter changes within the brain are well defined in schizophrenia. However, most studies focused on either grey matter changes or white matter integrity separately; only in limited number of studies these changes were interpreted in the same frame. In addition, the relationship of these findings with clinical variables is not clearly established. Here, we aimed to investigate the grey matter and white matter changes in schizophrenia patients and exhibit the relation of these imaging findings with clinical variables. METHODS: A total of 20 schizophrenia patients and 16 matched healthy controls underwent magnetic resonance imaging to investigate the grey matter and white matter alterations that occur in schizophrenia patients using voxel-based morphometry (VBM) and whole brain voxel-wise analysis of diffusion tensor imaging (DTI) parameters with SPM8, respectively. While the preprocessing steps ofVBM were performed with the default parameters of VBM8 toolbox, the preprocessing steps of DTI were carried out using FSL. Additionally, VBM results were correlated with clinical variables. RESULTS: Bilateral insula showed decreased grey matter volume in schizophrenia patients compared with healthy controls (P < 0.01). The opposite contrast did not show a significant difference. Psychiatric scores, duration of illness, and age were not correlated with the decreased grey matter volume of insula in schizophrenia patients. DTI analysis revealed a significant increase in mean, radial, and axial diffusivity, mainly of the fibers of bilateral anterior thalamic radiation and superior longitudinal fasciculus with left predominance, which intersected with bilateral subinsular white matter (P < 0.05). CONCLUSION: Our findings suggest that insula may be the main affected brain region in schizophrenia, which is also well supported by the literature. Our results were independent of disease duration and schizophrenia symptoms. White matter alterations were observed within bilateral anterior thalamic radiation and superior longitudinal fasciculus that intersects with subinsular white matter. Studies with larger sample sizes and more detailed clinical assessments are required to understand the function of insula in the neurobiology of schizophrenia.Publication Open Access A common genetic variation of melanoma inhibitory activity-2 labels a subtype of pancreatic adenocarcinoma with high endoplasmic reticulum stress levels.(Nature Publishing Group (NPG), 2015) Kong, Bo; Wu, Weiwei; Valkovska, Nataliya; Jager, Carsten; Hong, Xin; Nitsche, Ulrich; Friess, Helmut; Esposito, Irene; Kleeff, Joerg; Michalski, Christoph W.; N/A; Erkan, Murat Mert; Faculty Member; School of Medicine; 214689HNF1 homeoboxA(HNF1A)-mediated gene expression constitutes an essential component of the secretory pathway in the exocrine pancreas. Melanoma inhibitory activity 2 (MIA2), a protein facilitating protein secretion, is an HNF1A target. Protein secretion is precisely coordinated by the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) system. Here, we demonstrate that HNFA and MIA2 are expressed in a subset of human PDAC tissues and that HNF1A induced MIA2 in vitro. We identified a common germline variant of MIA2 (c.A617G:p.I141M) associated with a secretory defect of the MIA2 protein in PDAC cells. Patients carrying MIA2(I141M) survived longer after tumor resection but the survival benefit was restricted to those patients who received adjuvant chemotherapy. The MIA2(I141M) variant was associated with high expression of ER stress/UPR genes - in particular those of the ERN1/XBP arm - in human PDAC samples. Accordingly, PDAC cell lines expressing the MIA2(I141M) variant expressed high levels of ERN1 and were more sensitive to gemcitabine. These findings define an interaction between the common MIA2(I141M) variant and the ER stress/UPR system and specify a subgroup of PDAC patients who are more likely to benefit from adjuvant chemotherapy.Publication Open Access A communication theoretical analysis of FRET-based mobile ad hoc molecular nanonetworks(Institute of Electrical and Electronics Engineers (IEEE), 2014) Kuşcu, Murat; Akan, Özgür Barış; Faculty Member; College of EngineeringNanonetworks refer to a group of nano-sized machines with very basic operational capabilities communicating to each other in order to accomplish more complex tasks such as in-body drug delivery, or chemical defense. Realizing reliable and high-rate communication between these nanomachines is a fundamental problem for the practicality of these nanonetworks. Recently, we have proposed a molecular communication method based on Forster Resonance Energy Transfer (FRET) which is a nonradiative excited state energy transfer phenomenon observed among fluorescent molecules, i.e., fluorophores. We have modeled the FRET-based communication channel considering the fluorophores as single-molecular immobile nanomachines, and shown its reliability at high rates, and practicality at the current stage of nanotechnology. In this study, for the first time in the literature, we investigate the network of mobile nanomachines communicating through FRET. We introduce two novel mobile molecular nanonetworks: FRET-based mobile molecular sensor/actor nanonetwork (FRET-MSAN) which is a distributed system of mobile fluorophores acting as sensor or actor node; and FRET-based mobile ad hoc molecular nanonetwork (FRETMAMNET) which consists of fluorophore-based nanotransmitter, nanoreceivers and nanorelays. We model the single message propagation based on birth death processes with continuous time Markov chains. We evaluate the performance of FRETMSAN and FRET-MAMNET in terms of successful transmission probability and mean extinction time of the messages, system throughput, channel capacity and achievable communication rates.