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Publication Open Access “Noise Factory”: a qualitative study exploring healthcare providers’ perceptions of noise in the intensive care unit(Elsevier, 2020) Güner, Perihan; Kebapçı, Ayda; Faculty Member; School of Nursing; 203808Objectives: this study aimed to explore healthcare providers’ perceptions of noise in the intensive care unit. Design: a qualitative exploratory study was conducted using group interviews. Setting: the setting comprised a total of 15 participants (five physicians and ten registered nurses) working in an 18-bed medical surgical intensive care unit at a teaching hospital in Istanbul, Turkey. Semi-structured questions were formulated and used in focus group interviews, after which the recorded interviews were transcribed by the researchers. Thematic analysis was used to identify significant statements and initial codes. Findings: four themes were identified: the meaning of noise, sources of noise, effects of noise and prevention and management of noise. It was found that noise was an inevitable feature of the intensive care unit. The most common sources of noise were human-induced. It was also determined that device-induced noise, such as alarms, did not produce a lot of noise; however, when staff were late in responding, the sound transformed into noise. Furthermore, it was observed that efforts to decrease noise levels taken by staff had only a momentary effect, changing nothing in the long term because the entire team failed to implement any initiatives consistently. The majority of nurses stated that they were now becoming insensitive to the noise due to the constant exposure to device-induced noise. Conclusion: the data obtained from this study showed that especially human-induced noise threatened healthcare providers’ cognitive task functions, concentration and job performance, impaired communication and negatively affected patient safety. In addition, it was determined that any precautions taken to reduce noise were not fully effective. A team approach should be used in managing noise in intensive care units with better awareness.Publication Open Access "Whole" vs "fragmented" approach to EAACI pollen season definitions: a multicenter study in six Southern European cities(Wiley, 2020) Hoffmann, Tara Maria; Şahin, Aydan Acar; Aggelidis, Xenophon; Arasi, Stefania; Barbalace, Andrea; Bourgoin, Anne; Bregu, Blerina; Brighetti, Maria Antonia; Caeiro, Elsa; Sozmen, Sule Caglayan; Caminiti, Lucia; Charpin, Denis; Couto, Mariana; Delgado, Luis; Businco, Andrea Di Rienzo; Dimier, Claire; Dimou, Maria, V; Fonseca, Joao A.; Göksel, Özlem; Güvensen, Aykut; Hernandez, Dolores; Jang, Dah Tay; Kalpaklıoğlu, Füsun; Lame, Blerta; Llusar, Ruth; Makris, Michael P.; Mazon, Angel; Mesonjesi, Eris; Nieto, Antonio; Pahus, Laurie; Pajno, Giovanni Battista; Panasiti, Ilenia; Panetta, Valentina; Papadopoulos, Nikolaos G.; Pellegrini, Elisabetta; Pelosi, Simone; Pereira, Ana Margarida; Pereira, Mariana; Pinar, Munevver; Pfaar, Oliver; Potapova, Ekaterina; Priftanji, Alfred; Psarros, Fotis; Sfika, Ifigenia; Suarez, Javier; Thibaudon, Michel; Travaglini, Alessandro; Tripodi, Salvatore; Verdier, Valentine; Villella, Valeria; Xepapadaki, Paraskevi; Matricardi, Paolo M.; Dramburg, Stephanie; Öztürk, Ayşe Bilge; Saçkesen, Cansın; Yazıcı, Duygu; Faculty Member; Faculty Member; PhD Student; 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; 147629; 182537; N/ABackground: the adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. Objective To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. Methods: as part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. Results: the analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). Conclusion: the Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.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 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 microrobots from design to translation(Nature Portfolio, 2022) Department of Mechanical Engineering; N/A; Dabbagh, Sajjad Rahmani; Sarabi, Misagh Rezapour; Birtek, Mehmet Tuğrul; Sitti, Metin; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; 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); Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; Graduate School of Sciences and Engineering; School of Medicine; College of Engineering; N/A; N/A; N/A; N/A; 297104; 291971Microrobots have attracted the attention of scientists owing to their unique features to accomplish tasks in hard-to-reach sites in the human body. Microrobots can be precisely actuated and maneuvered individually or in a swarm for cargo delivery, sampling, surgery, and imaging applications. In addition, microrobots have found applications in the environmental sector (e.g., water treatment). Besides, recent advancements of three-dimensional (3D) printers have enabled the high-resolution fabrication of microrobots with a faster design-production turnaround time for users with limited micromanufacturing skills. Here, the latest end applications of 3D printed microrobots are reviewed (ranging from environmental to biomedical applications) along with a brief discussion over the feasible actuation methods (e.g., on- and off-board), and practical 3D printing technologies for microrobot fabrication. In addition, as a future perspective, we discussed the potential advantages of integration of microrobots with smart materials, and conceivable benefits of implementation of artificial intelligence (AI), as well as physical intelligence (PI). Moreover, in order to facilitate bench-to-bedside translation of microrobots, current challenges impeding clinical translation of microrobots are elaborated, including entry obstacles (e.g., immune system attacks) and cumbersome standard test procedures to ensure biocompatibility.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 19-year-old pregnant woman with pulmonary hypertension with progressive dyspnea(Elsevier, 2021) Avcı, Burçak Kılıçkıran; Tok, Özge Özden; Öngen, Zeki; Bozkaya, Tijen Alkan; Kalangos, Afksendiyos; Doctor; Faculty Member; School of Medicine; Koç University Hospital; N/A; 286247Case presentation: a 19-year-old pregnant woman at week 32 of gestation was referred to our clinic with progressive shortness of breath for the further evaluation and treatment of high-risk pregnancy. Her complaints had been existing since her childhood. Two years prior to her admission, she had been diagnosed with heart failure with preserved ejection fraction due to cardiomyopathy and associated pulmonary hypertension. The patient had no family history of any cardiac disease. She had never smoked or drunk alcohol. Her clinical condition had deteriorated progressively with the pregnancy.Publication Open Access A brand-new cardiorenal syndrome in the Coronavirus Disease- 2019 (COVID-19) setting(Oxford University Press (OUP), 2020) Apetrii, Mugurel; Enache, Stefana; Siriopol, Dimitrie; Burlacu, Alexandru; Kanbay, Asiye; Scripcariu, Dragos; Covic, Adrian; Kanbay, Mehmet; Faculty Member; School of Medicine; 110580Coronaviruses are a major pathogen for adults, causing up to one-third of community-acquired respiratory tract infections in adults during epidemics. Although the pandemic outbreak of coronavirus disease-2019 (COVID-19) targets preferentially patient’s lungs, recent data have documented that COVID-19 causes myocarditis, acute myocardial infarction, exacerbation of heart failure and acute kidney injury. Studies show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similar to its predecessor SARS-CoV, engages angiotensin-converting enzyme 2 (ACE2) as the entry receptor. ACE2 is also expressed in the heart, providing a link between coronaviruses and the cardiovascular system.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.