Search results for: modal excitation

Authors: Wonil Nam, Xiang Ren, Inyoung Kim, Masoud Agah, Wei Zhou

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Despite its ultrasensitive detection capability, surface-enhanced Raman spectroscopy (SERS) faces challenges as a quantitative biochemical analysis tool due to the significant dependence of local field intensity in hotspots on nanoscale geometric variations of plasmonic nanostructures. Therefore, despite enormous progress in plasmonic nanoengineering of high-performance SERS devices, it is still challenging to quantitatively correlate the measured SERS signals with the actual molecule concentrations at hotspots. A significant effort has been devoted to developing SERS calibration methods by introducing internal standards. It has been achieved by placing Raman tags at plasmonic hotspots. Raman tags undergo similar SERS enhancement at the same hotspots, and ratiometric SERS signals for analytes of interest can be generated with reduced dependence on geometrical variations. However, using Raman tags still faces challenges for real-world applications, including spatial competition between the analyte and tags in hotspots, spectral interference, laser-induced degradation/desorption due to plasmon-enhanced photochemical/photothermal effects. We show that electronic Raman scattering (ERS) signals from metallic nanostructures at hotspots can serve as the internal calibration standard to enable quantitative SERS analysis and improve biostatistical analysis. We perform SERS with Au-SiO₂ multilayered metal-insulator-metal nano laminated plasmonic nanostructures. Since the ERS signal is proportional to the volume density of electron-hole occupation in hotspots, the ERS signals exponentially increase when the wavenumber is approaching the zero value. By a long-pass filter, generally used in backscattered SERS configurations, to chop the ERS background continuum, we can observe an ERS pseudo-peak, IERS. Both ERS and SERS processes experience the |E|⁴ local enhancements during the excitation and inelastic scattering transitions. We calibrated IMRS of 10 μM Rhodamine 6G in solution by IERS. The results show that ERS calibration generates a new analytical value, ISERS/IERS, insensitive to variations from different hotspots and thus can quantitatively reflect the molecular concentration information. Given the calibration capability of ERS signals, we performed label-free SERS analysis of living biological systems using four different breast normal and cancer cell lines cultured on nano-laminated SERS devices. 2D Raman mapping over 100 μm × 100 μm, containing several cells, was conducted. The SERS spectra were subsequently analyzed by multivariate analysis using partial least square discriminant analysis. Remarkably, after ERS calibration, MCF-10A and MCF-7 cells are further separated while the two triple-negative breast cancer cells (MDA-MB-231 and HCC-1806) are more overlapped, in good agreement with the well-known cancer categorization regarding the degree of malignancy. To assess the strength of ERS calibration, we further carried out a drug efficacy study using MDA-MB-231 and different concentrations of anti-cancer drug paclitaxel (PTX). After ERS calibration, we can more clearly segregate the control/low-dosage groups (0 and 1.5 nM), the middle-dosage group (5 nM), and the group treated with half-maximal inhibitory concentration (IC50, 15 nM). Therefore, we envision that ERS calibrated SERS can find crucial opportunities in label-free molecular profiling of complicated biological systems.

Keywords: cancer cell drug efficacy, plasmonics, surface-enhanced Raman spectroscopy (SERS), SERS calibration

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Authors: Kareem Abdelwahed, Ahmed Salama, Ahmed Rabie, Ahmed Hamdy, Waleed Abdelfattah, Ahmed Abd El-Rahman

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Conventional vapor-compression refrigeration systems rely on typical refrigerants, such as CFC, HCFC and ammonia. Despite of their suitable thermodynamic properties and their stability in the atmosphere, their corresponding global warming potential and ozone depletion potential raise concerns about their usage. Thus, the need for new refrigeration systems, which are environment-friendly, inexpensive and simple in construction, has strongly motivated the development of thermoacoustic energy conversion systems. A thermoacoustic refrigerator (TAR) is a device that is mainly consisting of a resonator, a stack and two heat exchangers. Typically, the resonator is a long circular tube, made of copper or steel and filled with Helium as a the working gas, while the stack has short and relatively low thermal conductivity ceramic parallel plates aligned with the direction of the prevailing resonant wave. Typically, the resonator of a standing-wave refrigerator has one end closed and is bounded by the acoustic driver at the other end enabling the propagation of half-wavelength acoustic excitation. The hot and cold heat exchangers are made of copper to allow for efficient heat transfer between the working gas and the external heat source and sink respectively. TARs are interesting because they have no moving parts, unlike conventional refrigerators, and almost no environmental impact exists as they rely on the conversion of acoustic and heat energies. Their fabrication process is rather simpler and sizes span wide variety of length scales. The viscous and thermal interactions between the stack plates, heat exchangers' plates and the working gas significantly affect the flow field within the plates' channels, and the energy flux density at the plates' surfaces, respectively. Here, the design, the manufacture and the testing of a compact refrigeration system that is based on the thermoacoustic energy-conversion technology is reported. A 1-D linear acoustic model is carefully and specifically developed, which is followed by building the hardware and testing procedures. The system consists of two harmonically-oscillating pistons driven by a simple 1-HP rotary drive mechanism operating at a frequency of 42Hz -hereby, replacing typical expensive linear motors and loudspeakers-, and a thermoacoustic stack within which the energy conversion of sound into heat is taken place. Air at ambient conditions is used as the working gas while the amplitude of the driver's displacement reaches 19 mm. The 30-cm-long stack is a simple porous ceramic material having 100 square channels per square inch. During operation, both oscillating-gas pressure and solid-stack temperature are recorded for further analysis. Measurements show a maximum temperature difference of about 27 degrees between the stack hot and cold ends with a Carnot coefficient of performance of 11 and estimated cooling capacity of five Watts, when operating at ambient conditions. A dynamic pressure of 7-kPa-amplitude is recorded, yielding a drive ratio of 7% approximately, and found in a good agreement with theoretical prediction. The system behavior is clearly non-linear and significant non-linear loss mechanisms are evident. This work helps understanding the operation principles of thermoacoustic refrigerators and presents a keystone towards developing commercial thermoacoustic refrigerator units.

Keywords: refrigeration system, rotary drive mechanism, standing-wave, thermoacoustic refrigerator

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Authors: Mian Huang, Chi Ma, Junyu Lin, William Lu

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Introduction: Bone health attracts more attention recently and an intelligent question and answer (QA) chatbot for osteoporosis is helpful for science popularization. With Generative Pretrained Transformer (GPT) technology developing, we build an osteoporosis corpus dataset and then fine-tune LLaMA, a famous open-source GPT foundation large language model(LLM), on our self-constructed osteoporosis corpus. Evaluated by clinical orthopedic experts, our fine-tuned model outperforms vanilla LLaMA on osteoporosis QA task in Chinese. Three-dimensional quantitative computed tomography (QCT) measured bone mineral density (BMD) is considered as more accurate than DXA for BMD measurement in recent years. We develop an automatic Phantom-less QCT(PL-QCT) that is more efficient for BMD measurement since no need of an external phantom for calibration. Combined with LLM on osteoporosis, our PL-QCT provides efficient and accurate BMD measurement for our chatbot users. Material and Methods: We build an osteoporosis corpus containing about 30,000 Chinese literatures whose titles are related to osteoporosis. The whole process is done automatically, including crawling literatures in .pdf format, localizing text/figure/table region by layout segmentation algorithm and recognizing text by OCR algorithm. We train our model by continuous pre-training with Low-rank Adaptation (LoRA, rank=10) technology to adapt LLaMA-7B model to osteoporosis domain, whose basic principle is to mask the next word in the text and make the model predict that word. The loss function is defined as cross-entropy between the predicted and ground-truth word. Experiment is implemented on single NVIDIA A800 GPU for 15 days. Our automatic PL-QCT BMD measurement adopt AI-associated region-of-interest (ROI) generation algorithm for localizing vertebrae-parallel cylinder in cancellous bone. Due to no phantom for BMD calibration, we calculate ROI BMD by CT-BMD of personal muscle and fat. Results & Discussion: Clinical orthopaedic experts are invited to design 5 osteoporosis questions in Chinese, evaluating performance of vanilla LLaMA and our fine-tuned model. Our model outperforms LLaMA on over 80% of these questions, understanding ‘Expert Consensus on Osteoporosis’, ‘QCT for osteoporosis diagnosis’ and ‘Effect of age on osteoporosis’. Detailed results are shown in appendix. Future work may be done by training a larger LLM on the whole orthopaedics with more high-quality domain data, or a multi-modal GPT combining and understanding X-ray and medical text for orthopaedic computer-aided-diagnosis. However, GPT model gives unexpected outputs sometimes, such as repetitive text or seemingly normal but wrong answer (called ‘hallucination’). Even though GPT give correct answers, it cannot be considered as valid clinical diagnoses instead of clinical doctors. The PL-QCT BMD system provided by Bone’s QCT(Bone’s Technology(Shenzhen) Limited) achieves 0.1448mg/cm2(spine) and 0.0002 mg/cm2(hip) mean absolute error(MAE) and linear correlation coefficient R2=0.9970(spine) and R2=0.9991(hip)(compared to QCT-Pro(Mindways)) on 155 patients in three-center clinical trial in Guangzhou, China. Conclusion: This study builds a Chinese osteoporosis corpus and develops a fine-tuned and domain-adapted LLM as well as a PL-QCT BMD measurement system. Our fine-tuned GPT model shows better capability than LLaMA model on most testing questions on osteoporosis. Combined with our PL-QCT BMD system, we are looking forward to providing science popularization and early morning screening for potential osteoporotic patients.

Keywords: GPT, phantom-less QCT, large language model, osteoporosis

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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Authors: Teesta Dey

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Integrated Transport development with proper traffic management leads to sustainable growth of any urban sphere. Appropriate mass transport planning is essential for the populous cities in third world countries like India. The exponential growth of motor vehicles with unplanned road network is now the common feature of major urban centres in India. Kolkata, the third largest mega city in India, is not an exception of it. The imbalance between demand and supply of unplanned transport services in this city is manifested in the high economic and environmental costs borne by the associated society. With the passage of time, the growth and extent of passenger demand for rapid urban transport has outstripped proper infrastructural planning and causes severe transport problems in the overall urban realm. Hence Kolkata stands out in the world as one of the most crisis-ridden metropolises. The urban transport crisis of this city involves severe traffic congestion, the disparity in mass transport services on changing peripheral land uses, route overlapping, lowering of travel speed and faulty implementation of governmental plans as mostly induced by rapid growth of private vehicles on limited road space with huge carbon footprint. Therefore the paper will critically analyze the extant road network pattern for improving regional connectivity and accessibility, assess the degree of congestion, identify the deviation from demand and supply balance and finally evaluate the emerging alternate transport options as promoted by the government. For this purpose, linear, nodal and spatial transport network have been assessed based on certain selected indices viz. Road Degree, Traffic Volume, Shimbel Index, Direct Bus Connectivity, Average Travel and Waiting Tine Indices, Route Variety, Service Frequency, Bus Intensity, Concentration Analysis, Delay Rate, Quality of Traffic Transmission, Lane Length Duration Index and Modal Mix. Total 20 Traffic Intersection Points (TIPs) have been selected for the measurement of nodal accessibility. Critical Congestion Zones (CCZs) are delineated based on one km buffer zones of each TIP for congestion pattern analysis. A total of 480 bus routes are assessed for identifying the deficiency in network planning. Apart from bus services, the combined effects of other mass and para transit modes, containing metro rail, auto, cab and ferry services, are also analyzed. Based on systematic random sampling method, a total of 1500 daily urban passengers’ perceptions were studied for checking the ground realities. The outcome of this research identifies the spatial disparity among the 15 boroughs of the city with severe route overlapping and congestion problem. North and Central Kolkata-based mass transport services exceed the transport strength of south and peripheral Kolkata. Faulty infrastructural condition, service inadequacy, economic loss and workers’ inefficiency are the most dominant reasons behind the defective mass transport network plan. Hence there is an urgent need to revive the extant road based mass transport system of this city by implementing a holistic management approach by upgrading traffic infrastructure, designing new roads, better cooperation among different mass transport agencies, better coordination of transport and changing land use policies, large increase in funding and finally general passengers’ awareness.

Keywords: carbon footprint, critical congestion zones, direct bus connectivity, integrated transport development

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Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

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Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

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Authors: M. Agostini, A. Sonato, G. Greco, M. Travagliati, G. Ruffato, E. Gazzola, D. Liuni, F. Romanato, M. Cecchini

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Since their first demonstration in the early 1980s, surface plasmon resonance (SPR) sensors have been widely recognized as useful tools for detecting chemical and biological species, and the interest of the scientific community toward this technology has known a rapid growth in the past two decades owing to their high sensitivity, label-free operation and possibility of real-time detection. Recent works have suggested that a turning point in SPR sensor research would be the combination of SPR strategies with other technologies in order to reduce human handling of samples, improve integration and plasmonic sensitivity. In this light, microfluidics has been attracting growing interest. By properly designing microfluidic biochips it is possible to miniaturize the analyte-sensitive areas with an overall reduction of the chip dimension, reduce the liquid reagents and sample volume, improve automation, and increase the number of experiments in a single biochip by multiplexing approaches. However, as the fluidic channel dimensions approach the micron scale, laminar flows become dominant owing to the low Reynolds numbers that typically characterize microfluidics. In these environments mixing times are usually dominated by diffusion, which can be prohibitively long and lead to long-lasting biochemistry experiments. An elegant method to overcome these issues is to actively perturb the liquid laminar flow by exploiting surface acoustic waves (SAWs). With this work, we demonstrate a new approach for SPR biosensing based on the combination of microfluidics, SAW-induced mixing and the real-time phase-interrogation grating-coupling SPR technology. On a single lithium niobate (LN) substrate the nanostructured SPR sensing areas, interdigital transducer (IDT) for SAW generation and polydimethylsiloxane (PDMS) microfluidic chambers were fabricated. SAWs, impinging on the microfluidic chamber, generate acoustic streaming inside the fluid, leading to chaotic advection and thus improved fluid mixing, whilst analytes binding detection is made via SPR method based on SPP excitation via gold metallic grating upon azimuthal orientation and phase interrogation. Our device has been fully characterized in order to separate for the very first time the unwanted SAW heating effect with respect to the fluid stirring inside the microchamber that affect the molecules binding dynamics. Avidin/biotin assay and thiol-polyethylene glycol (bPEG-SH) were exploited as model biological interaction and non-fouling layer respectively. Biosensing kinetics time reduction with SAW-enhanced mixing resulted in a ≈ 82% improvement for bPEG-SH adsorption onto gold and ≈ 24% for avidin/biotin binding—≈ 50% and 18% respectively compared to the heating only condition. These results demonstrate that our biochip can significantly reduce the duration of bioreactions that usually require long times (e.g., PEG-based sensing layer, low concentration analyte detection). The sensing architecture here proposed represents a new promising technology satisfying the major biosensing requirements: scalability and high throughput capabilities. The detection system size and biochip dimension could be further reduced and integrated; in addition, the possibility of reducing biological experiment duration via SAW-driven active mixing and developing multiplexing platforms for parallel real-time sensing could be easily combined. In general, the technology reported in this study can be straightforwardly adapted to a great number of biological system and sensing geometry.

Keywords: biosensor, microfluidics, surface acoustic wave, surface plasmon resonance

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Authors: David J. Foran, Nhan Do, Samuel Ajjarapu, Wenjin Chen, Tahsin Kurc, Joel H. Saltz

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The large-scale data and computational requirements of investigators throughout the clinical and research communities demand an informatics infrastructure that supports both existing and new investigative and translational projects in a robust, secure environment. In some subspecialties of medicine and research, the capacity to generate data has outpaced the methods and technology used to aggregate, organize, access, and reliably retrieve this information. Leading health care centers now recognize the utility of establishing an enterprise-wide, clinical data warehouse. The primary benefits that can be realized through such efforts include cost savings, efficient tracking of outcomes, advanced clinical decision support, improved prognostic accuracy, and more reliable clinical trials matching. The overarching objective of the work presented here is the development and implementation of a flexible Intelligent Retrieval and Interrogation System (IRIS) that exploits the combined use of computational imaging, genomics, and data-mining capabilities to facilitate clinical assessments and translational research in oncology. The proposed System includes a multi-modal, Clinical & Research Data Warehouse (CRDW) that is tightly integrated with a suite of computational and machine-learning tools to provide insight into the underlying tumor characteristics that are not be apparent by human inspection alone. A key distinguishing feature of the System is a configurable Extract, Transform and Load (ETL) interface that enables it to adapt to different clinical and research data environments. This project is motivated by the growing emphasis on establishing Learning Health Systems in which cyclical hypothesis generation and evidence evaluation become integral to improving the quality of patient care. To facilitate iterative prototyping and optimization of the algorithms and workflows for the System, the team has already implemented a fully functional Warehouse that can reliably aggregate information originating from multiple data sources including EHR’s, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Radiology PAC systems, Digital Pathology archives, Unstructured Clinical Documents, and Next Generation Sequencing services. The System enables physicians to systematically mine and review the molecular, genomic, image-based, and correlated clinical information about patient tumors individually or as part of large cohorts to identify patterns that may influence treatment decisions and outcomes. The CRDW core system has facilitated peer-reviewed publications and funded projects, including an NIH-sponsored collaboration to enhance the cancer registries in Georgia, Kentucky, New Jersey, and New York, with machine-learning based classifications and quantitative pathomics, feature sets. The CRDW has also resulted in a collaboration with the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) at the U.S. Department of Veterans Affairs to develop algorithms and workflows to automate the analysis of lung adenocarcinoma. Those studies showed that combining computational nuclear signatures with traditional WHO criteria through the use of deep convolutional neural networks (CNNs) led to improved discrimination among tumor growth patterns. The team has also leveraged the Warehouse to support studies to investigate the potential of utilizing a combination of genomic and computational imaging signatures to characterize prostate cancer. The results of those studies show that integrating image biomarkers with genomic pathway scores is more strongly correlated with disease recurrence than using standard clinical markers.

Keywords: clinical data warehouse, decision support, data-mining, intelligent databases, machine-learning.

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