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1. Forecasting of In Situ Electron Energy Loss Spectroscopy

   Nicholas R. Lewis Yicheng Jin, Xiuyu Tang ( July 2022 , Computational materials)

   Forecasting models are a central part of many control systems, where high consequence decisions must be made on long latency control variables. These models are particularly relevant for emerging artificial intelligence (AI)-guided instrumentation, in which prescriptive knowledge is needed to guide autonomous decision-making. Here we describe the implementation of a long short-term memory model (LSTM) for forecasting of electron energy loss spectroscopy (EELS) data, one of the richest analytical probes of materials and chemical systems. We describe key considerations for data collection, preprocessing, training, validation, and benchmarking, showing how this approach can yield powerful predictive insight into order-disorder phase transitions. Finally, we comment on how such a model may integrate with emerging AI-guided instrumentation for powerful high-speed experimentation.
2. The Temple University Digital Pathology Corpus: The Breast Tissue Subset

   https://doi.org/10.1109/SPMB52430.2021.9672275  

   Wevodau, Z. ; Doshna, B. ; Jhala, N. ; Akhtar, I. ; Obeid, I. ; Picone, J. ( December 2021 , Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB))

   Obeid, I. (Ed.)

   The Neural Engineering Data Consortium (NEDC) is developing the Temple University Digital Pathology Corpus (TUDP), an open source database of high-resolution images from scanned pathology samples [1], as part of its National Science Foundation-funded Major Research Instrumentation grant titled “MRI: High Performance Digital Pathology Using Big Data and Machine Learning” [2]. The long-term goal of this project is to release one million images. We have currently scanned over 100,000 images and are in the process of annotating breast tissue data for our first official corpus release, v1.0.0. This release contains 3,505 annotated images of breast tissue including 74 patients with cancerous diagnoses (out of a total of 296 patients). In this poster, we will present an analysis of this corpus and discuss the challenges we have faced in efficiently producing high quality annotations of breast tissue. It is well known that state of the art algorithms in machine learning require vast amounts of data. Fields such as speech recognition [3], image recognition [4] and text processing [5] are able to deliver impressive performance with complex deep learning models because they have developed large corpora to support training of extremely high-dimensional models (e.g., billions of parameters). Other fields that do notmore »have access to such data resources must rely on techniques in which existing models can be adapted to new datasets [6]. A preliminary version of this breast corpus release was tested in a pilot study using a baseline machine learning system, ResNet18 [7], that leverages several open-source Python tools. The pilot corpus was divided into three sets: train, development, and evaluation. Portions of these slides were manually annotated [1] using the nine labels in Table 1 [8] to identify five to ten examples of pathological features on each slide. Not every pathological feature is annotated, meaning excluded areas can include focuses particular to these labels that are not used for training. A summary of the number of patches within each label is given in Table 2. To maintain a balanced training set, 1,000 patches of each label were used to train the machine learning model. Throughout all sets, only annotated patches were involved in model development. The performance of this model in identifying all the patches in the evaluation set can be seen in the confusion matrix of classification accuracy in Table 3. The highest performing labels were background, 97% correct identification, and artifact, 76% correct identification. A correlation exists between labels with more than 6,000 development patches and accurate performance on the evaluation set. Additionally, these results indicated a need to further refine the annotation of invasive ductal carcinoma (“indc”), inflammation (“infl”), nonneoplastic features (“nneo”), normal (“norm”) and suspicious (“susp”). This pilot experiment motivated changes to the corpus that will be discussed in detail in this poster presentation. To increase the accuracy of the machine learning model, we modified how we addressed underperforming labels. One common source of error arose with how non-background labels were converted into patches. Large areas of background within other labels were isolated within a patch resulting in connective tissue misrepresenting a non-background label. In response, the annotation overlay margins were revised to exclude benign connective tissue in non-background labels. Corresponding patient reports and supporting immunohistochemical stains further guided annotation reviews. The microscopic diagnoses given by the primary pathologist in these reports detail the pathological findings within each tissue site, but not within each specific slide. The microscopic diagnoses informed revisions specifically targeting annotated regions classified as cancerous, ensuring that the labels “indc” and “dcis” were used only in situations where a micropathologist diagnosed it as such. Further differentiation of cancerous and precancerous labels, as well as the location of their focus on a slide, could be accomplished with supplemental immunohistochemically (IHC) stained slides. When distinguishing whether a focus is a nonneoplastic feature versus a cancerous growth, pathologists employ antigen targeting stains to the tissue in question to confirm the diagnosis. For example, a nonneoplastic feature of usual ductal hyperplasia will display diffuse staining for cytokeratin 5 (CK5) and no diffuse staining for estrogen receptor (ER), while a cancerous growth of ductal carcinoma in situ will have negative or focally positive staining for CK5 and diffuse staining for ER [9]. Many tissue samples contain cancerous and non-cancerous features with morphological overlaps that cause variability between annotators. The informative fields IHC slides provide could play an integral role in machine model pathology diagnostics. Following the revisions made on all the annotations, a second experiment was run using ResNet18. Compared to the pilot study, an increase of model prediction accuracy was seen for the labels indc, infl, nneo, norm, and null. This increase is correlated with an increase in annotated area and annotation accuracy. Model performance in identifying the suspicious label decreased by 25% due to the decrease of 57% in the total annotated area described by this label. A summary of the model performance is given in Table 4, which shows the new prediction accuracy and the absolute change in error rate compared to Table 3. The breast tissue subset we are developing includes 3,505 annotated breast pathology slides from 296 patients. The average size of a scanned SVS file is 363 MB. The annotations are stored in an XML format. A CSV version of the annotation file is also available which provides a flat, or simple, annotation that is easy for machine learning researchers to access and interface to their systems. Each patient is identified by an anonymized medical reference number. Within each patient’s directory, one or more sessions are identified, also anonymized to the first of the month in which the sample was taken. These sessions are broken into groupings of tissue taken on that date (in this case, breast tissue). A deidentified patient report stored as a flat text file is also available. Within these slides there are a total of 16,971 total annotated regions with an average of 4.84 annotations per slide. Among those annotations, 8,035 are non-cancerous (normal, background, null, and artifact,) 6,222 are carcinogenic signs (inflammation, nonneoplastic and suspicious,) and 2,714 are cancerous labels (ductal carcinoma in situ and invasive ductal carcinoma in situ.) The individual patients are split up into three sets: train, development, and evaluation. Of the 74 cancerous patients, 20 were allotted for both the development and evaluation sets, while the remain 34 were allotted for train. The remaining 222 patients were split up to preserve the overall distribution of labels within the corpus. This was done in hope of creating control sets for comparable studies. Overall, the development and evaluation sets each have 80 patients, while the training set has 136 patients. In a related component of this project, slides from the Fox Chase Cancer Center (FCCC) Biosample Repository (https://www.foxchase.org/research/facilities/genetic-research-facilities/biosample-repository -facility) are being digitized in addition to slides provided by Temple University Hospital. This data includes 18 different types of tissue including approximately 38.5% urinary tissue and 16.5% gynecological tissue. These slides and the metadata provided with them are already anonymized and include diagnoses in a spreadsheet with sample and patient ID. We plan to release over 13,000 unannotated slides from the FCCC Corpus simultaneously with v1.0.0 of TUDP. Details of this release will also be discussed in this poster. Few digitally annotated databases of pathology samples like TUDP exist due to the extensive data collection and processing required. The breast corpus subset should be released by November 2021. By December 2021 we should also release the unannotated FCCC data. We are currently annotating urinary tract data as well. We expect to release about 5,600 processed TUH slides in this subset. We have an additional 53,000 unprocessed TUH slides digitized. Corpora of this size will stimulate the development of a new generation of deep learning technology. In clinical settings where resources are limited, an assistive diagnoses model could support pathologists’ workload and even help prioritize suspected cancerous cases. ACKNOWLEDGMENTS This material is supported by the National Science Foundation under grants nos. CNS-1726188 and 1925494. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. REFERENCES [1] N. Shawki et al., “The Temple University Digital Pathology Corpus,” in Signal Processing in Medicine and Biology: Emerging Trends in Research and Applications, 1st ed., I. Obeid, I. Selesnick, and J. Picone, Eds. New York City, New York, USA: Springer, 2020, pp. 67 104. https://www.springer.com/gp/book/9783030368432. [2] J. Picone, T. Farkas, I. Obeid, and Y. Persidsky, “MRI: High Performance Digital Pathology Using Big Data and Machine Learning.” Major Research Instrumentation (MRI), Division of Computer and Network Systems, Award No. 1726188, January 1, 2018 – December 31, 2021. https://www. isip.piconepress.com/projects/nsf_dpath/. [3] A. Gulati et al., “Conformer: Convolution-augmented Transformer for Speech Recognition,” in Proceedings of the Annual Conference of the International Speech Communication Association (INTERSPEECH), 2020, pp. 5036-5040. https://doi.org/10.21437/interspeech.2020-3015. [4] C.-J. Wu et al., “Machine Learning at Facebook: Understanding Inference at the Edge,” in Proceedings of the IEEE International Symposium on High Performance Computer Architecture (HPCA), 2019, pp. 331–344. https://ieeexplore.ieee.org/document/8675201. [5] I. Caswell and B. Liang, “Recent Advances in Google Translate,” Google AI Blog: The latest from Google Research, 2020. [Online]. Available: https://ai.googleblog.com/2020/06/recent-advances-in-google-translate.html. [Accessed: 01-Aug-2021]. [6] V. Khalkhali, N. Shawki, V. Shah, M. Golmohammadi, I. Obeid, and J. Picone, “Low Latency Real-Time Seizure Detection Using Transfer Deep Learning,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2021, pp. 1 7. https://www.isip. piconepress.com/publications/conference_proceedings/2021/ieee_spmb/eeg_transfer_learning/. [7] J. Picone, T. Farkas, I. Obeid, and Y. Persidsky, “MRI: High Performance Digital Pathology Using Big Data and Machine Learning,” Philadelphia, Pennsylvania, USA, 2020. https://www.isip.piconepress.com/publications/reports/2020/nsf/mri_dpath/. [8] I. Hunt, S. Husain, J. Simons, I. Obeid, and J. Picone, “Recent Advances in the Temple University Digital Pathology Corpus,” in Proceedings of the IEEE Signal Processing in Medicine and Biology Symposium (SPMB), 2019, pp. 1–4. https://ieeexplore.ieee.org/document/9037859. [9] A. P. Martinez, C. Cohen, K. Z. Hanley, and X. (Bill) Li, “Estrogen Receptor and Cytokeratin 5 Are Reliable Markers to Separate Usual Ductal Hyperplasia From Atypical Ductal Hyperplasia and Low-Grade Ductal Carcinoma In Situ,” Arch. Pathol. Lab. Med., vol. 140, no. 7, pp. 686–689, Apr. 2016. https://doi.org/10.5858/arpa.2015-0238-OA.« less
3. Mathematical modelling of the dynamics of image-informed tumor habitats in a murine model of glioma

   https://doi.org/10.1038/s41598-023-30010-6  

   Slavkova, Kalina P. ; Patel, Sahil H. ; Cacini, Zachary ; Kazerouni, Anum S. ; Gardner, Andrea L. ; Yankeelov, Thomas E. ; Hormuth, II, David A. ( February 2023 , Scientific Reports)

   Tumors exhibit high molecular, phenotypic, and physiological heterogeneity. In this effort, we employ quantitative magnetic resonance imaging (MRI) data to capture this heterogeneity through imaging-based subregions or “habitats” in a murine model of glioma. We then demonstrate the ability to model and predict the growth of the habitats using coupled ordinary differential equations (ODEs) in the presence and absence of radiotherapy. Female Wistar rats (N = 21) were inoculated intracranially with 10⁶C6 glioma cells, a subset of which received 20 Gy (N = 5) or 40 Gy (N = 8) of radiation. All rats underwent diffusion-weighted and dynamic contrast-enhanced MRI at up to seven time points. All MRI data at each visit were subsequently clustered usingk-means to identify physiological tumor habitats. A family of four models consisting of three coupled ODEs were developed and calibrated to the habitat time series of control and treated rats and evaluated for predictive capability. The Akaike Information Criterion was used for model selection, and the normalized sum-of-square-error (SSE) was used to evaluate goodness-of-fit in model calibration and prediction. Three tumor habitats with significantly different imaging data characteristics (p < 0.05) were identified: high-vascularity high-cellularity, low-vascularity high-cellularity, and low-vascularity low-cellularity. Model selection resulted in a five-parameter model whose predictions of habitat dynamics yielded SSEsmore »that were similar to the SSEs from the calibrated model. It is thus feasible to mathematically describe habitat dynamics in a preclinical model of glioma using biology-based ODEs, showing promise for forecasting heterogeneous tumor behavior.

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4. Extended-range statistical ENSO prediction through operator-theoretic techniques for nonlinear dynamics

   https://doi.org/10.1038/s41598-020-59128-7  

   Wang, Xinyang ; Slawinska, Joanna ; Giannakis, Dimitrios ( February 2020 , Scientific Reports)

   Forecasting the El Niño-Southern Oscillation (ENSO) has been a subject of vigorous research due to the important role of the phenomenon in climate dynamics and its worldwide socioeconomic impacts. Over the past decades, numerous models for ENSO prediction have been developed, among which statistical models approximating ENSO evolution by linear dynamics have received significant attention owing to their simplicity and comparable forecast skill to first-principles models at short lead times. Yet, due to highly nonlinear and chaotic dynamics (particularly during ENSO initiation), such models have limited skill for longer-term forecasts beyond half a year. To resolve this limitation, here we employ a new nonparametric statistical approach based on analog forecasting, called kernel analog forecasting (KAF), which avoids assumptions on the underlying dynamics through the use of nonlinear kernel methods for machine learning and dimension reduction of high-dimensional datasets. Through a rigorous connection with Koopman operator theory for dynamical systems, KAF yields statistically optimal predictions of future ENSO states as conditional expectations, given noisy and potentially incomplete data at forecast initialization. Here, using industrial-era Indo-Pacific sea surface temperature (SST) as training data, the method is shown to successfully predict the Niño 3.4 index in a 1998–2017 verification period out tomore »a 10-month lead, which corresponds to an increase of 3–8 months (depending on the decade) over a benchmark linear inverse model (LIM), while significantly improving upon the ENSO predictability “spring barrier”. In particular, KAF successfully predicts the historic 2015/16 El Niño at initialization times as early as June 2015, which is comparable to the skill of current dynamical models. An analysis of a 1300-yr control integration of a comprehensive climate model (CCSM4) further demonstrates that the enhanced predictability afforded by KAF holds over potentially much longer leads, extending to 24 months versus 18 months in the benchmark LIM. Probabilistic forecasts for the occurrence of El Niño/La Niña events are also performed and assessed via information-theoretic metrics, showing an improvement of skill over LIM approaches, thus opening an avenue for environmental risk assessment relevant in a variety of contexts.

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5. Modeling and tracking Covid-19 cases using Big Data analytics on HPCC system platform

   https://doi.org/10.1186/s40537-021-00423-z  

   Villanustre, Flavio ; Chala, Arjuna ; Dev, Roger ; Xu, Lili ; LexisNexis, Jesse Shaw ; Furht, Borko ; Khoshgoftaar, Taghi ( December 2021 , Journal of Big Data)

   Abstract This project is funded by the US National Science Foundation (NSF) through their NSF RAPID program under the title “Modeling Corona Spread Using Big Data Analytics.” The project is a joint effort between the Department of Computer & Electrical Engineering and Computer Science at FAU and a research group from LexisNexis Risk Solutions. The novel coronavirus Covid-19 originated in China in early December 2019 and has rapidly spread to many countries around the globe, with the number of confirmed cases increasing every day. Covid-19 is officially a pandemic. It is a novel infection with serious clinical manifestations, including death, and it has reached at least 124 countries and territories. Although the ultimate course and impact of Covid-19 are uncertain, it is not merely possible but likely that the disease will produce enough severe illness to overwhelm the worldwide health care infrastructure. Emerging viral pandemics can place extraordinary and sustained demands on public health and health systems and on providers of essential community services. Modeling the Covid-19 pandemic spread is challenging. But there are data that can be used to project resource demands. Estimates of the reproductive number (R) of SARS-CoV-2 show that at the beginning of the epidemic, each infectedmore »person spreads the virus to at least two others, on average (Emanuel et al. in N Engl J Med. 2020, Livingston and Bucher in JAMA 323(14):1335, 2020). A conservatively low estimate is that 5 % of the population could become infected within 3 months. Preliminary data from China and Italy regarding the distribution of case severity and fatality vary widely (Wu and McGoogan in JAMA 323(13):1239–42, 2020). A recent large-scale analysis from China suggests that 80 % of those infected either are asymptomatic or have mild symptoms; a finding that implies that demand for advanced medical services might apply to only 20 % of the total infected. Of patients infected with Covid-19, about 15 % have severe illness and 5 % have critical illness (Emanuel et al. in N Engl J Med. 2020). Overall, mortality ranges from 0.25 % to as high as 3.0 % (Emanuel et al. in N Engl J Med. 2020, Wilson et al. in Emerg Infect Dis 26(6):1339, 2020). Case fatality rates are much higher for vulnerable populations, such as persons over the age of 80 years (> 14 %) and those with coexisting conditions (10 % for those with cardiovascular disease and 7 % for those with diabetes) (Emanuel et al. in N Engl J Med. 2020). Overall, Covid-19 is substantially deadlier than seasonal influenza, which has a mortality of roughly 0.1 %. Public health efforts depend heavily on predicting how diseases such as those caused by Covid-19 spread across the globe. During the early days of a new outbreak, when reliable data are still scarce, researchers turn to mathematical models that can predict where people who could be infected are going and how likely they are to bring the disease with them. These computational methods use known statistical equations that calculate the probability of individuals transmitting the illness. Modern computational power allows these models to quickly incorporate multiple inputs, such as a given disease’s ability to pass from person to person and the movement patterns of potentially infected people traveling by air and land. This process sometimes involves making assumptions about unknown factors, such as an individual’s exact travel pattern. By plugging in different possible versions of each input, however, researchers can update the models as new information becomes available and compare their results to observed patterns for the illness. In this paper we describe the development a model of Corona spread by using innovative big data analytics techniques and tools. We leveraged our experience from research in modeling Ebola spread (Shaw et al. Modeling Ebola Spread and Using HPCC/KEL System. In: Big Data Technologies and Applications 2016 (pp. 347-385). Springer, Cham) to successfully model Corona spread, we will obtain new results, and help in reducing the number of Corona patients. We closely collaborated with LexisNexis, which is a leading US data analytics company and a member of our NSF I/UCRC for Advanced Knowledge Enablement. The lack of a comprehensive view and informative analysis of the status of the pandemic can also cause panic and instability within society. Our work proposes the HPCC Systems Covid-19 tracker, which provides a multi-level view of the pandemic with the informative virus spreading indicators in a timely manner. The system embeds a classical epidemiological model known as SIR and spreading indicators based on causal model. The data solution of the tracker is built on top of the Big Data processing platform HPCC Systems, from ingesting and tracking of various data sources to fast delivery of the data to the public. The HPCC Systems Covid-19 tracker presents the Covid-19 data on a daily, weekly, and cumulative basis up to global-level and down to the county-level. It also provides statistical analysis for each level such as new cases per 100,000 population. The primary analysis such as Contagion Risk and Infection State is based on causal model with a seven-day sliding window. Our work has been released as a publicly available website to the world and attracted a great volume of traffic. The project is open-sourced and available on GitHub. The system was developed on the LexisNexis HPCC Systems, which is briefly described in the paper.« less