Publications by Author: Nicholas D. Boltin

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Waugh, Mihyun L., Tyler Mills, Nicholas D. Boltin, Lauren Wolf, Patti Parker, Ronnie Horner, Thomas L Wheeler II, Richard L. Goodwin, and Melissa A. Moss. 2025. “Predicting Transvaginal Surgical Mesh Exposure Outcomes Using an Integrated Dataset of Blood Cytokine Levels and Medical Record Data: Machine Learning Approach”. Journal of Medical Internet Research. https://doi.org/doi:10.2196/59631.

Background:Transvaginal insertion of polypropylene mesh was extensively used in surgical procedures to treat pelvic organ prolapse (POP) due to its cost-efficiency and durability. However, studies have reported a high rate of complications, including mesh exposure through the vaginal wall. Developing predictive models via supervised machine learning holds promise in identifying risk factors associated with such complications, thereby facilitating better informed surgical decisions. Previous studies have demonstrated the efficacy of anticipating medical outcomes by employing supervised machine learning approaches that integrate patient health care data with laboratory findings. However, such an approach has not been adopted within the realm of POP mesh surgery.

Objective:We examined the efficacy of supervised machine learning to predict mesh exposure following transvaginal POP surgery using 3 different datasets: (1) patient medical record data, (2) biomaterial-induced blood cytokine levels, and (3) the integration of both.

Methods:Blood samples and medical record data were collected from 20 female patients who had prior surgical intervention for POP using transvaginal polypropylene mesh. Of these subjects, 10 had experienced mesh exposure through the vaginal wall following surgery, and 10 had not. Standardized medical record data, including vital signs, previous diagnoses, and social history, were acquired from patient records. In addition, cytokine levels in patient blood samples incubated with sterile polypropylene mesh were measured via multiplex assay. Datasets were created with patient medical record data alone, blood cytokine levels alone, and the integration of both data. The data were split into 70% and 30% for training and testing sets, respectively, for machine learning models that predicted the presence or absence of postsurgical mesh exposure.

Results:Upon training the models with patient medical record data, systolic blood pressure, pulse pressure, and a history of alcohol usage emerged as the most significant factors for predicting mesh exposure. Conversely, when the models were trained solely on blood cytokine levels, interleukin (IL)-1β and IL-12 p40 stood out as the most influential cytokines in predicting mesh exposure. Using the combined dataset, new factors emerged as the primary predictors of mesh exposure: IL-8, tumor necrosis factor-α, and the presence of hemorrhoids. Remarkably, models trained on the integrated dataset demonstrated superior predictive capabilities with a prediction accuracy as high as 94%, surpassing the predictive performance of individual datasets.

Conclusions:Supervised machine learning models demonstrated improved prediction accuracy when trained using a composite dataset that combined patient medical record data and biomaterial-induced blood cytokine levels, surpassing the performance of models trained with either dataset in isolation. This result underscores the advantage of integrating health care data with blood biomarkers, presenting a promising avenue for predicting surgical outcomes in not only POP mesh procedures but also other surgeries involving biomaterials. Such an approach has the potential to enhance informed decision-making for both patients and surgeons, ultimately elevating the standard of patient care.

JMIR Form Res 2025;9:e59631

Waugh, Mihyun L., Nicholas D. Boltin, Lauren Wolf, Jane Goodwin, Patti Parker, Ronnie Horner, Matthew Hermes, Thomas L Wheeler II, Richard L. Goodwin, and Melissa A. Moss. (2025) 2023. “Prediction of Pelvic Organ Prolapse Postsurgical Outcome Using Biomaterial-Induced Blood Cytokine Levels: Machine Learning Approach”. JMIR Formative Research 9.

Background: Pelvic organ prolapse (POP) refers to symptomatic descent of the vaginal wall. To reduce surgical failure rates, surgical correction can be augmented with the insertion of polypropylene mesh. This benefit is offset by the risk of mesh complication, predominantly mesh exposure through the vaginal wall. If mesh placement is under consideration as part of prolapse repair, patient selection and counseling would benefit from the prediction of mesh exposure; yet, no such reliable preoperative method currently exists. Past studies indicate that inflammation and associated cytokine release is correlated with mesh complication. While some degree of mesh-induced cytokine response accompanies implantation, excessive or persistent cytokine responses may elicit inflammation and implant rejection.

Objective: Here, we explore the levels of biomaterial-induced blood cytokines from patients who have undergone POP repair surgery to (1) identify correlations among cytokine expression and (2) predict postsurgical mesh exposure through the vaginal wall.

Methods: Blood samples from 20 female patients who previously underwent surgical intervention with transvaginal placement of polypropylene mesh to correct POP were collected for the study. These included 10 who experienced postsurgical mesh exposure through the vaginal wall and 10 who did not. Blood samples incubated with inflammatory agent lipopolysaccharide, with sterile polypropylene mesh, or alone were analyzed for plasma levels of 13 proinflammatory and anti-inflammatory cytokines using multiplex assay. Data were analyzed by principal component analysis (PCA) to uncover associations among cytokines and identify cytokine patterns that correlate with postsurgical mesh exposure through the vaginal wall. Supervised machine learning models were created to predict the presence or absence of mesh exposure and probe the number of cytokine measurements required for effective predictions.

Results: PCA revealed that proinflammatory cytokines interferon gamma, interleukin 12p70, and interleukin 2 are the largest contributors to the variance explained in PC 1, while anti-inflammatory cytokines interleukins 10, 4, and 6 are the largest contributors to the variance explained in PC 2. Additionally, PCA distinguished cytokine correlations that implicate prospective therapies to improve postsurgical outcomes. Among machine learning models trained with all 13 cytokines, the artificial neural network, the highest performing model, predicted POP surgical outcomes with 83% (15/18) accuracy; the same model predicted POP surgical outcomes with 78% (14/18) accuracy when trained with just 7 cytokines, demonstrating retention of predictive capability using a smaller cytokine group.

Conclusions: This preliminary study, incorporating a sample size of just 20 participants, identified correlations among cytokines and demonstrated the potential of this novel approach to predict mesh exposure through the vaginal wall following transvaginal POP repair surgery. Further study with a larger sample size will be pursued to confirm these results. If corroborated, this method could provide a personalized medicine approach to assist surgeons in their recommendation of POP repair surgeries with minimal potential for adverse outcomes.

JMIR Perioper Med 2023;6:e40402

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O’Brien, Wayne, Nicholas D. Boltin, Zhenyu Lu, Brianna M. Cassidy, Raymond G. Belliveau, Emory J. Straub, Stephanie A. DeJong, Stephen L. Morgan, and ML Myrick. (2015) 2015. “Chemical Contrast Observed in Thermal Images of Blood-Stained Fabrics Exposed to Steam”. Analyst 140 (18): 6222-25.

Thermal imaging is not ordinarily a good way to visualize chemical contrast. In recent work, however, we observed strong and reproducible images with chemical contrasts on blood-stained fabrics, especially on more hydrophobic fabrics like acrylic and polyester.

O’Brien, Wayne, Nicholas D. Boltin, Stephanie A. DeJong, Zhenyu Lu, Brianna M. Cassidy, Scott J. Hoy, Stephen L. Morgan, and ML Myrick. (2015) 2015. “An Improved-Efficiency Compact Lamp for the Thermal Infrared”. Applied Spectroscopy 69 (12): 1511-13.

A major type of infrared camera is sensitive to wavelengths in the 8–14 μm band and is mainly used for thermal imaging. Such cameras can also be used for general broadband infrared reflectance imaging when provided with a suitable light source. We report the design and properties of an infrared lamp using a heated alumina emitter suitable for active thermal infrared imaging, as well as comparisons to existing commercial light sources for this purpose. We find that the alumina lamp is a broadband non-blackbody source with a lower out-of-band emission intensity and therefore higher electrical efficiency for this application than existing commercial sources.

O’Brien, Wayne, ML Myrick, Nicholas D. Boltin, and Scott J. Hoy. (2014) 2014. Infrared Light Sources and Methods of Their Use and Manufacture. 14176201, issued 2014.

Infrared light sources, along with their methods of formation, are provided. The infrared light source can include a base Substrate defining an aperture; a filament extending through the aperture defined by the base substrate; a resistive metal wire wrapped around the filament to define a coil having a first end and a second end; a high temperature coating Sur rounding at least a portion of the filament and the coil; a first electrode electrically connected to the first end of the coil; and a second electrode electrically connected to the second end of the coil.

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Moss, Melissa A., Mihyun L. Waugh, Nicholas D. Boltin, Lauren Wolf, Ronnie Horner, Matthew Hermes, Thomas L Wheeler II, and Richard L. Goodwin. (2025) 2025. Predicting biomaterial-implant surgical outcomes. 18915993, issued 2025.

In general, the present disclosure is directed to systems and methods of evaluating a subject's risk of one or more complications associated with pelvic organ prolapse surgery. The method comprising: obtaining, by a computing system comprising one or more computing devices, sample data associated with the subject; obtaining, by a computing system comprising one or more computing devices, medical record data associated with the subject; inputting, by the computing system, the sample data into a machine-learned surgical model; receiving, by the computing system as an output of the machine-learned surgical model, one or more predictions of post-surgical complications of mesh exposure through a vaginal wall associated with the subject; and performing a pelvic organ prolapse repair surgery on the subject.

Meier, MacKenzie, Chris Kibler, Hailey Sparks, Michael Campanelli, Chris Koons, Brandon Williams, Ronald Pirallo, and Nicholas D. Boltin. 2025. “Neurocardiac Trauma Feedback System, An Investigational Study of Electroencephalography and Heartrate Variability Monitoring in Emergency Care Clinicians for the Early Detection of Acute Stress Disorder”. Big Data Conference.

Acute Stress Disorder (ASD) is a psychological response to a terrifying, traumatic, or surprising event and can be a precursor to Post Traumatic Stress Disorder (PTSD) if left untreated. The current method of diagnosing ASD is anecdotal in practice, with clinical evaluation involving patient history and physical examination within days following a traumatic event. Diagnostic tools typically include screenings and questionnaires, but they require significant training and often miss initial physiological symptoms. The addition of Artificial Intelligence (AI) data-driven decision support using electroencephalography (EEG) and heart rate monitoring of biopotential activity may aid in detecting early signs of trauma-related disorders. 

To test this hypothesis, participants from Greenville Memorial Hospital Emergency Department and Level 1 Trauma Center wore an EEG headset prior to their work shift to determine a reference signal (preliminary sample size of ~n=20). Participants then wore the EEG headset during their work shift while the timing of traumatic events and severity was recorded and biopotential data was collected and stored. De-identified data was exported and processed into various waveforms before being fed into an AI model to develop parameters to identify increased stress levels. 

The Acute Stress Center (ASC) developed an application that enables physicians to drag and drop EEG data into the application, select which waveforms are of interest to their research, and view summary statistics of their data and graphs indicating stressful events along their EEG waveform. In addition, ECG data is displayed alongside the EEG data to allow a visual comparison.

The prototype and application were both further enhanced to gather and evaluate heart rate in addition to EEG data. Data was collected outside of a hospital setting with lower stress levels to test the algorithm.  From preliminary testing, the addition of heart rate did not show much significance in predictors of traumatic responses, ranking second to last in feature importance. Furthermore, among both trials, the GammaMid waveform still proved to be the most important waveform in the indication of a traumatic response with a score of 100%. Additionally, correlations between waveforms and heart rate were fairly insignificant with the highest correlation of .26. Similarly to testing with only EEG waveforms, a plateau in accuracy occurs when 6 variables are included. However, in EEG only trials, accuracies of 95% were achieved, while in the heart rate trial a maximum accuracy of 80% could be achieved. Discrepancies in data could be attributed to the fact that data was collected in stressful situations rather than traumatic due to preliminary testing of the prototype before gathering data at Prisma Health. Variance in results may be seen in more high stress situations and will be evaluated in future work.

 

Moss, Melissa A., Mihyun L. Waugh, Nicholas D. Boltin, Lauren Wolf, Ronnie Horner, Matthew Hermes, Thomas L Wheeler II, Richard L. Goodwin, and Richard Michael Gower. (2023) 2023. Levels of immune response markers as adverse outcome predictors following biomaterial implant surgery. 17960462, issued 2023.

 

In general, the present disclosure is directed to systems and methods of evaluating a subject's risk of one or more complications associated with pelvic organ prolapse surgery. The method comprising: obtaining, by a computing system comprising one or more computing devices, sample data associated with the subject; inputting, by the computing system, the sample data into a machine-learned immune response model; receiving, by the computing system as an output of the machine-learned immune response model, one or more predictions of post-surgical complications of mesh exposure through the vaginal wall associated with the subject; and performing a pelvic organ prolapse repair surgery on the subject, wherein the surgery is performed based at least in part on the one or more predictions of post-surgical complications by the machine-learned immune response model associated with a likelihood of success.

Myrick, ML, Stephen L. Morgan, Stephanie A. DeJong, Nicholas D. Boltin, Zhenyu Lu, Jessica N. McCutcheon, Brianna M. Cassidy, Raymond G. Belliveau, Megan R. Pearl, and Wayne O’Brien. (2015) 2015. “Effect of Azimuthal Angle on Infrared Diffuse Reflection Spectra of Fabrics”. MJH Life Sciences 30: 23-25.

Infrared spectroscopy is an appealing technique for application to forensic samples because it offers the benefits of being non-destructive and non-hazardous, fast, reasonably sensitive, and resistant to some of the interferences of many commonly used techniques. Our research team has been focusing on detecting biological fluids on fabrics, which are inherently anisotropic substrates for spectroscopy. The work presented here investigates the effect of azimuthal angle of the sample on the infrared diffuse reflection spectra of fabrics with a goal of removing sampling differences as a source of analytic variation.

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Donevant, Sara B., Erik R. Svendsen, Jane V. Richter, Abbas S. Tavakoli, Jean B.r Craig, Nicholas D. Boltin, Homayoun Valafar, Salvatore Robert DiNardi, and Joan M. Culley. (2019) 2019. “Designing and Executing a Functional Exercise to Test a Novel Informatics Tool for Mass Casualty Triage”. Journal of the American Medical Informatics Association 26 (10).

Objective: The testing of informatics tools designed for use during mass casualty incidents presents a unique problem as there is no readily available population of victims or identical exposure setting. The purpose of this article is to describe the process of designing, planning, and executing a functional exercise to accomplish the research objective of validating an informatics tool specifically designed to identify and triage victims of irritant gas syndrome agents. Materials and Methods: During a 3-year time frame, the research team and partners developed the Emergency Department Informatics Computational Tool and planned a functional exercise to test it using medical records data from 298 patients seen in 1 emergency department following a chlorine gas exposure in 2005. Results: The research team learned valuable lessons throughout the planning process that will assist future researchers with developing a functional exercise to test informatics tools. Key considerations for a functional exercise include contributors, venue, and information technology needs (ie, hardware, software, and data collection methods). Discussion: Due to the nature of mass casualty incidents, testing informatics tools and technology for these incidents is challenging. Previous studies have shown a functional exercise as a viable option to test informatics tools developed for use during mass casualty incidents. Conclusion: Utilizing a functional exercise to test new mass casualty management technology and informatics tools involves a painstaking and complex planning process; however, it does allow researchers to address issues inherent in studying informatics tools for mas casualty incidents. Key words: chlorine exposure, disaster, functional exercise, informatics, mass casualty incident