Enhancing post-traumatic stress disorder patient assessment: leveraging natural language processing for research of domain criteria identification using electronic medical records.

BACKGROUND: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. METHODS: In our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories. RESULTS: The sentence transformer model demonstrated high F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. We found that 60.6% of PTSD women have at least one abnormal instance of the six RDoC domains as compared to PTSD men (51.3%), with 45.1% of PTSD women with higher levels of sensorimotor disturbances compared to men (41.3%). We also found that 57.3% of PTSD patients have at least one abnormal instance of the six RDoC domains based on our records. Also, veterans had the higher abnormalities of negative and positive valence systems (60% and 51.9% of veterans respectively) compared to non-veterans (59.1% and 49.2% respectively). The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption. CONCLUSIONS: The findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes.

Prediction of adverse events risk in patients with comorbid post-traumatic stress disorder and alcohol use disorder using electronic medical records by deep learning models.

BACKGROUND: Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population. METHODS: We analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, medications, co-morbidities, individual and neighborhood level social determinants of health (SDoH), psychotherapy and veteran data. RESULTS: DeepBiomarker2 achieved an area under the receiver operator curve (AUROC) of 0.94 on the prediction of adverse events among those PTSD+AUD patients. Medications such as vilazodone, dronabinol, tenofovir, suvorexant, modafinil, and lamivudine showed potential for risk reduction. SDoH parameters such as cognitive behavioral therapy and trauma focused psychotherapy lowered risk while active veteran status, income segregation, limited access to parks and greenery, low Gini index, limited English-speaking capacity, and younger patients increased risk. CONCLUSIONS: Our improved version of DeepBiomarker2 demonstrated its capability of predicting multiple adverse event risk with high accuracy and identifying potential risk and beneficial factors.

Enhancing post-traumatic stress disorder patient assessment: Leveraging Natural Language Processing for Research of Domain Criteria Identification using electronic medical records.

Background: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. Methods: In our study, we created an NLP workflow to analyze electronic medical record (EMR) data, and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, allmpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories. Results: The sentence transformer model demonstrated superior F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. Women had the highest abnormalities of sensorimotor systems, while veterans had the highest abnormalities of negative and positive valence systems. The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption. Conclusions: The findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes.

DeepBiomarker2: Prediction of Alcohol and Substance Use Disorder Risk in Post-Traumatic Stress Disorder Patients Using Electronic Medical Records and Multiple Social Determinants of Health.

Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. We developed DeepBiomarker2 by leveraging deep learning and natural language processing to analyze lab tests, medication use, diagnosis, social determinants of health (SDoH) parameters, and psychotherapy for outcome prediction. To increase the model's interpretability, we further refined our contribution analysis to identify key features by scaling with a factor from a reference feature. We applied DeepBiomarker2 to analyze the EMR data of 38,807 patients from the University of Pittsburgh Medical Center diagnosed with post-traumatic stress disorder (PTSD) to determine their risk of developing alcohol and substance use disorder (ASUD). DeepBiomarker2 predicted whether a PTSD patient would have a diagnosis of ASUD within the following 3 months with an average c-statistic (receiver operating characteristic AUC) of 0.93 and average F1 score, precision, and recall of 0.880, 0.895, and 0.866 in the test sets, respectively. Our study found that the medications clindamycin, enalapril, penicillin, valacyclovir, Xarelto/rivaroxaban, moxifloxacin, and atropine and the SDoH parameters access to psychotherapy, living in zip codes with a high normalized vegetative index, Gini index, and low-income segregation may have potential to reduce the risk of ASUDs in PTSD. In conclusion, the integration of SDoH information, coupled with the refined feature contribution analysis, empowers DeepBiomarker2 to accurately predict ASUD risk. Moreover, the model can further identify potential indicators of increased risk along with medications with beneficial effects.

Unveiling the Enigma: Exploring Risk Factors and Mechanisms for Psychotic Symptoms in Alzheimer's Disease through Electronic Medical Records with Deep Learning Models.

Around 50% of patients with Alzheimer's disease (AD) may experience psychotic symptoms after onset, resulting in a subtype of AD known as psychosis in AD (AD + P). This subtype is characterized by more rapid cognitive decline compared to AD patients without psychosis. Therefore, there is a great need to identify risk factors for the development of AD + P and explore potential treatment options. In this study, we enhanced our deep learning model, DeepBiomarker, to predict the onset of psychosis in AD utilizing data from electronic medical records (EMRs). The model demonstrated superior predictive capacity with an AUC (area under curve) of 0.907, significantly surpassing conventional risk prediction models. Utilizing a perturbation-based method, we identified key features from multiple medications, comorbidities, and abnormal laboratory tests, which notably influenced the prediction outcomes. Our findings demonstrated substantial agreement with existing studies, underscoring the vital role of metabolic syndrome, inflammation, and liver function pathways in AD + P. Importantly, the DeepBiomarker model not only offers a precise prediction of AD + P onset but also provides mechanistic understanding, potentially informing the development of innovative treatments. With additional validation, this approach could significantly contribute to early detection and prevention strategies for AD + P, thereby improving patient outcomes and quality of life.

Prediction of Adverse Events Risk in Patients with Comorbid Post- Traumatic Stress Disorder and Alcohol Use Disorder Using Electronic Medical Records by Deep Learning Models.

Background: Prediction of high-risk events in mental disorder patients is crucial. In our previous study, we developed a deep learning model: DeepBiomarker by using electronic medical records (EMR) to predict suicide related event (SRE) risk in post-traumatic stress disorder (PTSD) patients. Methods: We applied DeepBiomarker2 through data integration of multimodal information: lab test, medication, co-morbidities, and social determinants of health. We analyzed EMRs of 5,565 patients from University of Pittsburgh Medical Center with a diagnosis of PTSD and alcohol use disorder (AUD) on risk of developing an adverse event (opioid use disorder, SREs, depression and death). Results: DeepBiomarker2 predicted whether a PTSD + AUD patient will have a diagnosis of any adverse events (SREs, opioid use disorder, depression, death) within 3 months with area under the receiver operator curve (AUROC) of 0.94. We found piroxicam, vilazodone, dronabinol, tenofovir, suvorexant, empagliflozin, famciclovir, veramyst, amantadine, sulfasalazine, and lamivudine to have potential to reduce risk. Conclusions: DeepBiomarker2 can predict multiple adverse event risk with high accuracy and identify potential risk and beneficial factors. Our results offer suggestions for personalized interventions in a variety of clinical and diverse populations.

DeepBiomarker2: Prediction of alcohol and substance use disorder risk in post-traumatic stress disorder patients using electronic medical records and multiple social determinants of health.

Introduction: Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. In our previous study, we developed a deep learning-based model, DeepBiomarker by utilizing electronic medical records (EMR) to predict the outcomes of patients with suicide-related events in post-traumatic stress disorder (PTSD) patients. Methods: We improved our deep learning model to develop DeepBiomarker2 through data integration of multimodal information: lab tests, medication use, diagnosis, and social determinants of health (SDoH) parameters (both individual and neighborhood level) from EMR data for outcome prediction. We further refined our contribution analysis for identifying key factors. We applied DeepBiomarker2 to analyze EMR data of 38,807 patients from University of Pittsburgh Medical Center diagnosed with PTSD to determine their risk of developing alcohol and substance use disorder (ASUD). Results: DeepBiomarker2 predicted whether a PTSD patient will have a diagnosis of ASUD within the following 3 months with a c-statistic (receiver operating characteristic AUC) of 0·93. We used contribution analysis technology to identify key lab tests, medication use and diagnosis for ASUD prediction. These identified factors imply that the regulation of the energy metabolism, blood circulation, inflammation, and microbiome is involved in shaping the pathophysiological pathways promoting ASUD risks in PTSD patients. Our study found protective medications such as oxybutynin, magnesium oxide, clindamycin, cetirizine, montelukast and venlafaxine all have a potential to reduce risk of ASUDs. Discussion: DeepBiomarker2 can predict ASUD risk with high accuracy and can further identify potential risk factors along with medications with beneficial effects. We believe that our approach will help in personalized interventions of PTSD for a variety of clinical scenarios.

DeepBiomarker: Identifying Important Lab Tests from Electronic Medical Records for the Prediction of Suicide-Related Events among PTSD Patients.

Identifying patients with high risk of suicide is critical for suicide prevention. We examined lab tests together with medication use and diagnosis from electronic medical records (EMR) data for prediction of suicide-related events (SREs; suicidal ideations, attempts and deaths) in post-traumatic stress disorder (PTSD) patients, a population with a high risk of suicide. We developed DeepBiomarker, a deep-learning model through augmenting the data, including lab tests, and integrating contribution analysis for key factor identification. We applied DeepBiomarker to analyze EMR data of 38,807 PTSD patients from the University of Pittsburgh Medical Center. Our model predicted whether a patient would have an SRE within the following 3 months with an area under curve score of 0.930. Through contribution analysis, we identified important lab tests for suicide prediction. These identified factors imply that the regulation of the immune system, respiratory system, cardiovascular system, and gut microbiome were involved in shaping the pathophysiological pathways promoting depression and suicidal risks in PTSD patients. Our results showed that abnormal lab tests combined with medication use and diagnosis could facilitate predicting SRE risk. Moreover, this may imply beneficial effects for suicide prevention by treating comorbidities associated with these biomarkers.

Three dimensional engineered models to study hypoxia biology in breast cancer.

Breast cancer is the second leading cause of mortality among women worldwide. Despite the available therapeutic regimes, variable treatment response is reported among different breast cancer subtypes. Recently, the effects of the tumor microenvironment on tumor progression as well as treatment responses have been widely recognized. Hypoxia and hypoxia inducible factors in the tumor microenvironment have long been known as major players in tumor progression and survival. However, the majority of our understanding of hypoxia biology has been derived from two dimensional (2D) models. Although many hypoxia-targeted therapies have elicited promising results in vitro and in vivo, these results have not been successfully translated into clinical trials. These limitations of 2D models underscore the need to develop and integrate three dimensional (3D) models that recapitulate the complex tumor-stroma interactions in vivo. This review summarizes role of hypoxia in various hallmarks of cancer progression. We then compare traditional 2D experimental systems with novel 3D tissue-engineered models giving accounts of different bioengineering platforms available to develop 3D models and how these 3D models are being exploited to understand the role of hypoxia in breast cancer progression.

Recent Advancemnts in Biodegradable Ocular Implants.

The perpetuation of healthy vision is paramount in an individual. It has been observed that various drug delivery systems have been fabricated to develop vision quality in individuals. Systemic ocular drug therapies have limited efficacy due to poor bioavailability, systemic and toxic side effects and low patient compliance. Various drug systems which follow the ocular route of administration are manufactured to achieve optimized bioavailability along with better patient compliance. Ocular implant is one such example. It is divided into biodegradable and non-biodegradable drug delivery systems wherein the former is more beneficial. This review aims to demonstrate the current momentum in the formulation and optimization of various biodegradable ocular drug delivery systems and its characteristics.

Status of Agents Targeting the HGF/c-Met Axis in Lung Cancer.

Hepatocyte growth factor (HGF) is the ligand for the tyrosine kinase receptor c-Met (Mesenchymal Epithelial Transition Factor also known as Hepatocyte Growth Factor Receptor, HGFR), a receptor with expression throughout epithelial and endothelial cell types. Activation of c-Met enhances cell proliferation, invasion, survival, angiogenesis, and motility. The c-Met pathway also stimulates tissue repair in normal cells. A body of past research shows that increased levels of HGF and/or overexpression of c-Met are associated with poor prognosis in several solid tumors, including lung cancer, as well as cancers of the head and neck, gastro-intestinal tract, breast, ovary and cervix. The HGF/c-Met signaling network is complex; both ligand-dependent and ligand-independent signaling occur. This article will provide an update on signaling through the HGF/c-Met axis, the mechanism of action of HGF/c-Met inhibitors, the lung cancer patient populations most likely to benefit, and possible mechanisms of resistance to these inhibitors. Although c-Met as a target in non-small cell lung cancer (NSCLC) showed promise based on preclinical data, clinical responses in NSCLC patients have been disappointing in the absence of MET mutation or MET gene amplification. New therapeutics that selectively target c-Met or HGF, or that target c-Met and a wider spectrum of interacting tyrosine kinases, will be discussed.