United States

Background/Objective: 
In fast-paced clinical settings like labor and delivery, quick access to accurate, evidence-based guidance is critical. Traditional methods of sharing protocols can be inefficient, especially for trainees managing complex scenarios. Advances in artificial intelligence (AI) and large language models (LLMs) offer the potential to transform how critical clinical decision-making tools are disseminated, making them more accessible, responsive, and integrated into real-time learning. Our objective was to develop our own chatbot to facilitate quick retrieval and enhanced learning. 

Methods: 
The AI chatbot was developed by IUSM researchers using Microsoft Copilot Studio and made accessible via Microsoft Teams. The AI chatbot was built on a retrieval-augmented generation (RAG) framework, leveraging a fine-tuned LLM. The base LLM was augmented with domain-specific documents, including IUSM protocols – developed by the Maternal-Fetal Medicine division - which incorporate evidence-based practices and provide a consistent management strategy for OB conditions. The RAG architecture was configured to retrieve contextually relevant documents from the collection of protocols in response to user queries.

Results:
The chatbot retrieves information from the protocols based on a user’s query and generates a relevant answer with reference to the sources. Upon testing the chatbot, we learned that the chatbot was unable to retrieve information from figures, flowcharts, and diagrams. Therefore, figures were manually annotated and narrated, enabling the model to process and retrieve relevant visual information during inference. With other adjustments, the chatbot is able to read all aspects of the protocols and synthesize accurate answers to clinical questions.

Conclusion and Potential Impact: 
We optimized an RAG model AI chatbot for clinical education, demonstrating that existing educational material can be used to activate a chatbot to serve clinical needs with sufficient oversight to ensure clinical accuracy. Future directions include evaluating its impact on clinical decision making and student perception of the learning environment once the chatbot is more uniformly adopted. 


AMA Research Challenge 2025 

Optimization of a RAG Model Chatbot for Obstetric Medical Education

2021 Annual Conference of the North American Chapter of the Association for Computational Linguistics.

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Background
Cardiovascular disease remains the leading cause of death in the United States, primarily due to the unsuccessful recovery of cardiac tissue from oxygen-deprived injuries. The severity of these insults varies among individuals and is often influenced by genetic factors. Despite extensive research, the specific genes involved in hypoxic response still remain unclear. Therefore, this study aims to characterize gene expression variability in response to the hypoxic event, since identifying these genetic markers will be crucial for early intervention in populations at high risk for oxygen-related cardiac complications.

Methods
Hypoxic stress was induced on two genetically distinct mice strains: hypoxia-sensitive (CD1) and hypoxia-resistant (C57BL/6J). We then performed a microarray on cardiac tissue samples from these mice to quantify the expression patterns of coding and non-coding (lncRNAs) genes. Using correlational and enrichment analysis methods, we compared the differential gene expression patterns between the two mice strains. Previous studies have reported limited success in identifying hypoxia-associated genetic markers, thus justifying our study’s emphasis on non-coding RNA profiles.

Results
Our data revealed that the most significant lncRNA differential expression patterns are involved in energy metabolism and conservation. This specifically included “protein secretion” and “oxidation-reduction processes” according to GeneOntology (GO) term descriptions. In the “regulation in protein secretion” GO Term, we discovered that the lncRNA XR_001783868.2 exhibited a 28% increase in expression in response to hypoxia. This lncRNA overlaps with the coding gene Fhip1a/FAM160A1 and may play a role in regulating its gene expression in response to hypoxia.

Conclusion
lncRNAs associated with heightened sensitivity to hypoxia may serve as genetic markers for identifying individuals at increased risk of cardiovascular-related mortality, supporting the development of preventive and targeted treatment strategies.

A Search for Long-noncoding RNAs (lncRNAs) as Genetic Markers for Hypoxia Sensitivity in Mus Musculus

Background
Somatic mutations in an MLK family member, Mixed Lineage Kinase 4 (MLK4), have been reported to activate its kinase activity in colorectal cancers (CRCs). Analysis of the TCGA (The Cancer Genome Atlas) database revealed that increased MLK4 expression correlates with poor overall survival in colon cancers. Novel MLK4 inhibitors are being developed using various computational techniques and in vitro models to target different types of cancers. We aim to evaluate the effects of CEP-1347, a pan-MLK inhibitor, on MLK4 expression, apoptosis, and tumorigenesis in colon cancer cells.

Methods
Colon cancer cell line, HCT 116 cells were treated with CEP-1347 (500nM) every 24 hours for two days and untreated and DMSO (Dimethyl Sulfoxide) treated cells were used as controls. Cell extracts were primarily incubated with MLK4 antibody, and a western blot analysis was performed. Apoptosis was assessed by measuring Bax, Bcl-2, PARP, and caspase-3 expression using western blot analysis. Additionally, we conducted a wound healing assay on HCT 116 cells treated with CEP-1347(500nM) and cell migration evaluated every 24 hours for 7 days with untreated and DMSO treated cells as controls.

Results
The western blot analysis showed significantly reduced MLK4 expression in cells treated with CEP-1347 (p < 0.05). Our apoptosis assay demonstrated a significantly increased Bax/Bcl-2 ratio (p < 0.0005) alongside other apoptotic markers like cleaved PARP (p < 0.0005) and cleaved caspase-3 (p < 0.005) in CEP-1347 treated cells when compared to control or DMSO treated cells. The cell migration assay showed delayed wound closure in CEP-1347-treated cells, with control cells achieving full closure by day 5, whereas treated cells retained ~10% of the initial wound area by day 6.

Conclusion
Our results demonstrate that CEP-1347 effectively inhibits MLK4 kinase activity in colon cancer cells, leading to increased apoptosis and reduced migratory potential. These findings suggest that MLK4 inhibition may be a promising therapeutic strategy for treating intractable colon cancers unresponsive to current therapeutic approaches and warrant further investigation.

MLKs Inhibitor CEP-1347 Suppresses Tumorigenic Potential and Survival of Colon Cancer Cells

Background
Postoperative pain contributes to opioid use. Physicians struggle to limit the prescription of opioids post-operatively and upon discharge. The side effect of respiratory depression is concerning in obese patients, particularly those undergoing bariatric surgery, because they often suffer from sleep apnea and other restrictive lung diseases. This research studies the effects of a novel multimedia program delivered via a tablet device on pain-related outcomes in patients recovering from bariatric surgery. 

Methods
Patients scheduled for vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) surgery were randomized into an experimental (A) and control group (B). Group A received an iPad programmed with an educational video and four applications. Group B received the standard entertainment options. Pain scores, opioid medication use, and BMI were monitored inpatient and at follow-up visits. Tablet usage time in Group A was monitored, and both groups completed exit surveys about the interventions. Candidates were screened until 48 subjects were enrolled, 23 in Group A and 25 in Group B (control). All patients received an intraoperative transversus abdominis block and an oral regimen including acetaminophen, celecoxib, and tramadol; patients were discharged on tramadol 50-100 mg every 6 hours as needed for 28 days.

Results
• Question 1: mean response was 1.88/4 with a standard deviation of 1.05 (p = 0.721). 
• Question 2: 3/17 patients stated that the usage of the tablet helped with pain (p = 1.000). 7/17 stated that the usage of the tablet helped with anxiety (p = 1.000). 4/17 stated that it helped with sleep (p = 0.738). 6/17 stated that it helped with mood (p = 0.494). 4/17 endorsed it helping with unpleasant thoughts (p = 1.000). 
• Question 3: 5/17 stated that the tablet helped with less pain medication use. 12/17 stated that it did not (p = 0.197). 
• Question 4: 16 responded yes and 1 responded no (p = 1.000).
• Question 5: 8 responded yes and 9 responded no (p = 0.014). 
• Question 6: the mean was 2.0/4.0 with a standard deviation of 1.41, and the range was 0-3 (p = 0.211). 

Conclusion
Multimedia helped with all the areas queried, including crucial postoperative factors such as pain, anxiety, and sleep. The limitation of this study was the inability to control the multimedia resources that patients brought to the hospital on their own. All patients found multimedia to be at least “probably” helpful in the postoperative setting, with the control group continuing to use similar approaches at home.


A Digital Media Program for Postoperative Pain: A Survey of Bariatric Surgery Patients

Background
Immune checkpoint inhibitors (ICI) are first-line treatments for many advanced solid tumors. Patients with type 2 diabetes mellitus (T2DM) have decreased response rates to ICI, and poor glycemic control is associated with worse outcomes in cancer patients. Further adjunctive therapies to enhance ICI efficacy are needed.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as effective antihyperglycemic medications with concomitant cardiovascular benefits. SGLT2i are now approved in patients with T2DM and congestive heart failure (CHF). Pre-clinical studies suggest SGLT2i may help slow tumor growth in-vitro and in-vivo; however, there is a lack of clinical data regarding SGLT2i use in patients with advanced malignancy receiving ICI.

Methods
We performed a retrospective, matched cohort study of patients with stage IV malignancy and T2DM or CHF, who were treated with ICI using Epic Cosmos dataset (2013–2024). Ten solid tumor types, five ICI, and three SGLT2i were analyzed. Among 6,674 patients treated with ICI, 573 had at least one overlapping cycle of ICI and SGLT2i. 1:1 propensity score matching was conducted to balance baseline covariates, including cancer type, comorbidities, age at diagnosis, and sex. Kaplan-Meier curves were generated to examine survival differences, and Cox proportional hazards models were used to estimate hazard ratios (HR). The primary outcome was overall survival (OS) for the entire matched cohort and sub-groups by cancer, ICI, and SGLT2i types.

Results
Patients who received ICI and SGLT2i had significantly improved OS compared to those who received ICI alone (HR = 0.67, 95% CI: 0.57-0.78). Among cancer types, significant improvements in survival were observed in patients with renal cell carcinoma (RCC, HR = 0.58, 95% CI: 0.41–0.84) and non-small cell lung cancer (NSCLC, HR = 0.59, 95% CI: 0.42–0.84). Among ICI types, ipilimumab + nivolumab (HR = 0.50, 95% CI: 0.27-0.93) and pembrolizumab (HR = 0.58, 95% CI: 0.45-0.77) showed a significant improvement in survival when used with SGLT2i. There was no statistically significant difference in OS amongst the three SGLT2i types.

Conclusion
We observed encouraging improvements in OS in patients with T2DM or CHF receiving SGLT2i in addition to ICI across multiple solid tumor types. Patients with RCC and NSCLC derived the greatest benefit. Patients treated with either ipilimumab + nivolumab or pembrolizumab had the best responses to therapy. SGLT2i may be beneficial as adjunctive therapies in patients with advanced malignancy receiving ICI. Further prospective studies are needed to validate our observations and determine potential underlying mechanisms.


Improved survival with sodium-glucose cotransporter-2 inhibitors and immune checkpoint inhibitors in metastatic solid tumors

Introduction
The purpose of this study is to examine return to recreation outcomes in patients following surgical treatment of malignant musculoskeletal tumors and identify which sports and activities to which patients are able to return.

Methods
On October 31st, 2024, a systematic review of the literature was conducted utilizing Pubmed, Cochrane, and Embase (OVID) databases. Abstracts and titles were screened by two independent reviewers for studies that investigated return to sport, activity, or recreation after a musculoskeletal tumor resection.

Results
Across 8 studies (6 case series, 1 cohort, 1 cross sectional), a total of 223 patients (119 males, 86 females) underwent surgical resection of a malignant musculoskeletal tumor and were considered in follow-up evaluations of physical activity. Of the 223 patients, 66% (147/223) participated in some level of recreational physical activity post-operatively. Eight patients over a total of two studies returned to sport at their competitive level, with competitive sports including soccer and dancing. Across 5 studies, the most common post-surgery sport was cycling (n=37, 12.5%). Average follow-up duration ranged from 85 days to 230 months. A variety of surgical techniques were utilized over the 8 studies, including intra-articular and extra-articular surgery, rotationplasty, arthrodesis, graft, and megaprosthesis.

Conclusion
While upper limb tumor resections may have better return to sport at a higher level of activity than lower limb tumor resections, overall return to sport at any level is approximately 66%. Post-surgery activity scale is lower than pre-surgery activity scale, with the most common sport after surgical resection becoming cycling. However, the lack of quality data in current literature makes it difficult to allow for evidence-based decision-making on return to sport after resection of malignant musculoskeletal tumors. Further studies are necessary to evaluate return to sport based on age, tumor diagnosis, surgery type, and pre and post-activity levels after both upper and lower extremity malignant musculoskeletal tumor resections.

Return to Recreation after Surgery for Malignant Musculoskeletal Tumors: A Systematic Review

Background:
Glucagon-like peptide-1 receptor agonists (GLP-1) are increasingly prescribed for diabetes and obesity, yet their long-term effects on bone health remain unclear. Clinical trials commonly report neutral or protective effects of GLP-1s on bone mineral density (BMD) but seldom consider dietary intake or nutritional status in their analysis. Given the appetite-suppressing effects of GLP-1s, users may have inadequate intake of nutrients essential for bone health. Consequently, findings from GLP-1 users with normal BMD may be misleading, as patients may still suffer from underlying nutrient deficiencies or reduced muscle strength, both of which contribute to future skeletal fragility. This study aimed to develop a more comprehensive profile of bone health in GLP-1 users by examining dietary intake, serum biomarkers, grip strength, and BMD.
Methods:
Data were obtained from the 1999-2020 National Health and Nutrition Examination Survey. Nutrient intake was assessed using 24-hour dietary recalls and compared to the recommended daily value (DV). Serum markers, including total calcium, phosphorus, and 25-hydroxyvitamin D, were analyzed to identify subclinical deficiencies. Muscular strength was assessed via handgrip dynamometry, stratified by age and sex, and categorized into percentiles based on population reference standards. Femur and lumbar spine dual-energy x-ray absorptiometry (DEXA) scans were used to assess BMD and evaluate associations with nutrient intake, serum biomarkers, and grip strength. 
Results
Among GLP-1 users (n=150), intake of bone supporting nutrients was suboptimal with vitamin D (18% of DV), vitamin E (47% of DV) and potassium (49% of DV) below recommended levels. Serum vitamin D deficiency (<20 ng/ml) was observed in 33% of users, 64% of whom were female. In grip strength analysis (n=29), 29% of female GLP-1 users were below the age-and sex-adjusted 20th percentile compared to 13% of males. Median lumbar spine BMD increased with age in males from 0.97 g/cm2 (IQR: 0.93-1.07 g/cm2 n=4) in 40-49 year olds to 1.21 g/cm2 (IQR: 1.19-1.27 g/cm2 n=9) in 60-69 year olds while remaining stable with age (range: 1.01–1.10 g/cm2) in females. 
Conclusion
This study developed a comprehensive profile of bone health in GLP-1 users, showing that despite increased BMD in males and stable BMD in females, many individuals, particularly women, had vitamin deficiencies, reduced grip strength, and other indicators of skeletal vulnerability. Patients on GLP-1s would likely benefit from more comprehensive monitoring of bone health, not only through traditional imaging studies, but also regular assessment of nutritional status, serum testing, and monitoring for functional status changes.


Multimodal Assessment of Bone Health in GLP-1 Agonist Users

Introduction: Adequate sleep during childhood is important for learning, memory formation, and physical and mental well-being. In 2019, around 79,000 individuals passed away due to drug use. Insufficient sleep has been found to decrease positive emotions. Many drugs that are commonly abused - opioids, cocaine, or nicotine - flood the reward pathway with dopamine, reproducing positive emotions.

Research Questions: Is there an association between childhood sleep inadequacy and deaths from substance use in early adulthood? Are there differences in the types of drugs that are more likely to be used? 

Methods: This project was a correlational study using secondary data across all 50 states and the District of Columbia. Correlational testing was performed at a 95% Confidence Interval, and p-values < 0.05 were considered significant. The correlations between sleep inadequacy and 5 outcomes were explored: total substance abuse, alcohol use, amphetamine use, opioid use, and cocaine use. Data analyses were conducted using SAS Software 9.4, and maps were generated using Tableau. 

Results: West Virginia had the highest prevalence of substance use deaths for total substance use, cocaine use, amphetamine use, and opioid use. New Mexico had the highest prevalence of deaths from alcohol use. Mississippi had the lowest percentage of children meeting sleep guidelines, and Utah had the highest percentage of children meeting sleep guidelines. Total substance use, amphetamine use, opioid use, and cocaine use were positively correlated with less sleep during childhood, and Alcohol use was negatively correlated. Deaths from opioid use in early adulthood were significantly correlated with less sleep during childhood (p = 0.0132). 

Conclusions: Chronic sleep deprivation may dysregulate neurobiological pathways in the brain, potentially increasing susceptibility to opioid misuse later in life. Prevention and treatment services for sleep disorders and substance abuse are not equitable and accessible across all states and the District of Columbia.

Associations of Childhood Sleep Insufficiency to Substance Use Among U.S. Adults

Background
Acute myocardial infarction (AMI) is a leading contributor to cardiovascular mortality. Prior research suggests that areas with high social vulnerability, defined as those having worse social conditions such as low socioeconomic status (SES), have higher rates of AMI. Kentucky ranks fourth in the nation for cardiovascular disease, including AMI, and has elevated levels of social vulnerability. However, few studies have examined the link between social vulnerability and AMI-related outcomes in Kentucky. The purpose of our study is to examine the association of county-level social vulnerability index (SVI) with AMI hospitalization and mortality rates in Kentucky from 2016 to 2020. 

Methods
AMI hospitalization and mortality data for adults ≥35 years old were presented as five-year age-adjusted rates per 100,000 population and obtained from the Centers for Disease Control and Prevention (CDC). County-level scores for SVI overall and by its four subcategory themes (i.e., socioeconomic status, household characteristics, racial and ethnic minority status, and housing type and transportation) were also obtained from the CDC and categorized into quartiles, with Q1 representing the least socially vulnerable counties and Q4 the most. To examine the association between SVI overall and by its four themes with the study outcomes, we fit unadjusted and adjusted linear regression models. Beta coefficients and p-values were computed to assess the overall association between each independent variable in regression models; p-values ≤ 0.05 were considered statistically significant.

Results
Compared to the least vulnerable counties (Q1), the most vulnerable counties (Q4) on the overall SVI measure had higher age-adjusted AMI hospitalization rates (Q1= 389.2 per 100,000 vs Q4=519.4; p=0.001). In linear regression models simultaneously adjusting for the four subcategory themes, counties with high vulnerability on the socioeconomic status theme had increased AMI hospitalization rates (Q1= 404.3 vs Q4=505.0; p=0.008), while counties with high vulnerability on the racial and ethnic minority status theme (indicating a greater proportion of racial and ethnic minorities) had lower AMI hospitalization (Q1= 404.3 vs Q4=229.7; p <.0001) and mortality rates (Q1= 138.9 vs Q4=71.7; p=0.038). 

Conclusion
County-level interventions targeting overall social vulnerability and low SES may reduce poor AMI outcomes in the state. Counties with a larger proportion of racial and ethnic minorities may have lower AMI hospitalization and mortality rates because these counties are more likely to be urban and therefore may have better access to healthcare resources. Nonetheless, this unexpected finding warrants further investigation.

Examining the Association between County-Level Social Vulnerability and Acute Myocardial Infarction Hospitalizations and Mortality in Kentucky

Background 
The challenges that people with disabilities experience within emergency settings are uniquely complex. Disruptions in routine, painful procedures, and confusion can be especially agitating for this population – making the need for adequate sedation, pain management, and communication paramount. Anatomical and physiological differences and communication barriers can further complicate emergency visits. There is a lack of research evaluating current nationwide emergency medical service protocols for treating patients with various disabilities. This paper serves to initiate discussion regarding current practices and identifies potential areas for improvement. It also considers the expansion of such protocols into emergency departments, peri-operative care, and routine care. 

Methods 
The 30 existing statewide protocols were analyzed for the presence or absence of disability protocols within four categories: autism spectrum disorder, intellectual disability, orthopedic impairment, and/or speech/language impairments. Physiological differences and communication barriers were also outlined to contextualize challenges faced within each category. Behavioral health emergency protocols were analyzed to serve as a comparison, as these may be the only guidance available in the absence of disability protocols despite their lack of appropriateness. Within each protocol, special attention was paid to standing orders regarding medical guidance and behavioral guidance. Broadly, the authors define medical guidance as pharmacological management, and behavioral guidance as any communication or de-escalation techniques. Lastly, the availability of emergency care plans was also noted. 

Results 
We found that while most available statewide protocols have existing protocols for behavioral health emergencies, the majority did not have existing protocols for patients with disabilities. Within behavioral health protocols, adequate sedation and appropriate communication techniques were almost always addressed. Of note, the states that did not provide medical guidance for these patients only provided basic life support guidelines statewide, not advanced life support. Only two states provided the option for emergency care plans, either for medically complex patients or patients with disabilities. 


Conclusion 
There is currently a lack of appropriate guidance for providing emergency care to patients with disabilities, but documented plans for these patients could increase both provider and patient comfort. Given the unique challenges in providing adequate sedation, pain management, and communication for patients with disabilities, it would be sensible if more protocols were put in place to provide guidance in these areas. Similar protocols and guidelines may also be beneficial in emergency departments, peri-operative settings, and routine care as the need for appropriate sedation and communication for patients with disabilities is still relevant in these settings.

Analyzing Existing Protocols for Patients with Disabilities 
in the Emergency Setting  

Human papillomavirus (HPV) is a common sexually transmitted infection in the United States, with certain strains linked to multiple cancers. Although HPV vaccination effectively reduces cancer risk, uptake remains low, particularly in rural areas. This study aimed to assess parental attitudes and barriers toward HPV vaccination in rural East Texas. An Institutional Review Board–approved, bilingual, English and Spanish, anonymous 20-item survey was administered to parents at a pediatric clinic. The survey assessed demographics, vaccine knowledge, beliefs, and sources of information. Responses were analyzed by comparing parents who vaccinated their children (WV) with those who did not (WDV). A total of 49 parents completed the survey (WV=29; WDV=19). Significant differences were observed in perceptions of vaccine safety (p=0.001), understanding the purpose of the vaccine (p=0.02), comfort in requesting the HPV vaccine from providers (p=0.01), and perceived importance of youth vaccination (p=0.02). No differences were found by age, gender, race/ethnicity, education, or employment. Healthcare providers were the most common source of HPV information for both groups. WDV parents often declined vaccination due to a perceived lack of need and limited knowledge, while WV parents cited concerns about cost, insurance, and side effects. Both groups prioritized learning about vaccine effectiveness and side effects. Educational pamphlets were preferred across groups, though WV parents also valued provider discussions and personal testimonials. These findings suggest that provider-led education emphasizing safety, cancer prevention benefits, and early vaccination may increase uptake. Despite limitations of a small, single-site sample, the results highlight strategies to address HPV vaccine hesitancy in rural populations.

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