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Immune Infiltrate Profiling of Cutaneous Melanoma with Spatial Transcriptomics
Get PDFBackground and Objective:In 2023, an estimated 97,610 melanomas will be diagnosed in the U.S. Immunotherapy has revolutionized care for melanoma patients and highlighted the prognostic value of characterizing immune infiltrates in melanoma tissue. This project used spatial transcriptomics (ST) to analyze immune infiltrates in cutaneous melanoma specimens.
Methods:Visium Spatial Gene Expression platform generated datasets from formalin fixed paraffin embedded cutaneous melanoma specimens were analyzed using Loupe Browser software v6.5.0 (10x Genomics Inc.). Unsupervised clustering and manual region selection identified areas enriched in immune cell specific differentially expressed genes (DEGs). The transcript for Collagen alpha-1(XIX) chain (COL19A1) was identified as a DEG co-expressed with B cell marker DEGs. Fluorescence activated cell sorting was used to isolate primary B and T cells from mouse secondary lymphoid organs and human peripheral blood mononuclear cells to measure COL19A1 with quantitative PCR (qPCR).
Results:Transcripts for CD19 (B cell marker) were concentrated in an immune DEG- rich region adjacent to a melanoma micrometastasis in one specimen. There was overlap between the tertiary lymphoid structure [TLS] markers SELL, CXCR5, CCR7, and CXCL13 with CD19 and/or COL19A1. Though qPCR revealed minimal Col19a1 in mouse B and T cells, COL19A1 was abundant and specific for human B cells.
Conclusions & Potential Impact:This study demonstrates the feasibility and potential of using ST to characterize immune cell infiltrates in melanoma. Though COL19A1 expression is typically understood to be enriched in muscle and neuronal cells, the studies presented here suggest this transcript could be a novel human (but not mouse) B cell marker. Future studies are needed to determine if collagen XIX (protein) is expressed in B cells and if it is, what the biological functions of this protein are in B cells under physiologic and pathologic (e.g. melanoma) conditions
Geographic location as a variable to Home Gardening Interventions in Rural Indiana
Get PDFBackground/Objective: The purpose of this study was to evaluate attitudes of a wide variety of persons towards barriers to home gardening and desired interventions for home gardening in multiple locations in the Muncie, Indiana area. The health benefits of gardening are well known, but little research has been done evaluating the ability or interest in home gardening in areas with significant populations of minorities or those with low socioeconomic status. Taste enhancing herbs or fresh and nutritious vegetables in food insecure areas could be invaluable. This study evaluates which interventions were preferred and needed based on geographic location in Muncie. Our hypothesis was that respondents from a garden fair in Muncie would be more likely to want more information than respondents from other locations.
Methods: A survey designed for a research study focusing on barriers to home gardening was deemed to be appropriate to use for analysis for this study, because it included several questions about desired and needed interventions. The survey asked respondents to write contact information if follow-up interventions or classes were desired. Cross tabulation was used to analyze the relationship between multiple variables in the survey.
Results: There is a statistically significant relationship between where the person was surveyed and whether they wanted to sign up for more information. 68.8% of respondents at the Minnetrista Garden Fair desired more information, compared to 0% of respondents at the Yorktown Farmer’s Market.
Conclusion: There was in fact a relationship between location surveyed and desire for more information, but this relationship isn’t as simple as location. The type of event and number of people attending the event also likely impacted results. Scientific/Clinical/Policy Impact and Implications: Results from this study will be used in further work to develop gardening related information and programs for those surveyed who wish to participate
Clinician Perspectives on Risks and Benefits of Sharing Cardiovascular Implanted Electronic Device (CIED) Data with Patients
Get PDFBackground and Objective: Cardiovascular implantable electronic devices (CIEDs) are critical, life-saving devices that are essential for the clinical decision-making process due to the data they collect. Because not all patients have ready access to their device data, there may be a clinical care gap where the CIED data are not being used most effectively in the care of patients with CIEDs. However, sharing CIED data may risk harming clinician-patient relationships and necessitates further study into clinician’s perspectives on CIED data sharing. The objective of this study was to explore clinicians’ perspectives on sharing CIED data with their patients and explore the perceived benefits and concerns.
Methods: Clinicians involved in CIED care in the United States were recruited for semi-structured phone interviews. Participants were asked questions regarding their experiences and perspectives in sharing CIED data, and were presented scenarios to assess how they would leverage the CIED data in particular situations. Responses from the participants were analyzed by one researcher using thematic analysis.
Results: Of the 28 clinicians interviewed in this study, the majority were white (85.7%) and located in the midwestern United States (67.9%). Participants included cardiac device clinic nurses and electrophysiology nurses (28.6%), electrophysiologists (25%), electrophysiology advanced practice providers (APPs) (17.9%), cardiologists (14.3%), and cardiology APPs (14.3%). The following themes were identified: (1) Patient engagement with healthcare, (2) Patient selfadvocacy, (3) Patients cannot interpret CIED data, (4) One size does not fit all.
Conclusion and Potential Impact: Clinicians perceived both potential benefits and harms from CIED data sharing. Clinicians noted that CIED data sharing has the potential to increase patient participation in their healthcare, but it also can cause increased patient anxiety due to insufficient patient education. This study demonstrated some of the ways CIED data sharing may affect clinical practice involving CIEDs and the challenge of sharing complex data elements with patients
Prevalence of Positive Urine Drug Screen for Fentanyl and its Analogs in Indianapolis
Get PDFBackground and Hypothesis: IU Health Pathology Laboratory (IUHPL) recently added qualitative fentanyl screening to its test menu. However, fentanyl screening is not currently part of the urine drugs of abuse (DAU) panel which includes amphetamine, barbiturates,benzodiazepines, buprenorphine, cannabinoids, methadone, cocaine, opiates, oxycodone, and phencyclidine. Since fentanyl screen is a standalone test, we were interested in determining how often specimens had this ordered in conjunction with the DAU, as we suspected not all of them did. Our hypothesis was that positive urine drug screens may also be positive for fentanyl/fentanyl analogs.
Project Methods: Urine specimens sent for routine drug screens at IU Health Arnett, Ball, Bloomington, and IUHPL between June and mid-July 2023 were subjected to fentanyl screening. Specimen that screened positive were confirmed by LC-MS/MS for presence offentanyl and norfentanyl. Additionally, specimens were tested for 4ANPP (fentanyl precursor) and xylazine; if they were positive for either, they were sent to an outside laboratory to ascertain if other fentanyl analogs or designer opioids were present.
Results: Of the 1,893 DAU specimens received, 51.2% were positive for at least one drug class. Only 28 had an associated fentanyl screen order. Cannabinoids represented the most prevalent drug class with a 26.7% positivity rate. Only 1,724 samples were available to screen for fentanyl as part of this study. Of these, 214 specimens were positive for fentanyl, with a positivity screen rate of 12.4%. Confirmatory testing by LC-MS/MS indicated 206 of the 214 were true positives.
Conclusion and Impact: These results highlight the need for fentanyl testing and continued clinician education to increase awareness about the inability of standard urine drug screens to detect fentanyl. Dialogue between patients and clinicians would potentially decrease overdoses and/or result in more treatment referrals. Additionally, integrating fentanyl screening into the DAU panel will facilitate qualitative fentanyl testing
Artificial Intelligence in the Detection of Fatty Liver Disease
Get PDFBackground: The current gold standard for quantification of the fat content of the liver (i.e., nonalcoholic fatty liver disease, NAFLD) is the visual microscopic inspection of liver biopsies by pathologists. Percentage of macrosteatosis (%MaS), used in determining NAFLD diagnosis, is vital in determining the transplant suitability of a donor liver. A major limitation of this method is inevitable human error which causes interobserver variability and overestimation of %MaS which could cause a potential discard of donor livers. We hypothesize that artificial intelligence (AI) can assist pathologists in providing a more objective and accurate measure of %MaS.
Methods: Our literature review identified HALO (image analysis) and U-Net (deep-learning) as AI programs currently available for high-accuracy %MaS calculation in liver biopsies. We compared the pathologist-reported %MaS from de-novo liver transplant (LT) biopsy samples taken 2h post-reperfusion to the %MaS calculated by HALO and/or U-Net (Fig. 1). 250 patients had undergone de novo LT at Indiana University between 2019-2020, and 211 of these patients had sufficient data (liver enzyme tests, biopsy results) to be included. Each biopsy sample was digitized into 5 random non-overlapping tiles at 20x magnification using a Leica microscope. Early allograft dysfunction (EAD) is defined by the presence of at least one of the following: (i) INR >1.6 on postoperative day (POD) 7, (ii) total bilirubin >10 mg/dL on POD7, or (iii) AST/ALT >2000 IU/L within the first 7 days following LT.
Results: Our literature review identified that both HALO and U-Net estimated the %MaS in liver allograft biopsies significantly lower than pathologists\u27 estimation (Fig.1). Of 211 included patients, 46 (21.8%) had EAD. In this ongoing project, we found U-Net to have a 97.3% training accuracy with eight epochs (2000 biopsy images each). Tiles from the first ten patients are being analyzed by HALO and/or U-Net to calculate an average %MaS for each patient. These calculations will be compared to the %MaS estimation made by pathologists.
Conclusions: The rapidly evolving field of AI is emerging as a promising method in the quantification of the fat content of the liver with increased accuracy. AI will therefore help pathologists and transplant surgeons to determine liver transplant viability and better predict EAD in transplant patients
Ineffectiveness of mitoTEMPO on Cardiomyocyte S-phase Activity in TNNI3K-expressing Mice
Get PDFBackground and Hypothesis: The limited regenerative capacity of the mammalian adult myocardium is a significant roadblock for therapeutic approaches in cardiovascular disease. Cell cycle arrest following S-phase is widely considered a primary contributor to the reduced proliferative capacity of adult cardiomyocytes. Recently, expression of troponin I-interacting kinase (Tnni3k) was shown to increase cardiomyocyte S-phase activity in mice. Tnni3k was previously shown to enhance ROS formation and adverse cardiac remodeling following injury. Our primary hypothesis was that TNNI3K-induced cardiomyocyte DNA synthesis resulted from enhanced ROS signaling. To test this, cardiomyocyte S-phase activity in TNNI3K-expressing mice was compared between those treated with the ROS scavenging agent mitoTEMPO and untreated mice.
Project Methods: Transgenic mice expressing TNNI3K were subjected to 14 days infusion with mitoTEMPO (experimental group) or vehicle (control group). The mice were also subjected to 14 days infusion with bromodeoxyuridine (BrdU) to identify DNA synthesis during S-phase (all mice carried a cardiomyocyte-restricted nuclear-localized transgenic reporter to aid in cardiomyocyte nuclei identification). The proportion of cardiomyocytes in S-phase was determined and mean S-phase activity was compared between treatment groups. Ploidy analysis was also conducted to determine if cardiomyocytes completing S-phase progressed through karyokinesis.
Results: The percentage of cardiomyocytes in S-phase in the control and mitoTEMPO treated group were 0.819% ± 0.163% and 0.855% ± 0.138%, respectively (mean ± SEM, p=0.873). Ploidy analysis revealed no overt difference in DNA content in S-phase-positive cardiomyocyte nuclei between the groups. Hence, we have shown that there is no appreciable difference in cell cycle induction or progression in cardiomyocytes from control vs. mitoTEMPO treated mice expressing TNNI3K.
Conclusion and Potential Impact: These data suggest that (a) TNNI3K-induced cardiomyocyte S-phase activity is not secondary to elevated ROS activity, and (b) reduction of ROS activity does not relax the cell cycle block between S-phase and karyokinesis in adultcardiomyocytes
Health Disparities in Acidosis Risks
Get PDFBackground: Health disparities in acidosis risk are entangled with a range of factors including clinical conditions, genomic traits, and demographic features. Current clinical guidelines and policies on the safety of metformin have not yet taken holistic considerations of health disparities and other risk factors. The All of Us (AoU) research dataset provides comprehensive information including longitudinal real-world data for diseases and treatments, genetic data, and surveys for social determinants of health, with a focus on minority groups and the underserved population. This study leverages the AoU data to understand the health disparities in acidosis risk and provides real-world evidence to support clinical decisions.
Methods: A case-control design was used to identify risk factors associated with emergent acidosis events, with a 1:4 matching using propensity scores specified by enrollment date, number of diagnoses, and length of medical history. Risk factors were sex, age, race, ethnicity, metformin use, Charlson comorbidities, and insurance status. Adjusted odds ratios (aOR) were estimated using conditional logistic regression.
Results: The study includes the case group (n=2,666) and the control group (n=10,664). Health disparities were observed among participants. Compared with those who did not have health insurance, those with employer provided insurance (aOR: 0.49, 95%CI: 0.40 – 0.61), Medicare (aOR: 0.62, 95%CI: 0.52 – 0.74), or Medicaid (aOR: 0.80, 95%CI: 0.66 – 0.97) were less likely to develop acidosis. African Americans (aOR: 1.35, 95%CI: 1.15 – 1.58) showed higher acidosis risk. Other major risk factors include liver disease, renal disease, diabetes, and metformin use.
Conclusion: Health insurance coverage is a major determinant of acidosis risk. Patients with kidney and liver diseases or diabetes should be monitored carefully for signs of acidosis, especially if they have been prescribed metformin. In future work, for diabetes patients with both kidney and liver diseases, pharmacogenomics analysis will be performed for precision management of metformin-related acidosis risks
Introducing the Theory of Neurosocial Interdependence: Moving Beyond the Person-In-Environment Perspective in Social Work
Get PDFThoughts, emotions, and behaviors are linked fundamentally to the environments one inhabits. The person-in-environment perspective effectively captures these three aspects of the human experience and serves as a central fixture within social work research and practice. Many social workers use this perspective to guide every facet of the work they undertake, from case conceptualization to ethics of human subject research. At the same time, recent advancements in human neuroscience research and neuroimaging technologies have inspired social workers to embrace how the nervous system is integrally interconnected with one’s environments. In turn, human neuroscience has catalyzed more biologically-informed practice and research in the field of social work, centered on elucidating social and psychological developmental domains within systems. The popularity of the person-in-environment perspective and the integration of human neuroscience in the field of social work has created a nexus that heretofore has not been adequately integrated into the literature. The present paper addresses this gap with a novel theory known as neurosocial interdependence, which integrates insights from human neuroscience into the framework of the person-in-environment perspective. This paper also bolsters the development of the theory of neurosocial interdependence by introducing a novel testing instrument and measurement scale, exploring how these tools might be used to implement the theory of neurosocial interdependence within social work research and clinical settings
Enhancing Competency-Based Social Work Skills Through Service Learning and Interprofessional Education in a Student-Run Free Healthcare Clinic
Get PDFStudent-run free clinics (SRFC) offer students the opportunity to learn and work with students from other disciplines; however, there is very little research on the benefits of SRFC to social work students. The purpose of this article is to describe the qualitative student outcomes of a service learning (SL) and interprofessional education (IPE) experience in a SRFC designed to enhance the interprofessional competencies of BSW social work students. Students (n=38) enrolled in a service-learning course and participated in a semester-long SL and IPE experience at a university-affiliated interdisciplinary SRFC. Qualitative findings from student reflections indicated that students perceived that the overall experience facilitated the development of written and verbal communication skills, confidence, and professional identity. The research suggests that SL and IPE were beneficial to student development. We, therefore, recommend that other programs consider exposing BSW students to these experiences early in their program to enhance their educational experience
Mental Health Service Use Among Middle Eastern Migrant Women: Social Work\u27s Role in Promoting Mental Health Literacy
Get PDFMental Health Service Use Among Middle Eastern Migrant Women: Social Work\u27s Role in Promoting Mental Health LiteracyKrisztina BaltimoreWooksoo KimAbstract: Migrants who relocate to the United States from the Middle East are more likely to face a host of structural and individual barriers that can significantly contribute to their mental health issues and affect their psychological well-being. Addressing mental health problems and incentivizing help-seeking behavior is important among women who are more likely to face daily stressors in childcare, household responsibilities, and marital relationships. In this paper, we discuss factors that impact help-seeking for mental health problems among Middle Eastern migrant women including English language proficiency, structural challenges, and cultural factors such as shame and stigma. We argue that when considering its potential effectiveness, targeting mental health literacy may serve as the best direction for future research and social work intervention in order to enhance help-seeking behavior among this population. Recommendations for social workers include using community-based partnerships to provide educational resources regarding mental health services through healthcare centers, social service agencies, and local Muslim and Arab organizations