Automated spatial omics landscape analysis approach reveals novel tissue architectures in ulcerative colitis.

The utility of spatial omics in leveraging cellular interactions in normal and diseased states for precision medicine is hampered by a lack of strategies for matching disease states with spatial heterogeneity-guided cellular annotations. Here we use a spatial context-dependent approach that matches spatial pattern detection to cell annotation. Using this approach in existing datasets from ulcerative colitis patient colonic biopsies, we identified architectural complexities and associated difficult-to-detect rare cell types in ulcerative colitis germinal-center B cell follicles. Our approach deepens our understanding of health and disease pathogenesis, illustrates a strategy for automating nested architecture detection for highly multiplexed spatial biology data, and informs precision diagnosis and therapeutic strategies.

Association of a longitudinal, preclinical ultrasound curriculum with medical student performance.

INTRODUCTION: Point-of-care ultrasound (US) is used in clinical practice across many specialties. Ultrasound (US) curricula for medical students are increasingly common. Optimal timing, structure, and effect of ultrasound education during medical school remains poorly understood. This study aims to retrospectively determine the association between participation in a preclinical, longitudinal US curriculum and medical student academic performance. METHODS: All first-year medical students at a medical school in the Midwest region of the United States were offered a voluntary longitudinal US curriculum. Participants were selected by random lottery. The curriculum consisted of five three-hour hands on-sessions with matching asynchronous content covering anatomy and pathologic findings. Content was paired with organ system blocks in the standard first year curriculum at our medical school. Exam scores between the participating and non-participating students were compared to evaluate the objective impact of US education on performance in an existing curriculum. We hypothesized that there would be an association between participation in the curriculum and improved medical student performance. Secondary outcomes included shelf exam scores for the surgery, internal medicine, neurology clerkships and USMLE Step 1. A multivariable linear regression model was used to evaluate the association of US curriculum participation with student performance. Scores were adjusted for age, gender, MCAT percentile, and science or engineering degree. RESULTS: 76 of 178 students applied to participate in the curriculum, of which 51 were accepted. US curriculum students were compared to non-participating students (n = 127) from the same class. The US curriculum students performed better in cardiovascular anatomy (mean score 92.1 vs. 88.7, p = 0.048 after adjustment for multiple comparisons). There were no significant differences in cumulative cardiovascular exam scores, or in anatomy and cumulative exam scores for the gastroenterology and neurology blocks. The effect of US curriculum participation on cardiovascular anatomy scores was estimated to be an improvement of 3.48 points (95% CI 0.78-6.18). No significant differences were observed for USMLE Step 1 or clerkship shelf exams. There were no significant differences in either preclinical, clerkship or Step 1 score for the 25 students who applied and were not accepted and the 102 who did not apply. CONCLUSIONS: Participation in a preclinical longitudinal US curriculum was associated with improved exam performance in cardiovascular anatomy but not examination of other cardiovascular system concepts. Neither anatomy or comprehensive exam scores for neurology and gastrointestinal organ system blocks were improved.

Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood.

Neoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8+ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex (MHC) tetramers at high avidity by barcoded DNA linkers. The magnetic particles provide a convenient handle to isolate the desired cell populations, and the barcoded DNA enables multiplexed analysis. The method exhibits superior recovery of antigen-specific T cell populations relative to literature approaches. We applied the method to profile neoantigen-specific T cell populations in the tumor and blood of patients with metastatic melanoma over the course of anti-PD1 checkpoint inhibitor therapy. We show that the method has value for monitoring clinical responses to cancer immunotherapy and might help guide the development of personalized mutational neoantigen-specific T cell therapies and cancer vaccines.

Identifying Medical Student Mistreatment in the Obstetrics and Gynecology Clerkship.

OBJECTIVE: To characterize the mistreatment identified within the University of Michigan's Obstetrics and Gynecology (Ob/Gyn) clerkship and compare the rates of mistreatment to that of other clerkships in an effort to improve the learning environment. DESIGN: This is a retrospective cohort study looking at multiple sources of data from 2015 to 2018 about student mistreatment including end-of-rotation and teaching evaluations completed by students, as well as an online reporting system available to medical students. For evaluations, students were asked to rate their agreement with statements on a 5-point Likert scale (1 = strongly disagree, to 5 = strongly agree). Narrative comments were also solicited and evaluated. SETTING: University of Michigan Medical School and Michigan Medicine Ob/Gyn Department, Ann Arbor, Michigan. PARTICIPANTS: A total of 513 students rotated through the Ob/Gyn clerkship between 2015 and 2018 and were asked to complete evaluations. RESULTS: Five hundred and five of the 513 students completed evaluations between 2015 and 2018. In response to the statement, "Students are treated in a professional/respectful manner in this clerkship," the Ob/Gyn clerkship's mean scores on a 5-point scale were 4.45 (in 2015-2016), 4.52 (in 2016-2017), and 4.27 (in 2017-2018). These means, as well as the means to 3 other professionalism questions, were lower than the range of 4.42 to 4.84 for all other third-year clerkships over this time. The mean scores were also lower for Ob/gyn when compared to the Surgery clerkship. A total of 32 narrative comments were submitted by students between 2015 and 2017 related to mistreatment or unprofessional behavior. Frequent themes included students being treated as "stupid" or discouraged from asking questions (8 comments), being treated in an unprofessional manner by staff (7 comments), feeling ignored or marginalized by faculty (4 comments), and faculty unprofessional behavior toward others (4 comments). CONCLUSIONS: Students on the Ob/Gyn clerkship reported a higher rate of mistreatment compared to other clerkships. Efforts are being made by the Ob/Gyn department to communicate these data on mistreatment to educators in order to improve the Ob/Gyn culture and learning environment for medical students.

Palliative Care Matters: Lessons From the Loss of a Facility Dog.

Animal-assisted intervention is gaining attention as a stress reduction modality. Quantitative data demonstrate its effectiveness, as a recent study published in AJHPM supported that a Veterans Affairs (VA) hospital facility dog paired with a palliative care psychologist had a measurable impact on salivary cortisol levels and heart rate in hospitalized veterans. There remains an important role for qualitative insights. The Denver VA palliative care team learned a range of lessons from the sudden loss of their facility dog, many of which relate directly to palliative care. The importance of communication, adjusting to changing teams, and the need for consultation and support based in shared goals and values all became evident in the course of the facility dog's illness. After her death, lessons shifted to grief and loss and how providers, patients, and a community care for each other. People's connection to the facility dog ultimately proved to be a critical factor in helping them connect with one another.

Effects of VA Facility Dog on Hospitalized Veterans Seen by a Palliative Care Psychologist: An Innovative Approach to Impacting Stress Indicators.

The United States is home to 23 million veterans. In many instances, veterans with serious illness who seek healthcare at the VA receive care from a palliative care service. Animal-assisted intervention (AAI) is gaining attention as a therapeutic stress reducing modality; however, its effects have not been well studied in veterans receiving palliative care in an acute care setting. A crossover repeated-measures study was conducted to examine the effects of an animal-assisted intervention (AAI) in the form of a therapy dog on stress indicators in 25 veterans on the palliative care service at the VA Eastern Colorado Healthcare System in Denver, CO. Veterans had a visit from a therapy dog and the dog's handler, a clinical psychologist (experimental condition) and an unstructured visit with the clinical psychologist alone (control condition). Blood pressure, heart rate, and the salivary biomarkers cortisol, alpha-amylase, and immunoglobulin A were collected before, after, and 30-minutes after both the experimental and control conditions. Significant decreases in cortisol were found when the before time period was compared to the 30-minutes after time period for both the experimental ( p = 0.007) and control condition ( p = 0.036). A significant decrease in HR was also found when the before time period was compared to the 30-minutes after time period for both the experimental ( p = 0.0046) and control ( p = 0.0119) condition. Results of this study supported that a VA facility dog paired with a palliative care psychologist had a measurable impact on salivary cortisol levels and HR in veterans.