Leave of Absence and Medical Student Placement Into Graduate Medical Education by Race and Ethnicity.

This study examines the association between taking a leave of absence from medical school and placement into graduate medical education (GME) by race and ethnicity.

Outcomes of the Main Residency Match for Applicants With Disability.

This cohort study assesses match rates of US applicants with and without disability into specialty residence programs.

Prominent role of gut dysbiosis in the pathogenesis of cystic fibrosis-related liver disease in mice.

BACKGROUND & AIMS: Cystic fibrosis-related liver disease (CFLD) is a chronic cholangiopathy that increases morbidity and mortality in patients with CF. Current treatments are unsatisfactory, and incomplete understanding of CFLD pathogenesis hampers therapeutic development. We have previously shown that mouse CF cholangiocytes respond with excessive inflammation to LPS. Thus, we investigated the role of the gut-liver axis in the pathogenesis of CFLD. METHODS: Wild-type (WT), whole-body CFTR knockout (CFTR-KO) and gut-corrected (CFTR-KO-GC) mice were studied. Liver changes were assessed by immunohistochemistry and single-cell transcriptomics (scRNAseq), inflammatory mediators were analyzed by proteome array, faecal microbiota by 16S rRNAseq and gut permeability by FITC-dextran assay. RESULTS: The livers of CFTR-KO mice showed ductular proliferation and periportal inflammation, whereas livers of CFTR-KO-GC mice had no evident pathology. scRNAseq analysis of periportal cells showed increased presence of neutrophils, macrophages and T-cells and activation of pro-inflammatory and pathogen-mediated immune pathways in CFTR-KO livers, consistent with a response to gut-derived stimuli. CFTR-KO mice exhibited gut dysbiosis with enrichment of Enterobacteriaceae and Enterococcus spp., which was associated with increased intestinal permeability and mucosal inflammation, whereas gut dysbiosis and inflammation were absent in CFTR-KO-GC mice. Treatment with nonabsorbable antibiotics ameliorated intestinal permeability and liver inflammation in CFTR-KO mice. Faecal microbiota transfer from CFTR-KO to germ-free WT mice did not result in dysbiosis nor liver pathology, indicating that defective intestinal CFTR is required to maintain dysbiosis. CONCLUSION: Defective CFTR in the gut sustains a pathogenic microbiota, creates an inflammatory milieu, and alters intestinal permeability. These changes are necessary for the development of cholangiopathy. Restoring CFTR in the intestine or modulating the microbiota could be a promising strategy to prevent or attenuate liver disease. IMPACT AND IMPLICATIONS: Severe cystic fibrosis-related liver disease (CFLD) affects 10% of the patients and contributes to increased morbidity and mortality of CF patients. Treatment options remain limited due to a lack of understanding of the disease pathophysiology. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mediates Cl- and HCO3- secretion in the biliary epithelium and its defective function is thought to cause cholestasis and excessive inflammatory responses in CF. However, our study in CFTR-knockout mice demonstrates that microbial dysbiosis, combined with increased intestinal permeability caused by defective CFTR in the intestinal mucosa, acts as a necessary co-factor for the development of CFLD-like liver pathology in mice. These findings uncover a major role for the gut microbiota in CFLD pathogenesis and call for further investigation and clinical validation to develop targeted therapeutic strategies acting on the gut-liver axis in CF.

Socioeconomic Diversity in Admissions to MD-PhD Programs, 2014-2019.

This cohort study of applicants to US MD-PhD programs examines the association of application outcomes with family income.

A host-microbiota interactome reveals extensive transkingdom connectivity.

The myriad microorganisms that live in close association with humans have diverse effects on physiology, yet the molecular bases for these impacts remain mostly unknown1-3. Classical pathogens often invade host tissues and modulate immune responses through interactions with human extracellular and secreted proteins (the 'exoproteome'). Commensal microorganisms may also facilitate niche colonization and shape host biology by engaging host exoproteins; however, direct exoproteome-microbiota interactions remain largely unexplored. Here we developed and validated a novel technology, BASEHIT, that enables proteome-scale assessment of human exoproteome-microbiome interactions. Using BASEHIT, we interrogated more than 1.7 million potential interactions between 519 human-associated bacterial strains from diverse phylogenies and tissues of origin and 3,324 human exoproteins. The resulting interactome revealed an extensive network of transkingdom connectivity consisting of thousands of previously undescribed host-microorganism interactions involving 383 strains and 651 host proteins. Specific binding patterns within this network implied underlying biological logic; for example, conspecific strains exhibited shared exoprotein-binding patterns, and individual tissue isolates uniquely bound tissue-specific exoproteins. Furthermore, we observed dozens of unique and often strain-specific interactions with potential roles in niche colonization, tissue remodelling and immunomodulation, and found that strains with differing host interaction profiles had divergent interactions with host cells in vitro and effects on the host immune system in vivo. Overall, these studies expose a previously unexplored landscape of molecular-level host-microbiota interactions that may underlie causal effects of indigenous microorganisms on human health and disease.

Development of a Tool to Measure Student Perceptions of Equity and Inclusion in Medical Schools.

Importance: Creating an inclusive and equitable learning environment is a national priority. Nevertheless, data reflecting medical students' perception of the climate of equity and inclusion are limited. Objective: To develop and validate an instrument to measure students' perceptions of the climate of equity and inclusion in medical school using data collected annually by the Association of American Medical Colleges (AAMC). Design, Setting, and Participants: The Promoting Diversity, Group Inclusion, and Equity tool was developed in 3 stages. A Delphi panel of 9 members identified survey items from preexisting AAMC data sources. Exploratory and confirmatory factor analysis was performed on student responses to AAMC surveys to construct the tool, which underwent rigorous psychometric validation. Participants were undergraduate medical students at Liaison Committee on Medical Education-accredited medical schools in the US who completed the 2015 to 2019 AAMC Year 2 Questionnaire (Y2Q), the administrations of 2016 to 2020 AAMC Graduation Questionnaire (GQ), or both. Data were analyzed from August 2020 to November 2023. Exposures: Student race and ethnicity, sex, sexual orientation, and socioeconomic status. Main Outcomes and Measures: Development and psychometric validation of the tool, including construct validity, internal consistency, and criterion validity. Results: Delphi panel members identified 146 survey items from the Y2Q and GQ reflecting students' perception of the climate of equity and inclusion, and responses to these survey items were obtained from 54 906 students for the Y2Q cohort (median [IQR] age, 24 [23-26] years; 29 208 [52.75%] were female, 11 389 [20.57%] were Asian, 4089 [7.39%] were multiracial, and 33 373 [60.28%] were White) and 61 998 for the GQ cohort (median [IQR] age, 27 [26-28] years; 30 793 [49.67%] were female, 13 049 [21.05%] were Asian, 4136 [6.67%] were multiracial, and 38 215 [61.64%] were White). Exploratory and confirmatory factor analyses of student responses identified 8 factors for the Y2Q model (faculty role modeling; student empowerment; student fellowship; cultural humility; faculty support for students; fostering a collaborative and safe environment; discrimination: race, ethnicity, and gender; and discrimination: sexual orientation) and 5 factors for the GQ model (faculty role modeling; student empowerment; faculty support for students; discrimination: race, ethnicity, and gender; and discrimination: sexual orientation). Confirmatory factor analysis indicated acceptable model fit (root mean square error of approximation of 0.05 [Y2Q] and 0.06 [GQ] and comparative fit indices of 0.95 [Y2Q] and 0.94 [GQ]). Cronbach α for individual factors demonstrated internal consistency ranging from 0.69 to 0.92 (Y2Q) and 0.76 to 0.95 (GQ). Conclusions and Relevance: This study found that the new tool is a reliable and psychometrically valid measure of medical students' perceptions of equity and inclusion in the learning environment.

Medical Student Burnout by Race, Ethnicity, and Multiple Disability Status.

This cohort study examines the prevalence of burnout among students underrepresented in medicine by race and ethnicity with multiple disability types.

Association of Socioeconomic Status, Sex, Racial, and Ethnic Identity With Sustained and Cultivated Careers in Surgery.

OBJECTIVE: Examine the association between sex, race, ethnicity, and family income, and the intersectionality between these identities, and sustained or cultivated paths in surgery in medical school. METHODS: This retrospective cohort study examines US medical students who matriculated in academic years 2014-2015 and 2015-2016. Data were provided by the Association of American Medical Colleges, including self-reported sex, race, ethnicity, family income, interest in surgery at matriculation, and successful placement into a surgical residency at graduation. This study examined 2 outcomes: (1) sustained path in surgery between matriculation and graduation for students who entered medical school with an interest in surgery and (2) cultivated path in surgery for students who entered medical school not initially interested in surgery and who applied to and were successfully placed into a surgical residency at graduation. RESULTS: Among the 5074 students who reported interest in surgery at matriculation, 2108 (41.5%) had sustained path in surgery. Compared to male students, female students were significantly less likely to have sustained path in surgery [adjusted relative risk (aRR): 0.92 (0.85-0.98)], while Asian (aRR: 0.82, 95% CI: 0.74-0.91), Hispanic (aRR: 0.70, 95% CI: 0.59-0.83), and low-income (aRR: 0.85, 95% CI: 0.78-0.92) students were less likely to have a sustained path in surgery compared to their peers. Among the 17,586 students who reported an initial interest in a nonsurgical specialty, 1869 (10.6%) were placed into a surgical residency at graduation. Female students, regardless of race/ethnic identity and income, were significantly less likely to have cultivated paths in surgery compared to male students, with underrepresented in medicine female students reporting the lowest rates. CONCLUSIONS AND RELEVANCE: This study demonstrates the significant disparity in sustained and cultivated paths in surgery during undergraduate medical education. Innovative transformation of the surgical learning environment to promote surgical identity development and belonging for females, underrepresented in medicine, and low-income students is essential to diversify the surgical workforce.

Challenges Facing First-Generation College Graduates in Medical School: A Qualitative Analysis.

Importance: First-generation (FG) medical students remain underrepresented in medicine despite ongoing national efforts to increase diversity; understanding the challenges faced by this student population is essential to building holistic policies, practices, and learning environments that promote professional actualization. Although FG students have been extensively studied in the undergraduate literature, there is little research investigating how FG students experience medical education or opportunities for educators to intervene. Objective: To explore challenges that FG students experience in undergraduate medical education and identify opportunities to improve foundational FG support. Design, Setting, and Participants: This qualitative study was conducted using an online platform with 37 FG students enrolled in 27 US medical schools. An interprofessional team of medical educators and trainees conducted semistructured interviews from November 2021 through April 2022. Participants were recruited using a medical student listserv. Data were analyzed from April to November 2022. Main Outcomes and Measures: After conducting a preliminary analysis using open coding, a codebook was created and used in a thematic analysis; the codebook used a combination of deductive and inductive coding. Results: Among the 37 students recruited for this study, 21 (56.8%) were female; 23 (62.2%) were in the clinical phase of training; 1 (2.7%) was American Indian or Alaska Native, 7 (18.9%) were Hispanic, Latino, or of Spanish origin, 8 (21.6%) were non-Hispanic Asian or Asian American, 9 (24.3%) were non-Hispanic Black or African American, and 23 (32.4%) were non-Hispanic White; mean (SD) age was 27.3 (2.8) years. Participants described 4 major themes: (1) isolation and exclusion related to being a newcomer to medicine; (2) difficulty with access to basic resources (eg, food, rent, transportation) as well as educational (eg, books); (3) overall lack of faculty or institutional support to address these challenges; and (4) a sense of needing to rely on grit and resilience to survive. Conclusions and Relevance: Although grit and resilience are desirable traits, results of this study suggest that FG medical students face increased adversity with inadequate institutional support, which forces them to excessively rely on grit and resilience as survival (rather than educational) strategies. By applying the holistic model often used in admissions to the postmatriculation educational process, targeted and flexible initiatives can be created for FG students so that all students, regardless of background, can achieve robust professional actualization.

Intersectional Disparities in Emergency Medicine Residents' Performance Assessments by Race, Ethnicity, and Sex.

Importance: Previous studies have demonstrated sex-specific disparities in performance assessments among emergency medicine (EM) residents. However, less work has focused on intersectional disparities by ethnoracial identity and sex in resident performance assessments. Objective: To estimate intersectional sex-specific ethnoracial disparities in standardized EM resident assessments. Design, Setting, and Participants: This retrospective cohort study used data from the Association of American Medical Colleges and the Accreditation Council for Graduate Medical Education Milestones (Milestones) assessments to evaluate ratings for EM residents at 128 EM training programs in the US. Statistical analyses were conducted in June 2020 to January 2023. Exposure: Training and assessment environments in EM residency programs across comparison groups defined by ethnoracial identity (Asian, White, or groups underrepresented in medicine [URM], ie, African American/Black, American Indian/Alaska Native, Hispanic/Latine, and Native Hawaiian/Other Pacific Islander) and sex (female/male). Main Outcomes and Measures: Mean Milestone scores (scale, 0-9) across 6 core competency domains: interpersonal and communications skills, medical knowledge, patient care, practice-based learning and improvement, professionalism, and system-based practice. Overall assessment scores were calculated as the mean of the 6 competency scores. Results: The study sample comprised 128 ACGME-accredited programs and 16 634 assessments for 2708 EM residents of which 1913 (70.6%) were in 3-year and 795 (29.4%) in 4-year programs. Most of the residents were White (n = 2012; 74.3%), followed by Asian (n = 477; 17.6%), Hispanic or Latine (n = 213; 7.9%), African American or Black (n = 160; 5.9%), American Indian or Alaska Native (n = 24; 0.9%), and Native Hawaiian or Other Pacific Islander (n = 4; 0.1%). Approximately 14.3% (n = 386) and 34.6% (n = 936) were of URM groups and female, respectively. Compared with White male residents, URM female residents in 3-year programs were rated increasingly lower in the medical knowledge (URM female score, -0.47; 95% CI, -0.77 to -0.17), patient care (-0.18; 95% CI, -0.35 to -0.01), and practice-based learning and improvement (-0.37; 95% CI, -0.65 to -0.09) domains by postgraduate year 3 year-end assessment; URM female residents in 4-year programs were also rated lower in all 6 competencies over the assessment period. Conclusions and Relevance: This retrospective cohort study found that URM female residents were consistently rated lower than White male residents on Milestone assessments, findings that may reflect intersectional discrimination in physician competency evaluation. Eliminating sex-specific ethnoracial disparities in resident assessments may contribute to equitable health care by removing barriers to retention and promotion of underrepresented and minoritized trainees and facilitating diversity and representation among the emergency physician workforce.

Changing Faces: Factors Associated with the Intention to Pursue Plastic Surgery and Practice in Underserved Areas.

Improving the number of plastic and reconstructive surgeons who provide care to patients in underserved communities is critical to achieving health equity. We aimed to identify factors associated with graduating medical students' intentions to pursue plastic surgery and practice in underserved areas. Methods: De-identified data for US medical school graduates were obtained from the Association of American Medical Colleges for students who matriculated in academic years 2007-2008 and 2011-2012. Data collected included self-reported demographic and future practice intentions. Multivariate analysis was conducted to determine indicators of students' interest in plastic surgery, and their intention to practice in underserved areas. Results: Of the 57,307 graduating US medical students in our cohort who completed the Graduation Questionnaire, 532 (0.9%) reported an intention to pursue plastic surgery. Hispanic [adjusted odds ratio (aOR): 1.45; 95% confidence interval (95% CI), 1.07-1.98] and multiracial (aOR: 1.59; 95% CI, 1.03-2.45) students were more likely to pursue plastic surgery compared with other surgical specialties. Among students interested in plastic surgery, compared with non-Hispanic White students, Black (aOR: 6.15; 95% CI, 1.96-19.26) students were more likely to report intention to practice in underserved areas. Students with community-engagement experiences were more likely to report intention to practice in underserved areas. Conclusions: Diversity among medical trainees pursuing plastic and reconstructive surgery is critical for maintaining and expanding plastic surgery services rendered in underserved areas. These findings suggest that student demographics and experiences with community-engagement experiences are positive indicators of practicing in underserved communities.

Human Th17- and IgG3-associated autoimmunity induced by a translocating gut pathobiont.

Extraintestinal autoimmune diseases are multifactorial with translocating gut pathobionts implicated as instigators and perpetuators in mice. However, the microbial contributions to autoimmunity in humans remain largely unclear, including whether specific pathological human adaptive immune responses are triggered by such pathobionts. We show here that the translocating pathobiont Enterococcus gallinarum induces human IFNγ + Th17 differentiation and IgG3 subclass switch of anti- E. gallinarum RNA and correlating anti-human RNA autoantibody responses in patients with systemic lupus erythematosus and autoimmune hepatitis. Human Th17 induction by E. gallinarum is cell-contact dependent and involves TLR8-mediated human monocyte activation. In murine gnotobiotic lupus models, E. gallinarum translocation triggers IgG3 anti-RNA autoantibody titers that correlate with renal autoimmune pathophysiology and with disease activity in patients. Overall, we define cellular mechanisms of how a translocating pathobiont induces human T- and B-cell-dependent autoimmune responses, providing a framework for developing host- and microbiota-derived biomarkers and targeted therapies in extraintestinal autoimmune diseases. One Sentence Summary: Translocating pathobiont Enterococcus gallinarum promotes human Th17 and IgG3 autoantibody responses linked to disease activity in autoimmune patients.

Association of Racial and Ethnic Identity With Attrition From MD-PhD Training Programs.

This cohort study analyzes the attrition rates of students from MD-PhD training programs by race and ethnicity.

Sequential Chromogenic IHC: Spatial Analysis of Lymph Nodes Identifies Contact Interactions between Plasmacytoid Dendritic Cells and Plasmablasts.

Recent clinical observations have emphasized the critical role that the spatial organization of immune cells in lymphoid structures plays in the success of cancer immunotherapy and patient survival. However, implementing sequential chromogenic IHC (scIHC) to analyze multiple biomarkers on a single tissue section has been limited because of a lack of a standardized, rigorous guide to the development of customized biomarker panels and a need for user-friendly analysis pipelines that can extract meaningful data. In this context, we provide a comprehensive guide for the development of novel biomarker panels for scIHC, using practical examples and illustrations to highlight the most common complications that can arise during the setup of a new biomarker panel, and provide detailed instructions on how to prevent and detect cross-reactivity between secondary reagents and carryover between detection antibodies. We also developed a novel analysis pipeline based on non-rigid tissue deformation correction, Cellpose-inspired automated cell segmentation, and computational network masking of low-quality data. We applied this biomarker panel and pipeline to study regional lymph nodes from patients with head and neck cancer, identifying novel contact interactions between plasmablasts and plasmacytoid dendritic cells in vivo. Given that Toll-like receptors, which are highly expressed in plasmacytoid dendritic cells, play a key role in vaccine efficacy, the significance of this cell-cell interaction decisively warrants further studies. In summary, this work provides a streamlined approach to the development of customized biomarker panels for scIHC that will ultimately improve our understanding of immune responses in cancer. Significance: We present a comprehensive guide for developing customized biomarker panels to investigate cell-cell interactions in the context of immune responses in cancer. This approach revealed novel contact interactions between plasmablasts and plasmacytoid dendritic cells in lymph nodes from patients with head and neck cancer.

Medical student intentions to practice internal medicine in underserved areas associated with debt, identity and extracurricular participation.

BACKGROUND: Currently, Internal Medicine (IM) physicians do not reflect the ethno-racial diversity of the US population. Moreover, there is a shortage of IM physicians in Medically Underserved Areas (MUAs) in the US. The purpose of this study was to determine factors that influence medical students' intent to practice IM in MUAs. We hypothesized students with intentions to pursue a career in IM and work in MUAs were more likely than their peers to identify as underrepresented in medicine (URiM), report greater student debt loads, and report medical school experiences in cultural competencies. METHODS: We analyzed de-identified data of 67,050 graduating allopathic medical students who completed the Association of American Medical Colleges' (AAMC) Medical School annual Graduation Questionnaire (GQ) between 2012-2017 by multivariate logistic regression models, examining intent to practice IM in MUAs based on respondent characteristics. RESULTS: Of 8,363 students indicating an intent to pursue IM, 1,969 (23.54%) students also expressed an intent to practice in MUAs. Students awarded scholarships, (aOR: 1.23, [1.03-1.46]), with debt greater than $300,000 (aOR: 1.54, [1.21-1.95], and self-identified non-Hispanic Black/African American (aOR: 3.79 [2.95-4.87]) or Hispanic (aOR: 2.53, [2.05-3.11]) students were more likely than non-Hispanic White students to indicate intent to practice in MUAs. This pattern also existed for students who participated in a community-based research project (aOR: 1.55, [1.19-2.01]), had experiences related to health disparities (aOR: 2.13, [1.44-3.15]), or had experiences related to global health (aOR: 1.75, [1.34-2.28]). CONCLUSIONS: We identified experiences and characteristics that associate with intention to practice IM in MUAs, which can aid future curricular redesign by medical schools to expand and deepen comprehension of health disparities, access to community-based research, and global health experiences. Loan forgiveness programs and other initiatives to increase recruitment and retention of future physicians should also be developed.

Transition From Mentored to Independent NIH Funding by Gender and Department.

This study uses National Institutes of Health RePORTER data for mentored K awards and R01-equivalent grants to all departments in US schools of medicine to characterize K-award distribution and K-to-R transition by gender and department between 1997 and 2021.

Temporal Trends in Childhood Household Income Among Applicants and Matriculants to Medical School and the Likelihood of Acceptance by Income, 2014-2019.

This study examines trends in childhood household income among applicants and matriculants to medical school and the likelihood of acceptance by income.

Rates of National Institutes of Health Funding for Surgeon-Scientists, 1995-2020.

Importance: Surgeon-scientists are uniquely positioned to facilitate translation between the laboratory and clinical settings to drive innovation in patient care. However, surgeon-scientists face many challenges in pursuing research, such as increasing clinical demands that affect their competitiveness to apply for National Institutes of Health (NIH) funding compared with other scientists. Objective: To examine how NIH funding has been awarded to surgeon-scientists over time. Design, Setting, and Participants: This cross-sectional study used publicly available data from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditures and Results) database for research project grants awarded to departments of surgery between 1995 and 2020. Surgeon-scientists were defined as NIH-funded faculty holding an MD or MD-PhD degree with board certification in surgery; PhD scientists were NIH-funded faculty holding a PhD degree. Statistical analysis was performed from April 1 to August 31, 2022. Main Outcome: National Institutes of Health funding to surgeon-scientists compared with PhD scientists, as well as NIH funding to surgeon-scientists across surgical subspecialties. Results: Between 1995 and 2020, the number of NIH-funded investigators in surgical departments increased 1.9-fold from 968 to 1874 investigators, corresponding to a 4.0-fold increase in total funding (1995, $214 million; 2020, $861 million). Although the total amount of NIH funding to both surgeon-scientists and PhD scientists increased, the funding gap between surgeon-scientists and PhD scientists increased 2.8-fold from a $73 million difference in 1995 to a $208 million difference in 2020, favoring PhD scientists. National Institutes of Health funding to female surgeon-scientists increased significantly at a rate of 0.53% (95% CI, 0.48%-0.57%) per year from 4.8% of grants awarded to female surgeon-scientists in 1995 to 18.8% in 2020 (P < .001). However, substantial disparity remained, with female surgeon-scientists receiving less than 20% of NIH grants and funding dollars in 2020. In addition, although there was increased NIH funding to neurosurgeons and otolaryngologists, funding to urologists decreased significantly from 14.9% of all grants in 1995 to 7.5% in 2020 (annual percent change, -0.39% [95% CI, -0.47% to -0.30%]; P < .001). Despite surgical diseases making up 30% of the global disease burden, representation of surgeon-scientists among NIH investigators remains less than 2%. Conclusion and Relevance: This study suggests that research performed by surgeon-scientists continues to be underrepresented in the NIH funding portfolio, highlighting a fundamental need to support and fund more surgeon-scientists.