Factors associated with immune responses to SARS-CoV-2 vaccination in autoimmune disease individuals.

Patients with autoimmune diseases are at higher risk for severe infection due to their underlying disease and immunosuppressive treatments. In this real-world observational study of 463 autoimmune subjects, we examined risk factors for poor B and T cell responses to SARS-CoV-2 vaccination. We show a high frequency of inadequate anti-spike IgG responses to vaccination and boosting in the autoimmune population but minimal suppression of T cell responses. Low IgG responses in B cell-depleted multiple sclerosis (MS) subjects were associated with higher CD8 T cell responses. By contrast, subjects taking mycophenolate mofetil exhibited concordant suppression of B and T cell responses. Treatments with highest risk for low IgG anti-spike response included B cell depletion within the last year, fingolimod, and combination treatment with mycophenolate mofetil (MMF) and belimumab. Our data show that the mRNA-1273 (Moderna) vaccine, is the most effective vaccine in the autoimmune population. There was minimal induction of either disease flares or autoantibodies by vaccination and no significant effect of pre-existing anti-type I interferon antibodies on either vaccine response or breakthrough infections. The low frequency of breakthrough infections and lack of SARS-CoV-2-related deaths suggest that T cell immunity contributes to protection in autoimmune disease.

Exploration of potential immune mechanisms in cervical dystonia.

BACKGROUND: Although there are many possible causes for cervical dystonia (CD), a specific etiology cannot be identified in most cases. Prior studies have suggested a relationship between autoimmune disease and some cases of CD, pointing to possible immunological mechanisms. OBJECTIVE: The goal was to explore the potential role of multiple different immunological mechanisms in CD. METHODS: First, a broad screening test compared neuronal antibodies in controls and CD. Second, unbiased blood plasma proteomics provided a broad screen for potential biologic differences between controls and CD. Third, a multiplex immunoassay compared 37 markers associated with immunological processes in controls and CD. Fourth, relative immune cell frequencies were investigated in blood samples of controls and CD. Finally, sequencing studies investigated the association of HLA DQB1 and DRB1 alleles in controls versus CD. RESULTS: Screens for anti-neuronal antibodies did not reveal any obvious abnormalities. Plasma proteomics pointed towards certain abnormalities of immune mechanisms, and the multiplex assay pointed more specifically towards abnormalities in T lymphocytes. Abnormal immune cell frequencies were identified for some CD cases, and these cases clustered together as a potential subgroup. Studies of HLA alleles indicated a possible association between CD and DRB1*15:03, which is reported to mediate the penetrance of autoimmune disorders. CONCLUSIONS: Altogether, the association of CD with multiple different blood-based immune measures point to abnormalities in cell-mediated immunity that may play a pathogenic role for a subgroup of individuals with CD.

Environmental circadian disruption re-programs liver circadian gene expression.

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag, which impact millions of people worldwide, are ill-defined. Here, we provided the first comprehensive description of liver circadian gene expression under normal and after ECD conditions. We found that post-transcription and post-translation processes are dominant contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome is re-written by ECD. The re-writing, which is associated with changes of circadian cis-regulatory elements, RNA-processing and protein trafficking, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery.

Federated causal inference in heterogeneous observational data.

We are interested in estimating the effect of a treatment applied to individuals at multiple sites, where data is stored locally for each site. Due to privacy constraints, individual-level data cannot be shared across sites; the sites may also have heterogeneous populations and treatment assignment mechanisms. Motivated by these considerations, we develop federated methods to draw inferences on the average treatment effects of combined data across sites. Our methods first compute summary statistics locally using propensity scores and then aggregate these statistics across sites to obtain point and variance estimators of average treatment effects. We show that these estimators are consistent and asymptotically normal. To achieve these asymptotic properties, we find that the aggregation schemes need to account for the heterogeneity in treatment assignments and in outcomes across sites. We demonstrate the validity of our federated methods through a comparative study of two large medical claims databases.

Eos Promotes TH2 Differentiation by Interacting with and Propagating the Activity of STAT5.

The Ikaros zinc-finger transcription factor Eos has largely been associated with sustaining the immunosuppressive functions of regulatory T cells. Paradoxically, Eos has more recently been implicated in promoting proinflammatory responses in the dysregulated setting of autoimmunity. However, the precise role of Eos in regulating the differentiation and function of effector CD4+ T cell subsets remains unclear. In this study, we find that Eos is a positive regulator of the differentiation of murine CD4+ TH2 cells, an effector population that has been implicated in both immunity against helminthic parasites and the induction of allergic asthma. Using murine in vitro TH2 polarization and an in vivo house dust mite asthma model, we find that EosKO T cells exhibit reduced expression of key TH2 transcription factors, effector cytokines, and cytokine receptors. Mechanistically, we find that the IL-2/STAT5 axis and its downstream TH2 gene targets are one of the most significantly downregulated pathways in Eos-deficient cells. Consistent with these observations, we find that Eos forms, to our knowledge, a novel complex with and supports the tyrosine phosphorylation of STAT5. Collectively, these data define a regulatory mechanism whereby Eos propagates STAT5 activity to facilitate TH2 cell differentiation.

Cultured Skin Autograft in Subtotal Pediatric Scalp Avulsion.

ABSTRACT: Pediatric scalp avulsions represent a reconstructive challenge because of the unique features of scalp tissue. When microsurgical reimplantation is not feasible, alternative approaches such as skin grafting, free flap transfer with latissimus flap, or tissue expansion are considered. Generally, there is no consensus regarding management of this trauma, and, oftentimes, multiple reconstructive techniques may be needed for definitive coverage. This case study describes the reconstruction of a pediatric subtotal scalp avulsion using a dermal regeneration template and novel autologous homologous skin construct. This case was complicated by the absence of original tissue for reimplantation, excessive size of the defect relative to body habitus, and family concerns for future hair-bearing function. The reconstruction successfully provided definitive coverage and significantly reduced the size of the donor site and associated compilations. However, the hair-bearing potential of the tissue has yet to be determined.

The Heritability of Human Connectomes: a Causal Modeling Analysis.

The heritability of human connectomes is crucial for understanding the influence of genetic and environmental factors on variability in connectomes, and their implications for behavior and disease. However, current methods for studying heritability assume an associational rather than a causal effect, or rely on strong distributional assumptions that may not be appropriate for complex, high-dimensional connectomes. To address these limitations, we propose two solutions: first, we formalize heritability as a problem in causal inference, and identify measured covariates to control for unmeasured confounding, allowing us to make causal claims. Second, we leverage statistical models that capture the underlying structure and dependence within connectomes, enabling us to define different notions of connectome heritability by removing common structures such as scaling of edge weights between connectomes. We then develop a non-parametric test to detect whether causal heritability exists after taking principled steps to adjust for these commonalities, and apply it to diffusion connectomes estimated from the Human Connectome Project. Our findings reveal that heritability can still be detected even after adjusting for potential confounding like neuroanatomy, age, and sex. However, once we address for rescaling between connectomes, our causal tests are no longer significant. These results suggest that previous conclusions on connectome heritability may be driven by rescaling factors. Together, our manuscript highlights the importance for future works to continue to develop data-driven heritability models which faithfully reflect potential confounders and network structure.

Distinct transcriptomic and epigenomic modalities underpin human memory T cell subsets and their activation potential.

Human memory T cells (MTC) are poised to rapidly respond to antigen re-exposure. Here, we derived the transcriptional and epigenetic programs of resting and ex vivo activated, circulating CD4+ and CD8+ MTC subsets. A progressive gradient of gene expression from naïve to TCM to TEM is observed, which is accompanied by corresponding changes in chromatin accessibility. Transcriptional changes suggest adaptations of metabolism that are reflected in altered metabolic capacity. Other differences involve regulatory modalities comprised of discrete accessible chromatin patterns, transcription factor binding motif enrichment, and evidence of epigenetic priming. Basic-helix-loop-helix factor motifs for AHR and HIF1A distinguish subsets and predict transcription networks to sense environmental changes. Following stimulation, primed accessible chromatin correlate with an augmentation of MTC gene expression as well as effector transcription factor gene expression. These results identify coordinated epigenetic remodeling, metabolic, and transcriptional changes that enable MTC subsets to ultimately respond to antigen re-encounters more efficiently.

Meta-analyses of arsenic accumulation in Indica and Japonica rice grains.

Arsenic (As) is a worldwide concern because of its toxic effects on crop yield and prevalence in the food chain. Rice is consumed by half of the world's population and is known to accumulate As. The present study reviews the available literatures on As accumulation in different subspecies of rice grains (indica, japonica and aromatic) and performs meta-analyses for grain size and texture; these data include 120 studies conducted over the last 15 years across different parts of the world. Aromatic rice varieties accumulate less As with its 95% confidence interval (CI) being 73.90 - 80.94 µg kg-1 which is significantly lower than the As accumulation by either indica or japonica rice varieties with their overall 95% CI being 135.48 - 147.78 µg kg-1 and 204.71 - 212.25 µg kg-1, respectively. Japonica rice varieties accumulate higher As than indica rice grains and within each subspecies polished and/or shorter rice grains accumulated significantly lower As compared to larger and/or unpolished grains; 95% CIs for the polished indica and japonica rice varieties are seen to be 96.33 - 111.11 µg kg-1 and 203.34 - 211.09 µg kg-1, respectively, whereas the same for unpolished varieties are seen to be 215.99 - 238.18 µg kg-1 and 215.27 - 248.63 µg kg-1, respectively. This shows that rice-based As bioaccumulation in humans could be lowered by increased use of aromatic or polished indica rice varieties, followed by the cultivation of shorter polished grains of japonica rice. These findings will be important to inform policy on rice cultivation and dietary uptake of As for a large portion of the global population.

Anti-human immunodeficiency virus-1 activity of MoMo30 protein isolated from the traditional African medicinal plant Momordica balsamina.

BACKGROUND: Plants are used in traditional healing practices of many cultures worldwide. Momordica balsamina is a plant commonly used by traditional African healers as a part of a treatment for HIV/AIDS. It is typically given as a tea to patients with HIV/AIDS. Water-soluble extracts of this plant were found to contain anti-HIV activity. METHODS: We employed cell-based infectivity assays, surface plasmon resonance, and a molecular-cell model of the gp120-CD4 interaction to study the mechanism of action of the MoMo30-plant protein. Using Edman degradation results of the 15 N-terminal amino acids, we determined the gene sequence of the MoMo30-plant protein from an RNAseq library from total RNA extracted from Momordica balsamina. RESULTS: Here, we identify the active ingredient of water extracts of the leaves of Momordica balsamina as a 30 kDa protein we call MoMo30-plant. We have identified the gene for MoMo30 and found it is homologous to a group of plant lectins known as Hevamine A-like proteins. MoMo30-plant is distinct from other proteins previously reported agents from the Momordica species, such as ribosome-inactivating proteins such as MAP30 and Balsamin. MoMo30-plant binds to gp120 through its glycan groups and functions as a lectin or carbohydrate-binding agent (CBA). It inhibits HIV-1 at nanomolar levels and has minimal cellular toxicity at inhibitory levels. CONCLUSIONS: CBAs like MoMo30 can bind to glycans on the surface of the enveloped glycoprotein of HIV (gp120) and block entry. Exposure to CBAs has two effects on the virus. First, it blocks infection of susceptible cells. Secondly, MoMo30 drives the selection of viruses with altered glycosylation patterns, potentially altering their immunogenicity. Such an agent could represent a change in the treatment strategy for HIV/AIDS that allows a rapid reduction in viral loads while selecting for an underglycosylated virus, potentially facilitating the host immune response.

Aiolos represses CD4+ T cell cytotoxic programming via reciprocal regulation of TFH transcription factors and IL-2 sensitivity.

During intracellular infection, T follicular helper (TFH) and T helper 1 (TH1) cells promote humoral and cell-mediated responses, respectively. Another subset, CD4-cytotoxic T lymphocytes (CD4-CTLs), eliminate infected cells via functions typically associated with CD8+ T cells. The mechanisms underlying differentiation of these populations are incompletely understood. Here, we identify the transcription factor Aiolos as a reciprocal regulator of TFH and CD4-CTL programming. We find that Aiolos deficiency results in downregulation of key TFH transcription factors, and consequently reduced TFH differentiation and antibody production, during influenza virus infection. Conversely, CD4-CTL programming is elevated, including enhanced Eomes and cytolytic molecule expression. We further demonstrate that Aiolos deficiency allows for enhanced IL-2 sensitivity and increased STAT5 association with CD4-CTL gene targets, including Eomes, effector molecules, and IL2Ra. Thus, our collective findings identify Aiolos as a pivotal regulator of CD4-CTL and TFH programming and highlight its potential as a target for manipulating CD4+ T cell responses.

A randomized study on the value of self-directed versus traditional mentor-led microsurgical training.

Objective: Analyze efficacy of self-directed resident microvascular training versus a mentor-led course. Study Design: Randomized, single-blinded cohort study. Setting: Academic tertiary care center. Methods: Sixteen resident and fellow participants were randomized into two groups stratified by training year. Group A completed a self-directed microvascular course with instructional videos and self-directed lab sessions. Group B completed a traditional mentor-led microvascular course. Both groups spent equal time in the lab. Video recorded pre and post-course microsurgical skill assessments were performed to assess the efficacy of the training. Two microsurgeons, blinded to participant identity, evaluated the recordings and inspected each microvascular anastomosis (MVA). Videos were scored using an objective-structured assessment of technical skills (OSATS), a global rating scale (GRS), and quality of anastomosis scoring (QoA). Results: The pre-course assessment identified that the groups were well matched with only "Economy of Motion" on the GRS favoring the mentor led group (p = .02). This difference remained significant on the post assessment (p = .02) Both groups significantly improved in OSATS and GRS scoring (p < .05). There was no significant difference in OSATS improvement between the two groups (p = .36) or improvement in MVA quality between groups (p > .99). Time to completion of MVA significantly improved overall by a mean of 8 min and 9 s (p = .005) with no significant difference between post training times to complete (p = .63). Conclusion: Different microsurgical training models have previously been validated as effective methods for improved MVA performance. Our findings indicate that a self-directed microsurgical training model is an effective alternative to a traditional mentor driven models. Level of Evidence: Level 2.

The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings - The utility of a new screening assay.

Background: There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. Objectives: To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). Methods: We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. Results: The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. Conclusions: The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.

HECT domain interaction with ubiquitin binding sites on Tsg101-UEV controls HIV-1 egress, maturation, and infectivity.

The HECT domain of HECT E3 ligases consists of flexibly linked N- and C-terminal lobes, with a ubiquitin (Ub) donor site on the C-lobe that is directly involved in substrate modification. HECT ligases also possess a secondary Ub binding site in the N-lobe, which is thought to play a role in processivity, specificity, or regulation. Here, we report the use of paramagnetic solution NMR to characterize a complex formed between the isolated HECT domain of neural precursor cell-expressed developmentally downregulated 4-1 and the ubiquitin E2 variant (UEV) domain of tumor susceptibility gene 101 (Tsg101). Both proteins are involved in endosomal trafficking, a process driven by Ub signaling, and are hijacked by viral pathogens for particle assembly; however, a direct interaction between them has not been described, and the mechanism by which the HECT E3 ligase contributes to pathogen formation has not been elucidated. We provide evidence for their association, consisting of multiple sites on the neural precursor cell-expressed developmentally downregulated 4-1 HECT domain and elements of the Tsg101 UEV domain involved in noncovalent ubiquitin binding. Furthermore, we show using an established reporter assay that HECT residues perturbed by UEV proximity define determinants of viral maturation and infectivity. These results suggest the UEV interaction is a determinant of HECT activity in Ub signaling. As the endosomal trafficking pathway is hijacked by several human pathogens for egress, the HECT-UEV interaction could represent a potential novel target for therapeutic intervention.

Cryo-electron microscopy structures of human thyroid peroxidase (TPO) in complex with TPO antibodies.

Determination of the structure of the extracellular domain of human thyroid peroxidase (hTPO) by cryo-electron microscopy (cryo-EM) is described. TPO, purified to homogeneity was complexed with the hTPO monoclonal autoantibody 2G4 Fab and also with a mouse monoclonal TPO antibody 4F5 Fab (which competes with autoantibody binding to TPO). Both complexes were analysed by cryo-EM. The two structures (global resolution 3.92 and 3.4 Å for the 2G4 complex and 4F5 complex, respectively) show TPO as a monomer with four domains; the N-terminal domain, the peroxidase domain (POD), the complement control protein (CCP)-like domain and the epidermal growth factor-like domain which are all visible in the structures. The relative positions of the domains are fixed with a disulphide bond between cysteine residues Cys146 in the POD and Cys756 in the CCP domain preventing significant flexibility of the molecule. The entrance to the enzyme active site, the haem group and the calcium binding site are clearly visible on the opposite side of the TPO molecule from the 2G4 and 4F5 binding sites. Extensive interactions are seen between TPO and the two antibodies which both bind to distinct epitopes on the POD domain, including some residues in the immunodominant region B mainly via different residues. However, the epitopes of the two antibodies contain three shared TPO residues. This is the first high-resolution structure of TPO to be reported and it should help guide the development of new inhibitors of TPO enzyme activity for therapeutic applications.

IL-6/STAT3 Signaling Axis Enhances and Prolongs Pdcd1 Expression in Murine CD8 T Cells.

CD8 cytotoxic T cells are a potent line of defense against invading pathogens. To aid in curtailing aberrant immune responses, the activation status of CD8 T cells is highly regulated. One mechanism in which CD8 T cell responses are dampened is via signaling through the immune-inhibitory receptor Programmed Cell Death Protein-1, encoded by Pdcd1. Pdcd1 expression is regulated through engagement of the TCR, as well as by signaling from extracellular cytokines. Understanding such pathways has influenced the development of numerous clinical treatments. In this study, we showed that signals from the cytokine IL-6 enhanced Pdcd1 expression when paired with TCR stimulation in murine CD8 T cells. Mechanistically, signals from IL-6 were propagated through activation of the transcription factor STAT3, resulting in IL-6-dependent binding of STAT3 to Pdcd1 cis-regulatory elements. Intriguingly, IL-6 stimulation overcame B Lymphocyte Maturation Protein 1-mediated epigenetic repression of Pdcd1, which resulted in a transcriptionally permissive landscape marked by heightened histone acetylation. Furthermore, in vivo-activated CD8 T cells derived from lymphocytic choriomeningitis virus infection required STAT3 for optimal Programmed Cell Death Protein-1 surface expression. Importantly, STAT3 was the only member of the STAT family present at Pdcd1 regulatory elements in lymphocytic choriomeningitis virus Ag-specific CD8 T cells. Collectively, these data define mechanisms by which the IL-6/STAT3 signaling axis can enhance and prolong Pdcd1 expression in murine CD8 T cells.

Research Infrastructure Core Facilities at Research Centers in Minority Institutions: Part I-Research Resources Management, Operation, and Best Practices.

Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions (RCMI) Program fosters the development and implementation of innovative research aimed at improving minority health and reducing or eliminating health disparities. Currently, there are 21 RCMI Specialized (U54) Centers that share the same framework, comprising four required core components, namely the Administrative, Research Infrastructure, Investigator Development, and Community Engagement Cores. The Research Infrastructure Core (RIC) is fundamentally important for biomedical and health disparities research as a critical function domain. This paper aims to assess the research resources and services provided and evaluate the best practices in research resources management and networking across the RCMI Consortium. We conducted a REDCap-based survey and collected responses from 57 RIC Directors and Co-Directors from 98 core leaders. Our findings indicated that the RIC facilities across the 21 RCMI Centers provide access to major research equipment and are managed by experienced faculty and staff who provide expert consultative and technical services. However, several impediments to RIC facilities operation and management have been identified, and these are currently being addressed through implementation of cost-effective strategies and best practices of laboratory management and operation.

Identification of a Novel Anti-HIV-1 Protein from Momordica balsamina Leaf Extract.

Our lab investigates the anti-HIV-1 activity in Momordica balsamina (M. balsamina) leaf extract. Traditional Senegalese healers have used M. balsamina leaf extract as a part of a plant-based treatment for HIV/AIDS infections. Our overall goal is to define and validate the scientific basis for using M. balsamina leaf extract as a part of the traditional Senegalese treatment. As an initial characterization of this extract, we used activity-guided fractionation to determine the active ingredient's solubility and relative size. We found that M. balsamina leaf extract inhibits HIV-1 infection by >50% at concentrations of 0.02 mg/mL and above and is not toxic over its inhibitory range (0-0.5 mg/mL). We observed significantly more antiviral activity in direct water and acetonitrile extractions (p ≤ 0.05). We also observed significantly more antiviral activity in the aqueous phases of ethyl acetate, chloroform, and diethyl ether extractions (p ≤ 0.05). Though most of the antiviral activity partitioned into the aqueous layers, some antiviral activity was present in the organic layers. We show that the active agent in the plant extracts is at least 30 kD in size. Significantly more antiviral activity was retained in 3, 10, and 30 kD molecular weight cutoff filters (p ≤ 0.05). In contrast, most of the antiviral activity passed through the 100 kD filter (p ≤ 0.05). Because the active anti-HIV-1 agent presented as a large, amphiphilic molecule we ran the purified extract on an SDS-page gel. We show that the anti-HIV-1 activity in the leaf extracts is attributed to a 30 kDa protein we call MoMo30. This article describes how MoMo30 was determined to be responsible for its anti-HIV-1 activity.

Expected Impact of the Pass/Fail Scoring System for USMLE Step 1 on the Plastic Surgery Residency Selection Process: A National Survey of Plastics Program Directors.

BACKGROUND:  Traditionally, the United States Medical Licensing Examination (USMLE) Step 1 3-digit score has been used as a metric to stratify plastic surgery residency candidates. The transition to a pass/fail exam may impact the manner in which integrated plastic surgery residency program directors (PS-RPD) evaluate candidates. It may also limit opportunities for applicants to differentiate themselves from their counterparts. METHODS: A 14-question survey was distributed via email to 76 PS-RPDs collected from the American Medical Association (AMA) residency program site, FRIEDA. It was sent three times from March 3 - March 14, 2020. McNemar tests were performed on the current metrics of evaluation in comparison to metrics expected to be used in the absence of a 3-digit Step 1 score, assuming a P < 0.05 level for statistical significance.  Results: Of the 76 integrated plastics programs surveyed, 24 PS-RPDs responded (31.6% response rate); 91.3% of PS-RPDs strongly disagree or disagree that Step 1 should be pass/fail; 78.3% of PS-RPDs strongly disagree or disagree that diversity will increase. The top five evaluation metrics PS-RPDs expect to utilize following the transition to pass/fail are: letters of recommendation (87.0%; CI 72% - 100%; p=0.500), Step 2 score (78.3%; CI 60% - 96%; p=0.001), research (56.5%; CI 35% - 78%; p=0.125), elective rotation (56.5%; CI 35% - 78%; p=1.000), and personal knowledge of the applicant (52.2%; CI 30% - 74%; p=0.500).  Conclusions: In the absence of a Step 1 score, PS-RPDs may require more holistic metric(s) to evaluate the best fit for their program. This study found that PS-RPDs expect their candidate evaluation process to remain highly similar with the only statistically significant change being an increased emphasis on the candidate's Step 2 score.

Will Residency Program Directors Look at My United States Medical Licensing Examination (USMLE) Step 1 Score During the 2022-2023 Application Cycle? A National Survey of Program Directors.

Background The 2022-2023 residency match cycle will be the first cycle that program directors will have to consider some applicants with a numerical United States Medical Licensing Examination (USMLE) Step 1 score while other applicants will only report pass/fail for USMLE Step 1. Previous studies have explored how USMLE Step 1 becoming pass/fail will alter the residency selection process, but it is not yet known when program directors from each specialty expect those changes to be implemented. Methods Residency program director's contact information was extracted from the American Medical Association (AMA) residency program site, Fellowship and Residency Electronic Interactive Database (FREIDA). Of the 5190 programs, 4877 were determined eligible for this study of which 1274 (26.8%) responded. Results Of the 1274 US residency program directors included in this survey, 77.0% do not intend to adjust their usage of USMLE Step 1 as a metric in candidate evaluation until the score is no longer reported. Conclusion Residency candidates applying during the upcoming cycle can expect the majority of residency programs will not significantly alter their previous utilization of an applicant's USMLE Step 1 score during the current 2022-2023 residency match cycle.