Medical Student Attitudes toward USMLE Step 1 and Health Systems Science - A Multi-Institutional Survey.

Phenomenon: Because of its importance in residency selection, the United States Medical Licensing Examination Step 1 occupies a critical position in medical education, stimulating national debate about appropriate score use, equitable selection criteria, and the goals of undergraduate medical education. Yet, student perspectives on these issues and their implications for engagement with health systems science-related curricular content are relatively underexplored. Approach: We conducted an online survey of medical students at 19 American allopathic medical schools from March-July, 2019. Survey items were designed to elicit student opinions on the Step 1 examination and the impact of the examination on their engagement with new, non-test curricular content related to health systems science. Findings: A total of 2856 students participated in the survey, representing 23.5% of those invited. While 87% of students agreed that doing well on the Step 1 exam was their top priority, 56% disagreed that studying for Step 1 had a positive impact on engagement in the medical school curriculum. Eighty-two percent of students disagreed that Step 1 scores should be the top item residency programs use to offer interviews. When asked whether Step 1 results should be reported pass/fail with no numeric score, 55% of students agreed, while 33% disagreed. The majority of medical students agreed that health systems science topics were important but disagreed that studying for Step 1 helped learn this content. Students reported being more motivated to study a topic if it was on the exam, part of a course grade, prioritized by residency program directors, or if it would make them a better physician in the future. Insights: These results confirm the primacy of the United States Medical Licensing Examination Step 1 exam in preclinical medical education and demonstrate the need to balance the objectives of medical licensure and residency selection with the goals of the broader medical profession. The survey responses suggest several potential solutions to increase student engagement in health systems science curricula which may be especially important after Step 1 examination results are reported as pass/fail.

What's in a Transition? An Integrative Perspective on Transitions in Medical Education.

This Conversation Starters article presents a selected research abstract from the 2016 Association of American Medical Colleges Western Region Group on Educational Affairs annual spring meeting. The abstract is paired with the integrative commentary of three experts who shared their thoughts stimulated by the needs assessment study. These thoughts explore how the general theoretical mechanisms of transition may be integrated with cognitive load theory in order to design interventions and environments that foster transition.

Contribution of Basic Science Education to the Professional Identity Development of Medical Learners: A Critical Scoping Review.

PURPOSE: Professional identity development (PID) has become an important focus of medical education. To date, contributions of basic science education to physician PID have not been broadly explored. This review explores the literature surrounding the contribution of basic science education to the PID of medical learners and interprets findings critically in terms of the landscapes of practice (LoP) framework. METHOD: In this critical scoping review, the authors searched 12 different databases and professional organization websites from January 1988 to October 2022 for references relating to how, if at all, the basic science component of medical education contributes to the PID of medical learners. The LoP learning theory was chosen as a framework for critically interpreting the identified articles. RESULTS: Of the 6,674 identified references, 257 met the inclusion criteria. After data extraction, content analysis of recorded key findings was used to ensure all findings were incorporated into the synthesis. Findings aligned with and were critically interpreted in relation to the 3 LoP modes of identification: engagement (engaging in the work of a physician), imagination (imagining oneself becoming a "good doctor"), and alignment (aligning with the practices and expectations of a medical community or specialty). Within each mode of identification, it was possible to see how basic science may support, or catalyze, PID and how basic science may serve as a barrier, or an inhibitor, to PID or contribute to the development of negative aspects of identity development. CONCLUSIONS: The LoP learning theory suggests that the effect of basic science on physicians' PID is most effective if educators view themselves as guides through interfaces between their scientific disciplines and medicine. Learners need opportunities to be engaged, to imagine how their current learning activities and developing skills will be useful as future physicians, and to feel alignment with medical specialties.

Revealing the allosterome: systematic identification of metabolite-protein interactions.

Small molecule allostery modifies protein function but is not easily discovered. We introduce mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS), a method for identifying physiologically relevant, low-affinity metabolite-protein interactions using unmodified proteins and complex mixtures of unmodified metabolites. In a pilot experiment using five proteins, we identified 16 known and 13 novel interactions. The known interactions included substrates, products, intermediates, and allosteric regulators of their protein partners. MIDAS does not depend upon enzymatic measurements, but most of the new interactions affect the enzymatic activity of the protein partner. We found that the fatty acid palmitate interacts with both glucokinase and glycogen phosphorylase. Further characterization revealed that palmitate inhibited both enzymes, possibly providing a mechanism for sparing carbohydrate catabolism when fatty acids are abundant.

"Am I even a med-student anymore?" A Mixed-Methods Study of the Impact of the Initial Disruptions Caused by the COVID-19 Pandemic on Medical Student Professional Identity Formation.

Purpose: Developing a professional identity requires learners to integrate themselves into the medical profession and take on the role of doctor. The impact of COVID-19 on medical education has been widely investigated, but little attention has been paid to the impact of students' professional identify formation (PIF). The goal of this study was to investigate the impact that the onset of the COVID-19 pandemic had on medical students' PIF. Materials and Methods: An embedded mixed-methods design was utilized. Focus groups were conducted with a subset of year 1-4 students and coded using thematic analysis. Year 1-2 students were surveyed about their professional identity integration in the spring of 2020. Responses were analyzed using descriptive statistics and Wilcoxon signed rank and Mann-Whitney U tests. Results: Qualitative data were organized into six themes that touched on losses and challenges, reflection, and reevaluation of the physician career. Roughly 50% of MS1s and MS2s reported a change in their professional identity integration, but this was not statistically significant. Conclusions: Medical education does not occur in isolation and is influenced by disruptive local and global events. Students perceived challenges when in-person community interaction and hands-on clinical experiences were interrupted. Additionally, students reflected upon their own role and their future career goals. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01652-4.

Assessment for Learning with Ungraded and Graded Assessments.

Introduction: Assessment for learning has many benefits, but learners will still encounter high-stakes decisions about their performance throughout training. It is unknown if assessment for learning can be promoted with a combination model where scores from some assessments are factored into course grades and scores from other assessments are not used for course grading. Methods: At the University of Utah School of Medicine, year 1-2 medical students (MS) completed multiple-choice question quiz assessments and final examinations in six systems-based science courses. Quiz and final examination performance counted toward course grades for MS2017-MS2018. Starting with the MS2020 cohort, quizzes no longer counted toward course grades. Quiz, final examination, and Step 1 scores were compared between ungraded quiz and graded quiz cohorts with independent samples t-tests. Student and faculty feedback was collected. Results: Quiz performance was not different for the ungraded and graded cohorts (p = 0.173). Ungraded cohorts scored 4% higher on final examinations than graded cohorts (p ≤ 0.001, d = 0.88). Ungraded cohorts scored above the national average and 11 points higher on Step 1 compared to graded cohorts, who had scored below the national average (p ≤ 0.001, d = 0.64). During the study period, Step 1 scores increased by 2 points nationally. Student feedback was positive, and faculty felt it improved their relationship with students. Discussion: The change to ungraded quizzes did not negatively affect final examination or Step 1 performance, suggesting a combination of ungraded and graded assessments can effectively promote assessment for learning.

A Curriculum Design and Teaching Experience Created by and for Bioscience Postdoctoral Fellows in a Medical School.

Many medical school postdoctoral fellows (postdocs) lack training in curriculum design and student-centered instruction. A team of bioscience postdocs and a medical school curriculum assistant dean co-created an experience to fill this gap. Kern's and Kirkpatrick's frameworks were used for the design and evaluation, respectively, of both the postdoc experience and the undergraduate course they developed. Postdocs taught the course using student-centered methods, especially team-based learning and Just-in-Time Teaching. Following a successful pilot phase, this low resource postdoc experience and undergraduate course are regularly offered. Participating postdocs develop the knowledge, skills, and attitudes to effectively participate in medical school education.

Medical Biochemistry Without Rote Memorization: Multi-Institution Implementation and Student Perceptions of a Nationally Standardized Metabolic Map for Learning and Assessment.

Despite the growing number of patients worldwide with metabolism-related chronic diseases, medical biochemistry education is commonly perceived as focusing on recall of facts irrelevant for patient care. The authors suggest that this focus on rote memorization of pathways creates excessive cognitive load that may interfere with learners' development of an integrated understanding of metabolic regulation and dysregulation. This cognitive load can be minimized by providing appropriate references during learning and assessment. Biochemistry educators collaborated to develop a medically relevant pathways of human metabolism map (MetMap) that is now being used at many medical schools as a nationally standardized resource during learning and assessments. To assess impact, students from three medical schools were surveyed about its benefits and disadvantages. Responses were obtained from 481 students (84%) and were examined using thematic analysis. Five main themes emerged as perceived benefits of using the MetMap: (1) aids visual and mental organization, (2) promotes deep learning and applied understanding, (3) decreases emphasis on memorization, (4) reduces anxiety on exams, and (5) aids recall. Perceived disadvantages were (1) fear of underpreparation for licensing exams, (2) overwhelming nature of the map, and (3) reduced motivation for and time spent studying. Results affirm that students' perceive use of the MetMap promotes focus on broader metabolic concepts and deep versus surface learning, supporting a shift in cognitive load toward desired goals. Although the long-term impact on learning needs to be further studied, the use of the MetMap represents a step toward open-reference exams that reflect "real-world" practice.

The Two-Stage Examination: A Method to Assess Individual Competence and Collaborative Problem Solving in Medical Students.

PROBLEM: Effectively solving problems as a team under stressful conditions is central to medical practice; however, because summative examinations in medical education must test individual competence, they are typically solitary assessments. APPROACH: Using two-stage examinations, in which students first answer questions individually (Stage 1) and then discuss them in teams prior to resubmitting their answers (Stage 2), is one method for rectifying this discordance. On the basis of principles of social constructivism, the authors hypothesized that two-stage examinations would lead to better retention of, specifically, items answered incorrectly at Stage 1.In fall 2014, they divided 104 first-year medical students into two groups of 52 students. Groups alternated each week between taking one- and two-stage examinations such that each student completed 6 one-stage and 6 two-stage examinations. The authors reassessed 61 concepts on a final examination and, using the Wilcoxon signed ranked tests, compared performance for all concepts and for just those students initially missed, between Stages 1 and 2. OUTCOMES: Final examination performance on all previously assessed concepts was not significantly different between the one-and two-stage conditions (P = .77); however, performance on only concepts that students initially answered incorrectly on a prior examination improved by 12% for the two-stage condition relative to the one-stage condition (P = .02, r = 0.17). NEXT STEPS: Team assessment may be most useful for assessing concepts students find difficult, as opposed to all content. More research is needed to determine whether these results apply to all medical school topics and student cohorts.

A novel selection system for chromosome translocations in Saccharomyces cerevisiae.

Chromosomal translocations are common genetic abnormalities found in both leukemias and solid tumors. While much has been learned about the effects of specific translocations on cell proliferation, much less is known about what causes these chromosome rearrangements. This article describes the development and use of a system that genetically selects for rare translocation events using the yeast Saccharomyces cerevisiae. A translocation YAC was created that contains the breakpoint cluster region from the human MLL gene, a gene frequently involved in translocations in leukemia patients, flanked by positive and negative selection markers. A translocation between the YAC and a yeast chromosome, whose breakpoint falls within the MLL DNA, physically separates the markers and forms the basis for the selection. When RAD52 is deleted, essentially all of the selected and screened cells contain simple translocations. The detectable translocation rates are the same in haploids and diploids, although the mechanisms involved and true translocation rates may be distinct. A unique double-strand break induced within the MLL sequences increases the number of detectable translocation events 100- to 1000-fold. This novel system provides a tractable assay for answering basic mechanistic questions about the development of chromosomal translocations.

Nutrient sensing and metabolic decisions.

Cells have several sensory systems that detect energy and metabolic status and adjust flux through metabolic pathways accordingly. Many of these sensors and signaling pathways are conserved from yeast to mammals. In this review, we bring together information about five different nutrient-sensing pathways (AMP kinase, mTOR, PAS kinase, hexosamine biosynthesis and Sir2), highlighting their similarities, differences and roles in disease.

Whence cometh the allosterome?

Regulation of cellular functions can be accomplished by many mechanisms, including transcriptional regulation, alternative splicing, translational regulation, phosphorylation and other posttranslational covalent modifications, degradation, localization, protein-protein interactions, and small-molecule allosteric effectors. Largely because of advances in the techniques of molecular biology in the past few decades, our knowledge of regulation by most of these mechanisms has expanded enormously. Regulation by small-molecule, allosteric interactions is an exception. Many of the best-known allosteric regulators were discovered decades ago, when we knew little about all of these other forms of regulation. Allostery is the most direct, rapid, and efficient regulatory mechanism to sense changes in the concentration of small molecules and alter cellular responses to maintain homeostasis. In this perspective, we present the argument that allosteric regulation is underappreciated in the systems biology world and that many allosteric effectors remain to be discovered.

The Saccharomyces cerevisiae Smc2/4 condensin compacts DNA into (+) chiral structures without net supercoiling.

Smc2/4 forms the core of the Saccharomyces cerevisiae condensin, which promotes metaphase chromosome compaction. To understand how condensin manipulates DNA, we used two in vitro assays to study the role of SMC (structural maintenance of chromosome) proteins and ATP in reconfiguring the path of DNA. The first assay evaluated the topology of knots formed in the presence of topoisomerase II. Unexpectedly, both wild-type Smc2/4 and an ATPase mutant promoted (+) chiral knotting of nicked plasmids, revealing that ATP hydrolysis and the non-SMC condensins are not required to compact DNA chirally. The second assay measured Smc2/4-dependent changes in linking number (Lk). Smc2/4 did not induce (+) supercoiling, but instead induced broadening of topoisomer distributions in a cooperative manner without altering Lk(0). To explain chiral knotting in substrates devoid of chiral supercoiling, we propose that Smc2/4 directs chiral DNA compaction by constraining the duplex to retrace its own path. In this highly cooperative process, both (+) and (-) loops are sequestered (about one per kb), leaving net writhe and twist unchanged while broadening Lk. We have developed a quantitative theory to account for these results. Additionally, we have shown at higher molar stoichiometries that Smc2/4 prevents relaxation by topoisomerase I and nick closure by DNA ligase, indicating that Smc2/4 can saturate DNA. By electron microscopy of Smc2/4-DNA complexes, we observed primarily two protein-laden bound species: long flexible filaments and uniform rings or "doughnuts." Close packing of Smc2/4 on DNA explains the substrate protection we observed. Our results support the hypothesis that SMC proteins bind multiple DNA duplexes.

Biochemical analysis of the yeast condensin Smc2/4 complex: an ATPase that promotes knotting of circular DNA.

To better understand the contributions that the structural maintenance of chromosome proteins (SMCs) make to condensin activity, we have tested a number of biochemical, biophysical, and DNA-associated attributes of the Smc2p-Smc4p pair from budding yeast. Smc2p and Smc4p form a stable heterodimer, the "Smc2/4 complex," which upon analysis by sedimentation equilibrium appears to reversibly self-associate to form heterotetramers. Individually, neither Smc2p nor Smc4p hydrolyzes ATP; however, ATPase activity is recovered by equal molar mixing of both purified proteins. Hydrolysis activity is unaffected by the presence of DNA. Smc2/4 binds both linearized and circular plasmids, and the binding appears to be independent of adenylate nucleotide. High mole ratios of Smc2/4 to plasmid promote a geometric change in circular DNA that can be trapped as knots by type II topoisomerases but not as supercoils by a type I topoisomerase. Binding titration analyses reveal that two Smc2/4-DNA-bound states exist, one disrupted by and one resistant to salt challenge. Competition-displacement experiments show that Smc2/4-DNA-bound species formed at even high protein to DNA mole ratios remain reversible. Surprisingly, only linear and supercoiled DNA, not nicked-circular DNA, can completely displace Smc2/4 prebound to a labeled, nicked-circular DNA. To explain this geometry-dependent competition, we present two models of DNA binding by SMCs in which two DNA duplexes are captured within the inter-coil space of an Smc2/4 heterodimer. Based on these models, we propose a DNA displacement mechanism to explain how differences in geometry could affect the competitive potential of DNA.

Does it take two to untangle?

The structural integrity of mitotic chromosomes is essential for proper chromatid segregation. In this issue of Cell, show that vertebrates contain two distinct condensin complexes, both of which are required for normal mitotic chromosome morphology.