A call to action; national survey of teaching radiology curriculum to medical students.

Objectives: Radiology and medical imaging are important yet often an underrepresented facet of medical education. Notably, there is concern among radiologists that students do not receive enough radiology exposure and that they struggle to interpret image findings on entering residency. Therefore, this survey aims to identify how medical students perceive the radiology curriculum and to determine gaps in delivery. Material and Methods: Students were recruited from United States (US) medical schools and given a 21-question survey assessing their perception of the radiology curriculum as well as asking about their confidence levels regarding medical imaging. The inclusion criteria were age >18 and enrolled in US medical school. The surveys were completed in April-July 2020 by students across the US. Objective parameters were measured as percentage correct, while subjective parameters used a 4-point Likert scale. Results: A total of 472 medical students across 31 medical schools completed the surveys with a response rate of 69%. Responses represented all class years within medical schools and showed equal distribution among the future career plans. Students responded that didactic lectures were the most common teaching method and that radiologists were their primary teachers during preclinical education. Students were unfamiliar with the American College of Radiology appropriateness criteria with 65% responding they had never heard of it and 33% reporting that they have heard of it but never used it. In assessing students' perceptions of radiology education, 72% of students responded that they received too little, and 28% of students responded, "Just right." <1% of students responded that there was "Too much" radiology in their curriculum. Conclusion: Radiologists are increasing their educational representation in medical school curricula. Despite this, radiology continues to be under-represented with students desiring more exposure to medical imaging. Integrating the student's perceptions with existing curricula suggests that efforts should focus on increasing awareness of which studies are appropriate and teaching students how to systematically interpret an image.

Analyzing the Landscape of the 2021 Virtual Match: A Nationwide Survey of Radiology Programs' Stakeholders.

RATIONALE AND OBJECTIVES: We aimed to provide insights into the adaptive strategies, benefits, and challenges faced by the radiology programs during the 2021 residency virtual Match. Furthermore, we explored the potential impacts of related topics, such as diversity and social media use on the Match process and outcomes. MATERIALS AND METHODS: A cross-sectional survey of 31 questions was designed and distributed via e-mails to individuals involved radiology programs match process during the 2021 Match. Descriptive statistics were used to analyze the results of most questions. Two questions comparing the changes in factors influencing the selection of applicants on a Likert scale of 1-5 were analyzed using paired t-test and Wilcoxon signed-rank test where p-value <0.05 was considered statistically significant. RESULTS: Responses from 125 participants were analyzed. The following factors carried less weight in evaluating applicants during 2021 Match: away rotations (p < 0.01), no failed attempts in USMLE Step 1/CK (p < 0.01), grades in radiology clerkship (p < 0.04), and class rank/quartile (p < 0.04), while personal statements were more important (p < 0.03). Out of the 125 respondents, 80 (64%) and 58 (47%) strongly or somewhat agree on the effectiveness of virtual interviews in gauging applicants' candidacy and showing their programs' advantages, respectively. Advantages of virtual interviews included decreased cost, time flexibility, less faculty burden, and an increased number of offered interviews according to 81% (101/125), 46% (58/125), 40%, (50/125), and 34% (43/125), respectively. The most helpful platforms that showcased program advantages were program websites followed by Twitter and Instagram. CONCLUSION: Most radiology programs were able to adjust to the virtual interview process, and the majority agree on their effectiveness citing many benefits. However, there were mixed opinions if it could be sustained in future cycles.

Online Liver Imaging Course; Pivoting to Transform Radiology Education During the SARS-CoV-2 Pandemic.

PURPOSE: The SARS-CoV-2 pandemic has drastically disrupted radiology in-person education. The purpose of this study was to assess the implementation of a virtual teaching method using available technology and its role in the continuity of education of practicing radiologists and trainees during the pandemic. METHODS: The authors created the Online Liver Imaging Course (OLIC) that comprised 28 online comprehensive lectures delivered in real-time and on-demand over six weeks. Radiologists and radiology trainees were asked to register to attend the live sessions. At the end of the course, we conducted a 46-question survey among registrants addressing their training level, perception of virtual conferencing, and evaluation of the course content. RESULTS: One thousand four hundred and thirty four radiologists and trainees completed interest sign up forms before the start of the course with the first webinar having the highest number of live attendees (343 people). On average, there were 89 live participants per session and 750 YouTube views per recording (as of July 9, 2020). After the end of the course, 487 attendees from 37 countries responded to the postcourse survey for an overall response rate of (33%). Approximately (63%) of participants were practicing radiologists while (37%) were either fellows or residents and rarely medical students. The overwhelming majority (97%) found the OLIC webinar series to be beneficial. Essentially all attendees felt that the webinar sessions met (43%) or exceeded (57%) their expectations. When asked about their perception of virtual conferences after attending OLIC lectures, almost all attendees (99%) enjoyed the virtual conference with a majority (61%) of the respondents who enjoyed the virtual format more than in-person conferences, while (38%) enjoyed the webinar format but preferred in-person conferences. When asked about the willingness to attend virtual webinars in the future, (84%) said that they would attend future virtual conferences even if in-person conferences resume while (15%) were unsure. CONCLUSION: The success of the OLIC, attributed to many factors, indicates that videoconferencing technology provides an inexpensive alternative to in-person radiology conferences. The positive responses to our postcourse survey suggest that virtual education will remain to stay. Educational institutions and scientific societies should foster such models.

Dynamic human MutSα-MutLα complexes compact mismatched DNA.

DNA mismatch repair (MMR) corrects errors that occur during DNA replication. In humans, mutations in the proteins MutSα and MutLα that initiate MMR cause Lynch syndrome, the most common hereditary cancer. MutSα surveilles the DNA, and upon recognition of a replication error it undergoes adenosine triphosphate-dependent conformational changes and recruits MutLα. Subsequently, proliferating cell nuclear antigen (PCNA) activates MutLα to nick the error-containing strand to allow excision and resynthesis. The structure-function properties of these obligate MutSα-MutLα complexes remain mostly unexplored in higher eukaryotes, and models are predominately based on studies of prokaryotic proteins. Here, we utilize atomic force microscopy (AFM) coupled with other methods to reveal time- and concentration-dependent stoichiometries and conformations of assembling human MutSα-MutLα-DNA complexes. We find that they assemble into multimeric complexes comprising three to eight proteins around a mismatch on DNA. On the timescale of a few minutes, these complexes rearrange, folding and compacting the DNA. These observations contrast with dominant models of MMR initiation that envision diffusive MutS-MutL complexes that move away from the mismatch. Our results suggest MutSα localizes MutLα near the mismatch and promotes DNA configurations that could enhance MMR efficiency by facilitating MutLα nicking the DNA at multiple sites around the mismatch. In addition, such complexes may also protect the mismatch region from nucleosome reassembly until repair occurs, and they could potentially remodel adjacent nucleosomes.

The role of residents in medical students' neurology education: current status and future perspectives.

BACKGROUND: Neurophobia, a well-described fear of neurology, affects medical students worldwide and may be one of the factors contributing to a shortage of neurologists in the United States. Residents spend a considerable amount of time with medical students; therefore, we sought to understand better the impact neurology residents have on medical students during their neurology clerkship and their subsequent interest in neurology. We aimed to identify and implement strategies to decrease neurophobia and increase the number of students pursuing neurology as a career. METHODS: Third-year medical students (n = 234) of UTHealth's McGovern Medical School rotating through their neurology core clerkship completed two surveys regarding their rotation experiences. Surveys were completed anonymously before and after the clerkship to measure their interest and confidence in neurology and the impact of their interactions with the neurology residents during the clerkship. In parallel, residents participated in a teaching workshop focused on small group teaching to improve their teaching effectiveness. Non-parametrical comparison and ordinal regression analyses were utilized for data analyses. RESULTS: Medical students reported a statistically significant increase in their confidence in managing neurological conditions and interest in pursuing a neurology residency after their clerkship. There was a significant association between the medical students' overall rotation experience and the residents' teaching effectiveness. The overall clerkship experience correlated with the medical students' interest and confidence in neurology. There was a trend towards an increase in residents' teaching effectiveness and students' rotation experience after a resident teaching workshop. Additionally, of note, students who rotated on both and outpatient and inpatient sites during their clerkship reported an increased interest in neurology. CONCLUSION: Our study supports that resident-led teaching efforts are important in improving medical students' neurologic education and their interest in neurology. Our data also supports that the interest in neurology increased for medical students after their neurology clerkship. We examined future strategies to implement "near-peer" teaching activities to enhance the medical students' neurologic educational experience. These strategies could potentially mitigate neurophobia and ultimately lead to a much-needed increase in future neurologists.

The Facilitator Instrument for Team-Based Learning (FIT).

Construct: We sought to evaluate the quality of Team-Based Learning facilitation in both large and small group settings. Background: Team Based Learning (TBL) is an increasingly popular small group instructional strategy in health science education. TBL facilitation skills are unique and differ from those needed to lecture or facilitate other types of small groups. Measuring facilitation skills and providing feedback to TBL instructors is important, yet to date no valid instrument has been developed and published for this purpose. Approach: We created an 11-item instrument (ratings of each item on a 7-point scale) designed to assess TBL facilitation skills, considering major sources of validity. Twelve experts in TBL facilitation and training developed the content of the FIT. To ensure response processes were valid, we used an immediate retrospective probing technique with 4th year medical students who were not part of the study. The Facilitator Instrument for Team-Based Learning (FIT) was piloted with 2,840 medical students in 7 schools in large (year 1 and 2) and small (year 3) courses. The internal structure of the FIT was analyzed. Results: In total, 1,559 and 1,281 medical students in large and small TBL classes, respectively (response rate 88%) rated 33 TBL facilitators. The composite mean score for the FIT was 6.19 (SD = 1.10). Exploratory factor analysis and Cronbach's alpha indicated that all items loaded on 1 factor, accounting for 77% of the item variance. Cronbach's alpha for the 11 items was 0.97. Analysis of facilitator variables and course context indicated that FIT scores were statistically significantly correlated with type of class (pre-clinical or clinical) and size of class as well as the facilitator enjoyment in using TBL as a method. Gender and the amount that facilitators used TBL each year was weakly correlated, with other factors not correlated (years facilitating TBL, confidence in facilitating TBL, and age). Conclusions: Analysis of FIT scores from 2,840 medical students across multiple institutions and teaching settings suggests the utility of the FIT in determining the quality of TBL facilitation across a range of medical education settings. Future research is needed to further analyze course contexts and facilitator variables that may influence FIT scores with additional facilitators. Additionally, FIT scores should be correlated with additional measures of TBL facilitator quality, such as direct observations, especially if these data are used for summative decision-making purposes.

Soliciting feedback on the wards: a peer-to-peer workshop.

BACKGROUND: For medical students, soliciting feedback is a critical but difficult skill that merits proper training. This skill may be taught effectively by peers who have experienced challenges with feedback on the wards. METHODS: Two medical students developed and taught a workshop on feedback skills. The workshop was presented to 248 third-year students. The workshop trained students in soliciting, receiving and responding to feedback through interactive discussions of case scenarios. Students were given pre- and post-surveys to assess changes in their confidence in and attitudes towards the feedback process. RESULTS: There were statistically significant increases in students' likeliness to solicit feedback and confidence in their ability to solicit feedback. Students' view on the importance of feedback did not change. The most commonly cited barriers to feedback were time constraints, fear of negative feedback, emotions and skills when asking for feedback, and student-mentor relationship. The content the students valued the most was management of internal triggers to negative feedback. Students noted that the peer-to-peer format, case scenarios, and interactive questions were strengths of the workshop. DISCUSSION: Although medical students recognise the importance of feedback, they often lack the confidence and skills to obtain quality feedback. A peer-to-peer workshop on soliciting, receiving, and responding to feedback can be an effective method to improve students' confidence and skills in this area. More research needs to be done to conclude if this workshop increases the instances of students soliciting high-quality feedback on the wards and improves clinical performance.

DNA mismatch repair and the DNA damage response.

This review discusses the role of DNA mismatch repair (MMR) in the DNA damage response (DDR) that triggers cell cycle arrest and, in some cases, apoptosis. Although the focus is on findings from mammalian cells, much has been learned from studies in other organisms including bacteria and yeast [1,2]. MMR promotes a DDR mediated by a key signaling kinase, ATM and Rad3-related (ATR), in response to various types of DNA damage including some encountered in widely used chemotherapy regimes. An introduction to the DDR mediated by ATR reveals its immense complexity and highlights the many biological and mechanistic questions that remain. Recent findings and future directions are highlighted.

Cross-sectional longitudinal study of the academic half-day format in a hematology-oncology fellowship training program.

BACKGROUND: Few published studies have evaluated the effectiveness of changing the traditional curriculum of several hourly educational sessions per week to an academic half-day (AHD) educational format. This study describes our experience with implementing an AHD format in the Hematology-Oncology Fellowship Program at The University of Texas MD Anderson Cancer Center and evaluates the perceptions that learners had for this format. METHODS: Using a mixed quantitative and qualitative approach, we evaluated our AHD program using four yearly fellows' surveys to assess the Hematology-Oncology Fellows' perceptions of the effectiveness of the AHD format. We analyzed the fellows' perceptions using descriptive statistics and thematic analysis of the qualitative data collected from the surveys. We used a quality improvement approach by implementing and testing changes to the AHD over 4 years on the basis of the data collected from the yearly fellows' surveys. We also collected third-year fellows' Oncology In Training Exam (ITE) scores from 2008 to 2014. RESULTS: We found that the fellows perceived the AHD format favorably; fellows agreed that they had more motivation to attend AHD, more concentration during the sessions, more effective weekly work organization, and increased knowledge retention. We established the reliability of our survey tool (Cronbach's alpha = 0.83) as well as content and construct validity. We saw an increasing trend in ITE scores since the AHD was implemented. CONCLUSIONS: Our results contribute to further understanding the effect of the AHD format on trainees. Using a continuous evaluation and an educational quality improvement strategy, we found that the AHD curriculum was associated with a rising trend in learners' exam scores and increased learner satisfaction.

DNA mismatch repair: Dr. Jekyll and Mr. Hyde?

In this issue, Peña-Diaz et al. (2012) describe a pathway for somatic mutation in nonlymphoid cells termed noncanonical DNA mismatch repair, whereby the error-prone translesion polymerase Pol-η substitutes for high-fidelity replicative polymerases to resynthesize excised regions opposite DNA damage.

Biochemical analysis of the human mismatch repair proteins hMutSα MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D).

The heterodimeric human MSH2-MSH6 protein initiates DNA mismatch repair (MMR) by recognizing mismatched bases that result from replication errors. Msh2(G674A) or Msh6(T1217D) mice that have mutations in or near the ATP binding site of MSH2 or ATP hydrolysis catalytic site of MSH6 develop cancer and have a reduced lifespan due to loss of the MMR pathway (Lin, D. P., Wang, Y., Scherer, S. J., Clark, A. B., Yang, K., Avdievich, E., Jin, B., Werling, U., Parris, T., Kurihara, N., Umar, A., Kucherlapati, R., Lipkin, M., Kunkel, T. A., and Edelmann, W. (2004) Cancer Res. 64, 517-522; Yang, G., Scherer, S. J., Shell, S. S., Yang, K., Kim, M., Lipkin, M., Kucherlapati, R., Kolodner, R. D., and Edelmann, W. (2004) Cancer Cell 6, 139-150). Mouse embryonic fibroblasts from these mice retain an apoptotic response to DNA damage. Mutant human MutSα proteins MSH2(G674A)-MSH6(wt) and MSH2(wt)-MSH6(T1219D) are profiled in a variety of functional assays and as expected fail to support MMR in vitro, although they retain mismatch recognition activity. Kinetic analyses of DNA binding and ATPase activities and examination of the excision step of MMR reveal that the two mutants differ in their underlying molecular defects. MSH2(wt)-MSH6(T1219D) fails to couple nucleotide binding and mismatch recognition, whereas MSH2(G674A)-MSH6(wt) has a partial defect in nucleotide binding. Nevertheless, both mutant proteins remain bound to the mismatch and fail to promote efficient excision thereby inhibiting MMR in vitro in a dominant manner. Implications of these findings for MMR and DNA damage signaling by MMR proteins are discussed.

Somatic deletions of genes regulating MSH2 protein stability cause DNA mismatch repair deficiency and drug resistance in human leukemia cells.

DNA mismatch repair enzymes (for example, MSH2) maintain genomic integrity, and their deficiency predisposes to several human cancers and to drug resistance. We found that leukemia cells from a substantial proportion of children (∼11%) with newly diagnosed acute lymphoblastic leukemia have low or undetectable MSH2 protein levels, despite abundant wild-type MSH2 mRNA. Leukemia cells with low levels of MSH2 contained partial or complete somatic deletions of one to four genes that regulate MSH2 degradation (FRAP1 (also known as MTOR), HERC1, PRKCZ and PIK3C2B); we also found these deletions in individuals with adult acute lymphoblastic leukemia (16%) and sporadic colorectal cancer (13.5%). Knockdown of these genes in human leukemia cells recapitulated the MSH2 protein deficiency by enhancing MSH2 degradation, leading to substantial reduction in DNA mismatch repair and increased resistance to thiopurines. These findings reveal a previously unrecognized mechanism whereby somatic deletions of genes regulating MSH2 degradation result in undetectable levels of MSH2 protein in leukemia cells, DNA mismatch repair deficiency and drug resistance.

In vitro studies of DNA mismatch repair proteins.

The ability to monitor and characterize DNA mismatch repair activity in various mammalian cells is important for understanding mechanisms involved in mutagenesis and tumorigenesis. Since mismatch repair proteins recognize mismatches containing both normal and chemically altered or damaged bases, in vitro assays must accommodate a variety of mismatches in different sequence contexts. Here we describe the construction of DNA mismatch substrates containing G:T or O(6)meG:T mismatches, the purification of recombinant native human MutSα (MSH2-MSH6) and MutLα (MLH1-PMS2) proteins, and in vitro mismatch repair and excision assays that can be adapted to study mismatch repair in nuclear extracts from mismatch repair proficient and deficient cells.

Mechanism of MutS searching for DNA mismatches and signaling repair.

DNA mismatch repair is initiated by the recognition of mismatches by MutS proteins. The mechanism by which MutS searches for and recognizes mismatches and subsequently signals repair remains poorly understood. We used single-molecule analyses of atomic force microscopy images of MutS-DNA complexes, coupled with biochemical assays, to determine the distributions of conformational states, the DNA binding affinities, and the ATPase activities of wild type and two mutants of MutS, with alanine substitutions in the conserved Phe-Xaa-Glu mismatch recognition motif. We find that on homoduplex DNA, the conserved Glu, but not the Phe, facilitates MutS-induced DNA bending, whereas at mismatches, both Phe and Glu promote the formation of an unbent conformation. The data reveal an unusual role for the Phe residue in that it promotes the unbending, not bending, of DNA at mismatch sites. In addition, formation of the specific unbent MutS-DNA conformation at mismatches appears to be required for the inhibition of ATP hydrolysis by MutS that signals initiation of repair. These results provide a structural explanation for the mechanism by which MutS searches for and recognizes mismatches and for the observed phenotypes of mutants with substitutions in the Phe-Xaa-Glu motif.

The mismatch repair-mediated cell cycle checkpoint response to fluorodeoxyuridine.

The loss of DNA mismatch repair (MMR) is responsible for hereditary nonpolyposis colorectal cancer and a subset of sporadic tumors. Acquired resistance or tolerance to some anti-cancer drugs occurs when MMR function is impaired. 5-Fluorouracil (FU), an anti-cancer drug used in the treatment of advanced colorectal and other cancers, and its metabolites are incorporated into RNA and DNA and inhibit thymidylate synthase resulting in depletion of dTTP and incorporation in DNA of uracil. Although the MMR deficiency has been implicated in tolerance to FU, the mechanism of cell killing remains unclear. Here, we examine the cellular response to fluorodeoxyuridine (FdU) and the role of the MMR system. After brief exposure of cells to low doses of FdU, MMR mediates DNA damage signaling during S-phase and triggers arrest in G2/M in the first cell cycle in a manner requiring MutSalpha, MutLalpha, and DNA replication. Cell cycle arrest is mediated by ATR kinase and results in phosphorylation of Chk1 and SMC1. MutSalpha binds FdU:G mispairs in vitro consistent with its being a DNA damage sensor. Prolonged treatment with FdU results in an irreversible arrest in G2 that is independent of MMR status and leads to the accumulation of DNA lesions that are targeted by the base excision repair (BER) pathway. Thus, MMR can act as a direct sensor of FdU-mediated DNA lesions eliciting cell cycle arrest via the ATR/Chk1 pathway. However, at higher levels of damage, other damage surveillance pathways such as BER also play important roles.

DNA mismatch repair: molecular mechanism, cancer, and ageing.

DNA mismatch repair (MMR) proteins are ubiquitous players in a diverse array of important cellular functions. In its role in post-replication repair, MMR safeguards the genome correcting base mispairs arising as a result of replication errors. Loss of MMR results in greatly increased rates of spontaneous mutation in organisms ranging from bacteria to humans. Mutations in MMR genes cause hereditary nonpolyposis colorectal cancer, and loss of MMR is associated with a significant fraction of sporadic cancers. Given its prominence in mutation avoidance and its ability to target a range of DNA lesions, MMR has been under investigation in studies of ageing mechanisms. This review summarizes what is known about the molecular details of the MMR pathway and the role of MMR proteins in cancer susceptibility and ageing.