Whole-body low-dose computed tomography in patients with newly diagnosed multiple myeloma predicts cytogenetic risk: a deep learning radiogenomics study.

OBJECTIVE: To develop a whole-body low-dose CT (WBLDCT) deep learning model and determine its accuracy in predicting the presence of cytogenetic abnormalities in multiple myeloma (MM). MATERIALS AND METHODS: WBLDCTs of MM patients performed within a year of diagnosis were included. Cytogenetic assessments of clonal plasma cells via fluorescent in situ hybridization (FISH) were used to risk-stratify patients as high-risk (HR) or standard-risk (SR). Presence of any of del(17p), t(14;16), t(4;14), and t(14;20) on FISH was defined as HR. The dataset was evenly divided into five groups (folds) at the individual patient level for model training. Mean and standard deviation (SD) of the area under the receiver operating curve (AUROC) across the folds were recorded. RESULTS: One hundred fifty-one patients with MM were included in the study. The model performed best for t(4;14), mean (SD) AUROC of 0.874 (0.073). The lowest AUROC was observed for trisomies: AUROC of 0.717 (0.058). Two- and 5-year survival rates for HR cytogenetics were 87% and 71%, respectively, compared to 91% and 79% for SR cytogenetics. Survival predictions by the WBLDCT deep learning model revealed 2- and 5-year survival rates for patients with HR cytogenetics as 87% and 71%, respectively, compared to 92% and 81% for SR cytogenetics. CONCLUSION: A deep learning model trained on WBLDCT scans predicted the presence of cytogenetic abnormalities used for risk stratification in MM. Assessment of the model's performance revealed good to excellent classification of the various cytogenetic abnormalities.

Single-Session Endoscopic Ultrasound-Directed Transgastric Intervention for a Fine Needle Biopsy of Pancreatic Head Mass Using Endoscopic Through-the-Scope Suturing in a Patient With Roux-en-Y Gastric Bypass Anatomy.

Endoscopic ultrasound (EUS) is a diagnostic tool used to examine pancreatic lesions. In patients who have undergone Roux-en-Y gastric bypass, lesions of the pancreatic head can be difficult to access because of altered foregut anatomy. To access the excluded stomach for better visualization of the pancreatic head, EUS-directed transgastric intervention can be used in a 2-step fashion. We present an interesting case of a 62-year-old woman who underwent a single-session modified EUS-directed transgastric intervention with a fine needle biopsy of a pancreatic head mass. A novel through-the-scope suturing system, the X-tack system (Apollo Endosurgery, Austin, TX), was used to allow for a successful single-session procedure.

Photon-counting CT in Thoracic Imaging: Early Clinical Evidence and Incorporation Into Clinical Practice.

Photon-counting CT (PCCT) is an emerging advanced CT technology that differs from conventional CT in its ability to directly convert incident x-ray photon energies into electrical signals. The detector design also permits substantial improvements in spatial resolution and radiation dose efficiency and allows for concurrent high-pitch and high-temporal-resolution multienergy imaging. This review summarizes (a) key differences in PCCT image acquisition and image reconstruction compared with conventional CT; (b) early evidence for the clinical benefit of PCCT for high-spatial-resolution diagnostic tasks in thoracic imaging, such as assessment of airway and parenchymal diseases, as well as benefits of high-pitch and multienergy scanning; (c) anticipated radiation dose reduction, depending on the diagnostic task, and increased utility for routine low-dose thoracic CT imaging; (d) adaptations for thoracic imaging in children; (e) potential for further quantitation of thoracic diseases; and (f) limitations and trade-offs. Moreover, important points for conducting and interpreting clinical studies examining the benefit of PCCT relative to conventional CT and integration of PCCT systems into multivendor, multispecialty radiology practices are discussed.

Deep-learning for automated detection of MSU deposits on DECT: evaluating impact on efficiency and reader confidence.

Introduction: Dual-energy CT (DECT) is a non-invasive way to determine the presence of monosodium urate (MSU) crystals in the workup of gout. Color-coding distinguishes MSU from calcium following material decomposition and post-processing. Manually identifying these foci (most commonly labeled green) is tedious, and an automated detection system could streamline the process. This study aims to evaluate the impact of a deep-learning (DL) algorithm developed for detecting green pixelations on DECT on reader time, accuracy, and confidence. Methods: We collected a sample of positive and negative DECTs, reviewed twice-once with and once without the DL tool-with a 2-week washout period. An attending musculoskeletal radiologist and a fellow separately reviewed the cases, simulating clinical workflow. Metrics such as time taken, confidence in diagnosis, and the tool's helpfulness were recorded and statistically analyzed. Results: We included thirty DECTs from different patients. The DL tool significantly reduced the reading time for the trainee radiologist (p = 0.02), but not for the attending radiologist (p = 0.15). Diagnostic confidence remained unchanged for both (p = 0.45). However, the DL model identified tiny MSU deposits that led to a change in diagnosis in two cases for the in-training radiologist and one case for the attending radiologist. In 3/3 of these cases, the diagnosis was correct when using DL. Conclusions: The implementation of the developed DL model slightly reduced reading time for our less experienced reader and led to improved diagnostic accuracy. There was no statistically significant difference in diagnostic confidence when studies were interpreted without and with the DL model.

Marginal Zone B Cells Are Necessary for the Formation of Anti-donor IgG After Allogeneic Sensitization.

BACKGROUND: The formation of anti-major histocompatibility complex (MHC) antibodies is a significant barrier for many patients awaiting organ transplantation. Patients with preformed anti-MHC antibodies have limited options for suitable donors, and the formation of donor-specific anti-MHC antibodies after transplantation is a harbinger of graft rejection. Despite the recognized importance of anti-MHC antibodies, the mechanisms responsible for the differentiation of B cells after exposure to allogeneic antigens are poorly understood. METHODS: To evaluate the differentiation of B cells in response to allogeneic antigen, we used a model of H-2 b C57Bl/6 sensitization with H-2 d antigen. We used a class I MHC tetramer-based approach to identify allogeneic B cells and flow cytometric crossmatch to identify allogeneic IgM and IgG. RESULTS: We found that although the formation of anti-H-2 d IgG was robust, few class-switched B cells and germinal center B cells were formed. Antigen-specific B cells did not express classical memory B-cell markers after sensitization but had an IgM + CD21 + marginal zone B-cell phenotype. The frequency of marginal zone B cells increased after sensitization. Depletion of marginal zone B cells before sensitization or skin grafting resulted in a significant diminution of anti-H-2 d IgG and fewer germinal center B cells. Adoptive transfer experiments revealed that marginal zone B cells more efficiently differentiated into germinal center B cells and anti-donor IgG-producing cells than follicular B cells. CONCLUSIONS: These results demonstrate an important role for marginal zone B cells as a reservoir of alloreactive B cells that are activated by allogeneic antigens.

Water inside the Selectivity Filter of a K+ Ion Channel: Structural Heterogeneity, Picosecond Dynamics, and Hydrogen Bonding.

Water inside biological ion channels regulates the key properties of these proteins, such as selectivity, ion conductance, and gating. In this article, we measure the picosecond spectral diffusion of amide I vibrations of an isotope-labeled KcsA potassium channel using two-dimensional infrared (2D IR) spectroscopy. By combining waiting time (100-2000 fs) 2D IR measurements of the KcsA channel including 13C18O isotope-labeled Val76 and Gly77 residues with molecular dynamics simulations, we elucidated the site-specific dynamics of water and K+ ions inside the selectivity filter of KcsA. We observe inhomogeneous 2D line shapes with extremely slow spectral diffusion. Our simulations quantitatively reproduce the experiments and show that water is the only component with any appreciable dynamics, whereas K+ ions and the protein are essentially static on a picosecond timescale. By analyzing simulated and experimental vibrational frequencies, we find that water in the selectivity filter can be oriented to form hydrogen bonds with adjacent or nonadjacent carbonyl groups with the reorientation timescales being three times slower and comparable to that of water molecules in liquid, respectively. Water molecules can reside in the cavity sufficiently far from carbonyls and behave essentially like "free" gas-phase-like water with fast reorientation times. Remarkably, no interconversion between these configurations was observed on a picosecond timescale. These dynamics are in stark contrast with liquid water, which remains highly dynamic even in the presence of ions at high concentrations.

Pathogenic bacteria prevalence in cultured Nile tilapia in Southwest Mexico: A real-time PCR analysis.

The present study investigates molecular-based PCR techniques to estimate the prevalence of fish pathogens in southwest Mexico where recurrent mortality in the tilapia cultures has been observed. Sample of internal organs and lesions of Nile tilapia were taken and analysed in 2018, 2019, 2020 and 2022 to detect bacterial pathogens using PCR. No samples were taken in 2021 due to the COVID-19 pandemic. The real-time PCR conditions were optimized to allow a qualitative reliable detection of the bacteria from fixed fish tissue. A total of 599 pond- and cage-cultured tilapia from the southwestern Mexican Pacific (Guerrero, Oaxaca and Chiapas states) were analysed. In this tropical region, during 2018 and 2019 water temperatures of the tilapia cultures were generally with the optimal range to grow Nile tilapia, although extreme values were recorded on some farms. Most of the tilapia sampled were apparently healthy. No Francisella sp. was detected in any sample, and Staphylococcus sp. was the most prevalent (from 0% to 64%) bacteria from the three states over time. Low prevalence of Aeromonas sp. was found, from 0% to 4.3%, although the fish pathogen Aeromonas dhakensis was not detected. Sterptococcus iniae was only detected in Chiapas in 2019 at a low prevalence (1.4%), while the major tilapia pathogen S. agalactiae was detected at a high prevalence (from 0% to 59%) in the three Mexican states. This is the first detection of these pathogenic bacteria in rural farms using real-time PCR and constitutes a great risk for tilapia aquaculture in Mexico, as well as a potential dispersion of these pathogens to other aquaculture areas.

Staging of breast cancer in the breast and regional lymph nodes using contrast-enhanced photon-counting detector CT: accuracy and potential impact on patient management.

OBJECTIVES: To describe the feasibility and evaluate the performance of multiphasic photon-counting detector (PCD) CT for detecting breast cancer and nodal metastases with correlative dynamic breast MRI and digital mammography as the reference standard. METHODS: Adult females with biopsy-proven breast cancer undergoing staging breast MRI were prospectively recruited to undergo a multiphasic PCD-CT using a 3-phase protocol: a non-contrast ultra-high-resolution (UHR) scan and 2 intravenous contrast-enhanced scans with 50 and 180 s delay. Three breast radiologists compared CT characteristics of the index malignancy, regional lymphadenopathy, and extramammary findings to MRI. RESULTS: Thirteen patients underwent both an MRI and PCD-CT (mean age: 53 years, range: 36-75 years). Eleven of thirteen cases demonstrated suspicious mass or non-mass enhancement on PCD-CT when compared to MRI. All cases with metastatic lymphadenopathy (3/3 cases) demonstrated early avid enhancement similar to the index malignancy. All cases with multifocal or multicentric disease on MRI were also identified on PCD-CT (3/3 cases), including a 4 mm suspicious satellite lesion. Four of five patients with residual suspicious post-biopsy calcifications on mammograms were detected on the UHR PCD-CT scan. Owing to increased field-of-view at PCD-CT, a 5 mm thoracic vertebral metastasis was identified at PCD-CT and not with the breast MRI. CONCLUSIONS: A 3-phase PCD-CT scan protocol shows initial promising results in characterizing breast cancer and regional lymphadenopathy similar to MRI and detects microcalcifications in 80% of cases. ADVANCES IN KNOWLEDGE: UHR and spectral capabilities of PCD-CT may allow for comprehensive characterization of breast cancer and may represent an alternative to breast MRI in select cases.

A facile approach for incorporating tyrosine esters to probe ion-binding sites and backbone hydrogen bonds.

Amide-to-ester substitutions are used to study the role of the amide bonds of the protein backbone in protein structure, function, and folding. An amber suppressor tRNA/synthetase pair has been reported for incorporation of p-hydroxy-phenyl-L-lactic acid (HPLA), thereby introducing ester substitution at tyrosine residues. However, the application of this approach was limited due to the low yields of the modified proteins and the high cost of HPLA. Here we report the in vivo generation of HPLA from the significantly cheaper phenyl-L-lactic acid. We also construct an optimized plasmid with the HPLA suppressor tRNA/synthetase pair that provides higher yields of the modified proteins. The combination of the new plasmid and the in-situ generation of HPLA provides a facile and economical approach for introducing tyrosine ester substitutions. We demonstrate the utility of this approach by introducing tyrosine ester substitutions into the K+ channel KcsA and the integral membrane enzyme GlpG. We introduce the tyrosine ester in the selectivity filter of the M96V mutant of the KcsA to probe the role of the second ion binding site in the conformation of the selectivity filter and the process of inactivation. We use tyrosine ester substitutions in GlpG to perturb backbone H-bonds to investigate the contribution of these H-bonds to membrane protein stability. We anticipate that the approach developed in this study will facilitate further investigations using tyrosine ester substitutions.

Water inside the selectivity filter of a K+ ion channel: structural heterogeneity, picosecond dynamics, and hydrogen-bonding.

Water inside biological ion channels regulates the key properties of these proteins such as selectivity, ion conductance, and gating. In this Article we measure the picosecond spectral diffusion of amide I vibrations of an isotope labeled KcsA potassium channel using two-dimensional infrared (2D IR) spectroscopy. By combining waiting time (100 - 2000 fs) 2D IR measurements of the KcsA channel including 13C18O isotope labeled Val76 and Gly77 residues with molecular dynamics simulations, we elucidated the site-specific dynamics of water and K+ ions inside the selectivity filter of KcsA. We observe inhomogeneous 2D lineshapes with extremely slow spectral diffusion. Our simulations quantitatively reproduce the experiments and show that water is the only component with any appreciable dynamics, whereas K+ ions and the protein are essentially static on a picosecond timescale. By analyzing simulated and experimental vibrational frequencies, we find that water in the selectivity filter can be oriented to form hydrogen bonds with adjacent, or non-adjacent carbonyl groups with the reorientation timescales being three times slower and comparable to that of water molecules in liquid, respectively. Water molecules can reside in the cavity sufficiently far from carbonyls and behave essentially like "free" gas-phase-like water with fast reorientation times. Remarkably, no interconversion between these configurations were observed on a picosecond timescale. These dynamics are in stark contrast with liquid water that remains highly dynamic even in the presence of ions at high concentrations.

Management staff's perspectives on intervention strategies for workplace violence prevention in a tertiary health facility in Nigeria: a qualitative study.

Introduction: Health workers have increasingly become victims of workplace violence. However, negligible action has been given to developing workplace violence (WPV) prevention programs in hospital settings in low-middle-income countries. An effective workplace violence prevention program is crucial for preventing violence and managing the consequences of incidents. This study assessed management staff perspectives on intervention strategies for workplace violence prevention in a tertiary health facility in Nigeria. Methods: A qualitative study design was employed to explore the intervention strategies for preventing and managing workplace violence at a tertiary health facility in southeast Nigeria. Six focus group discussions were conducted with thirty-eight management-level staff. The interview transcripts were manually coded according to six predefined constructs of workplace violence: creating interdisciplinary harmony and WPV experiences, causes, prevention, program/policy contents, and implementation strategies. A manual thematic analysis approach was adopted, and the results were presented as narratives. Results: The findings revealed recognition, welfare, administrative control, and security as vital strategies for the WPV prevention program. The participants agreed that unanimity among staff could be promoted through respect for all cadres of staff and for people's perspectives (creating interdisciplinary harmony). Assaults and staff intimidation/victimization (experiences), attributed to unethical/poor health workers' behaviour and ethnic discrimination (causes), were viewed as preventable by ensuring patients'/caregivers' welfare through respectful and timely care and staff's welfare through incentives/remunerations and discouraging intimidation (prevention strategies). Furthermore, the staff expressed that the WPV program should employ administrative controls, including instituting WPV policy/unit, codes of ethics, and standard operating procedures across all workplace facets (program/policy contents), which should be implemented through awareness creation, enforcement of sanctions, and provision of appropriate and adequate security presence in the hospital (policy implementation strategies). Conclusion: Respect, patient/staff welfare, administrative control, and security are strong mechanisms to prevent workplace violence in tertiary hospitals. Hospital management should institutionalize workplace violence prevention programs/policies and ensure compliance.

Musculoskeletal CT Imaging: State-of-the-Art Advancements and Future Directions.

CT is one of the most widely used modalities for musculoskeletal imaging. Recent advancements in the field include the introduction of four-dimensional CT, which captures a CT image during motion; cone-beam CT, which uses flat-panel detectors to capture the lower extremities in weight-bearing mode; and dual-energy CT, which operates at two different x-ray potentials to improve the contrast resolution to facilitate the assessment of tissue material compositions such as tophaceous gout deposits and bone marrow edema. Most recently, photon-counting CT (PCCT) has been introduced. PCCT is a technique that uses photon-counting detectors to produce an image with higher spatial and contrast resolution than conventional multidetector CT systems. In addition, postprocessing techniques such as three-dimensional printing and cinematic rendering have used CT data to improve the generation of both physical and digital anatomic models. Last, advancements in the application of artificial intelligence to CT imaging have enabled the automatic evaluation of musculoskeletal pathologies. In this review, the authors discuss the current state of the above CT technologies, their respective advantages and disadvantages, and their projected future directions for various musculoskeletal applications.

Transplantation elicits a clonally diverse CD8+ T cell response that is comprised of potent CD43+ effectors.

CD8+ T cells mediate acute rejection of allografts, which threatens the long-term survival of transplanted organs. Using MHC class I tetramers, we find that allogeneic CD8+ T cells are present at an elevated naive precursor frequency relative to other epitopes, only modestly increase in number after grafting, and maintain high T cell receptor diversity throughout the immune response. While antigen-specific effector CD8+ T cells poorly express the canonical effector marker KLRG-1, expression of the activated glycoform of CD43 defines potent effectors after transplantation. Activated CD43+ effector T cells maintain high expression of the coreceptor induced T cell costimulator (ICOS) in the presence of CTLA-4 immunoglobulin (Ig), and dual CTLA-4 Ig/anti-ICOS treatment prolongs graft survival. These data demonstrate that graft-specific CD8+ T cells have a distinct response profile relative to anti-pathogen CD8+ T cells and that CD43 and ICOS are critical surface receptors that define potent effector CD8+ T cell populations that form after transplantation.

Probing Ion Configurations in the KcsA Selectivity Filter with Single-Isotope Labels and 2D IR Spectroscopy.

The potassium ion (K+) configurations of the selectivity filter of the KcsA ion channel protein are investigated with two-dimensional infrared (2D IR) spectroscopy of amide I vibrations. Single 13C-18O isotope labels are used, for the first time, to selectively probe the S1/S2 or S2/S3 binding sites in the selectivity filter. These binding sites have the largest differences in ion occupancy in two competing K+ transport mechanisms: soft-knock and hard-knock. According to the former, water molecules alternate between K+ ions in the selectivity filter while the latter assumes that K+ ions occupy the adjacent sites. Molecular dynamics simulations and computational spectroscopy are employed to interpret experimental 2D IR spectra. We find that in the closed conductive state of the KcsA channel, K+ ions do not occupy adjacent binding sites. The experimental data is consistent with simulated 2D IR spectra of soft-knock ion configurations. In contrast, the simulated spectra for the hard-knock ion configurations do not reproduce the experimental results. 2D IR spectra of the hard-knock mechanism have lower frequencies, homogeneous 2D lineshapes, and multiple peaks. In contrast, ion configurations of the soft-knock model produce 2D IR spectra with a single peak at a higher frequency and inhomogeneous lineshape. We conclude that under equilibrium conditions, in the absence of transmembrane voltage, both water and K+ ions occupy the selectivity filter of the KcsA channel in the closed conductive state. The ion configuration is central to the mechanism of ion transport through potassium channels.

Exploring the experiences of self-determination of individuals with mild intellectual disabilities and epilepsy.

BACKGROUND: While epilepsy can decrease quality of life and self-determination in individuals without intellectual disabilities, the impact of epilepsy on experienced self-determination in people with intellectual disabilities remains unclear. METHOD: We conducted semi-structured interviews with six adults (four men, two women) aged 30-61 with mild intellectual disabilities and drug-resistant epilepsy to investigate their experiences of self-determination. The data were analysed using Interpretative Phenomenological Analysis. RESULTS: Three main themes were identified: (A) I am a competent person with epilepsy; (B) My social needs: being accepted as I am and stability in relationships; and (C) Being in control. CONCLUSIONS: In this study, the impact of epilepsy on experienced self-determination of people with mild intellectual disabilities outweighs the influence of intellectual disabilities. Identity formation, friendships with peers, and autonomy support in risk management are identified as important topics in supporting this group.

Quantifying Uncertainty in Deep Learning of Radiologic Images.

In recent years, deep learning (DL) has shown impressive performance in radiologic image analysis. However, for a DL model to be useful in a real-world setting, its confidence in a prediction must also be known. Each DL model's output has an estimated probability, and these estimated probabilities are not always reliable. Uncertainty represents the trustworthiness (validity) of estimated probabilities. The higher the uncertainty, the lower the validity. Uncertainty quantification (UQ) methods determine the uncertainty level of each prediction. Predictions made without UQ methods are generally not trustworthy. By implementing UQ in medical DL models, users can be alerted when a model does not have enough information to make a confident decision. Consequently, a medical expert could reevaluate the uncertain cases, which would eventually lead to gaining more trust when using a model. This review focuses on recent trends using UQ methods in DL radiologic image analysis within a conceptual framework. Also discussed in this review are potential applications, challenges, and future directions of UQ in DL radiologic image analysis.

Incidence of complications related to shoulder arthroplasties identified on computed tomography.

PURPOSE: Determine incidence of shoulder arthroplasty complications identified on computed tomography (CT). MATERIALS AND METHODS: Retrospective institutional database review of patients with shoulder arthroplasties who underwent CT between 01/2006-11/2021 at a tertiary academic referral center with subspecialized orthopedic shoulder surgeons. CT reports were reviewed for arthroplasty type and complication. Data were stratified and summarized. Associations between complications and arthroplasty types were determined with Chi-squared goodness of fit test. RESULTS: Eight hundred twelve CTs in 797 unique patients were included (438 (53.9%) females and 374 (46.1%) males; mean age 67 ± 11 years). There were 403 total shoulder arthroplasties (TSA), 317 reverse total shoulder arthroplasties (rTSA), and 92 hemiarthroplasties (HA). Complications were present in 527/812 (64.9%) and incidences were: loosening/aseptic osteolysis 36.9%, periprosthetic failure 21.6%, periprosthetic fracture 12.3%, periprosthetic dislocation 6.8%, joint/pseudocapsule effusion 5.9%, prosthetic failure 4.8%, infection 3.8%, and periprosthetic collection 2.1%. Complications per arthroplasty were: 305/403 (75.7%) TSAs, 176/317 (55.5%) rTSAs, and 46/92 (50%) HAs (p < 0.001). Periprosthetic fracture (20.8%), prosthetic dislocation (9.8%), and prosthetic failure (7.9%) were highest in rTSAs (p < 0.001, p < 0.013, p < 0.001, respectively). Loosening/aseptic osteolysis most frequent in TSAs (54.1%) (p < 0.001). Periprosthetic failure most frequent in HA (32.6%) (p < 0.001). Significant associations were identified with joint/pseudocapsule effusion and loosening/aseptic osteolysis (p = 0.04) and prosthetic dislocation (p < .001). CONCLUSION: In this single tertiary academic referral center cohort, the incidence of shoulder arthroplasty complication identified on CT was 64.9% and the most commonly occurring complication was loosening/aseptic osteolysis (36.9%). TSA had the highest incidence of complication (75.7%).

Demise of the USMLE Step-2 CS exam: Rationalizing a way forward.

The COVID-19 pandemic has compelled rethinking and changes in medical education, the most controversial perhaps being the cancelation of USMLE Step-2 Clinical Skills exam (Step-2 CS). What started in March of 2020 as suspension of this professional licensure exam, because of concerns about infection risk for examinees, standardized patients (SPs), and administrators, soon became permanent cancelation in January 2021. Expectedly, it triggered debate in medical education circles. Positively, however, the USMLE regulatory agencies (NBME and FSMB) saw an opportunity to innovate an exam tainted with perceptions of validity deficits, cost, examinee inconvenience, and worries about future pandemics; they therefore called for a public debate to fashion a way forward. We have approached the issue by defining Clinical Skills (CS), exploring its epistemology and historic evolution, including assessment modalities from Hippocratic times to the modern era. We defined CS as the art of medicine manifest in the physician-patient encounter as history taking (driven by communication skills and cultural competence) and physical examination. We classified CS components into knowledge and psychomotor skill domains, established their relative importance in the physician process (clinical reasoning) of diagnosis, thus establishing a theoretical framework for developing valid, reliable, feasible, fair, and verifiable CS assessment. Given the concerns for COVID-19 and future pandemics, we established that CS can largely be assessed remotely, and what could not, can be assessed locally (school/regional consortia level) as part of a USMLE-regulated/supervised assessment regimen with established national standards, thus maintaining USMLE's fiduciary responsibilities. We have suggested a national/regional program for faculty development in CS curriculum development, and assessment, including standard setting skills. This pool of expert faculty will form the nucleus of our proposed USMLE-regulated External Peer Review Initiative (EPRI). Finally, we suggest that CS evolves into an academic discipline/department of its own, rooted in scholarship.