Physician educators' perceptions of experiences contributing to teaching.

INTRODUCTION: Physician educators are essential in training the next generation of physicians. However, physician educators' perspectives about what experiences they find beneficial to their teaching and the prevalence of these experiences remain unknown. Guided by social cognitive career theory (SCCT) and communities of practice (CoP), we explored what experiences physician educators perceive as beneficial in preparing them to teach. METHODS: In 2019, the Uniformed Services University School of Medicine in the United States surveyed its physician alumni to understand their education experiences during medical school, their current career path and what has contributed to their teaching role. Content analysis was applied to extract themes across the text response. Chi-square analysis was applied to examine if perceived contributing factors vary based on physician educators' gender, specialty and academic ranks. RESULTS: The five most prevalent contributing factors participants (n = 781) identified are (1) experiences gained during residency and fellowship (29.8%), (2) teaching as faculty member (28.9%) and (3) class experiences and peer interaction during medical school (26%). We organised three themes that reflected major avenues of how physician educators acquire teaching skills: reflection about quality teaching, journey as learners and learning by doing. Gender and clinical specialty were differentially associated with contributing factors such as faculty development and meta-reflection. CONCLUSION: The results are in line with theories of SCCT and CoP, in which we identified self-directed learning and regulation in shaping physician educators' teaching. The findings also revealed gaps and potential contexts for more formalised teaching practices to develop physician educators.

Quantitative assessment of preanalytic variables on clinical evaluation of PI3/AKT/mTOR signaling activity in diffuse glioma.

Biomarker-driven therapeutic clinical trials require implementation of standardized, evidence-based practices for sample collection. In diffuse glioma, phosphatidylinositol 3 (PI3)-kinase/AKT/mTOR (PI3/AKT/mTOR) signaling is an attractive therapeutic target for which window of opportunity clinical trials could facilitate identification of promising new agents. Yet, the relevant preanalytic variables and optimal tumor sampling methods necessary to measure pathway activity are unknown. To address this, we used a murine model for IDH-wildtype glioblastoma (GBM) and human tumor tissue, including IDH-wildtype GBM and IDH-mutant diffuse glioma. First, we determined the impact of delayed time-to-formalin fixation, or cold ischemia time (CIT), on the quantitative assessment of cellular expression of six phosphoproteins that are readouts of PI3K/AK/mTOR activity (phosphorylated -proline-rich Akt substrate of 40 kDa (p-PRAS40, T246), -mechanistic target of rapamycin (p-mTOR; S2448); -AKT (p-AKT, S473); -ribosomal protein S6 (p-RPS6, S240/244 and S235/236), and -eukaryotic initiation factor 4E-binding protein 1 (p-4EBP1, T37/46). With CITs ≥2 hours, typical of routine clinical handling, all had reduced or altered expression with p-RPS6 (S240/244) exhibiting relatively greater stability. A similar pattern was observed using patient tumor samples from the operating room with p-4EBP1 more sensitive to delayed fixation than p-RPS6 (S240/244). Many clinical trials utilize unstained slides for biomarker evaluation. Thus, we evaluated the impact of slide storage conditions on the detection of p-RPS6 (S240/244), p-4EBP1, and p-AKT. After 5 months, storage at -80ºC was required to preserve the expression of p-4EBP1 and p-AKT while p-RPS6 (240/244) expression was not stable regardless of storage temperature. Biomarker heterogeneity impacts optimal tumor sampling. Quantification of p-RPS6 (240/244) expression in multiple regionally distinct human tumor samples from eight patients revealed significant intratumoral heterogeneity. Thus, the accurate assessment of PI3K/AKT/mTOR signaling in diffuse glioma must overcome intratumoral heterogeneity and multiple preanalytic factors, including time-to-formalin fixation, slide storage conditions, and phosphoprotein of interest.

A rhPDGF-BB/bovine type I collagen/ß-TCP mixture for the treatment of critically sized non-union tibial defects: An in vivo study in rabbits.

Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/ß-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks.

Describing the Landscape of Medical Education Preprints on MedRxiv: Current Trends and Future Recommendations.

PURPOSE: A preprint is a version of a research manuscript posted to a preprint server prior to peer review. Preprints enable authors to quickly and openly share research, afford opportunities for expedient feedback, and enable immediate listing of research on grant and promotion applications. In medical education, most journals welcome preprints, which suggests preprints play a role in the field's discourse. Yet, little is known about medical education preprints, including author characteristics, preprint use, and ultimate publication status. This study provides an overview of preprints in medical education to better understand their role in the field's discourse. METHOD: The authors queried medRxiv, a preprint repository, to identify preprints categorized as "medical education" and downloaded related metadata. CrossRef was queried to gather information on preprints later published in journals. Data were analyzed using descriptive statistics. RESULTS: Between 2019 and 2022, 204 preprints were classified in medRxiv as "medical education," with most deposited in 2021 (n = 76, 37.3%). On average, preprint full-texts were downloaded 1,875.2 times, and all were promoted on social media. Preprints were authored, on average, by 5.9 authors. Corresponding authors were based in 41 countries, with 45.6% in the United States, United Kingdom, and Canada. Almost half (n = 101, 49.5%) became published articles in predominantly peer-reviewed journals. Preprints appeared in 65 peer-reviewed journals, with BMC Medical Education (n = 9, 8.9%) most represented. CONCLUSIONS: Medical education research is being deposited as preprints, which are promoted, heavily accessed, and subsequently published in peer-reviewed journals, including medical education journals. Considering the benefits of preprints and the slowness of medical education publishing, it is likely that preprint depositing will increase and preprints will be integrated into the field's discourse. The authors propose next steps to facilitate responsible and effective creation and use of preprints.

The effects of sleep deprivation and extreme exertion on cognitive performance at the world-record breaking Suffolk Back Yard Ultra-marathon.

Using a prospective observational design, this study investigated the hypothesis that competing in the Suffolk Back Yard Ultra-marathon, would result in impaired cognitive performance and examined whether pre-race sleep patterns could mitigate this. Fifteen runners (1 female) volunteered to undertake this study and eleven males were included in the final analysis. Before the race and after withdrawal participants completed the following cognitive performance tasks: 2 Choice Reaction Time (2CRT), Stroop, and the Tower Puzzle. Pre-race sleep strategies were subjectively recorded with a 7-day sleep diary. Following race withdrawal, reaction time increased (Δ 77±68 ms; p = 0.004) in the 2CRT and executive function was impaired in the Stroop task (Interference score Δ -4.3±5.6 a.u.; p = 0.028). Decision making was not affected in the Tower Puzzle task. There was a significant correlation between the pre-race 7-day average sleep scores and both 2CRT Δ throughput (r = 0.61; p = 0.045) and 2CRT Δ RT (r = -0.64; p = 0.034). This study supports the hypothesis that running an ultra-marathon, which includes at least one night of sleep deprivation, impairs cognitive performance and provides novel evidence suggesting good sleep quality, in the week prior to an ultra-marathon, could minimise these effects.

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma.

Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.

Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods.

Brain-machine interfaces (BMI) aim to restore function to persons living with spinal cord injuries by 'decoding' neural signals into behavior. Recently, nonlinear BMI decoders have outperformed previous state-of-the-art linear decoders, but few studies have investigated what specific improvements these nonlinear approaches provide. In this study, we compare how temporally convolved feedforward neural networks (tcFNNs) and linear approaches predict individuated finger movements in open and closed-loop settings. We show that nonlinear decoders generate more naturalistic movements, producing distributions of velocities 85.3% closer to true hand control than linear decoders. Addressing concerns that neural networks may come to inconsistent solutions, we find that regularization techniques improve the consistency of tcFNN convergence by 194.6%, along with improving average performance, and training speed. Finally, we show that tcFNN can leverage training data from multiple task variations to improve generalization. The results of this study show that nonlinear methods produce more naturalistic movements and show potential for generalizing over less constrained tasks. Teaser: A neural network decoder produces consistent naturalistic movements and shows potential for real-world generalization through task variations.

The Surgical Management of NCAA Division 1 College Football Injuries Post COVID-19: A Single Institution Retrospective Review.

ABSTRACT: Cohen, JL, Cade, WH, Harrah, TC, Costello II, JP, and Kaplan, LD. The surgical management of NCAA Division 1 college football injuries post COVID-19: A single institution retrospective review. J Strength Cond Res 38(5): 906-911, 2024-The unprecedented COVID-19 pandemic had a significant impact on college football operations, including athletes' training regimens. As a result of these changes, concern for increased injury susceptibility post COVID-19 regulations has become a point of discussion. The current study sought to evaluate the incidence of surgical injury among NCAA Division 1 college football players at the authors' institution during the first full season after start of the COVID-19 pandemic compared with previous years. Retrospective chart review was performed for all players who sustained injuries requiring surgery while a member of the NCAA Division 1 football program during the 2009-2021 seasons. A p -value of ≤0.05 was used to determine significance. A total of 23 surgical injuries occurred in 22 players during the 2021 season compared with 121 in 118 players in the 12 previous seasons combined ( p = 0.0178; RR = 1.47). There was a significant increase in shoulder injuries ( n = 13 vs. n = 31; p = <0.0001; RR = 3.05) and specifically a significant increase in labral tears ( n = 10 vs. n = 30; p = 0.0003; RR = 2.74). No difference was seen in knee injuries ( n = 10 vs. n = 77; p = 0.27; RR = 1.35) and specifically no difference in anterior cruciate ligament injuries ( n = 3 vs. n = 31; p = 0.77; RR = 1.17). This phenomenon is multifactorial in nature, but alterations to players' training and preparations because of the COVID-19 pandemic likely resulted in suboptimal conditioning, leading to the increased incidence of surgical injuries emphasizing the importance of adequate strength training and conditioning.

In Search of a "Metric System" for Measuring Faculty Effort: A Qualitative Study on Educational Value Units at U.S. Medical Schools.

PURPOSE: Faculty at academic health centers (AHCs) are charged with engaging in educational activities. Some faculty have developed educational value units (EVUs) to track the time and effort dedicated to these activities. Although several AHCs have adopted EVUs, there is limited description of how AHCs engage with EVU development and implementation. This study aimed to understand the collective experiences of AHCs with EVUs to illuminate benefits and barriers to their development, use, and sustainability. METHOD: Eleven faculty members based at 10 AHCs were interviewed between July and November 2022 to understand their experiences developing and implementing EVUs. Participants were asked to describe their experiences with EVUs and to reflect on benefits and barriers to their development, use, and sustainability. Transcripts were analyzed using thematic analysis. RESULTS: EVU initiatives have been designed and implemented in a variety of ways, with no AHCs engaging alike. Despite differences, the authors identified shared themes that highlighted benefits and barriers to EVU development and implementation. Within and between these themes, a series of tensions were identified in conjunction with the ways in which AHCs attempted to mitigate them. Related to barriers, the majority of participants abandoned or paused their EVU initiatives; however, no differences were identified between those AHCs that retained EVUs and those that did not. CONCLUSIONS: The collective themes identified suggest that AHCs implementing or sustaining an EVU initiative would need to balance benefits and barriers in light of their unique context. Study findings align with reviews on EVUs and provide additional nuance related to faculty motivation to engage in education and the difficulties of defining EVUs. The lack of differences observed between those AHCs that retained EVUs and those that did not suggests that EVUs may be challenging to implement because of the complexity of AHCs and their faculty.

Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.

Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors.

The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Striking up a Conversation: Exploring Advising in Graduate Programs in Health Professions Education.

INTRODUCTION: Advising is happening across the medical education continuum, within non-medical graduate education programs, and is central to the advancement of said learners. This suggests that advising should play a role in graduate health progressions education (HPE) programs. MATERIALS AND METHODS: To explore advising curricula among HPE programs, we conducted a website review of all published HPE programs on the Foundation for Advancement of International Medical Education and Research's website. RESULTS: We recognized the lack of information published on advisory roles in graduate HPE programs. This prompted a literature review, which revealed a similar gap. CONCLUSIONS: Advising serves to benefit a student, advisor, and program thus carrying importance and need for discussion. This article is intended to kick-start a scholarly discussion about advising within graduate HPE programs.

The effects of sleep deprivation, acute hypoxia, and exercise on cognitive performance: A multi-experiment combined stressors study.

INTRODUCTION: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2). METHODS: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (FIO2 = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2). RESULTS: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise. CONCLUSION: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings.

Effects of COVID-19 on Rate of Injury and Position-Specific Injury During the 2020 National Football League Season.

ABSTRACT: Costello II, JP, Wagner, JD, Dahl, VA, Cohen, JL, Reuter, AM, and Kaplan, LD. Effects of COVID-19 on rate of injury and position-specific injury during the 2020 National Football League season. J Strength Cond Res 38(1): 97-104, 2024-Because of the COVID-19 pandemic, the National Football League (NFL) made changes to its operations for the 2020 season. We hypothesize an increase in the rate of injuries during the 2020 season. Publicly available data were reviewed to identify NFL injuries from the 2015-2020 seasons. Player position, description of injury, date of injury, and injury setting were recorded. p ≤ 0.05 was considered statistically significant. For the 2020 season, compared with the 2015-2019 seasons, there was an increased risk of injury during the regular season overall relative risk (RR) = 1.308 ( p < 0.05), week (W)1 RR = 7.33 ( p < 0.05), W1-6 RR = 1.964 ( p < 0.05), W7-12 RR = 1.8909 ( p < 0.05), and during the postseason overall RR = 1.1444 ( p < 0.05), calculated using analysis of variance. There was an overall increased risk of abdominal or core injuries RR = 1.248 ( p < 0.05), groin or hip injuries RR = 2.534 ( p < 0.05), and hamstring injuries RR = 3.644 ( p < 0.05). There was an increased risk of hamstring injuries in cornerbacks RR = 3.219 ( p < 0.05) and running backs RR = 1.1394 ( p < 0.05), hip or groin injuries in guards RR = 1.105 ( p < 0.05), Achilles tendon injuries in safeties RR = 1.6976 ( p < 0.05), quadriceps injuries in running backs RR = 1.6191 ( p < 0.05), and arm injuries in defensive tackles RR = 1.221 ( p < 0.05). There was an increase in the overall rate of injuries in the 2020 NFL season, both in the regular season and postseason, compared with the 2015-2019 seasons. The overall rate of abdominal or core, groin or hip, and hamstring injuries increased. Specific player positions saw unique increases in rates of injuries. These findings may be due to numerous operational changes implemented, such as reduced in-person training and the elimination of the preseason, leading to suboptimal, sports-specific conditioning and increased risk of musculoskeletal injury.

Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression.

BACKGROUND: The TERT promoter mutation (TPM) is acquired in most IDH-wildtype glioblastomas (GBM) and IDH-mutant oligodendrogliomas (OD) enabling tumor cell immortality. Previous studies on TPM clonality show conflicting results. This study was performed to determine whether TPM is clonal on a tumor-wide scale. METHODS: We investigated TPM clonality in relation to presumed early events in 19 IDH-wildtype GBM and 10 IDH-mutant OD using 3-dimensional comprehensive tumor sampling. We performed Sanger sequencing on 264 tumor samples and deep amplicon sequencing on 187 tumor samples. We obtained tumor purity and copy number estimates from whole exome sequencing. TERT expression was assessed by RNA-seq and RNAscope. RESULTS: We detected TPM in 100% of tumor samples with quantifiable tumor purity (219 samples). Variant allele frequencies (VAF) of TPM correlate positively with chromosome 10 loss in GBM (R = 0.85), IDH1 mutation in OD (R = 0.87), and with tumor purity (R = 0.91 for GBM; R = 0.90 for OD). In comparison, oncogene amplification was tumor-wide for MDM4- and most EGFR-amplified cases but heterogeneous for MYCN and PDGFRA, and strikingly high in low-purity samples. TPM VAF was moderately correlated with TERT expression (R = 0.52 for GBM; R = 0.65 for OD). TERT expression was detected in a subset of cells, solely in TPM-positive samples, including samples equivocal for tumor. CONCLUSIONS: On a tumor-wide scale, TPM is among the earliest events in glioma evolution. Intercellular heterogeneity of TERT expression, however, suggests dynamic regulation during tumor growth. TERT expression may be a tumor cell-specific biomarker.

"De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade.

Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p < 0.01). All tumors had histologic features of the giant cell variant of glioblastoma. They lacked EGFR amplification, lacked combined trisomy of chromosome 7 plus monosomy of chromosome 10, and only rarely had TERT promoter mutation or CDKN2A homozygous deletion, which are hallmarks of conventional IDH-wildtype glioblastoma. Instead, they harbored frequent inactivating mutations in TP53, NF1, PTEN, ATRX, and SETD2 and recurrent activating mutations in PDGFRA. DNA methylation profiling revealed they did not align with known reference adult glioblastoma methylation classes, but instead had unique globally hypomethylated epigenomes and mostly classified as "Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass A". Five patients were treated with immune checkpoint blockade, four of whom survived greater than 3 years. The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.

Masters in health professions education programs as they choose to represent themselves: A website review.

Introduction: In an age of increasingly face-to-face, blended, and online Health Professions Education, students have more choices of institutions at which to study their degree. For an applicant, oftentimes, the first step is to learn more about a program through its website. Websites allow programs to convey their unique voice and to share their mission and values with others such as applicants, researchers, and academics. Additionally, as the number of master in health professions education (MHPE), or equivalent, programs rapidly grows, websites can share the priorities of these programs. Methods: In this study, we conducted a website review of 158 MHPE websites to explore their geographical distributions, missions, educational concentrations, and various programmatic components. Results: We compiled this information and synthesized pertinent aspects, such as program similarities and differences, or highlighted the omission of critical data. Conclusions: Given that websites are often the first point of contact for prospective applicants, curious collaborators, and potential faculty, the digital image of MHPE programs matters. We believe our findings demonstrate opportunities for growth within institutions and assist the field in identifying the priorities of MHPE programs. As programs begin to shape their websites with more intentionality, they can reflect their relative divergence/convergence compared to other programs as they see fit and, therefore, attract individuals to best match this identity. Periodic reviews of the breadth of programs, such as those undergone here, are necessary to capture diversifying goals, and serves to help advance the field of MHPE as a whole.

Lower Perioperative Complication Rates and Shorter Lengths of Hospital Stay Associated With Technology-Assisted Total Knee Arthroplasty Versus Conventional Instrumentation in Primary Total Knee Arthroplasty.

BACKGROUND: The use of technology allows increased precision in component positioning in total knee arthroplasty (TKA). The objectives of this study were to compare (1) perioperative complications and (2) resource utilization between robotic-assisted (RA) and computer-navigated (CN) versus conventional (CI) TKA. METHODS: A retrospective cohort study was performed using a national database to identify patients undergoing unilateral, primary elective TKA from January 2016 to December 2019. A total of 2,174,685 patients were identified and included RA (69,445), CN (112,225), or CI (1,993,015) TKA. Demographics, complications, lengths of stay, dispositions, and costs were compared between the cohorts. Binary logistic regression analysis was performed. RESULTS: The RA TKA cohort had lower rates of intraoperative fracture (0.05 versus 0.08%, P < .05), respiratory complications (0.6 versus 1.1%, P < .05), renal failure (1.3 versus 1.7%, P < .05), delirium (0.1 versus 0.2%, P < .05), gastrointestinal complications (0.04 versus 0.09%, P < .05), postoperative anemia (8.9 versus 13.9%, P < .05), blood transfusion (0.4 versus 0.9%, P < .05), pulmonary embolism, and deep vein thrombosis (0.1 versus 0.2%, P < .05), and mortality (0.01 versus 0.02%, P < .05) compared to conventional TKA, though the cohort did have higher rates of myocardial infarction (0.09 versus 0.07%, P < .05). The CN cohort had lower rates of myocardial infarction (0.02 versus 0.07%, P < .05), respiratory complications (0.8 versus 1.1%, P < .05), renal failure (1.5 versus 1.7%, P < .05), blood transfusion (0.8 versus 0.9%, P < .05), pulmonary embolism (0.08 versus 0.2%, P < .05), and deep vein thrombosis (0.2 versus 0.2%, P < .05) over CI TKA. Total cost was increased in RA (16,190 versus $15,133, P < .05) and CN (17,448 versus $15,133, P < .05). However, the length of hospital stay was decreased in both RA (1.8 versus 2.2 days, P < .05) and CN (2.1 versus 2.2 days, P < .05). CONCLUSIONS: Technology-assisted TKA was associated with lower perioperative complication rates and faster recovery.