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The practice of oncology continues to evolve over time. Educators find themselves in a position where they are no longer able to teach a topic in its entirety. Moreover, the rapid expansion of information available through research and discovery in the field of oncology makes it difficult for learners to process the constant barrage of new content. Lecturers continue to impart knowledge using didactic techniques, often trying to include as much material as possible in the time permitted. The question becomes: In the face of an impossibly large field, how can one assist learners in learning, and retaining, what is most important? The science of learning continues to develop, and we now recognize that there are ways to teach that optimally facilitate the retention and application of knowledge. By using these strategies, educators can make it easier for learners to absorb and retain key information. This article will touch upon several such techniques: cognitive load optimization, analogy, contrasting cases, elaboration, and just-in-time telling. By applying these methods to didactic presentations, educators can ensure that their lessons are heard, understood, and ultimately transformed into something unforgettable.

IntroductionAdamantinoma‐like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) EWSR1::FLI1 translocation. There is debate on whether ALES resembles more sarcoma or carcinoma.MethodsWe performed RNA sequencing from two ALES cases and compared findings with skeletal Ewing's sarcomas and nonneoplastic thyroid tissue. ALES was investigated by in situ hybridization (ISH) for high‐risk human papillomavirus (HPV) DNA and immunohistochemistry for the following antigens: keratin 7, keratin 20, keratin 5, keratins (AE1/AE3 and CAM5.2), CD45, CD20, CD5, CD99, chromogranin, synaptophysin, calcitonin, thyroglobulin, PAX8, TTF1, S100, p40, p63, p16, NUT, desmin, ER, FLI1, INI1, and myogenin.ResultsAn uncommon EWSR1::FLI transcript with retained EWSR1 exon 8 was detected in both ALES cases. Regulators of EWSR1::FLI1 splicing (HNRNPH1, SUPT6H, SF3B1) necessary for production of a functional fusion oncoprotein, as well as 53 genes (including TNNT1, NKX2.2) activated downstream to the EWSR1::FLI1 cascade, were overexpressed. Eighty‐six genes were uniquely overexpressed in ALES, most of which were related to squamous differentiation. Immunohistochemically, ALES strongly expressed keratins 5, AE1/AE3 and CAM5.2, p63, p40, p16, and focally CD99. INI1 was retained. The remaining immunostains and HPV DNA ISH were negative.ConclusionComparative transcriptomic profiling reveals overlapping features of ALES with skeletal Ewing's sarcoma and an epithelial carcinoma, as evidenced by immunohistochemical expression of keratin 5, p63, p40, CD99, the transcriptome profile, and detection of EWSR1::FLI1 fusion transcript by RNA sequencing.

Abstract Background Hepatitis B virus (HBV) vaccine seroprotection rates with conventional aluminum adjuvanted recombinant HBV vaccines, Engerix-B (HepB-alum) vaccine, among people with HIV (PWH) are varied. Heplisav-B (HepB-CpG) vaccine, a novel adjuvanted recombinant HBV vaccine, has shown higher seroprotection rates in immunocompetent patients but is not well studied in PWH. There are no published studies comparing seroprotection rates between HepB-alum and HepB-CpG in PWH. This study aims to evaluate and compare the seroprotection incidence of HepB-alum vs HepB-CpG in PWH at least 18 years of age. Methods This retrospective, observational cohort study included adults diagnosed with HIV who received a complete series of HepB-alum or HepB-CpG at a community health center in Phoenix, Arizona. Patients had a hepatitis B surface antibody <10 IU/L at the time of the first vaccine dose. The primary outcome was a comparison of seroconversion incidence between HepB-CpG and HepB-alum. Secondary outcomes included identifying factors associated with likelihood of response to HBV vaccination. Results A total of 120 patients were included in this study, 59 in the HepB-alum cohort and 61 in the HepB-CpG cohort. In the HepB-alum cohort, 57.6% achieved seroconversion, compared with 93.4% in the HepB-CpG cohort (P < .001). Those without diabetes were more likely to have response to a vaccine. Conclusions Among PWH at a single community health center, HepB-CpG provided a statistically higher incidence of seroprotection against HBV compared with HepB-alum.

Abstract Oncolytic viruses (OV) are live viruses that can selectively replicate in cancer cells. We have engineered an OV (CF33) to make it cancer-selective through the deletion of its J2R (thymidine kinase) gene. In addition, this virus has been armed with a reporter gene, human sodium iodide symporter (hNIS), to facilitate noninvasive imaging of tumors using PET. In this study, we evaluated the oncolytic properties of the virus (CF33-hNIS) in liver cancer model, and its usefulness in tumor imaging. The virus was found to efficiently kill liver cancer cells and the virus-mediated cell death exhibited characteristics of immunogenic death based on the analysis of 3 damage-associated molecular patterns: calreticulin, ATP, and high mobility group box-1. Furthermore, local or systemic administration of a single dose of the virus showed antitumor efficacy against a liver cancer xenograft model in mice and significantly increased survival of treated mice. Finally, PET scanning was performed following injection of the radioisotope I-124, for imaging of tumors, and a single dose of virus as low as 1E03 pfu, administered intra-tumorally or intravenously, allowed for PET imaging of tumors. In conclusion, CF33-hNIS is safe and effective in controlling human tumor xenografts in nude mice, and it also facilitates noninvasive imaging of tumors.

The concept of wellness, as proposed by Halbert L. Dunn, recognizes the importance of multiple dimensions, such as social and mental well-being, in maintaining overall health. Neglecting these dimensions can have long-term negative consequences on an individual's mental well-being. In the context of traditional in-person therapy sessions, efforts are made to manually identify underlying factors that contribute to mental disturbances, as these factors, if triggered, can potentially lead to severe mental health disorders. Our research focuses on introducing a meticulous task aimed at identifying indicators of wellness dimensions and detecting their presence in self-narrated human writings on the Reddit social media platform. We have mentioned Ethics and Broader Impact.

AbstractDirect cortical stimulation has been applied in epilepsy for nearly a century and has experienced a renaissance, given unprecedented opportunities to probe, excite, and inhibit the human brain. Evidence suggests stimulation can increase diagnostic and therapeutic utility in patients with drug‐resistant epilepsies. However, choosing appropriate stimulation parameters is not a trivial issue, and is further complicated by epilepsy being characterized by complex brain state dynamics. In this article derived from discussions at the ICTALS 2022 Conference (International Conference on Technology and Analysis for Seizures), we succinctly review the literature on cortical stimulation applied acutely and chronically to the epileptic brain for localization, monitoring, and therapeutic purposes. In particular, we discuss how stimulation is used to probe brain excitability, discuss evidence on the usefulness of stimulation to trigger and stop seizures, review therapeutic applications of stimulation, and finally discuss how stimulation parameters are impacted by brain dynamics. Although research has advanced considerably over the past decade, there are still significant hurdles to optimizing use of this technique. For example, it remains unclear to what extent short timescale diagnostic biomarkers can predict long‐term outcomes and to what extent these biomarkers add information to already existing biomarkers from passive electroencephalographic recordings. Further questions include the extent to which closed loop stimulation offers advantages over open loop stimulation, what the optimal closed loop timescales may be, and whether biomarker‐informed stimulation can lead to seizure freedom. The ultimate goal of bioelectronic medicine remains not just to stop seizures but rather to cure epilepsy and its comorbidities.

Importance Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures Amount and intensity of physical activity. Main Outcomes and Measures The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient’s exercise category. Results Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Abstract Purpose: Clinical trials reported 25% to 30% pathologic complete response (pCR) rates in HER2+ patients with breast cancer treated with anti-HER2 therapies without chemotherapy. We hypothesize that a multiparameter classifier can identify patients with HER2-“addicted” tumors who may benefit from a chemotherapy-sparing strategy. Experimental Design: Baseline HER2+ breast cancer specimens from the TBCRC023 and PAMELA trials, which included neoadjuvant treatment with lapatinib and trastuzumab, were used. In the case of estrogen receptor–positive (ER+) tumors, endocrine therapy was also administered. HER2 protein and gene amplification (ratio), HER2-enriched (HER2-E), and PIK3CA mutation status were assessed by dual gene protein assay (GPA), research-based PAM50, and targeted DNA-sequencing. GPA cutoffs and classifier of response were constructed in TBCRC023 using a decision tree algorithm, then validated in PAMELA. Results: In TBCRC023, 72 breast cancer specimens had GPA, PAM50, and sequencing data, of which 15 had pCR. Recursive partitioning identified cutoffs of HER2 ratio ≥ 4.6 and %3+ IHC staining ≥ 97.5%. With PAM50 and sequencing data, the model added HER2-E and PIK3CA wild-type (WT). For clinical implementation, the classifier was locked as HER2 ratio ≥ 4.5, %3+ IHC staining ≥ 90%, and PIK3CA-WT and HER2-E, yielding 55% and 94% positive (PPV) and negative (NPV) predictive values, respectively. Independent validation using 44 PAMELA cases with all three biomarkers yielded 47% PPV and 82% NPV. Importantly, our classifier's high NPV signifies its strength in accurately identifying patients who may not be good candidates for treatment deescalation. Conclusions: Our multiparameter classifier differentially identifies patients who may benefit from HER2-targeted therapy alone from those who need chemotherapy and predicts pCR to anti-HER2 therapy alone comparable with chemotherapy plus dual anti-HER2 therapy in unselected patients.