Faculty Bibliography

INTRODUCTION/UNASSIGNED:Over the past decade, the growth of accelerated three-year MD (3YMD) programs has flourished. In 2015, with support from the Josiah Macy Jr. Foundation, the Consortium of Medical Pathway Programs (CAMPP) started with eight North American medical schools. The objective of this paper is to evaluate the current state of the 3YMD programs. MATERIAL AND METHODS/UNASSIGNED:Since 2015, the CAMPP has tracked new and prospective 3YMD programs. An electronic survey collecting curricular and programmatic information about the programs was disseminated to all members of the CAMPP in August 2023. The survey included elements related to year of initiation, number of graduates, and curricular elements. RESULTS/UNASSIGNED:Of the schools with known established three-year MD programs, 29 of 32 programs responded (response rate 90%). There is growth of Accelerated Medical Pathway Programs over time with almost 20% of United States Allopathic Medical Schools having or developing an accelerated program. There have been 817 graduates from these programs from 2013-2023. Most schools include an opportunity for a 'directed pathway' experience for students. A directed pathway is where a student completes the MD degree in three-years and then has a direct placement into an affiliated residency program, provided they meet the goals and objectives of the curriculum. Most of the schools report a mission to reduce medical student debt and build a workforce for a specialty, for a population of patients, or geographical distribution. CONCLUSIONS/UNASSIGNED:Accelerated three-year medical pathway programs have grown significantly over the last decade, consistent with an overall effort to redesign medical curricula, reduce debt and contribute to the workforce.

Diet and exercise are modifiable lifestyle factors known to have a major influence on metabolism. Clinical practice addresses diseases of altered metabolism such as diabetes or hypertension by altering these factors. Despite enormous public interest, there are limited defined diet and exercise regimens for cancer patients. Nevertheless, the molecular basis of cancer has converged over the past 15 years on an essential role for altered metabolism in cancer. However, our understanding of the molecular mechanisms that underlie the impact of diet and exercise on cancer metabolism is in its very early stages. In this work, we propose conceptual frameworks for understanding the consequences of diet and exercise on cancer cell metabolism and tumor biology and also highlight recent developments. By advancing our mechanistic understanding, we also discuss actionable ways that such interventions could eventually reach the mainstay of both medical oncology and cancer control and prevention.

Family life dramatically changed following the COVID-19 pandemic onset. Parents faced school and childcare closures, employment changes, and other disruptions to daily life. This study utilized online survey data collected in late April 2020 (N = 1,009) of parents' experiences parenting children from 0 to 12 years during the COVID-19 pandemic. Parents in the study were primarily White (82%), married (82%), and women (89%) with one or two children (75.1%). This qualitative study explored the challenges and rewards of parenting during a public health crisis. Parents responded to separate open-ended questions asking about the rewards and challenges of parenting during COVID-19. The responses to each question were coded independently and then combined to identify broader overarching themes. Using descriptive qualitative analysis, we identified six themes related to both parenting challenges and rewards: shifting roles and responsibilities, structure and routine changes, staying at home, relationship changes, parental adaptation and well-being, child well-being, and emotional experiences. A subset of parents reported the same experiences as being both rewarding and challenging, which reflects the duality and complexity of parenting during the pandemic. These findings are interpreted through a positive psychology lens and highlight the benefit finding that exists even when parents are in extremely stressful situations. We discuss the implications of this research for better supporting parents both during and outside of major crises. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

OBJECTIVE/UNASSIGNED:This study aimed to examine racial-ethnic differences in engagement with and clinical outcomes of a collaborative care model (CoCM) implemented in primary care outpatient clinics in an urban academic medical center. METHODS/UNASSIGNED:Adult patients (N=4,911) who screened positive for symptoms of depression, anxiety, or both on the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 scale and who identified as non-Hispanic Black, Hispanic, or non-Hispanic White were offered participation in a CoCM implementation. The primary outcome was treatment engagement, defined as receipt of any follow-up visit, minimally adequate 4-week follow-up (at least one visit), and minimally adequate 16-week follow-up (at least three visits) after initial assessment. Secondary outcomes were response and remission of depression or anxiety. RESULTS/UNASSIGNED:After adjustment of analyses for sociodemographic covariates, Black and Hispanic participants were significantly less likely than White participants to have received any or minimally adequate follow-up. Black and Hispanic participants who received any or minimally adequate 16-week follow-up were more likely than White participants to demonstrate depression symptom response and remission of anxiety symptoms. CONCLUSIONS/UNASSIGNED:This CoCM implementation appears to have been effective in treating depression and anxiety among Black and Hispanic patients. However, significant disparities in receipt of follow-up care were observed. Efforts must be made to improve the retention of patients from racial-ethnic minority groups in collaborative care.

Live imaging of translation based on tag recognition by a single-chain antibody is a powerful technique to assess translation regulation in living cells. However, this approach is challenging and requires optimization in terms of expression level and detection sensitivity of the system, especially in a multicellular organism. Here, we improved existing fluorescent tools and developed new ones to image and quantify nascent translation in the living Drosophila embryo and in mammalian cells. We tested and characterized five different green fluorescent protein variants fused to the single-chain fragment variable (scFv) and uncovered photobleaching, aggregation, and intensity disparities. Using different strengths of germline and somatic drivers, we determined that the availability of the scFv is critical in order to detect translation throughout development. We introduced a new translation imaging method based on a nanobody/tag system named ALFA-array, allowing the sensitive and simultaneous detection of the translation of several distinct mRNA species. Finally, we developed a largely improved RNA imaging system based on an MCP-tdStaygold fusion.

Lung cancer is one of the leading causes of cancer-related deaths in men and women worldwide. Current treatments have limited efficacy, cause significant side effects, and cells can develop drug resistance. New therapeutic strategies are needed to discover alternative anticancer agents with high efficacy and low-toxicity. TMBP, a biphenyl obtained by laccase-biotransformation of 2,6-dimethoxyphenol, possesses antitumor activity against A549 adenocarcinoma cells. Without causing damage to sheep erythrocytes and mouse peritoneal macrophages of BALB/c mice. In addition to being classified as a good oral drug according to in-silico studies. This study evaluated the in-vitro cytotoxic effect of TMBP on lung-cancer cell-line NCI-H460 and reports mechanisms on immunomodulation and cell death. TMBP treatment (12.5-200 μM) inhibited cell proliferation at 24, 48, and 72 h. After 24-h treatment, TMBP at IC₅₀ (154 μM) induced various morphological and ultrastructural changes in NCI-H460, reduced migration and immunofluorescence staining of N-cadherin and β-catenin, induced increased reactive oxygen species and nitric oxide with reduced superoxide radical-anion, increased superoxide dismutase activity and reduced glutathione reductase. Treatment also caused metabolic stress, reduced glucose-uptake, intracellular lactate dehydrogenase and lactate levels, mitochondrial depolarization, increased lipid droplets, and autophagic vacuoles. TMBP induced cell-cycle arrest in the G2/M phase, death by apoptosis, increased caspase-3/7, and reduced STAT-3 immunofluorescence staining. The anticancer effect was accompanied by decreasing PI3K, AKT, ARG-1, and NF-κB levels, and increasing iNOS. These results suggest its potential as a candidate for use in future lung anticancer drug design studies.

INTRODUCTION/UNASSIGNED:The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and coronavirus disease 2019 (COVID-19). OBJECTIVE/UNASSIGNED:The objective was to identify a potential association between Thr92Ala-DIO2 polymorphism and body composition (appendicular muscle mass, myosteatosis, and fat distribution) and to determine whether they reflect the severity or mortality associated with the disease. METHODS/UNASSIGNED:In this prospective cohort study (June-August 2020), 181 patients hospitalized with moderate-to-severe COVID-19 underwent a non-contrast-enhanced computed tomography (CT) of the thorax to assess body composition, laboratory tests, and genotyping for the Thr92Ala-DIO2 polymorphism. RESULTS/UNASSIGNED:In total, 181 consecutive patients were stratified into three subgroups according to the genotype: Thr/Thr (n = 64), Thr/Ala (n = 96), and Ala/Ala (n = 21). The prevalence of low muscle area (MA) (< 92 cm²) was 52.5%. Low MA was less frequent in Ala/Thr patients (44.8%) than in Thr/Thr (60.9%) or Ala/Ala patients (61.9%) (P = 0.027). Multivariate logistic regression analysis confirmed that the Thr/Ala allele was associated with a reduced risk of low MA (41% to 69%) and myosteatosis (62% to 72%) compared with Thr/Thr + Ala/Ala (overdominant model). Kaplan-Meier curves showed that patients with low muscle mass and homozygosity had lower survival rates than the other groups. Notably, the heterozygotes with MA ≥92 cm² exhibited the best survival rate. CONCLUSION/UNASSIGNED:Thr92Ala-DIO2 heterozygosity is associated with increased skeletal MA and less myosteatosis in patients with COVID-19. The protective effect of Thr92Ala-DIO2 heterozygosity on COVID-19 mortality is restricted to patients with reduced MA.

INTRODUCTION/BACKGROUND:Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium, with forceps biopsies (FBs) failing to yield intestinal metaplasia (IM). Repeat endoscopy is then often necessary to confirm a BE diagnosis. The aim of this study was to assess the yield of IM leading to a diagnosis of BE by the addition of wide-area transepithelial sampling (WATS-3D) to FB in the screening of patients with GERD. METHODS:We performed a prospective registry study of patients with GERD undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm columnar-lined epithelium), possible short-segment BE (1 to <3 cm), and possible long-segment BE (≥3 cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results affected patient management. RESULTS:Of 23,933 patients, 6,829 (28.5%) met endoscopic criteria for BE. Of these, 2,878 (42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and absolute yield was 18.1%. One thousand three hundred seventeen patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107 (44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. DISCUSSION/CONCLUSIONS:The addition of WATS-3D to FB in patients with GERD being screened for BE resulted in confirmation of BE in an additional one-fifth of patients. Furthermore, dysplasia diagnoses approximately doubled.

CIC-rearranged sarcomas comprise a group of exceptionally aggressive round-cell sarcomas. These tumors most commonly demonstrate CIC::DUX4 fusion and show similar histopathology to Ewing sarcomas, though lesions mimicking vascular neoplasms have recently been described. Here, we describe a case of a patient with CIC::DUX4 fusion sarcoma identified using RNA-based molecular testing who was initially diagnosed with an endothelial neoplasm. The tumor showed extensive vasoformative growth, complete WT1 negativity, and global positive staining for ERG, CD31, and DUX4 by immunohistochemistry. Methylation testing of the tumor clustered more closely with angiosarcomas than with CIC-rearranged sarcomas. Our findings suggest that CIC::DUX4 fused neoplasms may demonstrate a more diverse phenotypic range than previously appreciated and offer evidence that both molecular and immunohistochemical studies are needed for accurate diagnosis.