Holistic Review in Family Medicine Residency Programs: A CERA Study.

Background And Objectives: Interest in using holistic review for residency recruitment as a strategy to improve the diversity of the physician workforce has increased. However, no data are published on the prevalence of holistic review in the selection process for family medicine residency programs. We designed this study to assess programs' knowledge, skills, and attitudes; prevalence; barriers to implementation; and program characteristics associated with the use of holistic review.

SHARPening Residency Selection: Implementing a Systematic Holistic Application Review Process.

Problem: Traditional metrics used in residency application review processes are systematically biased against applicants from minoritized communities that are underrepresented in medicine (URiM). These biases harm not just URiM applicants but also residency programs and patients. Although several residency programs have implemented holistic reviews to mitigate these biases, few tested tools exist that can be adapted and implemented in a wide variety of settings within academic medicine.

A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer.

The MYC proto-oncogene (MYC) is one of the most frequently overexpressed genes in breast cancer that drives cancer stem cell-like traits, resulting in aggressive disease progression and poor prognosis. In this study, we identified zinc finger transcription factor 148 (ZNF148, also called Zfp148 and ZBP-89) as a direct target of MYC. ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC in breast cancer.

A systematic review of the sensitivity and specificity of lateral flow devices in the detection of SARS-CoV-2.

Background: Lateral flow devices (LFDs) are viral antigen tests for the detection of SARS-CoV-2 that produce a rapid result, are inexpensive and easy to operate. They have been advocated for use by the World Health Organisation to help control outbreaks and break the chain of transmission of COVID-19 infections. There are now several studies assessing their accuracy but as yet no systematic review.

Glasses Versus Observation for Moderate Bilateral Astigmatism in 1- to <7-Year-Olds.

Purpose: To compare visual outcomes in children with moderate bilateral astigmatism treated with glasses with those who were merely observed.

Design: Retrospective case series.

Methods: The medical records of all children 1 to <7 years of age who were diagnosed with moderate bilateral astigmatism (+1.

The Emerging Roles of RNA mA Methylation and Demethylation as Critical Regulators of Tumorigenesis, Drug Sensitivity, and Resistance.

RNA -methyladenosine (mA) modification occurs in approximately 25% of mRNAs at the transcriptome-wide level. RNA mA is regulated by the RNA mA methyltransferases methyltransferase-like 3 (METTL3), METTL14, and METTL16 (writers), demethylases FTO and ALKBH5 (erasers), and binding proteins YTHDC1-2, YTHDF1-3, IGF2BP1-3, and SND1 (readers). These RNA mA modification proteins are frequently upregulated or downregulated in human cancer tissues and are often associated with poor patient prognosis.

The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant.

An Improved Protocol for Establishment of AML Patient-Derived Xenograft Models.

Patient-derived xenografts (PDXs) are the most valuable tool for preclinical drug testing because they retain the genetic diversity and phenotypic heterogeneity of the original tumor. Acute myeloid leukemia (AML) remains difficult to engraft in immunodeficient mice. This is particularly true for long-term frozen patient specimens.

Targeted Therapy of -Rearranged Neuroblastoma with BET Bromodomain Inhibitor and Proteasome Inhibitor Combination Therapy.

Purpose: gene rearrangement with transcriptional superenhancers leads to overexpression and neuroblastoma. No targeted therapy is available for clinical trials in patients with -rearranged neuroblastoma.

Experimental Design: Anticancer agents exerting the best synergistic anticancer effects with BET bromodomain inhibitors were identified by screening an FDA-approved oncology drug library.

Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia.

Signals driving aberrant self-renewal in the heterogeneous leukemia stem cell (LSC) pool determine aggressiveness of acute myeloid leukemia (AML). We report that a positive modulator of canonical WNT signaling pathway, RSPO-LGR4, upregulates key self-renewal genes and is essential for LSC self-renewal in a subset of AML. RSPO2/3 serve as stem cell growth factors to block differentiation and promote proliferation of primary AML patient blasts.

The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.

The majority of patients with neuroblastoma due to MYCN oncogene amplification and consequent N-Myc oncoprotein over-expression die of the disease. Here our analyses of RNA sequencing data identify the long noncoding RNA lncNB1 as one of the transcripts most over-expressed in MYCN-amplified, compared with MYCN-non-amplified, human neuroblastoma cells and also the most over-expressed in neuroblastoma compared with all other cancers. lncNB1 binds to the ribosomal protein RPL35 to enhance E2F1 protein synthesis, leading to DEPDC1B gene transcription.

Diplopia after strabismus surgery for adults with nondiplopic childhood-onset strabismus.

Purpose: To describe frequency of postoperative diplopia after strabismus surgery in nondiplopic adults with childhood-onset strabismus and to report health-related quality-of-life (HRQOL) outcomes.

Methods: We prospectively enrolled 79 adults with no diplopia in any gaze who had childhood-onset strabismus and were scheduled for strabismus surgery. Diplopia was assessed preoperatively and at 6 weeks and 1 year postoperatively using a standardized diplopia questionnaire with 5 response options in 7 gaze positions.

Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development.

Erythroid maturation requires the concerted action of a core set of transcription factors. We previously identified the Krüppel-type zinc finger transcription factor Zfp148 (also called ZBP-89) as an interacting partner of the master erythroid transcription factor GATA1. Here we report the conditional knockout of Zfp148 in mice.

JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma.

Chromosome 17q21-ter is commonly gained in neuroblastoma, but it is unclear which gene in the region is important for tumorigenesis. The JMJD6 gene at 17q21-ter activates gene transcription. Here we show that JMJD6 forms protein complexes with N-Myc and BRD4, and is important for E2F2, N-Myc and c-Myc transcription.

JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis.

Abnormal metabolism is a fundamental hallmark of cancer and represents a therapeutic opportunity, yet its regulation by oncogenes remains poorly understood. Here, we uncover that JMJD1C, a jumonji C (JmjC)-containing H3K9 demethylase, is a critical regulator of aberrant metabolic processes in homeobox A9 (HOXA9)-dependent acute myeloid leukemia (AML). JMJD1C overexpression increases in vivo cell proliferation and tumorigenicity through demethylase-independent upregulation of a glycolytic and oxidative program, which sustains leukemic cell bioenergetics and contributes to an aggressive AML phenotype in vivo.

A Randomized Comparison of Pain Control and Functional Mobility between Proximal and Distal Adductor Canal Blocks for Total Knee Replacement.

Background: Adductor canal blocks (ACBs) have become a popular technique for postoperative pain control in total knee arthroplasty patients. Proximal and distal ACB have been compared previously, but important postoperative outcomes have yet to be assessed.

Aims: The primary objective of this study is to compare postoperative analgesia between proximal and distal ACB.

Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study.

Objective: The virtual patient (VP) is a computer program that simulates real-life clinical scenarios and allows learners to make diagnostic and therapeutic decisions in a safe environment. Although many VP cases are available, few focus on junior trainees as their target audience. In addition, there is wide variability in trainees' clinical rotation experiences, based on local practice and referral patterns, duty hour restrictions, and competing educational requirements.

G Protein-Coupled Receptor Signaling in Stem Cells and Cancer.

G protein-coupled receptors (GPCRs) are a large superfamily of cell-surface signaling proteins that bind extracellular ligands and transduce signals into cells via heterotrimeric G proteins. GPCRs are highly tractable drug targets. Aberrant expression of GPCRs and G proteins has been observed in various cancers and their importance in cancer stem cells has begun to be appreciated.