Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain.

Systemic Deletion of ARRDC4 Improves Cardiac Reserve and Exercise Capacity in Diabetes.

Background: Exercise intolerance is an independent predictor of poor prognosis in diabetes. The underlying mechanism of the association between hyperglycemia and exercise intolerance remains undefined. We recently demonstrated that the interaction between ARRDC4 (arrestin domain-containing protein 4) and GLUT1 (glucose transporter 1) regulates cardiac metabolism.

Multi-institutional Protocol Guidance for Pediatric Photon-counting CT.

Performing CT in children comes with unique challenges such as greater degrees of patient motion, smaller and densely packed anatomy, and potential risks of radiation exposure. The technical advancements of photon-counting detector (PCD) CT enable decreased radiation dose and noise, as well as increased spatial and contrast resolution across all ages, compared with conventional energy-integrating detector CT. It is therefore valuable to review the relevant technical aspects and principles specific to protocol development on the new PCD CT platform to realize the potential benefits for this population.

Distinct autoantibody profiles across checkpoint inhibitor types and toxicities.

Immune checkpoint inhibitors (ICI) are increasingly used in combination. To understand the effects of different ICI categories, we characterized changes in circulating autoantibodies in patients enrolled in the E4412 trial (NCT01896999) of brentuximab vedotin (BV) plus ipilimumab, BV plus nivolumab, or BV plus ipilimumab-nivolumab for Hodgkin Lymphoma. Cycle 2 Day 1 (C2D1) autoantibody levels were compared to pre-treatment baseline.

Large-Scale Whole-Genome Analysis of HTLV-1-Associated Myelopathy Identified Hereditary Spastic Paraplegias.

Objectives: Distinguishing human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy from hereditary spastic paraplegia in patients infected with HTLV-1 is challenging due to overlapping clinical symptoms. The aim of this study was to explore the possibility that hereditary spastic paraplegia is inherently present in patients diagnosed with HTLV-1-associated myelopathy.

Methods: We performed whole-genome sequencing on 315 unrelated patients registered in the HTLV-1-Associated Myelopathy patient registry "HAM-net," from 2013 to 2022 in Japan.

Trends and Clinical Outcomes of Fungal Keratitis in Canada: A 20-year Retrospective Multicentre Study.

Purpose: An increase in fungal and particularly filamentous keratitis has been observed in many geographic areas, mostly in contact lens wearers. This study seeks to characterize long-term trends in fungal keratitis in a continental climate area to provide guidance for diagnosis and treatment.

Design: Retrospective multicentric case series.

Disparities in Teleneurology Use in Medicaid Beneficiaries With Epilepsy by Practice Setting: Promoting Health Equity in Academic Centers.

Background And Objectives: Medicaid beneficiaries in many American academic medical centers can receive care in a separate facility than those not covered by Medicaid. We aimed to identify possible disparities in care by evaluating the association between facility type (integrated or Medicaid-only ) and telehealth utilization in people with epilepsy.

Methods: We performed retrospective analyses using structured data from the Mount Sinai Health System electronic medical record data from January 2003 to August 2021.

Addressing the Shortage of Academic Nurse Educators: Recommendations for Educational Institutions Based on Nominal Group Technique Research.

Aim: The purpose of this qualitative study was twofold: 1) explore factors contributing to the shortage of academic nurse educators (ANEs) and 2) identify opportunities to address these factors from the perspectives of nursing education institutions.

Background: The nurse faculty shortage is a major national concern, with inadequate recruitment and retention. Addressing the nursing faculty shortage is important to maintain a sustained nursing workforce.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

A benchmarked, high-efficiency prime editing platform for multiplexed dropout screening.

Prime editing installs precise edits into the genome with minimal unwanted byproducts, but low and variable editing efficiencies have complicated application of the approach to high-throughput functional genomics. Leveraging several recent advances, we assembled a prime editing platform capable of high-efficiency substitution editing across a set of engineered prime editing guide RNAs (epegRNAs) and corresponding target sequences (80% median intended editing). Then, using a custom library of 240,000 epegRNAs targeting >17,000 codons with 175 different substitution types, we benchmarked our platform for functional interrogation of small substitution variants (1-3 nucleotides) targeted to essential genes.

Improving prime editing with an endogenous small RNA-binding protein.

Prime editing enables the precise modification of genomes through reverse transcription of template sequences appended to the 3' ends of CRISPR-Cas guide RNAs. To identify cellular determinants of prime editing, we developed scalable prime editing reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as the strongest mediator of prime editing: the small RNA-binding exonuclease protection factor La.

mTOR Inhibition Prolongs Survival and Has Beneficial Effects on Heart Function After Onset of Lamin A/C Gene Mutation Cardiomyopathy in Mice.

Background: Mutations in encoding nuclear envelope proteins lamin A/C cause dilated cardiomyopathy. Activation of the AKT/mTOR (RAC-α serine/threonine-protein kinase/mammalian target of rapamycin) pathway is implicated as a potential pathophysiologic mechanism. The aim of this study was to assess whether pharmacological inhibition of mTOR signaling has beneficial effects on heart function and prolongs survival in a mouse model of the disease, after onset of heart failure.

Enhancing Whole-Brain Magnetic Field Homogeneity for 3D-Magnetic Resonance Spectroscopic Imaging with a Novel Unified Coil: A Preliminary Study.

The spectral quality of magnetic resonance spectroscopic imaging (MRSI) can be affected by strong magnetic field inhomogeneities, posing a challenge for 3D-MRSI's widespread clinical use with standard scanner-equipped 2nd-order shim coils. To overcome this, we designed an empirical unified shim-RF head coil (32-ch RF receive and 51-ch shim) for 3D-MRSI improvement. We compared its shimming performance and 3D-MRSI brain coverages against the standard scanner shim (2nd-order spherical harmonic (SH) shim coils) and integrated parallel reception, excitation, and shimming (iPRES) 32-ch AC/DC head coil.

High-threshold and low-overhead fault-tolerant quantum memory.

The accumulation of physical errors prevents the execution of large-scale algorithms in current quantum computers. Quantum error correction promises a solution by encoding k logical qubits onto a larger number n of physical qubits, such that the physical errors are suppressed enough to allow running a desired computation with tolerable fidelity. Quantum error correction becomes practically realizable once the physical error rate is below a threshold value that depends on the choice of quantum code, syndrome measurement circuit and decoding algorithm.

Reliable Off-Resonance Correction in High-Field Cardiac MRI Using Autonomous Cardiac B Segmentation with Dual-Modality Deep Neural Networks.

B0 field inhomogeneity is a long-lasting issue for Cardiac MRI (CMR) in high-field (3T and above) scanners. The inhomogeneous B0 fields can lead to corrupted image quality, prolonged scan time, and false diagnosis. B0 shimming is the most straightforward way to improve the B0 homogeneity.

Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade.

Background: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment.

Methods: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and β-blockers.