Identifying key underlying regulatory networks and predicting targets of orphan C/D box snoRNAs in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder characterized principally by initial symptoms of neonatal hypotonia and failure-to-thrive in infancy, followed by hyperphagia and obesity. It is well established that PWS is caused by loss of paternal expression of the imprinted region on chromosome 15q11-q13. While most PWS cases exhibit megabase-scale deletions of the paternal chromosome 15q11-q13 allele, several PWS patients have been identified harboring a much smaller deletion encompassing primarily .

CT Findings and Patterns of e-Cigarette or Vaping Product Use-Associated Lung Injury: A Multicenter Cohort of 160 Cases.

Background: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown.

Research Question: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior?

Study Design And Methods: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed.

Specific ZNF274 binding interference at SNORD116 activates the maternal transcripts in Prader-Willi syndrome neurons.

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity. This disorder is caused by the absence of paternally expressed gene products from chromosome 15q11-q13. We previously demonstrated that knocking out ZNF274, a Kruppel-associated box-A-domain zinc finger protein capable of recruiting epigenetic machinery to deposit the H3K9me3 repressive histone modification, can activate expression from the normally silent maternal allele of SNORD116 in neurons derived from PWS induced pluripotent stem cells (iPSCs).

Prader-Willi syndrome: reflections on seminal studies and future therapies.

Prader-Willi syndrome (PWS) is caused by the loss of function of the paternally inherited 15q11-q13 locus. This region is governed by genomic imprinting, a phenomenon in which genes are expressed exclusively from one parental allele. The genomic imprinting of the 15q11-q13 locus is established in the germline and is largely controlled by a bipartite imprinting centre.

Visual scoring of aortic valve calcifications on low-dose CT in lung cancer screening.

Objectives: To evaluate risk factors for prevalence and progression of aortic valve calcification (AVC) in lung cancer screening participants and also to assess the sensitivity and reliability of visual AVCs on low-dose CT (LDCT) for predicting aortic stenosis (AS) in high-risk smokers.

Methods: We reviewed 1225 consecutive participants in annual LDCT screening for lung cancer at the Mount Sinai Hospital between 2010 and 2017. Sensitivity and specificity of moderate/severe AVC score on LDCT to identify AS on echocardiogram were calculated for 126 participants who had both within 12 months.

Defining the impact of mutation accumulation on replicative lifespan in yeast using cancer-associated mutator phenotypes.

Mutations accumulate within somatic cells and have been proposed to contribute to aging. It is unclear what level of mutation burden may be required to consistently reduce cellular lifespan. Human cancers driven by a mutator phenotype represent an intriguing model to test this hypothesis, since they carry the highest mutation burdens of any human cell.

Zinc finger protein 274 regulates imprinted expression of transcripts in Prader-Willi syndrome neurons.

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity and is caused by the absence of paternal contribution to chromosome 15q11-q13. Using induced pluripotent stem cell (iPSC) models of PWS, we previously discovered an epigenetic complex that is comprised of the zinc-finger protein ZNF274 and the SET domain bifurcated 1 (SETDB1) histone H3 lysine 9 (H3K9) methyltransferase and that silences the maternal alleles at the PWS locus. Here, we have knocked out ZNF274 and rescued the expression of silent maternal alleles in neurons derived from PWS iPSC lines, without affecting DNA methylation at the PWS-Imprinting Center (PWS-IC).

Cardiac Applications of PET-MR.

Purpose Of Review: The purpose of this study was to provide an overview of the clinical applications of PET-MR in the setting of cardiac imaging with emphasis on specific scenarios where both techniques together provided added information.

Recent Findings: Synergy of cardiac PET and MR fusion may hold similar promise eliminating ionizing radiation and improving tissue contrast. Future development of new hybrid scanners, use of new imaging tracers, and clinical applications are significant factors which will influence its use.

Residue-specific structures and membrane locations of pH-low insertion peptide by solid-state nuclear magnetic resonance.

The pH-low insertion peptide (pHLIP) binds to a membrane at pH 7.4 unstructured but folds across the bilayer as a transmembrane helix at pH∼6. Despite their promising applications as imaging probes and drug carriers that target cancer cells for cytoplasmic cargo delivery, the mechanism of pH modulation on pHLIP-membrane interactions has not been completely understood.

Noncanonical amino acids to improve the pH response of pHLIP insertion at tumor acidity.

The pH low insertion peptide (pHLIP) offers the potential to deliver drugs selectively to the cytoplasm of cancer cells based on tumor acidosis. The WT pHLIP inserts into membranes with a pH50 of 6.1, while most solid tumors have extracellular pH (pH(e)) of 6.

Phase I study of oxaliplatin in combination with gemcitabine, irinotecan, and 5-fluorouracil/leucovorin (G-FLIE) in patients with metastatic solid tumors including adenocarcinoma of the pancreas.

Purpose: The aims of this study were to establish the maximum tolerated dose (MTD) of oxaliplatin in combination with fixed doses of gemcitabine, irinotecan, and 5-fluorouracil/leucovorin (G-FLIE) in solid tumors, including advanced pancreatic cancer, and to evaluate the toxicity of the regimen.

Methods: Patients with metastatic solid tumors were treated with a regimen consisting of gemcitabine (500 mg/m(2) by fixed-dose-rate infusion), irinotecan (120 mg/m(2)), leucovorin 300 mg, bolus/infusion 5-fluorouracil (400 and 1,500 mg/m2, respectively), and oxaliplatin at doses from 50 to 85 mg/m(2) according to the escalation schema. Treatment was repeated every 14 days.

Rational design of DNA sequence-based strategies for subtyping Listeria monocytogenes.

The ability to differentiate bacteria beyond the species level is essential for identifying and tracking infectious disease outbreaks and to improve our knowledge of the population genetics, epidemiology, and ecology of bacterial pathogens. Commonly used subtyping methods, such as serotyping, phage typing, ribotyping, and pulsed-field gel electrophoresis, can yield ambiguous results that are difficult to standardize and share among laboratories. DNA sequence-based subtyping strategies can reduce interpretation ambiguity.