OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma.

Functional cellular heterogeneity in tumours often underlies incomplete response to therapy and relapse. Previously, we demonstrated that the growth of the paediatric brain malignancy, sonic hedgehog subgroup medulloblastoma, is rooted in a dysregulated developmental hierarchy, the apex of which is defined by characteristically quiescent SOX2 stem-like cells. Integrating gene expression and chromatin accessibility patterns in distinct cellular compartments, we identify the transcription factor Olig2 as regulating the stem cell fate transition from quiescence to activation, driving the generation of downstream neoplastic progenitors.

Suppressing recurrence in Sonic Hedgehog subgroup medulloblastoma using the OLIG2 inhibitor CT-179.

OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies to target this tumor cell population. Here, we investigate the therapeutic potential of the brain-penetrant orally bioavailable, OLIG2 inhibitor CT-179, using SHH-MB explant organoids, PDX and GEM SHH-MB models. We find that CT-179 disrupts OLIG2 dimerization, phosphorylation and DNA binding and alters tumor cell-cycle kinetics, increasing differentiation and apoptosis.

Preventing recurrence in Sonic Hedgehog Subgroup Medulloblastoma using the OLIG2 inhibitor CT-179.

Recurrence is the primary life-threatening complication for medulloblastoma (MB). In Sonic Hedgehog (SHH)-subgroup MB, OLIG2-expressing tumor stem cells drive recurrence. We investigated the anti-tumor potential of the small-molecule OLIG2 inhibitor CT-179, using SHH-MB patient-derived organoids, patient-derived xenograft (PDX) tumors and mice genetically-engineered to develop SHH-MB.

Ophthalmology Patient Perceptions of Open Payments Information.

Importance: Since 2014, medical industry payment data to physicians have been public via the Open Payments database. Patient opinions regarding these data help us to understand concerns and policymakers to improve reporting mechanisms for such payments.

Objective: To assess patient perceptions of Open Payments information.

Improvement in Both Primary and Eccentric Ocular Alignment After Thyroid Eye Disease-Strabismus Surgery With Tenon's Recession.

Purpose: To evaluate the improvement in primary and eccentric gaze ocular alignment in thyroid eye disease (TED) patients undergoing horizontal strabismus surgery with Tenon's recession.

Methods: This is an Institutional Review Board-approved retrospective analysis of TED patients undergoing horizontal strabismus surgery for esotropia. The study included all patients from 2007 to 2016 operated on by a single surgeon at Columbia University Medical Center.

Vitrectomy for macular hole following Nd:YAG laser injury.

The Q-switched Nd:YAG laser can cause significant ocular injury, because it can emit an invisible and powerful load of energy in a short period of time. One of these injuries is macular hole formation. We report the case of a 21-year-old woman who presented with acute floaters in her left eye after exposure to a Q-switched Nd:YAG laser.

SURGICAL TREATMENT OF A MACULAR HOLE IN X-LINKED RETINOSCHISIS.

Purpose: To report a case of full-thickness macular hole in a patient with X-linked retinoschisis and the outcome after surgical repair.

Methods: A 15-year-old boy with a history of X-linked retinoschisis presented to his ophthalmologist for routine follow-up and was found to have a Stage-3 macular hole in his left eye. His vision was 20/200.

Quantitative Fundus Autofluorescence and Optical Coherence Tomography in ABCA4 Carriers.

Purpose: To assess whether carriers of ABCA4 mutations have increased RPE lipofuscin levels based on quantitative fundus autofluorescence (qAF) and whether spectral-domain optical coherence tomography (SD-OCT) reveals structural abnormalities in this cohort.

Methods: Seventy-five individuals who are heterozygous for ABCA4 mutations (mean age, 47.3 years; range, 9-82 years) were recruited as family members of affected patients from 46 unrelated families.

Generation of Bright, Spatially Coherent Soft X-Ray High Harmonics in a Hollow Waveguide Using Two-Color Synthesized Laser Pulses.

We investigate the efficient generation of low-divergence high-order harmonics driven by waveform-optimized laser pulses in a gas-filled hollow waveguide. The drive waveform is obtained by synthesizing two-color laser pulses, optimized such that highest harmonic yields are emitted from each atom. Optimization of the gas pressure and waveguide configuration has enabled us to produce bright and spatially coherent harmonics extending from the extreme ultraviolet to soft x rays.

High-energy, kHz, picosecond hybrid Yb-doped chirped-pulse amplifier.

We report on a diode-pumped, hybrid Yb-doped chirped-pulse amplification (CPA) laser system with a compact pulse stretcher and compressor, consisting of Yb-doped fiber preamplifiers, a room-temperature Yb:KYW regenerative amplifier (RGA), and cryogenic Yb:YAG multi-pass amplifiers. The RGA provides a relatively broad amplification bandwidth and thereby a long pulse duration to mitigate B-integral in the CPA chain. The ~1030-nm laser pulses are amplified up to 70 mJ at 1-kHz repetition rate, currently limited by available optics apertures, and then compressed to ~6 ps with high efficiency.

Three-octave-spanning supercontinuum generation and sub-two-cycle self-compression of mid-infrared filaments in dielectrics.

We experimentally and numerically investigate the spectral and temporal structure of mid-infrared (mid-IR) filaments in bulk dielectrics with normal and anomalous group velocity dispersion (GVD) pumped by a 2.1 μm optical parametric chirped-pulse amplifier (OPCPA). The formation of stable and robust filaments with several microjoules of pulse energy is observed.

Multi-mJ, kHz, ps deep-ultraviolet source.

We demonstrate a 0.56-GW, 1-kHz, 4.2-ps, 2.

Survey of pharmacy involvement in hospital medication reconciliation programs across the United States.

Objective: The objective of this study is to conduct a review of pertinent literature, assess pharmacy involvement in medication reconciliation, and offer insight into best practices for hospitals to implement and enhance their medication reconciliation programs.

Method: Pharmacists in hospitals nationwide were asked to complete an anonymous survey via the American College of Clinical Pharmacy online database. The multiple choice survey analyzed the roles that healthcare professionals play in medication reconciliation programs at hospitals.

Multi-mJ, kHz, 2.1 μm optical parametric chirped-pulse amplifier and high-flux soft x-ray high-harmonic generation.

We report on a multi-mJ 2.1 μm optical parametric chirped-pulse amplification (OPCPA) system operating at 1 kHz repetition rate, pumped by a picosecond cryogenic Yb:YAG laser, and the demonstration of soft x-ray high-harmonic generation (HHG) with a flux of ∼2×10(8)  photon/s/1% bandwidth at 160 eV in Ar. The 1 kHz cryogenic Yb:YAG pump laser amplifies pulses up to 56 mJ and delivers compressed 42 mJ, 17 ps pulses to the 2.

Muscle and nerve biopsies: techniques for the neurologist and neurosurgeon.

Objective: Muscle and nerve biopsies are commonly performed procedures for the diagnosis of neuromuscular disorders. Neurologists and neurosurgeons are often consulted to perform these procedures in clinical practice. We provide guidelines in the performance of muscle and nerve biopsies.