Frequency of false-positive FISH 1p/19q codeletion in adult diffuse astrocytic gliomas

Oligodendroglioma is genetically defined by concomitant IDH (IDH1/IDH2) mutation and whole-arm 1p/19q codeletion. Codeletion of 1p/19q traditionally evaluated by fluorescence in situ hybridization (FISH) cannot distinguish partial from whole-arm 1p/19q codeletion. Partial 1p/19q codeletion called positive by FISH is diagnostically a "false-positive" result. Chromosomal microarray (CMA) discriminates partial from whole-arm 1p/19q codeletion. Herein, we aimed to estimate the frequency of partial 1p/19q codeletion that would lead to a false-positive FISH result

SeekFusion - A Clinically Validated Fusion Transcript Detection Pipeline for PCR-Based Next-Generation Sequencing of RNA

Detecting gene fusions involving driver oncogenes is pivotal in clinical diagnosis and treatment of cancer patients. Recent developments in next-generation sequencing (NGS) technologies have enabled improved assays for bioinformatics-based gene fusions detection. In clinical applications, where a small number of fusions are clinically actionable, targeted polymerase chain reaction (PCR)-based NGS chemistries, such as the QIAseq RNAscan assay, aim to improve accuracy compared to standard RNA sequencing. Existing informatics methods for gene fusion detection in NGS-based RNA sequencing assays traditionally use a transcriptome-based spliced alignment approach or a de-novo assembly approach. Transcriptome-based spliced alignment methods face challenges with short read mapping yielding low quality alignments. De-novo assembly-based methods yield longer contigs from short reads that can be more sensitive for genomic rearrangements, but face performance and scalability challenges. Consequently, there exists a need for a method to efficiently and accurately detect fusions in targeted PCR-based NGS chemistries. We describe SeekFusion, a highly accurate and computationally efficient pipeline enabling identification of gene fusions from PCR-based NGS chemistries. Utilizing biological samples processed with the QIAseq RNAscan assay and in-silico simulated data we demonstrate that SeekFusion gene fusion detection accuracy outperforms popular existing methods such as STAR-Fusion, TOPHAT-Fusion and JAFFA-hybrid. We also present results from 4,484 patient samples tested for neurological tumors and sarcoma, encompassing details on some novel fusions identified

Drivers of vaccine hesitancy among vulnerable populations in India: a cross-sectional multi-state study

ObjectivesIndia’s Covid-19 vaccination campaign engaged frontline workers (FLWs) to encourage vaccination among vulnerable segments of society. The FLWs report encountering a variety of barriers to vaccination and are often unsuccessful despite multiple visits to the same person. This cross-sectional study aims to pinpoint which of these barriers drive vaccine hesitancy among these segments, to help streamline vaccine communication, including FLW training, to better safeguard the population.MethodsTrained field enumerators contacted 893 individuals from five states across India and collected self-reported assessments of fifteen vaccination barriers (identified through discussions with FLWs), current vaccination status and future vaccination intentions, and covariates (demographics/comorbidities). Factor analysis of the fifteen barriers yielded two factors, one relating to fear of vaccine adverse effects and a second focused on peripheral concerns regarding the vaccine. The covariates significantly associated with current vaccination status were combined under a latent class regime to yield three cluster types (health access, financial strength, and demographics). The primary analysis examined the effect of the two barrier factors, the covariate clusters, and comorbidity, on current vaccination status and future vaccine intentions.ResultsFear of vaccine adverse effects was the primary driver of vaccine hesitancy; peripheral concerns frequently mentioned by the FLWs had no impact. Although cluster membership and the presence of comorbidities predicted vaccine uptake, neither of them materially altered the effect of fear of vaccine adverse effects with the following exception: fear of adverse effects was not associated with vaccination status among young Muslim men.ConclusionSubject to limitations, these results indicate that interventions to decrease vaccine hesitancy should focus primarily on fear associated with vaccines rather than spend resources trying to address peripheral concerns

Microwave spectro-polarimetry of matter and radiation across space and time

From Springer Nature via Jisc Publications RouterHistory: received 2020-07-29, accepted 2021-03-02, registration 2021-03-03, pub-print 2021-06, pub-electronic 2021-07-03, online 2021-07-03Publication status: PublishedAbstract: This paper discusses the science case for a sensitive spectro-polarimetric survey of the microwave sky. Such a survey would provide a tomographic and dynamic census of the three-dimensional distribution of hot gas, velocity flows, early metals, dust, and mass distribution in the entire Hubble volume, exploit CMB temperature and polarisation anisotropies down to fundamental limits, and track energy injection and absorption into the radiation background across cosmic times by measuring spectral distortions of the CMB blackbody emission. In addition to its exceptional capability for cosmology and fundamental physics, such a survey would provide an unprecedented view of microwave emissions at sub-arcminute to few-arcminute angular resolution in hundreds of frequency channels, a data set that would be of immense legacy value for many branches of astrophysics. We propose that this survey be carried out with a large space mission featuring a broad-band polarised imager and a moderate resolution spectro-imager at the focus of a 3.5 m aperture telescope actively cooled to about 8K, complemented with absolutely-calibrated Fourier Transform Spectrometer modules observing at degree-scale angular resolution in the 10–2000 GHz frequency range. We propose two observing modes: a survey mode to map the entire sky as well as a few selected wide fields, and an observatory mode for deeper observations of regions of specific interest

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer