Devising Isolation Forest-Based Method to Investigate the sRNAome of Using sRNA-seq Data.

Small non-coding RNAs (sRNAs) regulate the synthesis of virulence factors and other pathogenic traits, which enables the bacteria to survive and proliferate after host infection. While high-throughput sequencing data have proved useful in identifying sRNAs from the intergenic regions (IGRs) of the genome, it remains a challenge to present a complete genome-wide map of the expression of the sRNAs. Moreover, existing methodologies necessitate multiple dependencies for executing their algorithm and also lack a targeted approach for the sRNA identification.

Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC.

Introduction: Although gene-level copy number alterations have been studied as a potential biomarker of immunotherapy efficacy in NSCLC, the impact of aneuploidy burden and chromosomal arm-level events on immune checkpoint inhibitor (ICI) efficacy in NSCLC is uncertain.

Methods: Patients who received programmed cell death protein 1 or programmed death-ligand 1 (PD-L1) inhibitor at two academic centers were included. Across all 22 chromosomes analyzed, an arm was considered altered if at least 70% of its territory was either gained or deleted.

Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC.

Introduction: Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized.

Methods: In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT.

Results: Among 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS).

Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status.

Introduction: STK11 and KEAP1 mutations (STK11 mutant [STK11] and KEAP1) are among the most often mutated genes in lung adenocarcinoma (LUAD). Although STK11 has been associated with resistance to programmed death-(ligand)1 (PD-[L]1) inhibition in KRAS LUAD, its impact on immunotherapy efficacy in KRAS wild-type (KRAS) LUAD is currently unknown. Whether KEAP1 differentially affects outcomes to PD-(L)1 inhibition in KRAS and KRAS LUAD is also unknown.

Tumor relevant protein functional interactions identified using bipartite graph analyses.

An increased surge of -omics data for the diseases such as cancer allows for deriving insights into the affiliated protein interactions. We used bipartite network principles to build protein functional associations of the differentially regulated genes in 18 cancer types. This approach allowed us to combine expression data to functional associations in many cancers simultaneously.

Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy.

Background: Prior antibiotic therapy (pATB) is known to impair efficacy of single-agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut dysbiosis. Whether ATB also affects outcomes to chemo-immunotherapy combinations is still unknown.

Patients And Methods: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small-cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at eight referral institutions.

Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC.

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown.

Methods: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC.

Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer.

Purpose: DNA damage response and repair (DDR) gene alterations are associated with increased tumor-infiltrating lymphocytes, higher genomic instability, and higher tumor mutational burden (TMB) in cancer. Whether DDR alterations are associated with clinical outcomes to programmed death ligand 1 [PD-(L)1] blockade in non-small cell lung cancer (NSCLC) is unknown.

Experimental Design: Tumors from patients treated with PD-(L)1 inhibitors were analyzed using targeted next-generation sequencing (NGS).

Molecular Mechanisms of Acquired Resistance to MET Tyrosine Kinase Inhibitors in Patients with MET Exon 14-Mutant NSCLC.

Purpose: Molecular mechanisms of acquired resistance to MET tyrosine kinase inhibitors (TKI) are poorly understood. We aimed to characterize the genomic mechanisms of resistance to type I and type II MET TKIs and their impact on sequential MET TKI therapy outcomes in patients with metastatic exon 14-mutant NSCLC.

Experimental Design: Genomic alterations occurring at the time of progression on MET TKIs were studied using plasma and tissue next-generation sequencing (NGS).

Immune-Related Adverse Events Requiring Hospitalization: Spectrum of Toxicity, Treatment, and Outcomes.

Purpose: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs). The proportion of patients who are hospitalized for irAEs and their spectrum, management, and outcomes are not well described.

Methods: We report the proportion of hospitalized patients in an academic center who were treated with ICIs from May to December 2017.

Lung cancer and family-centered concerns.

Background: Genetic and environmental interactions predispose certain groups to lung cancer, including families. Families or caregiving units experience the disease interdependently. We have previously evaluated the concerns and preferences of patients in addressing the lung cancer experience and cancer risks in their families.

Photon-efficient imaging with a single-photon camera.

Reconstructing a scene's 3D structure and reflectivity accurately with an active imaging system operating in low-light-level conditions has wide-ranging applications, spanning biological imaging to remote sensing. Here we propose and experimentally demonstrate a depth and reflectivity imaging system with a single-photon camera that generates high-quality images from ∼1 detected signal photon per pixel. Previous achievements of similar photon efficiency have been with conventional raster-scanning data collection using single-pixel photon counters capable of ∼10-ps time tagging.

Classical imaging with undetected photons.

Barreto Lemos et al. [Nature 512, 409-412 (2014)] reported an experiment in which a non-degenerate parametric downconverter and a non-degenerate optical parametric amplifier--used as a wavelength-converting phase conjugator--were employed to image object transparencies in a manner akin to ghost imaging. Their experiment, however, relied on single-photon detection, rather than the photon-coincidence measurements employed in ghost imaging with a parametric downconverter source.

Infective endarteritis in a case of supravalvular aortic stenosis.

Supravalvular aortic stenosis is the rarest form of congenital left ventricular outflow tract obstruction. It can be associated with Williams syndrome or it may be an isolated anomaly. Although infective endocarditis is common in valvular aortic stenosis, in supravalvular aortic stenosis infective endocarditis/endarteritis is rarely reported.

Ghost imaging without discord.

Ragy and Adesso argue that quantum discord is involved in the formation of a pseudothermal ghost image. We show that quantum discord plays no role in spatial light modulator ghost imaging, i.e.

Classical far-field phase-sensitive ghost imaging.

We report the first (to our knowledge) far-field ghost images formed with phase-sensitive classical-state light and compare them with ghost images of the same object formed with conventional phase-insensitive classical-state light. To generate signal and reference beams with phase-sensitive cross correlation, we used a pair of synchronized spatial light modulators that imposed random, spatially varying, anticorrelated phase modulation on the outputs from 50-50 beam splitting of a laser beam. In agreement with theory, we found the phase-sensitive image to be inverted, whereas the phase-insensitive image is erect, with both having comparable spatial resolutions and signal-to-noise ratios.

Experimental realization of phase-conjugate optical coherence tomography.

We demonstrate phase-conjugate optical coherence tomography (PC-OCT) using a classical source of phase-sensitive cross-correlated beams to achieve measurement improvements shared by quantum OCT (Q-OCT): a factor-of-2 enhancement in axial resolution and even-order dispersion cancellation. Compared with coincidence counting used in Q-OCT, PC-OCT employs standard photodetection that results in much faster data acquisitions. This work belongs to a new class of classical techniques inspired by quantum methods that have advantages once thought to be exclusively quantum mechanical.

Classical low-coherence interferometry based on broadband parametric fluorescence and amplification.

We demonstrate that single-mode broadband amplified spontaneous parametric downconversion, combined with optical parametric amplification, can be used as a classical source of phase-sensitive cross-correlated beams. We first study the single spatial mode emission and the spectral brightness properties of the parametric fluorescence, produced in periodically poled MgO-doped lithium niobate. Using the same single-pass bulk-crystal configuration for a pulsed optical parametric amplifier, we achieve a gain of approximately 20 dB at an average pump power of 2W, and explain the pulse narrowing observed at the output of both parametric fluorescence and amplification in the regime of high gain.