Same-Slide Spatial Multi-Omics Integration Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment.

The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization to provide systems-level understanding of diseases. Both technologies currently remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex, spatial resolution, and analytical approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Circular RNAs trigger nonsense-mediated mRNA decay.

Circular RNAs (circRNAs) are covalently closed single-stranded RNAs produced predominantly through a back-splicing process. They play regulatory roles in various biological and physiological processes; however, the molecular mechanisms by which circRNAs operate remain unclear. Herein, we demonstrate that circRNAs facilitate rapid mRNA degradation through RNA-RNA interactions between circRNAs and the 3' untranslated regions (3' UTRs) of mRNAs.

Unique events improve episodic richness, enhance mood, and alter the perception of time during isolation.

Living in isolation is associated with a lack of stimulating experiences, which negatively impacts quality of life and increases risk of advancing cognitive decline for older adults. We examined how engaging in unique events would enhance memory and improve well-being during the COVID-19 pandemic lockdowns, a period characterized by social isolation and monotonous daily experiences lacking diversity. Over 8-weeks during lockdowns, 18 healthy older adults used a smartphone-based application called "HippoCamera", capturing a total of 670 unique and routine events with short audio-video cues that were later replayed to prompt memory.

DeepSomatic: Accurate somatic small variant discovery for multiple sequencing technologies.

Somatic variant detection is an integral part of cancer genomics analysis. While most methods have focused on short-read sequencing, long-read technologies now offer potential advantages in terms of repeat mapping and variant phasing. We present DeepSomatic, a deep learning method for detecting somatic SNVs and insertions and deletions (indels) from both short-read and long-read data, with modes for whole-genome and exome sequencing, and able to run on tumor-normal, tumor-only, and with FFPE-prepared samples.

Local read haplotagging enables accurate long-read small variant calling.

Long-read sequencing technology has enabled variant detection in difficult-to-map regions of the genome and enabled rapid genetic diagnosis in clinical settings. Rapidly evolving third-generation sequencing platforms like Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) are introducing newer platforms and data types. It has been demonstrated that variant calling methods based on deep neural networks can use local haplotyping information with long-reads to improve the genotyping accuracy.

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer.

Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.

Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults.

Determination of Spin-Parity Quantum Numbers of X(2370) as 0^{-+} from J/ψ→γK_{S}^{0}K_{S}^{0}η^{'}.

Based on (10087±44)×10^{6}  J/ψ events collected with the BESIII detector, a partial wave analysis of the decay J/ψ→γK_{S}^{0}K_{S}^{0}η^{'} is performed. The mass and width of the X(2370) are measured to be 2395±11(stat)_{-94}^{+26}(syst)  MeV/c^{2} and 188_{-17}^{+18}(stat)_{-33}^{+124}(syst)  MeV, respectively. The corresponding product branching fraction is B[J/ψ→γX(2370)]×B[X(2370)→f_{0}(980)η^{'}]×B[f_{0}(980)→K_{S}^{0}K_{S}^{0}]=(1.

Multi-site sulfonation of lignin for the synthesis of a high-performance dye dispersant.

Sulfonated lignin-based dye dispersants have intensively attracted attention due to their low cost, renewability and abundant sources. However, their utilization is limited by the low content of sulfonic groups and high content of hydroxyl groups in their complex lignin structure, which results in various problems such as high reducing rate of dye, severe staining of the fibers and uneven dyeing. Here, the multi-site sulfonated lignin-based dispersants were prepared with high sulfonic group content (2.

Observation of D^{+}→K_{S}^{0}a_{0}(980)^{+} in the Amplitude Analysis of D^{+}→K_{S}^{0}π^{+}η.

We perform for the first time an amplitude analysis of the decay D^{+}→K_{S}^{0}π^{+}η and report the observation of the decay D^{+}→K_{S}^{0}a_{0}(980)^{+} using 2.93  fb^{-1} of e^{+}e^{-} collision data taken at a center-of-mass energy of 3.773 GeV with the BESIII detector.

Observation of Significant Flavor-SU(3) Breaking in the Kaon Wave Function at 12

We present cross sections for the reaction e^{+}e^{-}→K_{S}^{0}K_{L}^{0} at center-of-mass energies ranging from 3.51 to 4.95 GeV using data samples collected in the BESIII experiment, corresponding to a total integrated luminosity of 26.

Severus: accurate detection and characterization of somatic structural variation in tumor genomes using long reads.

Most current studies rely on short-read sequencing to detect somatic structural variation (SV) in cancer genomes. Long-read sequencing offers the advantage of better mappability and long-range phasing, which results in substantial improvements in germline SV detection. However, current long-read SV detection methods do not generalize well to the analysis of somatic SVs in tumor genomes with complex rearrangements, heterogeneity, and aneuploidy.

Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.

Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients.

Discovery, Pathogenesis, and Complete Genome Characterization of Herpesvirus.

In 2015 and 2016, two Barramundi () farms in Singapore reported a disease outbreak characterized by lethargic behavior, pronounced inappetence, generalized skin lesions, erosions of the fins and tail, and ultimately high mortality in their fish. Next-generation sequencing and PCR confirmed presence of a novel virus belonging to the family, herpesvirus (LCHV), which was subsequently isolated and cultured. We characterize, for the first time, the complete genome of two cultured LCHV isolates.

Regulation of immune signal integration and memory by inflammation-induced chromosome conformation.

3-dimensional (3D) genome conformation is central to gene expression regulation, yet our understanding of its contribution to rapid transcriptional responses, signal integration, and memory in immune cells is limited. Here, we study the molecular regulation of the inflammatory response in primary macrophages using integrated transcriptomic, epigenomic, and chromosome conformation data, including base pair-resolution Micro-Capture C. We demonstrate that interleukin-4 (IL-4) primes the inflammatory response in macrophages by stably rewiring 3D genome conformation, juxtaposing endotoxin-, interferon-gamma-, and dexamethasone-responsive enhancers in close proximity to their cognate gene promoters.

Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.

Mammalian switch/sucrose non-fermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, a first-in-class, orally bioavailable proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients.