A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.

On the Cryptic Speciation in the Mosses with East Asia-East North America Disjunction: A Case Study of Two Poorly Understood Mosses from the Southern Extremity of the Russian Far East.

A survey of the moss flora of the southernmost part of the Russian Primorsky Territory yielded several intriguing taxa, whose identity is assessed herein based on an integrative morpho-molecular approach. was previously known in inland Asia only from the Sino-Himalayan region and the new locality is distant from the earlier known ones to ca. 3000 km.

Shared rare genetic variants in multiplex autism families suggest a social memory gene under selection.

Autism spectrum disorder (ASD) affects up to 1 in 59 children, and is one of the most common neurodevelopmental disorders. Recent genomic studies have highlighted the role of rare variants in ASD. This study aimed to identify genes affected by rare variants shared by siblings with ASD and validate the function of a candidate gene FRRS1L.

Transgender Identity and Attention Deficit Hyperactivity Disorder Symptoms: Findings From the Adolescent Brain Cognitive Development Study.

Purpose: The purpose of this study was to examine associations between identifying as transgender and attention deficit hyperactivity disorder (ADHD) symptoms in US early adolescents.

Methods: We analyzed cross-sectional data from the Adolescent Brain Cognitive Development Study (Year 3, 2019-2021) to estimate associations between gender identity and ADHD symptoms using the Child Behavior Checklist Diagnostic and Statistical Manual of Mental Disorders-oriented attention problem scale scores, adjusting for age, sex, ethnicity, parent education, household income, and study site. Additional models adjusted for stress problems and depression symptoms.

Prognostic and predictive role of immune microenvironment in colorectal cancer.

Colorectal cancer (CRC) represents a molecularly heterogeneous disease and one of the most frequent causes of cancer-related death worldwide. The traditional classification of CRC is based on pathomorphological and molecular characteristics of tumor cells (mucinous, ring-cell carcinomas, ), analysis of mechanisms of carcinogenesis involved (chromosomal instability, microsatellite instability, CpG island methylator phenotype) and mutational statuses of commonly altered genes (KRAS, NRAS, BRAF, APC, ), as well as expression signatures (CMS 1-4). It is also suggested that the tumor microenvironment is a key player in tumor progression and metastasis in CRC.

Role of UPF1 in lncRNA-HEIH regulation for hepatocellular carcinoma therapy.

UPF1, a novel posttranscriptional regulator, regulates the abundance of transcripts, including long noncoding RNAs (lncRNAs), and thus plays an important role in cell homeostasis. In this study, we revealed that UPF1 regulates the abundance of hepatocellular carcinoma upregulated EZH2-associated lncRNA (lncRNA-HEIH) by binding the CG-rich motif, thereby regulating hepatocellular carcinoma (HCC) tumorigenesis. UPF1-bound lncRNA-HEIH was susceptible to degradation mediated by UPF1 phosphorylation via SMG1 and SMG5.

Epigenomic Profiling Advises Therapeutic Potential of Leukotriene Receptor Inhibitors for a Subset of Triple-Negative Breast Tumors.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes.

Impact of the STK11/KRAS co-mutation on the response to immunotherapy in a real-world pan-cancer cohort.

Introduction: Immune checkpoint inhibitors are highly effective in treating various cancers. We analyzed the significance of the co-mutation in relation to the efficacy of immune checkpoint inhibitors in pan-cancer patient cohort.

Methods: We analyzed data from open-access research: MSK-IMPACT (molecular profiling data from patients receiving systemic antitumor therapy) and MSK-TMB (molecular profiling data from patients receiving immune checkpoint inhibitors).

Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (oG) can change RNA-RNA interactions via oG•A base pairing, but its regulatory roles remain elusive. Here, on the basis of oG-induced guanine-to-thymine (oG > T) variations featured in sequencing, we discovered widespread position-specific oGs in tumour microRNAs, preferentially oxidized towards 5' end seed regions (positions 2-8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma.

DNA Methylation and Prospects for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy for Triple-Negative and Luminal B Breast Cancer.

Despite advances in the diagnosis and treatment of breast cancer (BC), the main cause of deaths is resistance to existing therapies. An approach to improve the effectiveness of therapy in patients with aggressive BC subtypes is neoadjuvant chemotherapy (NACT). Yet, the response to NACT for aggressive subtypes is less than 65% according to large clinical trials.

Utility of public knowledge bases for the interpretation of comprehensive tumor molecular profiling results.

With the growing use of comprehensive tumor molecular profiling (CTMP), the therapeutic landscape of cancer is rapidly evolving. NGS produces large amounts of genomic data requiring complex analysis and subsequent interpretation. We sought to determine the utility of publicly available knowledge bases (KB) for the interpretation of the cancer mutational profile in clinical practice.

Mind the target: circulating tumour DNA in gastrointestinal malignancies.

Purpose Of Review: Circulating tumour DNA (ctDNA) is an appealing minimally invasive tool with significant theranostic potential. In this review, we highlighted recent studies evaluating three major applications of ctDNA in gastrointestinal malignancies.

Recent Findings: ctDNA demonstrated a strong prognostic value in colorectal and gastroesophageal cancers in assessing minimal residual disease after radical surgery.

Clinical significance of molecular subtypes of gastrointestinal tract adenocarcinoma.

Adenocarcinomas of the gastrointestinal tract (esophagus, stomach, and colon) represent a heterogeneous group of diseases with distinct etiology, clinical features, treatment approaches, and prognosis. Studies are ongoing to isolate molecular genetic subtypes, perform complete biological characterization of the tumor, determine prognostic groups, and find predictive markers to the effectiveness of therapy. Separate molecular genetic classifications were created for esophageal adenocarcinoma [The Cancer Genome Atlas (TCGA)], stomach cancer (TCGA, Asian Cancer Research Group), and colon cancer (Colorectal Cancer Subtyping Consortium).

MHA Herbarium: Collections of mosses from Yana-Indigirka Region, Yakutia, Russia.

Background: The Skvortsov Herbarium of the Tsitsin Main Botanical Garden, Russian Academy of Sciences (MHA) in the 1945-1980s dealt with vascular plants and only scattered occasional collections of bryophytes and lichens were accumulated there without special arrangement. Since the late 1980s, the bryophyte studies in the MHA Herbarium became permanent and several projects were started since then, including the currently conducted "Moss Flora of Russia". There are many white spots on the map of bryophyte exploration of Russia, but one of the most conspicuous was Yakutia, the largest administrative unit of Russia, covering 3,081,000 km.

Psychodiagnostics as a Mandatory Element of Patient Protocols in Dentistry.

Objectives: This study aims at performing psychodiagnostics of the patients` condition with removable and fixed dentures both before and after dental treatment.

Materials And Methods: The first group included 200 patients with fixed-type dentures, and the second group consisted of 200 patients with removable dental devices. The control group included 200 patients with healthy teeth.

AGO-accessible anticancer siRNAs designed with synergistic miRNA-like activity.

Small interfering RNAs (siRNAs) therapeutically induce RNA interference (RNAi) of disease-causing genes, but they also silence hundreds of seed-matched off-targets as behaving similar to microRNAs (miRNAs). miRNAs control the pathophysiology of tumors, wherein their accessible binding sites can be sequenced by Argonaute crosslinking immunoprecipitation (AGO CLIP). Herein, based on AGO CLIP, we develop potent anticancer siRNAs utilizing miRNA-like activity (mi/siRNAs).

Cell Division Patterns in the Peristomial Layers of the Moss Genus Two Hypotheses and a Third Solution.

The Chilean endemic genus belongs to the Gigaspermaceae, one of the most basal groups of arthrodontous mosses. While none of the species in this family has a peristome, earlier stages of sporophyte development often disclose its basic structure. The study of sporophytes at the early stages of development was conducted to identify possible similarities with , the genus sister to Gigaspermaceae plus all other arthrodontous mosses in the moss phylogenetic tree.

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG.

Background & Aims: Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms.

Methods: We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016.

Epstein-Barr virus-associated gastric cancer: disease that requires special approach.

Epstein-Barr virus-associated gastric cancer [EBV-associated GC, EBV( +) GC] is a distinct molecular subtype of gastrointestinal (GI) cancers. It accounts for up to 10% of all molecular subtypes of gastric cancer (GC). It has unique genetic and epigenetic features, which determine its definitive phenotype with male and younger age predominance, proximal stomach localization, and diffuse adenocarcinoma histology.