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Let F=≺F,R≻ be a finite Kripke frame.Acongruence of F is a bisimulation of F that is also an equivalence relation on F. The set of all congruences of F is a lattice under the inclusion ordering. In this article, we investigate this lattice in the case that F is a finite line frame. We give concrete descriptions of the join and meet of two congruences with a non-trivial upper bound. Through these descriptions we show that for every non-trivial congruence ρ, the interval [IdF,ρ] embeds into the lattice of divisors of a suitable positive integer.We also prove that any two congruences with a non-trivial upper bound permute. [ABSTRACT FROM AUTHOR]

Biomarkers that are clinically useful for the diagnosis and treatment of schizophrenia are lacking. Biomarkers are critical tools that reduce the incidence of misdiagnosis, identify subgroups of patients, assist in the proper characterization of patient phenotypes, predict response to treatment or the development of side effects, and can serve as targets for novel therapeutic interventions. In this study, we evaluated small (< 200 nucleotide) and long (> 200 nucleotide) RNAs found in extracellular vesicles (EVs) isolated from the cerebrospinal fluid (CSF) and plasma of individuals with schizophrenia spectrum disorders (SSD) and healthy volunteers (HV). As EVs carry cargo from all tissues in the body, they act as a potential proxy for the tissue of origin, including cells from the brain. We compared the transcriptomic features of EVs from these two biofluids and examined their ability to discriminate between SSD and HV participants, identifying a total of 141 differentially expressed genes, some of which have been previously associated with SSD. Next, we evaluated the potential cell-types that give rise to the SSD-associated CSF RNA cargo, and found the majority were predominantly expressed in excitatory neurons. Our results highlight the potential of EVs as both a source of schizophrenia relevant biomarkers, and molecular insight into disease mechanisms.

Diagnosing, selecting therapy for, and monitoring cancer in patients using a minimally invasive blood test represents a significant advance in precision medicine. Wide variability exists in how circulating tumor DNA (ctDNA) assays are developed, validated, and reported in the literature, which hinders clinical adoption and may negatively impact patient care. Standardization is needed for factors affecting ctDNA assay performance and reporting, including pre-analytical variables, analytical considerations, and elements of laboratory assay reporting. The Association for Molecular Pathology Clinical Practice Committee's Liquid Biopsy Working Group (LBxWG), including organizational representation from the American Society of Clinical Oncology and the College of American Pathologists, has undertaken a full-text data extraction of 1228 ctDNA publications that describe assays performed in patients with lymphoma and solid tumor malignancies. With an emphasis on clinical assay validation, the LBxWG has developed a set of 13 best practice consensus recommendations for validating, reporting, and publishing clinical ctDNA assays. Recommendations include reporting key pre-analytical considerations and assay performance metrics; this analysis demonstrates these elements are inconsistently included in publications. The LBxWG recommendations are intended to assist clinical laboratories with validating and reporting ctDNA assays and to ensure high-quality data are included in publications. It is expected that these recommendations will need to be updated as the body of literature continues to mature., Competing Interests: Disclosure Statement C.M.L.’s spouse is an employee of Bayer. C.D.G. is an officer and director of OncoMEDx, Inc., and serves on the Board of Directors of GOAL Consortium. J.R. is an employee of Invitae and holds restricted stock units that were given as part of J.R.’s employment benefits. K.M.R. has participated in projects that received funding from GSK and Abbott but has not been the principal investigator on these projects. L.J.T. is an employee of Dartmouth Health, serves on College of American Pathologists’ Molecular Oncology Committee, and holds personal stocks in GSK and BioNTech. A.M.T. has received clinical trial research funding through the institution from OBI Pharma USA Inc., Agenus, Parker Institute for Cancer Immunotherapy, Tempus, Tvardi, and IMMATICS, and has a consulting or advisory role at Vincerx, Diaccurate, BrYet, NEX-I, MacroGenics, and BioEclipse. The remaining authors have declared no related conflicts of interest., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

CIViC (Clinical Interpretation of Variants in Cancer; civicdb.org) is a crowd-sourced, public domain knowledgebase composed of literature-derived evidence characterizing the clinical utility of cancer variants. As clinical sequencing becomes more prevalent in cancer management, the need for cancer variant interpretation has grown beyond the capability of any single institution. CIViC contains peer-reviewed, published literature curated and expertly-moderated into structured data units (Evidence Items) that can be accessed globally and in real time, reducing barriers to clinical variant knowledge sharing. We have extended CIViC's functionality to support emergent variant interpretation guidelines, increase interoperability with other variant resources, and promote widespread dissemination of structured curated data. To support the full breadth of variant interpretation from basic to translational, including integration of somatic and germline variant knowledge and inference of drug response, we have enabled curation of three new Evidence Types (Predisposing, Oncogenic and Functional). The growing CIViC knowledgebase has over 300 contributors and distributes clinically-relevant cancer variant data currently representing >3200 variants in >470 genes from >3100 publications., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Comprehensive characterization of somatic genomic alterations has led to fundamental shifts in our understanding of tumor biology. In clinical practice, these studies can lead to modifications of diagnosis and/or specific treatment implications, fulfilling the promise of personalized medicine. Herein, we describe a 78-yr-old woman under surveillance for long-standing untreated chronic lymphocytic leukemia (CLL). Molecular studies from a peripheral blood specimen revealed a TP53 p.V157F mutation, whereas karyotype and fluorescence in situ hybridization (FISH) identified a 17p deletion, trisomy 12, and no evidence of IGH-CCND1 rearrangement. Positron emission tomography-computed tomography scan identified multistation intra-abdominal lymphadenopathy and a pulmonary nodule, and subsequent pulmonary wedge resection confirmed the presence of a concurrent lung adenocarcinoma. Targeted next-generation sequencing of the lung tumor identified an EGFR in-frame exon 19 deletion, two TP53 mutations (p.P152Q, p.V157F), and, unexpectedly, a IGH-CCND1 rearrangement. Follow-up immunohistochemistry (IHC) studies demonstrated a cyclin D1-positive lymphoid aggregate within the lung adenocarcinoma. The presence of the TP53 p.V157F mutation in the lung resection, detection of an IGH-CCND1 rearrangement, and cyclin D1 positivity by IHC led to revision of the patient's hematologic diagnosis and confirmed the extranodal presence of mantle cell lymphoma within the lung mass, thus representing a "tumor in tumor." Manual review of the sequencing data suggested the IGH-CCND1 rearrangement occurred via an insertional event, whose size precluded detection by original FISH studies. Thus, routine imaging for this patient's known hematologic malignancy led to detection of an unexpected solid tumor, whose subsequent precision medicine studies in the solid tumor redefined the original hematological diagnosis., (© 2021 Terraf et al.; Published by Cold Spring Harbor Laboratory Press.)

Chromosome 1q41-q42 deletions have recently been associated with a recognizable neurodevelopmental syndrome of early childhood (OMIM 612530). Within this group, a predominant phenotype of developmental delay (DD), intellectual disability (ID), epilepsy, distinct dysmorphology, and brain anomalies on magnetic resonance imaging/computed tomography has emerged. Previous reports of patients with de novo deletions at 1q41-q42 have led to the identification of an evolving smallest region of overlap which has included several potentially causal genes including DISP1, TP53BP2, and FBXO28. In a recent report, a cohort of patients with de novo mutations in WDR26 was described that shared many of the clinical features originally described in the 1q41-q42 microdeletion syndrome (MDS). Here, we describe a novel germline FBXO28 frameshift mutation in a 3-year-old girl with intractable epilepsy, ID, DD, and other features which overlap those of the 1q41-q42 MDS. Through a familial whole-exome sequencing study, we identified a de novo FBXO28 c.972&#95;973delACinsG (p.Arg325GlufsX3) frameshift mutation in the proband. The frameshift and resulting premature nonsense mutation have not been reported in any genomic database. This child does not have a large 1q41-q42 deletion, nor does she harbor a WDR26 mutation. Our case joins a previously reported patient also in whom FBXO28 was affected but WDR26 was not. These findings support the idea that FBXO28 is a monogenic disease gene and contributes to the complex neurodevelopmental phenotype of the 1q41-q42 gene deletion syndrome., (© 2018 Wiley Periodicals, Inc.)

Due to pluripotency of embryonic stem (ES) cells, these cells are an invaluable in vitro model that investigates the influence of different physical and chemical cues on differentiation/development pathway of specialized cells. We sought the effect of roughness and alignment, as topomorpholocial properties of scaffolds on differentiation of green fluorescent protein-expressing ES (GFP-ES) cells into three germ layers derivates simultaneously. Furthermore, the effect of Matrigel as a natural extracellular matrix in combination with poly(lactic-co-glycolic acid) (PLGA) nanofibrous scaffolds on differentiation of mouse ES cells has been investigated. The PLGA nanofibrous scaffolds with different height and distribution of roughness and alignments were fabricated. Then, the different cell differentiation fats of GFP-ES cells plated on PLGA and PLGA/Matrigel scaffolds were analyzed by gene expression profiling. The findings demonstrated that distinct ranges of roughness, height, and distribution can support/promote a specific cell differentiation fate on scaffolds. Coating of scaffolds with Matrigel has a synergistic effect in differentiation of mesoderm-derived cells and germ cells from ES cells, whereas it inhibits the derivation of endodermal cell lineages. It was concluded that the topomorpholocial cues such as roughness and alignment should be considered in addition to other scaffolds properties to design an efficient electrospun scaffold for specific tissue engineering.