Prognostic Value of Combined Tumor Marker and Controlling Nutritional Status (CONUT) Score in Colorectal Cancer Patients

[Background] Nutritional status is strongly associated with prognosis in cancer patients. Controlling Nutritional Status (CONUT) score is a nutritional marker based on serum albumin, cholesterol, and total lymphocyte count. We investigated the prognostic significance of a combination of the tumor marker carcinoembryonic antigen (CEA) and CONUT score (T-CONUT) in colorectal cancer (CRC) patients. [Methods] A total of 522 patients who underwent surgery for CRC at our hospital were retrospectively enrolled in this study. [Results] Patients were divided into groups based on the results of receiver operating characteristic (ROC) curve analysis as follows: CONUThigh (CONUT score ? 3) and CONUTlow (CONUT score < 3), and CEAlow (< 5 ng/mL) and CEAhigh (? 5 ng/mL). The 5-year overall survival (OS) rates of patients in the CONUTlow and CONUThigh groups were 76.0% and 53.9%, respectively (P < 0.0001), and in the CEAlow and CEAhigh groups were 80.7% and 47.6%, respectively (P < 0.0001). Regarding T-CONUT, the 5-year OS rates of patients with CEAlow/CONUTlow, CEAlow/CONUThigh, CEAhigh/CONUTlow, and CEAhigh/CONUThigh were 84.7%, 69%, 55.3%, and 36.1%, respectively (P < 0.0001). Multivariate analysis identified T-CONUT score as an independent prognostic indicator in CRC patients. [Conclusion] T-CONUT may be a useful tool for predicting prognosis in CRC patients

Honeycomb-Layered Oxides With Silver Atom Bilayers and Emergence of Non-Abelian SU(2) Interactions

Honeycomb-layered oxides with monovalent or divalent, monolayered cationic lattices generally exhibit myriad crystalline features encompassing rich electrochemistry, geometries, and disorders, which particularly places them as attractive material candidates for next-generation energy storage applications. Herein, global honeycomb-layered oxide compositions, Ag2M2TeO6 ((Formula presented.).) exhibiting (Formula presented.) atom bilayers with sub-valent states within Ag-rich crystalline domains of Ag6M2TeO6 and (Formula presented.) -deficient domains of (Formula presented.) ((Formula presented.)). The (Formula presented.) -rich material characterized by aberration-corrected transmission electron microscopy reveals local atomic structural disorders characterized by aperiodic stacking and incoherency in the bilayer arrangement of (Formula presented.) atoms. Meanwhile, the global material not only displays high ionic conductivity but also manifests oxygen-hole electrochemistry during silver-ion extraction. Within the (Formula presented.) -rich domains, the bilayered structure, argentophilic interactions therein and the expected (Formula presented.) sub-valent states ((Formula presented.), etc.) are theoretically understood via spontaneous symmetry breaking of SU(2) 7 U(1) gauge symmetry interactions amongst 3 degenerate mass-less chiral fermion states, justified by electron occupancy of silver (Formula presented.) and 5s orbitals on a bifurcated honeycomb lattice. This implies that bilayered frameworks have research applications that go beyond the confines of energy storage

RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS

Repulsive guidance molecule A (RGMa) was originally identified as a neuronal growth cone–collapsing factor. Previous reports have demonstrated the multifunctional roles of RGMa mediated by neogenin1. However, the pathogenic involvement of RGMa in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we demonstrated that RGMa concentration was elevated in the cerebrospinal fluid of both patients with ALS and transgenic mice overexpressing the mutant human superoxide dismutase1 (mSOD1 mice). Treatment with humanized anti-RGMa monoclonal antibody ameliorated the clinical symptoms in mSOD1 mice. Histochemical analysis revealed that the anti-RGMa antibody significantly decreased mutant SOD1 protein accumulation in the motor neurons of mSOD1 mice via inhibition of actin depolymerization. In vitro analysis revealed that the anti-RGMa antibody inhibited the cellular uptake of the mutant SOD1 protein, presumably by reinforcing the neuronal actin barrier. Collectively, these data suggest that RGMa leads to the collapse of the neuronal actin barrier and promotes aberrant protein deposition, resulting in exacerbation of the ALS pathology.Shimizu Mikito, Shiraishi Naoyuki, Tada Satoru, et al. RGMa collapses the neuronal actin barrier against disease-implicated protein and exacerbates ALS. Science Advances 9, 686 (2023); https://doi.org/10.1126/sciadv.adg3193

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Interactive Music Recommendation System for Adapting Personal Affection: IMRAPA

Part 11: PostersInternational audienceWe have so various types of entertainment, and music is one of the most popular one. In this paper, we proposed music recommendation system that interactively adapts a user’s personal affection with only a simple operation, in which both acoustic and meta features are used. The more a user uses the proposed system, the better the system adapts the user’s personal affection and recommends the suitable songs. Through the evaluational experiment, we confirmed that the proposed system could recommend songs adapting user’s personal affection even if the personal affection variated