The N400event-related potential in aphasia

Although the N400 component of event-related potentials (ERPs) is suggested to reflect language processing, exactly which language processing functions N400 is sensitive to is not clear. We investigated this component in aphasic patients with some impairments of language processing. Meaningful and meaningless words in Kana (Japanese characters) were used as stimuli under a visual oddball paradigm. Increases in N400 latency and amplitude in the aphasic group were significant in comparison with the control group. In the aphasic group, N400 latency correlated significantly with the performance intelligence quotient employed besides language quotients. Moreover, the N400effects were seen more clearly in the left hemisphere than in the right hemisphere for both groups. We propose that the abnormal variations in amplitude or latency of N400 in the aphasic group reflect language processing functions (controlled processing and automatic processing) that are different between slight and severe cases of aphasia. Moreover, N400 effects are sensitive to intellectual abilities besides language ability. We also suggest that N400 effects in the left hemisphere for the aphasic group are a reflection of active language processing as the substitution function

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Magnifying endoscope with NBI to predict the depth of invasion in laryngo-pharyngeal cancer.

[Objectives/Hypothesis]To examine if macroscopic classification with a magnifying gastrointestinal endoscope with narrow band imaging (ME-NBI) is useful in predicting pathological depth of tumor invasion in laryngo-pharyngeal cancer. [Study Design]Retrospective study. [Methods]Preoperative endoscopy reports and postoperative pathological reports on 139 laryngo-pharyngeal cancer lesions were retrospectively reviewed, and the association between macroscopic findings in the lesions and the depth of tumor invasion was analyzed statistically. [Results]The ratios of lesions macroscopically classified as 0-I (superficial and protruding), 0-IIa (slightly elevated), 0-IIb (true flat), 0-IIc (slightly depressed), and 0-III (superficial and excavated) in the preoperative endoscopy reports were 3%, 25%, 71%, 1%, and 0%, respectively. Regarding the depth of tumor invasion in the postoperative pathological reports, the ratios of lesions classified as EP (carcinoma in situ), SEP (tumor invades subepithelial layer), and MP (tumor invades muscularis propria) were 73%, 26%, and 1%, respectively. The ratios of subepithelial invasion or muscular invasion in 0-I, 0-IIa, and 0-IIb were 100%, 54%, and 14%, respectively, and showed significant difference (P < 0.0001). Only one of 139 lesions invaded the muscular propria. [Conclusions]This study is the first one to show that macroscopic findings by ME-NBI predict the depth of tumor invasion in superficial laryngo-pharyngeal cancer. It was indicated that there is a little chance of muscular invasion if the lesion is endoscopically diagnosed as 0-I or 0-II. A new T stage classification based on the depth of tumor invasion may be needed in order to adapt the classification to include transoral surgery

Narrow-band imaging for the head and neck region and the upper gastrointestinal tract.

Endoscopy is essential for the diagnosis and treatment of cancers derived from the gastrointestinal tract. However, a conventional white-light image has technical limitations in detecting small or superficial lesions. Narrow-band imaging, especially with magnification, allows visualization of microstructure patterns and microvascular patterns on the mucosal surface. These technical breakthroughs enable endoscopists to easily detect small pre-neoplastic and neoplastic lesions and to make a differential diagnosis of these lesions. Appropriate diagnosis with narrow-band imaging contributes to minimally invasive endoscopic resection

Efficacy of preventive endoscopic balloon dilation for esophageal stricture after endoscopic resection.

We earlier reported that mucosal defect involving over three-fourths of the circumference of the esophagus after endoscopic mucosal resection (EMR) is a risk factor for the development of the stricture. Although endoscopic balloon dilation (EBD) is a useful procedure to relieve the stricture, there is no standard strategy for preventing development of the stricture. The aim of this study was to evaluate the efficacy and the safety of preventive EBD