ER, PgR, Ki67, p27Kip1, and histological grade as predictors of pathological complete response in patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy using taxanes followed by fluorouracil, epirubicin, and cyclophosphamide concomitant with trastuzumab

Patient and tumor characteristics at baseline. (PDF 6 kb

Binary systems and their nuclear explosions

Peer ReviewedPreprin

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

Changes in Income Distribution and Labor Market under the "Growth and Crisis" in Thailand

Abstract: Thailand experienced high economic growth and severe economic crisis during these 10 years. In this period structural shifts both in economic and labor markets have been taken place with the change of income distribution. Using 13 years of Socio Economic Survey Data, this paper examines the impact of the crisis on changes in labor market and income distribution

Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis: Stage 1

In seronegative arthritis with extremity edema, the differential diagnosis between remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) and seronegative rheumatoid arthritis (SNRA) is difficult. We compared the clinical characteristics of RS3PE and SNRA and those of such patients with and without malignancies. We retrospectively examined patients diagnosed with RS3PE (McCarty criteria) and SNRA at our hospital in 2007–2020. Malignancy was diagnosed within 2 years before or after RS3PE or SNRA diagnosis. Overall, 24 RS3PE and 124 SNRA patients were enrolled. The mean ages were 79.0 and 66.5 years, and men comprised 54.2% and 37.1% of RS3PE and SNRA patients, respectively. RS3PE patients had higher inflammation levels (p p p p = 0.02). Overall, odds ratios (ORs) for malignancy were higher for older age (OR 1.06, p = 0.04), male sex (OR 4.34, p = 0.02), RS3PE patients (OR 4.83, p = 0.01), and patients with extremity edema (OR 4.83, p = 0.01). RS3PE patients had higher inflammation levels and associated factors of malignancy than SNRA patients. Patients who are older, male, with extremity edema, or with RS3PE should be screened for malignancies

Comparing the Clinical and Laboratory Features of Remitting Seronegative Symmetrical Synovitis with Pitting Edema and Seronegative Rheumatoid Arthritis

In seronegative arthritis with extremity edema, it is difficult to differentiate between remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) and seronegative rheumatoid arthritis (SNRA). We compared the clinical characteristics of RS3PE and SNRA in patients with and without malignancies. We retrospectively examined patients diagnosed with RS3PE (McCarty criteria) and SNRA at our hospital in 2007–2020. Malignancy was diagnosed within 2 years before or after RS3PE or SNRA diagnosis. Overall, 24 RS3PE and 124 SNRA patients were enrolled. The median ages were 79.5 and 68.5 years, and men comprised 54.2% and 37.1% of RS3PE and SNRA patients, respectively. RS3PE patients had higher inflammation levels (p = 0.004) and more incidences of malignancy (p = 0.034). Matching for age and sex, RS3PE patients had higher inflammation levels (p = 0.021) and more incidences of malignancy (p = 0.005). Overall, odds ratios (ORs) for malignancy were higher for older age (OR 1.06, p = 0.037), male sex (OR 4.34, p = 0.007), RS3PE patients (OR 4.83, p = 0.034), and patients with extremity edema (OR 4.83, p = 0.034). Inflammation levels and associated factors of malignancy were higher in RS3PE patients than in SNRA patients. Patients who are older, male, with extremity edema, or had RS3PE should be screened for malignancies