Short-run Economic Assessment of the Transportation Recovery Policy After an Earthquake

This paper develops a short-run economic damage assessment model. The model contains two sub models. One is the conventional traffic assignment model, which calculates traveling time under the damaged transportation infrastructure. The other is the economic damage assessment model, which determines the decrease in production level in the short run. This method facilitates the identification of critical infrastructure that could reduce the economic damage when the disaster occurs. As a case study, we applied this model to several recovery plans for transport facilities. The results suggest that the proposed comprehensive model should be considered as a prevention plan

Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction

心房細動の遺伝的基盤を解明 --大規模ゲノムデータによる病態解明と遺伝的リスクスコア構築--. 京都大学プレスリリース. 2023-01-20.Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9, 826 cases among 150, 272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77, 690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications

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

Short-run Economic Assessment of the Transportation Recovery Policy After an Earthquake

This paper develops a short-run economic damage assessment model. The model contains two sub models. One is the conventional traffic assignment model, which calculates traveling time under the damaged transportation infrastructure. The other is the economic damage assessment model, which determines the decrease in production level in the short run. This method facilitates the identification of critical infrastructure that could reduce the economic damage when the disaster occurs. As a case study, we applied this model to several recovery plans for transport facilities. The results suggest that the proposed comprehensive model should be considered as a prevention plan

Risk Factor Analysis of Proximal Junctional Kyphosis after Surgical Treatment of Adult Spinal Deformity with Oblique Lateral Interbody Fusion

Study Design: A single-center retrospective study. Purpose: To investigate the prevalence of proximal junctional kyphosis (PJK) and its risk factors after surgical treatment of adult spinal deformity (ASD) with oblique lateral interbody fusion (OLIF). Overview of Literature: Correction of ASD using OLIF has been developed because it is less invasive, and enables correction of severe deformities. Although PJK is a well-recognized complication after the correction of spinal deformity, few studies have evaluated the prevalence and risk factors for PJK after OLIF for ASD. Methods: We reviewed 74 patients who underwent surgery for ASD. PJK was defined as a proximal junction sagittal Cobb angle exceeding 10 degrees, and at least 10 degrees greater than the preoperative measurement. We investigated the following as risk factors: age, sex, body mass index, medical history, number of fused segments, number of interbody fusions, number of OLIFs, number of osteotomies, level of upper instrumented vertebrae, lowest instrumented vertebrae, and radiographic parameters. Results: The mean follow-up duration was 22.4 months and the mean age of the patients was 73.6 years. PJK was present in 19/74 patients (25.7%) and absent in 55/74 (74.3%). In the univariate analysis, those with PJK had a significantly higher proportion of patients with a history of vertebral compression fracture (7/19 patients [36.8%] vs. 6/55 patients [10.9%], p=0.027). Those with PJK had a significantly higher proportion of patients with fusion to the pelvis (18/19 patients [94.7%] vs. 34/55 patients [61.8%], p=0.016). According to the multivariate analysis, fusion to the pelvis was a significant risk factor for PJK. Conclusions: Fusion to the pelvis was the most important risk factor for PJK. A history of vertebral compression fracture served as an additional risk factor for PJK. Clinicians should consider these factors before treating ASD patients with OLIF

Comparison of Outcomes of Oblique Lateral Interbody Fusion with Percutaneous Posterior Fixation in Lateral Position and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis

Study Design: Single-center retrospective study. Purpose: To compare the physical function and quality of life (QOL) parameters of two minimally invasive surgical (MIS) procedures: oblique lateral interbody fusion with percutaneous posterior fixation in lateral position (OLIF-LPF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for single-level degenerative spondylolisthesis (DS). Overview of Literature: To date, many options for the surgical treatment of lumbar DS and reports have described the effectiveness of minimally invasive lateral access surgery and MIS-TLIF. However, there is still a paucity of comparative data regarding the physical function and QOL outcomes of OLIF and MIS-TLIF. Methods: Eighty-six patients were enrolled in this study (group O: OLIF-LPF, n=38; group T: MIS-TLIF, n=48). We evaluated the operation time, estimated blood loss (EBL), postoperative laboratory data, preoperative and postoperative radiographic parameters, overall functional outcome with the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) effectiveness rate, and Visual Analog Scale (VAS) score for low back pain, leg pain, and leg numbness. Results: No statistical differences in operation time, EBL, and C-reactive protein level, 5 days postoperatively, between groups O and T. With respect to radiological outcome, preoperative and postoperative disc height change was significantly greater in group O than in group T (3.8 vs. 1.8 mm, p<0.05). Both groups showed postoperative improvements in the clinical outcome scores of all JOABPEQ domains, but the effectiveness rate increase in the psychological domain was significantly higher in group O than in group T (47.1% vs. 14.6%, p<0.05). No differences in the preoperative and postoperative VAS score change were noted between the two groups in any of the items. Conclusions: The changes in physical function and QOL parameters after OLIF-LPF and MIS-TLIF were almost equivalent; however, OLIF-LPF had significant superiority in the psychological domain