Development of pericardial fat count images using a combination of three different deep-learning models

Rationale and Objectives: Pericardial fat (PF), the thoracic visceral fat surrounding the heart, promotes the development of coronary artery disease by inducing inflammation of the coronary arteries. For evaluating PF, this study aimed to generate pericardial fat count images (PFCIs) from chest radiographs (CXRs) using a dedicated deep-learning model. Materials and Methods: The data of 269 consecutive patients who underwent coronary computed tomography (CT) were reviewed. Patients with metal implants, pleural effusion, history of thoracic surgery, or that of malignancy were excluded. Thus, the data of 191 patients were used. PFCIs were generated from the projection of three-dimensional CT images, where fat accumulation was represented by a high pixel value. Three different deep-learning models, including CycleGAN, were combined in the proposed method to generate PFCIs from CXRs. A single CycleGAN-based model was used to generate PFCIs from CXRs for comparison with the proposed method. To evaluate the image quality of the generated PFCIs, structural similarity index measure (SSIM), mean squared error (MSE), and mean absolute error (MAE) of (i) the PFCI generated using the proposed method and (ii) the PFCI generated using the single model were compared. Results: The mean SSIM, MSE, and MAE were as follows: 0.856, 0.0128, and 0.0357, respectively, for the proposed model; and 0.762, 0.0198, and 0.0504, respectively, for the single CycleGAN-based model. Conclusion: PFCIs generated from CXRs with the proposed model showed better performance than those with the single model. PFCI evaluation without CT may be possible with the proposed method

Recommendations related to the analytical equivalence assessment of gene panel testing

Advances in cancer genome care over the past few years have included the development of gene panel testing for various biomarkers. This article summarizes issues and provides recommendations related to analytical performance evaluations for new oncology gene panels. The scope of these recommendations includes comprehensive genomic profiling assays related to gene panel testing that uses histological or serum specimens to detect gene mutations. As a research project of the Japan Agency for Medical Research and Development Research on Regulatory Science of Pharmaceuticals and Medical Devices, we convened the working group committee that consisted of more than 30 experts from academia, industry, and government. We have discussed the points that should be considered to allow maximal simplification of assessments using clinical specimens in evaluating accuracy and limit of detection in equivalence and analytical performance for three years. We provide recommendations specific to each type of gene mutation as well as to reference standards or specimens used for evaluations. In addition, in order to facilitate the discussion on the analytical performance of gene panel tests by multidisciplinary tumor boards of hospitals, the present recommendations also describe the items that companies are expected to provide information on in their packaging inserts and reports, and the items that are expected to be discussed by multidisciplinary tumor boards. Our working group document will be important for participants in multidisciplinary tumor boards including medical oncologists and genome scientists, and developers of gene panels not only in Japan but also in other countries

Model experiment of magnetic field amplification in laser-produced plasmas via the Richtmyer-Meshkov instability

A model experiment of magnetic field amplification (MFA) via the Richtmyer-Meshkov instability (RMI) in supernova remnants (SNRs) was performed using a high-power laser. In order to account for very-fast acceleration of cosmic rays observed in SNRs, it is considered that the magnetic field has to be amplified by orders of magnitude from its background level. A possible mechanism for the MFA in SNRs is stretching and mixing of the magnetic field via the RMI when shock waves pass through dense molecular clouds in interstellar media. In order to model the astrophysical phenomenon in laboratories, there are three necessary factors for the RMI to be operative: a shock wave, an external magnetic field, and density inhomogeneity. By irradiating a double-foil target with several laser beams with focal spot displacement under influence of an external magnetic field, shock waves were excited and passed through the density inhomogeneity. Radiative hydrodynamic simulations show that the RMI evolves as the density inhomogeneity is shocked, resulting in higher MFA

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

Volcanic ash in dirt layers from the Allan Hills bare ice area in Victoria Land, Antarctica

Dirt layers were found in the Allan Hills bare ice area in Victoria Land, Antarctica. They contain volcanic ash consisting of abundant glass shards with subordinate crystal fragments of plagioclase, titanaugite, olivine, kaersutite, titanomagnetite, etc. Tephra samples collected from each of 8 dirt layers are classified into three groups based on the petrography, morphology and major element chemistry. Moreover, the major element chemistry of the glass shards indicates that these tephras comprise two rock series : one is evolved basanitoid series toward nephelinite, and the other basanitoid-trachybasalt-trachyte series. Accordingly, these tephras may have been derived from at least two different volcanoes. If the tephra sources are restricted to two volcanoes, the transportation distance of the tephras estimated from their grain size is less than 1000km. This estimation suggests that the tephra sources are restricted within Victoria Land. The tephras of basanitoid-trachybasalt-trachyte are similar in composition to some of the lavas of Quaternary volcanoes in Victoria Land. However, the tephras of the evolved basanitoid are different in composition from any Quaternary volcanic rocks hitherto reported from Antarctica. It will probably be confirmed in the future that some volcanoes in Victoria Land erupted such basanitoid ejecta

Regional difference of attenuation of radio waves within Antarctic ice sheet

The attenuation of radio waves within the ice sheet is caused by absorption loss due to dielectric and electric properties of ice and geometric loss due to spreading of radio waves. The dielectric structure of the ice sheet can be derived by estimating the attenuation. This estimation is useful for the design of the future radio echo sounder. The inland traverse party of the 23rd Japanese Antarctic Research Expedition in 1982 measured an ice thickness by radio echo sounding which operated on 60MHz. Calculations of the attenuation rate of radio waves were made by reading the rate of decrease of the strength of internal echoes on the photographs of the A-scope display records. Values of the attenuation coefficient (dB/100m) in the present study change between about 1.2 and about 3,and become smaller with increase of surface elevation of the ice sheet. But the attenuation coefficient in the bare ice field, the Meteorite Ice Field, around the Yamato Mountains is remarkably high. The regional difference of the attenuation coefficient is caused mainly by the temperature distribution with depth in the ice sheet. But it is considered that the high value of the effective attenuation coefficient in the bare ice field is due to not only different temperature distribution but also different dielectric properties of the bare ice