Relationship between the dose titration and adherence of mirogabalin in patients with peripheral neuropathic pain depending on renal function: a nationwide electronic medical record database study

[Background] Mirogabalin has been attracting attention for treating peripheral neuropathic pain. The package insert recommends that mirogabalin should be titrated depending on renal function. Here, we investigated the relationship between dose titration patterns and adherence, and persistence of mirogabalin treatment. [Research design and methods] Peripheral neuropathic pain patients who initiated mirogabalin between March 2020 and May 2021 were identified using an electronic medical record database. The dose titration pattern was described according to degrees of renal function. Regression analyses were performed to compare adherence and persistence between the patients with and without titration. [Results] Of the 4, 138 identified patients, 1, 696 (41.0%) titrated the dose within 45 days and were more adherent than those without titration (Adjusted odds ratio: 1.75, 95% CI 1.21, 2.54). Of the total 952 patients with renal function parameters, 229 (24.1%) titrated to the effective dose within 45 days and were less likely to discontinue than those without titration (Adjusted hazard ratio: 0.57, 95% CI 0.40, 0.81). [Conclusion] Mirogabalin dose titration was associated with better adherence and persistence. It is important for mirogabalin treatment to determine the initial prescription dose based on renal function and subsequent dose titration according to the package insert. [Trial registration] UMIN00004731

A Galaxy Merger Scenario for the NGC 1550 Galaxy from Metal Distributions in the X-ray Emitting Plasma

The elliptical galaxy NGC 1550 at a redshift of $z=0.01239$, identified with an extended X-ray source RX J0419+0225, was observed with {\it XMM-Newton} for 31 ks. From the X-ray data and archival near infra-red data of Two Micron All Sky survay, we derive the profiles of components constituting the NGC 1550 system; the gas mass, total mass, metal mass, and galaxy luminosity. The metals (oxygen, silicon, and iron) are extended to $\sim 200$ kpc from the center, wherein $\sim$ 70% of the $K$-band luminosity is carried by NGC 1550 itself. As first revealed with {\it ASCA}, the data reconfirms the presence of a dark halo, of which the mass ($1.6 \times 10^{13} M_{\odot}$) is typical of a galaxy group rather than of a single galaxy. Within 210 kpc, the $K$-band mass-to-light ratio reaches $75 M_{\odot}/L_{\odot}$, which is comparable to those of clusters of galaxies. The iron-mass-to-light ratio profile (silicon- and oxygen mass-to-light ratio profiles as well) exhibits about two orders of magnitude decrease toward the center. Further studies comparing mass densities of metals with those of the other cluster components reveal that the iron (as well as silicon) in the ICM traces very well the total gravitating mass, whereas the stellar component is significantly more concentrated to within several tens kpc of the NGC 1550 nucleus. Thus, in the central region, the amount of metals is significantly depleted for the luminous galaxy light. Among a few possible explanations of this effect, the most likely scenario is that galaxies in this system were initially much more extended than today, and gradually fell to the center and merged into NGC 1550.Comment: 31 pages, 10 figures, 2 table

Geographical Contents in Primary School : An Analysis of the English Geography Textbook “Collins Primary Geography”

In this study, we have analyzed the English geography textbook “Collins Primary Geography”, in order to clarify the characteristics of geographical contents in primary school. Results of this study are as follows: age (grade)-appropriate teaching through different process of leaning (awareness, understanding, cognition and value judgement) and physical, human, environmental geography and topography as a content. However, there are no contents across physical and human geography, one of the features of geography, in the textbook.本稿は，2016年度前期開講の地理認識内容学特講（由井担当）の一部をもとに，加筆・修正を加えたものである

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

Binding Refinement for Multiplexer Reduction

In behavioral synthesis for resource shared architecture, multiplexers are inserted between registers and functional units as a result of binding if necessary. Multiplexer optimization in binding is important for performance, area and power of a synthesized circuit. In this paper, we propose a binding algorithm to reduce total amount of multiplexer ports. Unlike most of the previous works in which binding is performed by a constructive algorithm, our approach is based on an iterative improvement algorithm. Starting point of our approach is initial functional unit binding and initial register binding. Both functional unit binding and register binding are modified by local improvements based on taboo search iteratively. The binding in each iteration is feasible, hence actual value of total amount of multiplexer ports can be optimized. The smart neighborhood which considers an effect of sharing of connection is used in the proposed method for effective reduction of total amount of multiplexer ports. Additionally, the massive modification of binding is performed by regular intervals to achieve a further reduction of total amount of multiplexer ports and further robustness for an initial binding. Experimental results show that our approach can reduce total amount of multiplexer ports by 30% on an average compared to a traditional binding algorithm with computation time of several seconds to a few minutes. Also, results of robustness evaluation show that our approach barely depends on initial binding

Improvement Technique of Binding for Multiplexer Reduction

リソース共有型の動作合成では，バインディングの結果としてレジスタや演算器の入力側に必要に応じてマルチプレクサが挿入される．マルチプレクサは合成結果の回路の性能低下や面積増大の原因となるため，バインディングにおいて発生するマルチプレクサは少ないほうが望ましい．本論文では，マルチプレクサの総入力数削減を目的としたバインディング改善手法を提案する．提案手法は，適当な演算器バインディングおよびレジスタバインディングを初期解として，タブーサーチをベースとした局所改善によって演算器バインディングおよびレジスタバインディングの変更を反復して行なう．実験の結果，提案手法はマルチプレクサの総入力数を既存研究に対して平均で約 30％削減することが可能であり，計算時間は数秒から数分であった．In Behavioral Synthesis for resource shared architecture, multiplexers are inserted between registers and functional units as a result of binding if necessary. Multiplexer optimization in binding is important for performance and area of synthesized circuit. In this paper, we propose an improvement technique of binding to reduce total amount of multiplexer ports. In our approach, starting point is initial register binding and initial functional unit binding. Both functional unit binging and register binding are modified by local improvements based on taboo search iteratively. Experimental results show that our approach is able to reduce total amount of multiplexer ports by 30％ on an average compared to a traditional binding algorithm. Computation time of our approach is several seconds to a few minutes

Area Optimized Pipeline Scheduling with Initiation Interval and Allocation Constraints

本稿では，パイプライン回路を対象とした動作合成における，スループット制約下での回路の総面積最小化を目的としたパイプラインスケジューリング手法を提案する．既存手法の多くがリソース制約とイニシエーション・インターバルの制約下でパイプラインスケジューリングを行うのに対して，提案手法ではアロケーションとイニシエーション・インターバルの制約下でパイプラインスケジューリングを行う．そのため，リソース制約が原因となって実行可能解が得られないという問題が発生しない．また，各演算を割り当て可能なクロックサイクルがリソース制約によって制限されないため，各種の演算器の面積とレジスタの面積を考慮し，回路の総面積が小さくなるようにパイプラインスケジューリングを行うことが可能である．実験の結果，提案手法は既存手法に対して回路の総面積を平均で約30%削減し，実行時間も実用の範囲内であった．In this paper, a pipeline scheduling algorithm for minimizing total circuit area under throughput constraint is presented for behavioral synthesis targeted for pipelined circuit. While most previous works perform pipeline scheduling with constraints of initiation interval and resource, proposed method performs pipeline scheduling with constraints of allocation and initiation interval. Therefore, the cituation in which a feasible solution cannot be achieved because of resource constraint is not occured in proposed method. Additionally, pipeline scheduling for minimizing total circuit area can be performed with considering area of each type of functional unit and register because clock cycles to which each operation can be bound is not limited by resource constraint. Experimental results show that proposed method can reduce total circuit area by about 30% on an average compared to previous methods. Also, computation time of proposed method is well with in utility