地域がん登録資料に基づくがん患者の治癒確率の推定

要旨ありがん統計データおよびその解析研究ノー

Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives

Functionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of functional lipids for the preparation of targeted nanoparticles using microfluidic devices. While searching for a lipid with high solubility and dispersibility in solvents, which is one of the requirements, we noted that KK-(EK)4-lipid imparts nonspecific cellular association to polyethylene glycol (PEG)-modified (PEGylated) liposomes, such as cell-penetrating peptides (CPPs). We investigated whether KK-(EK)4-lipid, which has a near-neutral charge, is a novel CPP-modified lipid that enhances the intracellular translocation of nanoparticles. However, the cellular association mechanism of KK-(EK)4-lipid is unknown. Therefore, we synthesized (EK)n-lipid derivatives based on the sequence of KK-(EK)4-lipid and determined the sequence sites involved in cellular association. In addition, KK-(EK)4-lipid was applied to extracellular vesicles (EVs) and mRNA encapsulated lipid nanoparticles (mRNA-LNPs). KK-(EK)4-lipid-modified EVs and mRNA-LNPs showed higher cellular association and in vitro protein expression, respectively, compared to unmodified ones. We elucidated KK-(EK)4-lipid to have potential for applicability in the intracellular delivery of liposomes, EVs, and mRNA-LNPs

Is oral food challenge useful to avoid complete elimination in Japanese patients diagnosed with or suspected of having IgE-dependent hen's egg allergy? A systematic review

Background: IgE-mediated egg allergy is a common food allergy worldwide. Patients with egg allergy are known to easily achieve tolerance compared to other allergens such as nuts. Oral food challenge (OFC) is often performed on patients diagnosed with or suspected of having IgE-mediated food allergy, but whether hen's egg OFC is useful in IgE-dependent egg allergy patients to avoid complete elimination remains unknown. Methods: We identified articles in which OFCs were performed in Japanese patients diagnosed with or suspected of having IgE-mediated egg allergy. We evaluated whether the OFCs were useful to avoid the complete elimination of eggs by assessing the following: (1) the number of patients who could avoid complete elimination; (2) the number of patients who experienced serious adverse events (SAEs); or (3) adverse events (AEs); (4) improvement in quality of life (QOL); and (5) immunological changes. Results: Fifty-nine articles were selected in the study; all the references were case series or case studies in which OFC was compared to pre-challenge conditions. The overall negative ratio against egg OFC was 62.7%, but an additional 71.9% of OFC-positive patients could take eggs when expanded to partial elimination. Of the 4182 cases, 1146 showed AEs in the OFC, and two cases reached an SAE. Two reports showed an improvement in QOL and immunological changes, although the evidence was weak. Conclusions: OFCs against eggs may be useful to avoid complete elimination, but medical professionals should proceed with the test safely and carefully

海浜植物ハマヒルガオ(ヒルガオ科) における葉の厚さの地理的分化: 海岸と内陸淡水湖の集団間の比較

琵琶湖に内陸隔離されている海浜植物ハマヒルガオCalystegia soldanella（L.）Roem. et Schult. が，海岸の個体との間で葉の厚さに分化を起こしているかを検証した。比較をしたのは，琵琶湖の自生地6集団と海岸の自生地9 集団である。葉の厚さを測定して多重比較検定にかけたところ，5 グループに分類された。そのうちの1 グループに全ての琵琶湖の集団が含まれ，海岸の集団は残りの4 グループに含まれた。琵琶湖のハマヒルガオの葉は，海岸のものに比べて，有意に厚さが薄くなっていることが示唆された。琵琶湖は淡水湖であるために，塩ストレスへの適応が不要であることが，その要因の一つとして考えられる

Impact of Chronic Kidney Disease on the Presence and Severity of Aortic Stenosis in Patients at High Risk for Coronary Artery Disease

<p>Abstract</p> <p>Objective</p> <p>We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD).</p> <p>Methods</p> <p>One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index).</p> <p>Results</p> <p>Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0cm²). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm²/m², *p < 0.05 vs. group 1: 1.65 ± 0.32 cm²/m², and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm²/m²) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec).</p> <p>Conclusion</p> <p>CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.</p

Detecting loci under recent positive selection in dairy and beef cattle by combining different genome-wide scan methods

As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP) data generated from dairy and beef cattle (taurine and indicine). The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10(-7)) population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3) in Brown Swiss (P = 3.82×10(-12)), and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection

A specification-aware modeling of mental model theory for syllogistic reasoning

Computational cognitive models can embody the structures and processes proposed in a cognitive theory. However, they do not necessarily reveal the theory’s underlying assumptions and specifications. This study aims to bridge the gap between cognitive theory and its computational implementation, focus- ing on a case of mental model theory on human reasoning. Using a mathematics-based and statically-typed programming language (Haskell), we provide a specification-aware compu- tational implementation of syllogistic reasoning with mental models

Towards a Formalization of Mental Model Reasoning for Syllogistic Fragments

Abstract. In this study, Johnson-Laird and his colleagues ’ mental model reasoning is formally analyzed as a non-sentential reasoning. Based on the recent developments in implementations of mental model theory, we formulate a mental model reasoning for syllogistic fragments in a way satisfying the requirement of formal specification such as mental model definition.