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Introduction: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation., Methods: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients., Results: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes., Conclusion: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takeshi Arashiro is an unpaid consultant for the World Health Organization. The other authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

High serum levels of triglycerides (TG) and low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of coronary heart disease in humans. Herein, we first reported that the C3H/HeNSlc (C3H-S) mouse, a C3H/HeN-derived substrain, is a novel model for dyslipidemia. C3H-S showed hypertriglyceridemia and low total cholesterol (TC), HDL-C, and phospholipid (PL) concentrations. To identify the gene locus causing dyslipidemia in C3H-S, we performed genetic analysis. In F2 intercrosses between C3H-S mice and strains with normal serum lipids, the locus associated with serum lipids was identified as 163-168 Mb on chromosome 2. The phospholipid transfer protein (Pltp) gene was a candidate gene within this locus. Pltp expression and serum PLTP activity were markedly lower in C3H-S mice. Pltp expression was negatively correlated with serum TG and positively correlated with serum TC and HDL-C in F2 mice. Genome sequencing analysis revealed that an endogenous retrovirus (ERV) sequence called intracisternal A particle was inserted into intron 12 of Pltp in C3H-S. These results suggest that ERV insertion within Pltp causes aberrant splicing, leading to reduced Pltp expression in C3H-S. This study demonstrated the contribution of C3H-S to our understanding of the relationship between TG, TC, and PL metabolism via PLTP., (© 2023. Springer Nature Limited.)

This protocol introduces a method for generating strictly controlled and objectively defined stimuli for figure recognition experiments. A (6, n) figure consists of n line segments that are spanned between n pairs of points located at the vertices of an invisible regular hexagon. The structural properties (graph invariants) and superficial features (non-graph invariants) of each (6, n) figure with n values ranging from 1 to 6 are calculated and stored in a database. Using this database, experimenters can systematically extract appropriate figures depending on the purpose of the experiment. Furthermore, if the database does not contain necessary information, new feature values can sometimes be calculated ad hoc from the formation of a specific (6, n) figure. Let us call a mirror-reflected pair of figures an axisymmetric (Ax) pair. An Ax pair of figures is known to be more difficult to discriminate than a non-identical pair in the decision of whether the shapes of a given pair are rotated-to-be-identical (Idr). The purpose of the present experiment is to examine whether the sameness of line lengths between two figures in a pair causes the discrimination of the pair to be as difficult as that of an Ax pair. Mutually isomorphic figures share common structural properties despite differences in shape. Ax pairs and Idr pairs are special cases of isomorphic pairs. Furthermore, an Ax pair and Idr pair share most of the superficial feature values, except the relative direction from one location to another location across an axis of symmetry is opposite for an Ax pair. Three types of mutually isomorphic (6, 4) figure pairs were generated: Idr; Ax; and non-identical, non-axisymmetric, isomorphic (Nd) pairs. Nd pairs were further classified into three subcategories according to the superficial feature values of the degree of line length differences.

A previous study by the author found that discrimination latencies for figure pairs with the same topological structure (isomorphic pairs) were longer than for pairs with different topological structures (nonisomorphic pairs). These results suggest that topological sensitivity occurs during figure recognition. However, sameness was judged in terms of both shape and orientation. Using this criterion, faster discrimination of nonisomorphic pairs may have arisen from the detection of differences in the corresponding locations of the paired figures, which is not a topological property. The current study examined whether topological sensitivity occurs even when identity judgments are based on the sameness of shapes, irrespective of their orientation, where the sameness of location is not ensured. The current results suggested the involvement of topological sensitivity, indicating that processing of structural properties (invariant features) of a figure may be prioritized over processing of superficial features, such as location, length, and angles, in figure recognition.

This study used a series of six closely related experiments to examine whether individuals use topological structures to discriminate figures. Strict control was exerted over the selection of stimuli, which were a specific type of randomly generated lined figures that can be classified using isomorphic sets defined by graph theory. Any two figures within an isomorphic set possessed the same topological structure. The experiments described here used a same/different discrimination task with simultaneously presented pairs of figures: (a) identical pairs (Id pairs), in which each pair of figures had the same topological and superficial properties; (b) nonidentical and isomorphic pairs (Iso pairs), in which each pair had the same topological but different superficial properties; and (c) nonidentical and nonisomorphic pairs (Noniso pairs), in which each pair had different topological properties. Within these experiments I varied the conditions related to the intersecting line segments, presentation of points defining each figure, figure complexity, stimulus aspect ratios, and the parity of the total line-segment lengths between the figures in each pair. These variations showed that the latencies for making accurate discriminations were shorter for Noniso pairs than for Iso pairs, suggesting that individuals are sensitive to topology when distinguishing figures.