Diverse Phenotypic Manifestations in a Family with a Novel RYR2 E4107A Variant.

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.

Correction: 12-year observation of tweets about rubella in Japan: A retrospective infodemiology study.

[This corrects the article DOI: 10.1371/journal.pone.0285101.].

12-year observation of tweets about rubella in Japan: A retrospective infodemiology study.

Although rubella is an infectious disease that can be prevented by vaccination, there have been periodic epidemics in Japan, mainly among adult males. One of the reasons for this is the lack of interest in vaccination among the target adult male population. To clarify the reality of the discussion about rubella and provide basic resource for enlightening activities for rubella prevention, we collected and analyzed Twitter posts about rubella in Japanese between January 2010 and May 2022. We examined time series, number of tweets per account, tweeted contents, and retweet network. We found that the weekly number of rubella reports and the number of Twitter posts fluctuate simultaneously. During the 2018 rubella epidemic, the number of tweets increased due to the start of the rubella routine vaccination program and the use of cartoons to raise awareness. While 80% of the accounts posted three times or fewer during the period, some accounts posted multiple times per day for more than 12 years. Medical terms such as vaccines and antibodies were frequently used in the tweet contexts. In the retweet activity, a variety of actors, including mass media, medical professionals, and even rubella sufferers, contributed to disseminate rubella-related information.

A two-phase model of collective memory decay with a dynamical switching point.

Public memories of significant events shared within societies and groups have been conceptualized and studied as collective memory since the 1920s. Thanks to the recent advancement in digitization of public-domain knowledge and online user behaviors, collective memory has now become a subject of rigorous quantitative investigation using large-scale empirical data. Earlier studies, however, typically considered only one dynamical process applied to data obtained in just one specific event category. Here we propose a two-phase mathematical model of collective memory decay that combines exponential and power-law phases, which represent fast (linear) and slow (nonlinear) decay dynamics, respectively. We applied the proposed model to the Wikipedia page view data for articles on significant events in five categories: earthquakes, deaths of notable persons, aviation accidents, mass murder incidents, and terrorist attacks. Results showed that the proposed two-phase model compared favorably with other existing models of collective memory decay in most of the event categories. The estimated model parameters were found to be similar across all the event categories. The proposed model also allowed for detection of a dynamical switching point when the dominant decay dynamics exhibit a phase shift from exponential to power-law. Such decay phase shifts typically occurred about 10 to 11 days after the peak in all of the five event categories.

Oozing-type rupture caused by right ventricular intramural hematoma after right ventricular infarction.

An 81-year-old man was admitted to the hospital because of decreased level of consciousness. He had bradycardia (27 beats/min). Electrocardiography showed ST-segment elevation in leads II, III, and aVF and ST-segment depression in leads aVL, V1. Transthoracic echocardiography (TTE) visualized reduced motion of the left ventricular (LV) inferior wall and right ventricular (RV) free wall. Coronary angiography revealed occlusion of the right coronary artery. A primary percutaneous coronary intervention was successfully performed with temporary pacemaker backup. On the third day, the sinus rhythm recovered, and the temporary pacemaker was removed. On the fifth day, a sudden cardiac arrest occurred. Extracorporeal cardiopulmonary resuscitation was performed. TTE showed a high-echoic effusion around the right ventricle, indicating a hematoma. The drainage was ineffective. He died on the eighth day. An autopsy showed the infarcted lesion and an intramural hematoma in the RV. However, no definite perforation of the myocardium was detected. The hematoma extended to the epicardium surface, indicative of oozing-type RV rupture induced by RV infarction. The oozing-type rupture induced by RV infarction might develop asymptomatically without influence on the vital signs of the patient. Frequent echocardiographic evaluation is essential in cases of RV infarction taking care of silent oozing-type rupture. Learning objective: Inferior left ventricular infarction sometimes complicates right ventricular (RV) infarction. The typical manifestations of RV infarction include low blood pressure, low cardiac output, and elevated right atrium pressure. Although the frequency is low, fatal complications of oozing-type RV rupture might progress asymptomatically. Frequent echocardiographic screening is necessary to detect them.

Music Roles Affect the Selection of Consumption Means: A Questionnaire Survey of People's Expectations for Music and Exploratory Factor Analysis.

People listen to music for various purposes, and the roles that listeners expect from music can vary from person to person. In recent years, "subscription-based streaming services" (hereinafter referred to as "subscription") have increased their share in the music market, thereby changing the way people listen to music. Though, the impact of this change on the role of music, is yet to be explored. This study analyzed survey data to reveal the relationship between the expected roles of music and the choice of music consumption means, including subscription. In particular, we obtained that a factor in the use of subscription is the expectation of constructing a personal identity. We also found that both purchase and live usage are affected by two factors: the expectation of fan identity construction and the expectation of artist contribution. This indicates that subscription is not an alternative to the existing means, but a new kind of consumption means in the music market. It was also found that subscription facilitates the construction of personal identity through music. Supplementary Information: The online version contains supplementary material available at 10.1007/s12626-022-00115-x.

Dataset of identified scholars mentioned in acknowledgement statements.

Acknowledgements represent scholars' relationships as part of the research contribution. While co-authors and citations are often provided as a well-formatted bibliometric database, acknowledged individuals are difficult to identify because they appear as part of the statements in the paper. We identify acknowledged scholars who appeared in papers published in open-access journals by referring to the co-author and citation relationships stored in the Microsoft Academic Graph (MAG). Therefore, the constructed dataset is compatible with MAG, which accelerates and expands the acknowledgements as a data source of scholarly relationships similar to collaboration and citation analysis. Moreover, the implemented code is publicly available; thus, it can be applied in other studies.

Classification of endogenous and exogenous bursts in collective emotions based on Weibo comments during COVID-19.

Bursts and collective emotion have been widely studied in social physics field where researchers use mathematical models to understand human social dynamics. However, few researches recognize and separately analyze the internal and external influence on burst behaviors. To bridge this gap, we introduce a non-parametric approach to classify an interevent time series into five scenarios: random arrival, endogenous burst, endogenous non-burst, exogenous burst and exogenous non-burst. In order to process large-scale social media data, we first segment the interevent time series into sections by detecting change points. Then we use the rule-based algorithm to classify the time series based on its distribution. To validate our model, we analyze 27.2 million COVID-19 related comments collected from Chinese social media between January to October 2020. We adopt the emotion category called Profile of Mood States which consists of six emotions: Anger, Depression, Fatigue, Vigor, Tension and Confusion. This enables us to compare the burst features of different collective emotions during the COVID-19 period. The burst detection and classification approach introduced in this paper can also be applied to analyzing other complex systems, including but not limited to social media, financial market and signal processing.

[Online harassment in Japan: Dissecting the targeting of a female journalist]. / 日本におけるオンライン・ハラスメントの現状と対策：Twitterã§ã®å¥³æ€§è¨˜è€ ã®ãƒ„ã‚¤ãƒ¼ãƒˆã€Œç‚Žä¸Šã€ã‚’ä¾‹ã«.

Harassment on the Internet, particularly on social media such as Twitter, has reached a level where it can, without exaggeration, be characterised as a real-world societal problem in Japan. However, studies on this phenomenon in the Japanese language environment, especially adopting a victim-centric perspective, are rare. In this paper, we incorporated the concept of online harassment and reviewed existing studies about online harassment from Japan and abroad. We then conducted a detailed case analysis of the "flaming" of a female journalist and those who targeted her on Twitter. Based on our analysis, we observed that there were three layers of users who targeted the journalist: influencers, users who responded to the instigation by influencers, and trolls. Each harassed the journalist, but in a different manner. Given Japan's particular difficulty of imposing domestic regulations on social media companies that are mostly from abroad, we propose and describe possible measures that individuals and their employers should consider taking.

Identifying long-term periodic cycles and memories of collective emotion in online social media.

Collective emotion has been traditionally evaluated by questionnaire survey on a limited number of people. Recently, big data of written texts on the Internet has been available for analyzing collective emotion for very large scales. Although short-term reflection between collective emotion and real social phenomena has been widely studied, long-term dynamics of collective emotion has not been studied so far due to the lack of long persistent data sets. In this study, we extracted collective emotion over a 10-year period from 3.6 billion Japanese blog articles. Firstly, we find that collective emotion shows clear periodic cycles, i.e., weekly and seasonal behaviors, accompanied with pulses caused by natural disasters. For example, April is represented by high Tension, probably due to starting school in Japan. We also identified long-term memory in the collective emotion that is characterized by the power-law decay of the autocorrelation function over several months.

Configuration model for correlation matrices preserving the node strength.

Correlation matrices are a major type of multivariate data. To examine properties of a given correlation matrix, a common practice is to compare the same quantity between the original correlation matrix and reference correlation matrices, such as those derived from random matrix theory, that partially preserve properties of the original matrix. We propose a model to generate such reference correlation and covariance matrices for the given matrix. Correlation matrices are often analyzed as networks, which are heterogeneous across nodes in terms of the total connectivity to other nodes for each node. Given this background, the present algorithm generates random networks that preserve the expectation of total connectivity of each node to other nodes, akin to configuration models for conventional networks. Our algorithm is derived from the maximum entropy principle. We will apply the proposed algorithm to measurement of clustering coefficients and community detection, both of which require a null model to assess the statistical significance of the obtained results.

Statistical properties of fluctuations of time series representing appearances of words in nationwide blog data and their applications: An example of modeling fluctuation scalings of nonstationary time series.

To elucidate the nontrivial empirical statistical properties of fluctuations of a typical nonsteady time series representing the appearance of words in blogs, we investigated approximately 3×10^{9} Japanese blog articles over a period of six years and analyze some corresponding mathematical models. First, we introduce a solvable nonsteady extension of the random diffusion model, which can be deduced by modeling the behavior of heterogeneous random bloggers. Next, we deduce theoretical expressions for both the temporal and ensemble fluctuation scalings of this model, and demonstrate that these expressions can reproduce all empirical scalings over eight orders of magnitude. Furthermore, we show that the model can reproduce other statistical properties of time series representing the appearance of words in blogs, such as functional forms of the probability density and correlations in the total number of blogs. As an application, we quantify the abnormality of special nationwide events by measuring the fluctuation scalings of 1771 basic adjectives.

Rumor diffusion and convergence during the 3.11 earthquake: a twitter case study.

We focus on Internet rumors and present an empirical analysis and simulation results of their diffusion and convergence during emergencies. In particular, we study one rumor that appeared in the immediate aftermath of the Great East Japan Earthquake on March 11, 2011, which later turned out to be misinformation. By investigating whole Japanese tweets that were sent one week after the quake, we show that one correction tweet, which originated from a city hall account, diffused enormously. We also demonstrate a stochastic agent-based model, which is inspired by contagion model of epidemics SIR, can reproduce observed rumor dynamics. Our model can estimate the rumor infection rate as well as the number of people who still believe in the rumor that cannot be observed directly. For applications, rumor diffusion sizes can be estimated in various scenarios by combining our model with the real data.

Empirical analysis of collective human behavior for extraordinary events in the blogosphere.

To uncover an underlying mechanism of collective human dynamics, we survey more than 1.8 billion blog entries and observe the statistical properties of word appearances. We focus on words that show dynamic growth and decay with a tendency to diverge on a certain day. After careful pretreatment and the use of a fitting method, we found power laws generally approximate the functional forms of growth and decay with various exponents values between -0.1 and -2.5. We also observe news words whose frequencies increase suddenly and decay following power laws. In order to explain these dynamics, we propose a simple model of posting blogs involving a keyword, and its validity is checked directly from the data. The model suggests that bloggers are not only responding to the latest number of blogs but also suffering deadline pressure from the divergence day. Our empirical results can be used for predicting the number of blogs in advance and for estimating the period to return to the normal fluctuation level.

Engineered biosynthesis of plant polyketides: chain length control in an octaketide-producing plant type III polyketide synthase.

The chalcone synthase (CHS) superfamily of type III polyketide synthases (PKSs) produces a variety of plant secondary metabolites with remarkable structural diversity and biological activities (e.g., chalcones, stilbenes, benzophenones, acrydones, phloroglucinols, resorcinols, pyrones, and chromones). Here we describe an octaketide-producing novel plant-specific type III PKS from aloe (Aloe arborescens) sharing 50-60% amino acid sequence identity with other plant CHS-superfamily enzymes. A recombinant enzyme expressed in Escherichia coli catalyzed seven successive decarboxylative condensations of malonyl-CoA to yield aromatic octaketides SEK4 and SEK4b, the longest polyketides known to be synthesized by the structurally simple type III PKS. Surprisingly, site-directed mutagenesis revealed that a single residue Gly207 (corresponding to the CHS's active site Thr197) determines the polyketide chain length and product specificity. Small-to-large substitutions (G207A, G207T, G207M, G207L, G207F, and G207W) resulted in loss of the octaketide-forming activity and concomitant formation of shorter chain length polyketides (from triketide to heptaketide) including a pentaketide chromone, 2,7-dihydroxy-5-methylchromone, and a hexaketide pyrone, 6-(2,4-dihydroxy-6-methylphenyl)-4-hydroxy-2-pyrone, depending on the size of the side chain. Notably, the functional diversity of the type III PKS was shown to evolve from simple steric modulation of the chemically inert single residue lining the active-site cavity accompanied by conservation of the Cys-His-Asn catalytic triad. This provided novel strategies for the engineered biosynthesis of pharmaceutically important plant polyketides.

A plant type III polyketide synthase that produces pentaketide chromone.

A novel plant-specific type III polyketide synthase (PKS) that catalyzes formation of a pentaketide chromone, 5,7-dihydroxy-2-methylchromone, from five molecules of malonyl-CoA, was cloned and sequenced from aloe (Aloe arborescens). Site-directed mutagenesis revealed that Met207 (corresponding to Thr197 in CHS) determines the polyketide chain length and the product specificity of the enzyme; remarkably, replacement of a single amino acid residue, Met207, with Gly yielded a mutant enzyme that efficiently produces aromatic octaketides, SEK4 and SEK4b, the products of the minimal PKS for actinorhodin (act from Streptomyces coelicolor), from eight molecules of malonyl-CoA. This provided new insights into the catalytic functions and specificities of the CHS-superfamily type III PKS enzymes.

Enzymatic reactions by five chalcone synthase homologs from hop (Humulus lupulus L.).

The enzyme activities encoded in five cDNAs for chalcone synthase (CHS) homologs from hop were investigated. Only valerophenone synthase (VPS) and CHS_H1 showed both naringenin-chalcone and phlorisovalerophenone forming activity. Narigenin-chalcone production by VPS was much lower than by CHS_H1. Therefore, it is highly possible that flavonoid depends mainly on CHS_H1, while bitter acid biosynthesis depends mainly on VPS and CHS_H1.

Site-directed mutagenesis of benzalacetone synthase. The role of the Phe215 in plant type III polyketide synthases.

Benzalacetone synthase (BAS) and chalcone synthase (CHS) are plant-specific type III polyketide synthases (PKSs) that share approximately 70% amino acid sequence identity. BAS catalyzes a one-step decarboxylative condensation of 4-coumaroyl-CoA with malonyl-CoA to produce a diketide benzalacetone, whereas CHS performs sequential condensations with three malonyl-CoA to generate a tetraketide chalcone. A homology model suggested that BAS has the same overall fold as CHS with cavity volume almost as large as that of CHS. One of the most characteristic features is that Rheum palmatum BAS lacks active site Phe-215; the residues 214LF conserved in type III PKSs are uniquely replaced by IL. Our observation that the BAS I214L/L215F mutant exhibited chalcone-forming activity in a pH-dependent manner supported a hypothesis that the absence of Phe-215 in BAS accounts for the interruption of the polyketide chain elongation at the diketide stage. On the other hand, Phe-215 mutants of Scutellaria baicalensis CHS (L214I/F215L, F215W, F215Y, F215S, F215A, F215H, and F215C) afforded increased levels of truncated products; however, none of them generated benzalacetone. These results confirmed the critical role of Phe-215 in the polyketide formation reactions and provided structural basis for understanding the structure-function relationship of the plant type III PKSs.