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This cross-cultural study compared judgments of moral wrongness for physical and emotional harm with varying combinations of in-group vs. out-group agents and victims across six countries: the United States of America (N = 937), the United Kingdom (N = 995), Romania (N = 782), Brazil (N = 856), South Korea (N = 1776), and China (N = 1008). Consistent with our hypothesis we found evidence of an insider agent effect, where moral violations committed by outsider agents are generally considered more morally wrong than the same violations done by insider agents. We also found support for an insider victim effect where moral violations that were committed against an insider victim generally were seen as more morally wrong than when the same violations were committed against an outsider, and this effect held across all countries. These findings provide evidence that the insider versus outsider status of agents and victims does affect moral judgments. However, the interactions of these identities with collectivism, psychological closeness, and type of harm (emotional or physical) are more complex than what is suggested by previous literature. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04986-3.
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Introduction: Quantifying the transmissibility over time, particularly by region and age, using parameters such as serial interval and time-varying reproduction number, helps in formulating targeted interventions. Moreover, considering the impact of geographical factors on transmission provides valuable insights into the effectiveness of control measures. Methods: Drawing on a comprehensive dataset of COVID-19 cases in South Korea, we analyzed transmission dynamics with a focus on age and regional variations. The dataset, compiled through the efforts of dedicated epidemiologists, includes information on symptom onset dates, enabling detailed investigations. The pandemic was divided into distinct phases, aligning with changes in policies, emergence of variants, and vaccination efforts. We analyzed various interventions such as social distancing, vaccination rates, school closures, and population density. Key parameters like serial interval, heatmaps, and time-varying reproduction numbers were used to quantify age and region-specific transmission trends. Results: Analysis of transmission pairs within age groups highlighted the significant impact of school closure policies on the spread among individuals aged 0-19. This analysis also shed light on transmission dynamics within familial and educational settings. Changes in confirmed cases over time revealed a decrease in spread among individuals aged 65 and older, attributed to higher vaccination rates. Conversely, densely populated metropolitan areas experienced an increase in confirmed cases. Examination of time-varying reproduction numbers by region uncovered heterogeneity in transmission patterns, with regions implementing strict social distancing measures showing both increased confirmed cases and delayed spread, indicating the effectiveness of these policies. Discussion: Our findings underscore the importance of evaluating and tailoring epidemic control policies based on key COVID-19 parameters. The analysis of social distancing measures, school closures, and vaccine impact provides valuable insights into controlling transmission. By quantifying the impact of these interventions on different age groups and regions, we contribute to the ongoing efforts to combat the COVID-19 pandemic effectively.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , SARS-CoV-2 , República da Coreia/epidemiologia , PolíticasRESUMO
Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Although clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing holds immense potential for genetic manipulation, its clinical application is hindered by the absence of an efficient heart-targeted drug delivery system. Herein, we developed CRISPR-Cas9 ribonucleoprotein (RNP)-loaded extracellular vesicles (EVs) conjugated with cardiac-targeting peptide (T) for precise cardiac-specific genome editing. RNP complexes containing Cas9 and single guide RNA targeting miR-34a, an MI-associated molecular target, were loaded into EVs (EV@RNP). Gene editing by EV@RNP attenuated hydrogen peroxide-induced apoptosis in cardiomyocytes via miR-34a inhibition, evidenced by increased B-cell lymphoma 2 levels, decreased Bcl-2-associated X protein levels, and the cleavage of caspase-3. Additionally, to improve cardiac targeting in vivo, we used click chemistry to form functional T-EV@RNP by conjugating T peptides to EV@RNP. Consequently, T-EV@RNP-mediated miR-34a genome editing might exert a protective effect against MI, reducing apoptosis, ameliorating MI injury, and facilitating the recovery of cardiac function. In conclusion, the genome editing delivery system established by loading CRISPR/Cas9 RNP with cardiac-targeting EVs is a powerful approach for precise and tissue-specific gene therapy for cardiovascular disease.
Assuntos
Sistemas CRISPR-Cas , Vesículas Extracelulares , Edição de Genes , MicroRNAs , Infarto do Miocárdio , Miócitos Cardíacos , Ribonucleoproteínas , Edição de Genes/métodos , Vesículas Extracelulares/metabolismo , Animais , Ribonucleoproteínas/genética , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/terapia , Infarto do Miocárdio/genética , MicroRNAs/administração & dosagem , MicroRNAs/genética , Apoptose/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Humanos , Proteína 9 Associada à CRISPR/genética , Peptídeos/química , CamundongosRESUMO
Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy that is predominantly inherited and characterized by cardiac arrhythmias and structural abnormalities. TMEM43 (transmembrane protein 43) is one of the well-known genetic culprits behind ACM. In this study, we successfully generated an induced pluripotent stem cell (iPSC) line, YCMi010-A, derived from a male patient diagnosed with ACM. Although these iPSCs harbored a heterozygous intronic splice variant, TMEM43 c.443-2A > G, they still displayed normal cellular morphology and were confirmed to express pluripotency markers. YCMi010-A iPSC line is a promising model for investigating the pathomechanisms associated with ACM and exploring potential therapeutic strategies.