Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous cardiac muscle disorder with a diverse natural history, characterized by unexplained left ventricular hypertrophy (LVH), with histopathological hallmarks including myocyte enlargement, myocyte disarray and myocardial fibrosis. Although these features can cause significant cardiac symptoms, many young individuals with HCM are asymptomatic or mildly symptomatic. Sudden cardiac death (SCD) may occur as the initial clinical manifestation. Over the past few decades, HCM has been considered a disease of sarcomere, and typically as an autosomal dominant disease with variable expressivity and incomplete penetrance. Important insights into the genetic landscape of HCM have enhanced our understanding of the molecular pathogenesis, empowered gene-based diagnostic testing to identify at-risk individuals, and offered potential targets for the development of therapeutic agents. This article reviews the current knowledge on the clinical genetics and management of HCM.

Taking photos by mobile phones has become an indispensable part of people's daily life with the popularity of smartphones. However professional photography content is also needed for taking high-quality photos by mobile phones as ones taken by professional cameras. Existing learning tools for photography can't provide photographic practice while presenting theoretical content, nor give real-time photography guidance according to the environment. Mobile augmented reality (AR) technology provides a new way to solve these problems by creating a real learning situation. Therefore, an innovative AR-based mobile photography application (ARMPA) is designed and developed as a method to connect theory and practice. Based on Learning-by-Doing instructional strategy, the ARMPA can timely and synchronously display the theoretical content of photography in the form of text and images corresponding to learners' practical operation. Moreover, it can provide learners real-time interaction and guidance by using AR environment sensing technology. The effect of ARMPA on learning gain and cognitive load is assessed by traditional methods of pre/post-test and questionnaires. To objectively explore the effectiveness of ARMPA from a cognitive and emotional perspective, we measure and extract four emotional state indexes of electroencephalogram (EEG) including engagement (ENG), relaxation (MED), interest (INT) and focus (FOC). Compared to traditional two-dimension (2 D) application (APP), ARMPA improves learners’ learning gains, decreases learners’ cognitive loads. The participants in the AR group achieve better emotional states than those in the 2 D group. This study provides some empirical evidence for AR technology to boost mobile phone photography.

Messenger RNA (mRNA) vaccines against SARS-CoV-2 are highly effective and were instrumental in curbing the COVID-19 pandemic. However, rare cases of noninfective myocarditis, particularly in young males and typically after the second dose, have been observed. Here, we explore the mediators of this myocarditis to better understand and to enhance the safety of future mRNA vaccines. Through analysis of human plasma data and in vitro experiments with human macrophages and T cells, we identified increased C-X-C motif chemokine ligand 10 (CXCL10) and interferon-γ (IFN-γ) after exposure to BNT162b2 (Pfizer) or mRNA-1273 (Moderna). Neutralization of CXCL10 and IFN-γ during the second dose (21 days after the first dose) reduced vaccine-induced cardiac injury in mice. Neutralization also reduced cardiac stress markers such as the release of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and expression of inflammatory genes in human induced pluripotent stem cell (iPSC)–derived cardiac spheroids. When exposed to these cytokines in vitro, human iPSC-derived cardiomyocytes (iPSC-CMs) exhibited impaired contractility, arrhythmogenicity, and proinflammatory gene expression patterns. Genistein, a phytoestrogen implicated in reducing cardiovascular inflammation, mitigated these effects in iPSC-CMs. In mice exposed to these cytokines or receiving BNT162b2 vaccination, genistein treatment reduced cardiac injury markers and attenuated infiltration of neutrophils and macrophages into the heart. These findings implicate CXCL10–IFN-γ signaling as a contributor to myocardial injury in experimental models of mRNA vaccination and indicate that pharmacologic modulation, such as with genistein, may mitigate cytokine-driven injury.

Analysis of large-scale human genomic data has yielded unexplained mutations known to cause severe disease in healthy individuals. Here, we report the unexpected recovery of a rare dominant lethal mutation in TPM1, a sarcomeric actin-binding protein, in eight individuals with large atrial septal defect (ASD) in a five-generation pedigree. Mice with Tpm1 mutation exhibit early embryonic lethality with disrupted myofibril assembly and no heartbeat. However, patient-induced pluripotent-stem-cell-derived cardiomyocytes show normal beating with mild myofilament defect, indicating disease suppression. A variant in TLN2, another myofilament actin-binding protein, is identified as a candidate suppressor. Mouse CRISPR knock-in (KI) of both the TLN2 and TPM1 variants rescues heart beating, with near-term fetuses exhibiting large ASD. Thus, the role of TPM1 in ASD pathogenesis unfolds with suppression of its embryonic lethality by protective TLN2 variant. These findings provide evidence that genetic resiliency can arise with genetic suppression of a deleterious mutation.