Genetic intratumour heterogeneity and clonal evolution in extramammary Paget's disease.

All tumour cells in a patient have shared and non-shared genetic alterations, and the diversity of mutations is described as intratumoural heterogeneity (ITH). Multiregion sequencing is a genome sequencing analytical technique used for multiple, spatially-separated biopsy tissues that may further our understanding of ITH and tumour evolution. Although genetic mutations in extramammary Paget's disease (EMPD) have recently been detected by next-generation sequencing analysis, there have been no reports of ITH based on multiregion sequencing in EMPD.

Modeling and predicting individual variation in COVID-19 vaccine-elicited antibody response in the general population.

As we learned during the COVID-19 pandemic, vaccines are one of the most important tools in infectious disease control. To date, an unprecedentedly large volume of high-quality data on COVID-19 vaccinations have been accumulated. For preparedness in future pandemics beyond COVID-19, these valuable datasets should be analyzed to best shape an effective vaccination strategy.

Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers.

Chronic infection with hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. Thus, quantifying and understanding the dynamics of cccDNA are essential for developing effective treatment strategies and new drugs.

Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts.

Modeling COVID-19 vaccine booster-elicited antibody response and impact of infection history.

The 3-dose COVID-19 vaccine (booster vaccination) has been offered worldwide. As booster vaccinations continue, it is important to understand the antibody dynamics elicited by booster vaccination in order to evaluate and develop vaccination needs and strategies. Here, we investigated longitudinal data by monitoring IgG antibodies against the receptor binding domain (RBD) in health care workers.

Antibody Profiling of Microbial Antigens in the Blood of COVID-19 mRNA Vaccine Recipients Using Microbial Protein Microarrays.

Although studies have demonstrated that infections with various viruses, bacteria, and parasites can modulate the immune system, no study has investigated changes in antibodies against microbial antigens after the COVID-19 mRNA vaccination. IgG antibodies against microbial antigens in the blood of vaccinees were comprehensively analyzed using microbial protein microarrays that carried approximately 5000 microbe-derived proteins. Changes in antibodies against microbial antigens were scrutinized in healthy participants enrolled in the Fukushima Vaccination Community Survey conducted in Fukushima Prefecture, Japan, after their second and third COVID-19 mRNA vaccinations.

Hematopoietic cell-derived IL-15 supports NK cell development in scattered and clustered localization within the bone marrow.

Natural killer (NK) cells are innate immune cells critical for protective immune responses against infection and cancer. Although NK cells differentiate in the bone marrow (BM) in an interleukin-15 (IL-15)-dependent manner, the cellular source of IL-15 remains elusive. Using NK cell reporter mice, we show that NK cells are localized in the BM in scattered and clustered manners.

Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation for analyzing extracellular viral markers.

Chronic infection of hepatitis B virus (HBV) is caused by the persistence of closed circular DNA (cccDNA) in the nucleus of infected hepatocytes. Despite available therapeutic anti-HBV agents, eliminating the cccDNA remains challenging. The quantifying and understanding dynamics of cccDNA are essential for developing effective treatment strategies and new drugs.

Blood flow kinetic energy is a novel marker for right ventricular global systolic function in patients with left ventricular assist device therapy.

Objectives: Right ventricular (RV) failure remains a major concern in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We aimed to measure the kinetic energy of blood in the RV outflow tract (KE-RVOT) - a new marker of RV global systolic function. We also aimed to assess the relationship of KE-RVOT to other echocardiographic parameters in all subjects and assess the relationship of KE-RVOT to hemodynamic parameters of RV performance in HF patients.

Preoperative Left Ventricular Energy Loss in the Operating Theater Reflects Subjective Symptoms in Chronic Aortic Regurgitation.

Background: There is currently no subjective, definitive evaluation method for therapeutic indication other than symptoms in aortic regurgitation. Energy loss, a novel parameter of cardiac workload, can be visualized and quantified using echocardiography vector flow mapping. The purpose of the present study was to evaluate whether energy loss in patients with chronic aortic regurgitation can quantify their subjective symptoms more clearly than other conventional metrics.

Lifestyle changes during the coronavirus disease 2019 pandemic impact metabolic dysfunction-associated fatty liver disease.

Background And Aims: The coronavirus disease 2019 (COVID-19) pandemic precipitated lifestyle changes. We aimed to clarify whether COVID-19-induced lifestyle changes affected the development of metabolic dysfunction-associated fatty liver disease (MAFLD).

Methods: This retrospective longitudinal study included 973 participants who underwent health check-ups between 2018 and 2020.

Expression of Cancer Stem Cell Markers EpCAM and CD90 Is Correlated with Anti- and Pro-Oncogenic EphA2 Signaling in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Additionally, the efficacy of targeted molecular therapies with multiple tyrosine kinase inhibitors is limited. In this study, we focused on the cellular signaling pathways common to diverse HCC cells and used quantitative reverse phase protein array (RPPA) and statistical analyses to elucidate the molecular mechanisms determining its malignancy.

Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data.

Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data.

Effectiveness of dispatcher instructions-dependent or independent bystander cardiopulmonary resuscitation on neurological survival among patients with out-of-hospital cardiac arrest.

Background: We evaluated the association between survival and bystandercardiopulmonary resuscitation (CPR) with or without dispatcher instructions (DI) considering the time from emergency call receipt by the dispatch center to emergency medical services (EMS) personnel's contact with the patient (i.e. time to EMS arrival).

Flow-dynamics assessment of mitral-valve surgery by intraoperative vector flow mapping.

Objectives: We assessed vortex patterns and energy loss in left ventricular flow in patients who underwent mitral valve repair or replacement with bioprosthetic valves.

Methods: Vector flow mapping was performed before and after the procedure in 15 and 17 patients who underwent repair and replacement, respectively. The preprocedure mitral-septal angle was measured in all patients.

Vector flow mapping analysis of left ventricular energetic performance in healthy adult volunteers.

Background: Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle).

Secretory glands and microvascular systems imaged in aqueous solution by atmospheric scanning electron microscopy (ASEM).

Exocrine glands, e.g., salivary and pancreatic glands, play an important role in digestive enzyme secretion, while endocrine glands, e.

Visualization of Ca2+ Filling Mechanisms upon Synaptic Inputs in the Endoplasmic Reticulum of Cerebellar Purkinje Cells.

The endoplasmic reticulum (ER) plays crucial roles in intracellular Ca(2+) signaling, serving as both a source and sink of Ca(2+), and regulating a variety of physiological and pathophysiological events in neurons in the brain. However, spatiotemporal Ca(2+) dynamics within the ER in central neurons remain to be characterized. In this study, we visualized synaptic activity-dependent ER Ca(2+) dynamics in mouse cerebellar Purkinje cells (PCs) using an ER-targeted genetically encoded Ca(2+) indicator, G-CEPIA1er.

Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells.

Genetically identical cells in a uniform external environment can exhibit different phenotypes, which are often masked by conventional measurements that average over cell populations. Although most studies on this topic have used microorganisms, differentiated mammalian cells have rarely been explored. Here, we report that only approximately 40% of clonal human embryonic kidney 293 cells respond with an intracellular Ca(2+) increase when ryanodine receptor Ca(2+) release channels in the endoplasmic reticulum are maximally activated by caffeine.