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Abstract Patients with coronavirus disease 2019 (COVID-19) often experience acute kidney injury, linked to disease severity or mortality, along with renal tubular dysfunction and megalin loss in proximal tubules. Megalin plays a crucial role in kidney vitamin D metabolism. However, the impact of megalin loss on vitamin D metabolism during COVID-19 is unclear. This study investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection reduces megalin expression in proximal tubules and its subsequent effect on vitamin D metabolism in mice expressing human angiotensin converting enzyme 2 (K18-hACE2 mice). Histological and immunohistochemical staining analyses revealed glomerular and capillary congestion, and elevated renal neutrophil gelatinase-associated lipocalin levels, indicative of acute kidney injury in K18-hACE2 mice. In SARS-CoV-2-infected mice, immunohistochemical staining revealed suppressed megalin protein levels. Decreased vitamin D receptor (VDR) localization in the nucleus and increased mRNA expression of VDR, CYP27B1, and CYP24A1 were observed by quantitative PCR in SARS-CoV-2-infected mice. Serum vitamin D levels remained similar in infected and vehicle-treated mice, but an increase in tumor necrosis factor-alpha and a decrease in IL-4 mRNA expression were observed in the kidneys of the SARS-CoV-2 group. These findings suggest that megalin loss in SARS-CoV-2 infection may impact the local role of vitamin D in kidney immunomodulation, even when blood vitamin D levels remain unchanged.

Abstract Background/Objectives Very high‐power and short‐duration (vHPSD) ablation with QDOT MICRO™ facilitates speedy and safe ablation for pulmonary vein isolation. A brief time interval between ablating two neighboring sites with vHPSD may potentially influence the size and geometry of the lesions. This study evaluates lesion formation when delivering adjacent applications using vHPSD at various inter‐lesion times (ILTs). Methods Radiofrequency applications were conducted by QDOT MICRO™ catheter with 90 W of strength and 4 s duration. Fresh swine heart tissue on the epicardium was ablated with 10 g of the contact force. Lesions were created using a single application (SA) and double applications (DA) of adjacent lesions with a 6 mm distance between them as measured on the 3D mapping system. The DA was performed with various ILTs, 60 s (DA‐60 s), 10 s (DA‐10 s), 5 s (DA‐5 s), and 0 s (DA‐0 s). Results Out of 90 lesions, 79 were analyzed. Eleven lesions were excluded for one steam pop event, seven out of the target distance, and three divided lesions of two applications. There were no significant differences in surface diameter, cross‐sectional diameter, and maximal lesion depth in each application among the groups. The intermediate lesion depth was significantly more profound in groups with shorter and immediate ILT (DA‐10, 5, and 0 s) compared to the group with a prolonged ILT between two applications (DA‐60 s) (2.99, 3.03, 3.16 mm vs. 2.42 mm, respectively; p

IntroductionThe rapid adoption of telework, accelerated by advancements in ICT and the COVID-19 pandemic, offers potential benefits for wellbeing and environmental impact. However, telework’s effects on work productivity, work-life balance, and social connectedness remain complex, particularly within hybrid models combining work-from-home (WFH) and in office days.MethodsThis study assessed telework’s impact by comparing WFH and office days. A survey of 1,500 full-time workers in Japan’s Tokyo Metropolitan Region focused on daily time allocation, and telework preferences during telework periods. Principal component and cluster analyses were used to identify groups with distinct work and lifestyle patterns.ResultsSix telework-related groups emerged, reflecting diverse experiences in productivity and daily life. Groups such as the “Overall Increase” and “Housework and Rest Increase” reported gains in leisure and family time, positively impacting wellbeing. In contrast, the “Unsuitable for WFH” group faced increased office-day workloads and reduced WFH productivity, indicating that telework’s effectiveness depends on job and individual characteristics.ConclusionThe findings highlight telework’s potential to enhance wellbeing and sustainability but also underscore the need for tailored policies that address diverse job requirements and personal characteristics. This study contributes to sustainable telework strategies by offering insights into effective support systems that balance flexibility, productivity, and environmental sustainability, aiming both for an enhanced personal life and societal benefits.

BackgroundAcute lymphoblastic leukemia (ALL)-based therapeutic regimens have markedly improved the survival of children with ALL and lymphoblastic lymphoma (LBL). However, survivors are at risk of secondary neoplasms. Few studies on such secondary neoplasms have been conducted outside of Europe and the United States. The aim of this study was to evaluate the incidence of, risk factors for, and outcomes of secondary neoplasms in long-term survivors of ALL and LBL at a tertiary pediatric oncology center in Mie prefecture, Japan.ProcedureWe retrospectively reviewed 188 patients with ALL and LBL who were treated with an ALL-based therapeutic regimen at Mie University Hospital from January 1, 1977 to December 31, 2022 and followed up.ResultsTen patients developed secondary neoplasms, with 10-year and 20-year cumulative incidences of 2.9% [standard error (SE) = 1.5%] and 5.5% (SE = 2.3%), respectively. The median interval between the primary-cancer diagnosis and secondary-neoplasm diagnosis was 18.5 years (range: 7.8–41.7 years). All 10 secondary neoplasms were central nervous system (CNS) tumors (6 meningiomas and 4 high-grade gliomas). Radiotherapy (p = 0.007) and CNS involvement in the primary cancer (p

Chemotherapy using anticancer agents and radiotherapy of cancers frequently induce the development of stomatitis as a side effect. In the present study, hydrogels for effective stomatitis healing under anticancer drug administration were developed using three components, namely proline, carboxyvinyl polymer, and water (denoted proline gels). Characterization including tilting, Fourier transform infrared spectra, and viscoelasticity measurements indicated that proline gels with proline concentrations over 300 μmol/g could retain water on the tongue of mice. The degradation and release behavior of proline gels in serological environments were evaluated, revealing that proline gels were degraded by serological salt concentrations, and the cumulative amount of proline released from proline gels depended on the concentration of proline in the gel. Proline gels were applied to the stomatitis area on the tongue of mice under anticancer drug administration, with subsequent reduction in the stomatitis area and regeneration of the mucosal epithelium layer, demonstrating effective stomatitis healing by proline gels with proline concentrations over 500 μmol/g. Other control samples including the carboxyvinyl polymer or proline alone did not reduce the stomatitis area in model mice. These results suggested that the proline gel is promising for the mucosa regeneration of anticancer drug-induced stomatitis.

ABSTRACT Human parainfluenza virus (HPIV) causes respiratory infections, which are exacerbated in children and older people. Correct evaluation of viral characteristics is essential for the study of countermeasures. However, adaptation of viruses to cultured cells during isolation or propagation might select laboratory passage-associated mutations that modify the characteristics of the virus. It was previously reported that adaptation of HPIV3, but not other HPIVs, was avoided in human airway epithelia. To examine the influence of laboratory passage on the genomes of HPIV1–HPIV4, we evaluated the occurrence of mutations after passage in primary human bronchial/tracheal epithelial cell air-liquid interface (HBTEC-ALI) culture and conventional cultured cells (Vero cells expressing the transmembrane protease, serine 2, and normal Vero cells). The occurrence of mutations was significantly lower in HBTEC-ALI than in conventional culture. In HBTEC-ALI culture, most of the mutations were silent or remained at low variant frequency, resulting in less impact on the viral consensus sequence. In contrast, passage in conventional culture induced or selected genetic mutations at high frequency with passage-associated unique substitutions. High mutagenesis of hemagglutinin-neuraminidase was commonly observed in all four HPIVs, and mutations even occurred in a single passage. In addition, in HPIV1 and HPIV2, mutations in the large protein were more frequent. These results indicate that passage in HBTEC-ALI culture is more suitable than conventional culture for maintaining the original characteristics of clinical isolates in all four HPIVs, which can help with the understanding of viral pathogenesis.IMPORTANCEAdaptation of viruses to cultured cells can increase the risk of misinterpretation in virological characterization of clinical isolates. In human parainfluenza virus (HPIV) 3, it has been reported that the human airway epithelial and lung organoid models are preferable for the study of viral characteristics of clinical strains without mutations. Therefore, we analyzed clinical isolates of all four HPIVs for the occurrence of mutations after five laboratory passages in human bronchial/tracheal epithelial cell air-liquid interface (HBTEC-ALI) or conventional culture. We found a high risk of hemagglutinin-neuraminidase mutagenesis in all four HPIVs in conventional cultured cells. In addition, in HPIV1 and HPIV2, mutations of the large protein were also more frequent in conventional cultured cells than in HBTEC-ALI culture. HBTEC-ALI culture was useful for maintaining the original sequence and characteristics of clinical isolates in all four HPIVs. The present study contributes to the understanding of HPIV pathogenesis and antiviral strategies.

Common sense is a dynamic concept and it is natural that our (statistical) common sense lags behind the development of statistical science. What is not so easy to understand is why common sense lags behind as much as it does. We conduct a survey among Japanese students and provide examples and tentative explanations of a number of statistical questions where common sense and statistical science diverge. Supplementary materials for this article are available online.

A strategy to control the diastereoselectivity of bond formation at a prochiral attached-ring bridgehead is reported. An unusual stereodivergent Michael reaction relies on basic vs. Lewis acidic conditions and non-covalent interactions to control re- vs. si- facial selectivity en route to fully substituted attached-rings. This divergency reflects differential engagement of one rotational isomer of the attached-ring system. The successful synthesis of an erythro subtarget diastereomer ultimately leads to a short formal synthesis of merrilactone A.