Enhanced Far-Field Thermal Radiation through a Polaritonic Waveguide.

We experimentally demonstrate the enhancement of the far-field thermal radiation between two nonabsorbent Si microplates coated with energy-absorbent silicon dioxide (SiO_{2}) nanolayers supporting the propagation of surface phonon polaritons. By measuring the radiative thermal conductance between two coated Si plates, we find that its values are twice those obtained without the SiO_{2} coating. This twofold increase results from the hybridization of polaritons with guided modes inside Si and is well predicted by fluctuational electrodynamics and an analytical model based on a two-dimensional density of polariton states. These findings could be applied to thermal management in microelectronics, silicon photonics, energy conversion, atmospheric sciences, and astrophysics.

PNPO-PLP axis senses prolonged hypoxia in macrophages by regulating lysosomal activity.

Oxygen is critical for all metazoan organisms on the earth and impacts various biological processes in physiological and pathological conditions. While oxygen-sensing systems inducing acute hypoxic responses, including the hypoxia-inducible factor pathway, have been identified, those operating in prolonged hypoxia remain to be elucidated. Here we show that pyridoxine 5'-phosphate oxidase (PNPO), which catalyses bioactivation of vitamin B6, serves as an oxygen sensor and regulates lysosomal activity in macrophages. Decreased PNPO activity under prolonged hypoxia reduced an active form of vitamin B6, pyridoxal 5'-phosphate (PLP), and inhibited lysosomal acidification, which in macrophages led to iron dysregulation, TET2 protein loss and delayed resolution of the inflammatory response. Among PLP-dependent metabolism, supersulfide synthesis was suppressed in prolonged hypoxia, resulting in the lysosomal inhibition and consequent proinflammatory phenotypes of macrophages. The PNPO-PLP axis creates a distinct layer of oxygen sensing that gradually shuts down PLP-dependent metabolism in response to prolonged oxygen deprivation.

Efficient Separation of Methanol Single-Micron Droplets by Tailing Phenomenon Using a PDMS Microfluidic Device.

Microdroplet-based fluidic systems have the advantages of small size, short diffusion time, and no cross-contamination; consequently, droplets often provide a fast and precise reaction environment as well as an analytical environment for individual molecules. In order to handle diverse reactions, we developed a method to create organic single-micron droplets (S-MDs) smaller than 5 µm in diameter dispersed in silicone oil without surfactant. The S-MD generation microflow device consists of a mother droplet (MoD) generator and a tapered separation channel featuring multiple side channels. The tapered channel enhanced the shear forces to form tails from the MoDs, causing them to break up. Surface treatment with the fluoropolymer CYTOP protected PDMS fluid devices from organic fluids. The tailing separation of methanol droplets was accomplished without the use of surfactants. The generation of tiny organic droplets may offer new insights into chemical separation and help study the scaling effects of various chemical reactions.

Disease Control and Treatment Satisfaction in Patients with Chronic Spontaneous Urticaria in Japan.

Background: Chronic spontaneous urticaria (CSU), characterized by the recurrence of pruritic hives and/or angioedema for >6 weeks with no identifiable trigger, has a negative impact on health-related quality of life (HRQoL). Methods: The objective of this web-based cross-sectional study was to evaluate disease control, disease burden, and treatment satisfaction in Japanese adults with CSU using the Urticaria Control Test (UCT), HRQoL outcomes, and the Treatment Satisfaction Questionnaire for Medication-9 items (TSQM-9). Results: In total, 529 adults were included in the analysis (59.9% female), with a mean ± standard deviation (SD) in CSU duration of 13.2 ± 13.0 years. Based on UCT scores, two-thirds of patients had poor (score of 0-7; 23.6%) or insufficient (score of 8-11; 43.3%) symptom control, and one-third had good control (score of 12-16; 33.1%). Overall treatment satisfaction was not high, with mean ± SD TSQM-9 scores of 55.5 ± 17.6% for effectiveness, 68.2 ± 18.8% for convenience, and 59.2 ± 18.4% for global satisfaction. No apparent differences in TSQM-9 scores were observed between patients receiving different medications. HRQoL outcomes were worse among patients with poor/insufficient symptom control. Conclusions: Japanese adults with CSU have a high disease burden, and better treatment options are needed to increase treatment satisfaction.

Changes in chronic myeloid leukemia treatment modalities and outcomes after introduction of second-generation tyrosine kinase inhibitors as first-line therapy: a multi-institutional retrospective study by the CML Cooperative Study Group.

This study investigated changes in treatment modalities and outcomes of chronic myeloid leukemia in the chronic phase (CP-CML) after the approval of second-generation tyrosine kinase inhibitors (2G-TKIs) for first-line therapy. Patients were grouped into those who underwent TKI therapy up to December 2010 (imatinib era group, n = 185) and after January 2011 (2G-TKI era group, n = 425). All patients in the imatinib era group were initially treated with imatinib, whereas patients in the 2G-TKI era group were mostly treated with dasatinib (55%) or nilotinib (36%). However, outcomes including progression-free survival, overall survival, and CML-related death (CRD) did not differ significantly between groups. When stratified by risk scores, the prognostic performance of the ELTS score was superior to that of the Sokal score. Even though both scoring systems predicted CRD in the imatinib era, only the ELTS score predicted CRD in the 2G-TKI era. Notably, the outcome of patients classified as high-risk by ELTS score was more favorable in the 2G-TKI era group than in the imatinib era group. Thus, expanding treatment options may have improved patient outcomes in CP-CML, particularly in patients classified as high-risk by ELTS score.

Multiple Transitions between Y Chromosome and Autosome in Tago's Brown Frog Species Complex.

Sex chromosome turnover is the transition between sex chromosomes and autosomes. Although many cases have been reported in poikilothermic vertebrates, their evolutionary causes and genetic mechanisms remain unclear. In this study, we report multiple transitions between the Y chromosome and autosome in the Japanese Tago's brown frog complex. Using chromosome banding and molecular analyses (sex-linked and autosomal single nucleotide polymorphisms, SNPs, from the nuclear genome), we investigated the frogs of geographic populations ranging from northern to southern Japan of two species, Rana tagoi and Rana sakuraii (2n = 26). Particularly, the Chiba populations of East Japan and Akita populations of North Japan in R. tagoi have been, for the first time, investigated here. As a result, we identified three different sex chromosomes, namely chromosomes 3, 7, and 13, in the populations of the two species. Furthermore, we found that the transition between the Y chromosome (chromosome 7) and autosome was repeated through hybridization between two or three different populations belonging to the two species, followed by restricted chromosome introgression. These dynamic sex chromosome turnovers represent the first such findings in vertebrates and imply that speciation associated with inter- or intraspecific hybridization plays an important role in sex chromosome turnover in frogs.

Correlation Analysis of Clinician- and Patient-Reported Outcomes Among Japanese Adults with Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic relapsing condition with high disease burden and impact on health-related quality of life (HRQoL). Correlations between clinician- and patient-reported outcomes tend to be poor, and limited data in Asian patients are available. METHODS: ADDRESS-J was a prospective, non-interventional, longitudinal study that evaluated the real-world effectiveness and safety of AD treatment in Japanese adults (aged 20-59 years) with moderate-to-severe AD. Three clinician-reported AD severity outcomes (Investigator's Global Assessment, Eczema Area and Severity Index, and body surface area affected), three dermatological patient-reported outcomes (Patient-Oriented Eczema Measure, Dermatology Life Quality Index, and Worst Itch Numerical Rating Scale), and two general HRQoL patient-reported outcomes (5-dimension EuroQoL questionnaire and EuroQol Visual Analog Scale) were collected at baseline and every 3 months throughout the 24-month observation period. Four biomarkers were also analyzed when available (thymus and activation-regulated chemokine [TARC], lactate dehydrogenase [LDH], total immunoglobulin E [IgE], and peripheral blood eosinophil counts [PB EOS]). Spearman's correlation coefficients were calculated using all available pooled data from baseline through 24 months. RESULTS: Correlations between the three clinician-reported outcomes were high/very high (Spearman's correlation coefficients 0.76-0.92); those between the three dermatological patient-reported outcomes were moderate (0.53-0.64), and those between the clinician-reported and dermatological patient-reported outcomes were low/moderate (0.37-0.51). Correlations between the general HRQoL patient-reported outcomes and the clinician-reported and dermatological patient-reported outcomes were negligible-moderate (0.26-0.60). Biomarker correlations with the clinician-reported and dermatological patient-reported outcomes were low/moderate for TARC and LDH (0.44-0.63), but negligible/low for PB EOS and total IgE (0.01-0.41). CONCLUSIONS: These results show that clinician- and patient-reported outcomes do not necessarily correlate well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when assessing disease severity/impact, planning treatment, and assessing response to treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) Identifier UMIN000022623.

Atopic dermatitis (AD) is a long-term recurring skin disease that needs monitoring over time. Various measures (outcomes) are used to assess the severity of AD and its effect on patients. Some outcomes are based on examinations used by clinicians (doctors). Others are based on questionnaires used by patients themselves to report how severe they feel their AD is, and how it affects their lives. It is not known how well these different measures correlate with one another (how a severity score given by one outcome agrees with that given by another outcome), especially in Asian patients. This analysis used information from ADDRESS-J, a study that followed Japanese adults with moderate-to-severe AD who were treated for AD in the real world for a period of 2 years. It used a statistical method to compare three clinician-reported severity outcomes, three dermatological (skin-related) patient-reported outcomes, and two general health-related quality of life patient-reported outcomes. Agreement between the three clinician-reported outcomes was high or very high. Agreement between the three dermatological patient-reported outcomes was moderate. However, importantly, agreement between the clinician-reported outcomes and the dermatological patient-reported outcomes was low or moderate. Agreement between the general health-related quality of life outcomes and all other dermatological outcomes (whether clinician- or patient-reported) was low or moderate. The study showed that clinician-reported and patient-reported AD outcomes do not necessarily agree well in Japanese adults with AD. This highlights the importance of including patient-reported outcomes when evaluating AD, planning treatment, or judging how well patients are responding to treatment.

Comparison of standardized prophylactic high-dose and intrathecal methotrexate for DLBCL with a high risk of CNS relapse.

The efficacy of high-dose methotrexate (HD-MTX) for central nervous system (CNS) relapse prophylaxis in patients with high-risk diffuse large B-cell lymphoma (DLBCL) is controversial. We compared the prophylactic effects of HD-MTX and intrathecal methotrexate (IT-MTX) on CNS relapse in high-risk DLBCL, in a multicenter retrospective study. A total of 132 patients with DLBCL at high risk of CNS relapse who received frontline chemotherapy and IT-MTX from 2003 to 2013 (n = 34) or HD-MTX from 2014 to 2020 (n = 98) were included. After a median follow-up of 52 months (range: 9-174), 11 patients had isolated CNS relapse: six (6.1%) in the HD-MTX group and five (14.7%) in the IT-MTX group. The median time until CNS relapse was 38 months (range: 11-122), and the cumulative incidence of CNS relapse at 3 years was 3.9% in the HD-MTX group and 6.1% in the IT-MTX group (P = 0.93). Similar results were obtained after adjusting for background factors using propensity score-matched analysis (4.5% HD-MTX vs. 7.6% IT-MTX, P = 0.84). The CNS relapse rate in HD-MTX-treated patients was equivalent to that in IT-MTX patients, demonstrating that HD-MTX was not superior to IT-MTX in preventing CNS relapse.

Real-world data of AML in Japan: results of JALSG clinical observational study-11 (JALSG-CS-11).

This report covers acute myeloid leukemia (AML) results from a multicenter, prospective observational study of AML, myelodysplastic syndromes, and chronic myelomonocytic leukemia in Japan. From August 2011 to January 2016, 3728 AML patients were registered. Among them, 42% were younger than 65, and the male-to-female ratio was 1.57:1. With a median follow-up time of 1807 days (95% confidence interval [CI]: 1732-1844 days), the estimated 5-year overall survival (OS) rate in AML patients (n = 3707) was 31.1% (95% CI: 29.5-32.8%). Trial-enrolled patients had a 1.7-fold higher OS rate than non-enrolled patients (5-year OS, 58.9% [95% CI: 54.5-63.1%] vs 35.5% [33.3-37.8%], p < 0.0001). Women had a higher OS rate than men (5-year OS, 34% [95% CI; 31.4-36.7%] vs 27.7% [25.7-29.7%], p < 0.0001). The OS rate was lower in patients aged 40 and older than those under 40, and even lower in those over 65 (5-year OS for ages < 40, 40-64, 65-74, ≥ 75: 74.5% [95% CI; 69.3-79.0%] vs 47.5% [44.4-50.6%] vs 19.3% [16.8-22.0%] vs 7.3% [5.5-9.4%], respectively). This is the first paper to present large-scale data on survival and clinical characteristics in Japanese AML patients.

Real-world data of MDS and CMML in Japan: results of JALSG clinical observational study-11 (JALSG-CS-11).

We conducted a multicenter, prospective observational study of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML) in Japan. From August 2011 to January 2016, we enrolled 6568 patients. Herein, we report the results for MDS (n = 2747) and CMML (n = 182). The percentage of patients aged 65 years or older was 79.5% for MDS and 79.7% for CMML. The estimated overall survival (OS) rate and cumulative incidence of AML evolution at 5 years were 32.3% (95% confidence interval: 30.2-34.5%) and 25.7% (23.9-27.6%) for MDS, and 15.0% (8.9-22.7%) and 39.4% (31.1-47.6%) for CMML. Both diseases were more common in men. The most common treatment for MDS was azacitidine, which was used in 45.4% of higher-risk and 12.7% of lower-risk MDS patients. The 5-year OS rate after treatment with azacitidine was 12.1% (9.5-15.1%) for of higher-risk MDS patients and 33.9% (25.6-42.4%) for lower-risk patients. The second most common treatment was erythropoiesis-stimulating agents, given to just 20% of lower-risk patients. This is the first paper presenting large-scale, Japanese data on survival and clinical characteristics in patients with MDS and CMML.

Disease burden and treatment satisfaction in patients with prurigo nodularis in Japan.

Prurigo nodularis (PN) is a chronic inflammatory skin disorder with a high disease burden. In this cross-sectional, web-based survey, Global Questions (GQ), the Numerical Rating Scales (NRS) for pruritus, burning sensation and sleep disturbance, the Short-Form-8 (SF-8) Health Survey, Dermatology Life Quality Index (DLQI), Patient Health Questionnaire 9 (PHQ-9), Work Productivity and Activity Impairment (WPAI), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) scores were used to assess the current disease burden and treatment satisfaction among patients with PN in Japan. In total, 97 patients were included (55.7% male, median age 51 years, median duration of PN 36 months). Based on GQ scores, 35.1% of patients had mild disease, 50.5% moderate, and 14.4% severe disease. Disease burden increased as the severity of PN increased, as indicated by worsening of pruritus NRS scores and quality of life (DLQI, PHQ-9, WPAI presenteeism, work productivity loss, and activity impairment scores). Patients with comorbid atopic dermatitis (AD) also had more intense pruritus than those without AD. Mean ± standard deviation TSQM-9 scores for effectiveness, convenience, and global satisfaction were 54.7 ± 18.1%, 62.4 ± 15.2%, and 57.4 ± 15.9%, respectively. TSQM-9 scores were lowest in patients receiving the most intensive guideline-directed treatment (i.e., topical corticosteroids + systemic oral corticosteroids or cyclosporine), highlighting an unmet need for more effective treatment options for patients with PN. In summary, Japanese patients with PN reported increased disease burden and reduced treatment satisfaction with increased disease severity, despite the use of guideline-recommended therapies.

Prognostic significance of the CFA ratio for newly diagnosed acute myeloid leukemia: A multicenter retrospective study.

The CFA ratio, calculated using pretreatment C-reactive protein (CRP), fibrinogen, and albumin levels (CRP × fibrinogen/albumin), was previously reported to be a significant prognostic factor for acute myeloid leukemia (AML). This multicenter retrospective study evaluated the prognostic value of the CFA ratio in 328 adult patients with newly diagnosed AML from April 2000 to March 2018. The median age was 49.5 years (range, 15-75 years), and 60.7% of the population were males. According to the European LeukemiaNet (ELN) risk classification, 67 patients (20.4%) were in the favorable-risk group, 197 patients (60.1%) in the intermediate-risk group, and 58 patients (17.7%) in the adverse-risk group. The median CFA ratio was 1.07 (0-67.69). Based on the calculated cutoff CFA ratio of 1.44, the cohort included 176 and 152 patients with low and high CFA ratios, respectively. At a median follow-up of 91.2 months, the 7-year overall survival (OS) and disease-free survival (DFS) rates were 51.2% and 48.6%, respectively, in the overall cohort. The 7-year OS rates were 61.7% and 39.0% in the low and high CFA ratio groups, respectively (p < 0.001). The 7-year DFS rates were 58.1% and 37.0% in the low and high CFA ratio groups, respectively (p = 0.004). In univariate analysis, age ≥50 years, male sex, ELN risk class, and comorbidities were associated with poor OS. Age, ELN risk class, comorbidities, and high CFA ratio were associated with poor OS in multivariate analysis. Subgroup analysis revealed that the CFA ratio was significant in the intermediate and adverse ELN risk classes. These findings indicate the prognostic significance of the CFA ratio in AML.

Cryo-EM structures of human zinc transporter ZnT7 reveal the mechanism of Zn2+ uptake into the Golgi apparatus.

Zinc ions (Zn2+) are vital to most cells, with the intracellular concentrations of Zn2+ being tightly regulated by multiple zinc transporters located at the plasma and organelle membranes. We herein present the 2.2-3.1 Å-resolution cryo-EM structures of a Golgi-localized human Zn2+/H+ antiporter ZnT7 (hZnT7) in Zn2+-bound and unbound forms. Cryo-EM analyses show that hZnT7 exists as a dimer via tight interactions in both the cytosolic and transmembrane (TM) domains of two protomers, each of which contains a single Zn2+-binding site in its TM domain. hZnT7 undergoes a TM-helix rearrangement to create a negatively charged cytosolic cavity for Zn2+ entry in the inward-facing conformation and widens the luminal cavity for Zn2+ release in the outward-facing conformation. An exceptionally long cytosolic histidine-rich loop characteristic of hZnT7 binds two Zn2+ ions, seemingly facilitating Zn2+ recruitment to the TM metal transport pathway. These structures permit mechanisms of hZnT7-mediated Zn2+ uptake into the Golgi to be proposed.

Is neonatal uterine bleeding responsible for early-onset endometriosis?

BACKGROUND: It has been hypothesized that the origin of early-onset endometriosis could be from endometrial mesenchymal stem cells (eMSCs) in neonatal uterine blood (NUB). There is no information on the possible mechanistic basis linking an association between NUB/neonatal endometrium and development of early-onset endometriosis. In this study we performed a series of experiments to clarify the mechanistic link between NUB and/or neonatal endometrium and development of early-onset endometriosis. METHODS: We retrospectively collected postmortem neonatal endometria (n = 15) and prospectively collected NUB (n = 18) of female babies for the analysis of different biological markers including eMSCs. Immunohistochemical analysis of neonatal endometria was performed to examine the expression patterns of ovarian steroid receptors (ER/PGR), decidualization (prolactin, IGFBP1), pre-decidualization (Glycodelin A, α-SMA), proliferation (Ki-67 index), vascularity (CD31 + cells), immunocompetent CD68+, CD45+, CD56 + cells and some putative markers of eMSCs. Cell transfer method and immunocytochemistry were used to investigate the eMSCs and/or endometrial cells in NUB. RESULTS: Immunohistochemical analysis of postmortem neonatal endometria revealed variable staining response to ER/PGR, decidual markers, and substantial proliferative and angiogenic activity. A moderate to strong immunoexpression of Glycodelin-A was found in both neonatal and adult endometria. The tissue infiltration of CD56+, CD45 + and CD68 + immunocompetent cells was significantly low in neonatal endometria than that in adult endometria (p = 0.0003, p < 0.0001, p = 0.034, respectively). No eMSCs or even endometrial cells were detected in NUB. However, a variable expression of some phenotypes of eMSCs (CD90/CD105) was found in neonatal endometria. CONCLUSIONS: Based on our serial experiments we did not find any supporting evidence for the role of NUB in early-onset endometriosis. Neonatal endometria showed variable expression of ovarian steroid receptors, decidualization, and a substantial amount of proliferative and angiogenic activity. As an alternative mechanism, a significantly less tissue accumulation of immunocompetent cells in neonatal endometria may explain the survival of ER + and PGR + cells should they make entry into the pelvis and consequent development of early endometriosis with the onset of ovarian function. Future study with large sample size and application of modified technological tools is warranted to test the NUB hypothesis and to clarify their biological or clinical significance. TRIAL REGISTRATION: not applicable.

Clinical management of second-generation tyrosine kinase inhibitor therapy in patients with newly diagnosed chronic myeloid leukemia in the chronic phase, focusing on age and dose effects.

ABL1-tyrosine kinase inhibitors (TKIs) are an established treatment choice for patients with chronic myeloid leukemia in the chronic phase (CML-CP). However, effects of TKI dose modification have not been well investigated. In this study, we retrospectively analyzed 178 patients with newly diagnosed CML-CP who were treated with dasatinib or nilotinib, focusing on age and dose effects. Efficacy as measured by cumulative major molecular response (MMR) and molecular response 4.5 rates did not differ significantly between the younger group and elderly group. Elderly patients who started nilotinib at a reduced dose had similar or better efficacy outcomes (including cumulative MMR and continuation ratios) than other groups, and elderly patients who started dasatinib at a reduced dose had the lowest MMR ratio and longest MMR duration. Effects of dose modification based on age and TKI selection can be attributed to flexible management of TKI therapy in real-world practice, but further studies are required to validate the findings of this study.

Silicon chambers for enhanced incubation and imaging of microfluidic droplets.

Droplet microfluidics has become a powerful tool in life sciences, underlying digital assays, single-cell sequencing or directed evolution, and it is making foray in physical sciences as well. Imaging and incubation of droplets are crucial, yet they are encumbered by the poor optical, thermal and mechanical properties of PDMS, a material commonly used in microfluidics labs. Here we show that Si is an ideal material for droplet chambers. Si chambers pack droplets in a crystalline and immobile monolayer, are immune to evaporation or sagging, boost the number of collected photons, and tightly control the temperature field sensed by droplets. We use the mechanical and optical benefits of Si chambers to image ≈1 million of droplets from a multiplexed digital assay - with an acquisition rate similar to the best in-line methods. Lastly, we demonstrate their applicability with a demanding assay that maps the thermal dependence of Michaelis-Menten constants with an array of ≈150 000 droplets. The design of the Si chambers is streamlined to avoid complicated fabrication and improve reproducibility, which makes Si a complementary material to PDMS in the toolbox of droplet microfluidics.

Management and Risk Factors for Pleural Effusion in Japanese Patients with Chronic Myeloid Leukemia Treated with First-line Dasatinib in Real-world Clinical Practice.

Objective Pleural effusion (PE) is a common adverse event that occurs during dasatinib therapy for chronic myeloid leukemia (CML). However, the pathomechanism of PE and appropriate management of Asian patients with CML have not been elucidated. This study investigated the incidence rate, risk, and appropriate management of PE in Asian patients with CML treated with dasatinib. Methods We retrospectively collected data on patients in the chronic phase of CML who received first-line dasatinib therapy and were registered in the CML-Cooperative Study Group database. Patients We identified 44 cases of PE in a series of 89 patients and analyzed previously reported risk factors and effective management of PE. Results A univariate analysis revealed that age, diabetes mellitus, chronic renal failure, hypertension, the history of cardiovascular events, and dasatinib dose were significantly associated with PE. A multivariate analysis revealed that age ≥65 years old was the only independent risk factor for PE. Dasatinib dose reduction and switching to a tyrosine kinase inhibitor showed a statistically significant difference in effectively reducing PE volume compared to single diuretic use. Conclusion Although further studies are warranted, our observations showed that advanced age is a significant risk factor for PE, and tyrosine kinase inhibitor dose reduction or replacement of dasatinib may be an effective management strategy for PE in Asian CML patients who received first-line treatment with dasatinib in real-world clinical practice.

Regional Difference in the Impact of COVID-19 Pandemic on Domain-Specific Physical Activity, Sedentary Behavior, Sleeping Time, and Step Count: Web-Based Cross-sectional Nationwide Survey and Accelerometer-Based Observational Study.

BACKGROUND: Physical activity (PA) and sedentary behavior (SB) have been affected by the COVID-19 pandemic and its restrictive environments, such as social distancing and lockdown measures. However, regional differences in the changes in domain-specific PA and SB in response to the COVID-19 pandemic are not clearly understood. OBJECTIVE: This study aimed to examine regional differences in domain-specific PA and SB, as well as sleeping time in response to the COVID-19 pandemic in Japan. METHODS: A web-based cross-sectional nationwide survey and an accelerometer-based longitudinal observation were conducted. In the web-based survey, we recruited 150 Japanese men and 150 Japanese women for each of the following age groups: 20s, 30s, 40s, 50s, 60s, and 70s (n=1800). A total of 1627 adults provided valid responses to web-based surveillance from June to July 2020. Participants were recruited from urban (Greater Tokyo Area, n=1028), urban-rural (regional core cities, n=459), or rural (regional small and medium cities, n=140) areas. They answered sociodemographic and health-related questions and retrospectively registered the PA data of their average day before and during the COVID-19 pandemic in a web-based PA record system. In the accelerometer-based observation, PA and step count data were obtained using a triaxial accelerometer on people living in urban (n=370) and rural (n=308) areas. RESULTS: Before the COVID-19 pandemic, there were no significant differences between these 3 regions in the time spent sleeping, staying at home, working or studying, and exercising (P>.05). By contrast, people living in urban areas had a longer duration of SB and transportation and a shorter duration of moderate-to-vigorous PA and lying or napping time compared with people living in rural areas (P>.05). During the COVID-19 pandemic, a significant decrease was observed in transportation time in urban (-7.2 min/day, P<.001) and urban-rural (-2.0 min/day, P=.009) areas but not in rural (-0.4 min/day, P=.52) areas. The moderate-to-vigorous PA was decreased in urban (-31.3 min/day, P<.001) and urban-rural (-30.0 min/day, P<.001) areas but not in rural areas (-17.3 min/day, P=.08). A significant increase was observed in time spent sleeping in urban (+22.4 min/day, P<.001) and urban-rural (+24.2 min/day, P<.001) but not in rural areas (+3.9 min/day, P=.74). Lying or napping was increased in urban (+14.9 min/day, P<.001) but not in rural areas (-6.9 min/day, P=.68). PA and step count obtained using an accelerometer significantly decreased in urban (P<.05) but not in rural areas (P>.05). CONCLUSIONS: The effect of the COVID-19 pandemic on PA and SB was significantly dependent on living area, even in a single country. The effects of PA and SB were greater in the Greater Tokyo Area and regional core cities but were not observed in regional small and medium cities in Japan.