HIV incidence before and during the COVID-19 pandemic in Japan.

At the end of 2022, a total of 20,003 diagnoses of human immunodeficiency virus (HIV) infection and 8,983 cases of acquired immunodeficiency syndrome (AIDS) among Japanese nationals, and 3,860 HIV diagnoses and 1,575 AIDS cases among foreign residents, had been notified to the government in Japan. This study updates the estimate of HIV incidence, including during the COVID-19 pandemic. It aimed to reconstruct the incidence of HIV and understand how the disruption caused by COVID-19 affected the epidemiology of HIV. Using a median incubation period of 10.0 years, the number of undiagnosed HIV infections was estimated to be 3,209 (95% confidence interval (CI): 2,642, 3,710) at the end of 2022. This figure has declined steadily over the past 10 years. Assuming that the median incubation period was 10.0 years, the proportion of diagnosed HIV infections, including surviving AIDS cases, was 89.3% (95% CI: 87.8%, 91.0%). When AIDS cases were excluded, the proportion was 86.2% (95% CI: 84.3%, 88.3%). During the COVID-19 pandemic, the estimated annual diagnosis rate was slightly lower than during earlier time intervals, at around 16.5% (95% CI: 14.9%, 18.1%). Japan may already have achieved diagnostic coverage of 90%, given its 9% increment in the diagnosed proportion during the past 5 years. The incidence of HIV infection continued to decrease even during the COVID-19 pandemic from 2020 to 2022, and the annual rate of diagnosis decreased slightly to 16.5%. Monitoring the recovery of diagnosis along with the effective reproduction number is vital in the future.

Evaluation of the exit screening policy among travelers arriving from Asian and pacific nations.

BACKGROUND: The Japanese government has instituted border control measures against COVID-19, including entry and exit screening of people arriving from overseas. We sought to evaluate the effectiveness of the exit screening policy in Japan in reducing the risk of importing COVID-19 cases among travelers from Asian and Pacific countries. METHODS: The study period was stratified based on the timing of exit screening: (i) the control period (the pre-exit screening period from 25 October 2020 to 16 January 2021), (ii) the time period with the Alpha variant from 17 January to 10 April 2021, and (iii) the time period with the Delta variant from 2 May to 2 October 2021. Incidence data in the countries of origin were used to adjust for the risk of infection among travelers. The positivity rate of entry screening in Japan was compared among the three different study periods, adjusting for the risk of infection in the country of origin. RESULTS: The adjusted relative risk of positivity was greatly reduced and substantially below the value of 1 during the Alpha variant period compared with the control period. Although the relative risks increased when comparing the Delta variant period against control, the estimate remained below 1, except for among travelers from India and Myanmar. The relative risk reduction was greatest in high-income countries, with estimates of 100% and 96% risk reduction during the Alpha and Delta variant periods, respectively, followed by upper-middle-income countries with estimates of 90% and 76%, respectively. CONCLUSIONS: Even in the presence of the Alpha and Delta variants, exit screening clearly reduced the risk of infection among travelers arriving from Asian and Pacific nations. As the testing relies on the country of origin, the effectiveness varied greatly by the socioeconomic income status and epidemiological situation of those countries. Test standardization and quality assurance may be required in low- and middle-income countries.

Estimating the effective reproduction number of COVID-19 from population-wide wastewater data: An application in Kagawa, Japan.

Although epidemiological surveillance of COVID-19 has been gradually downgraded globally, the transmission of COVID-19 continues. It is critical to quantify the transmission dynamics of COVID-19 using multiple datasets including wastewater virus concentration data. Herein, we propose a comprehensive method for estimating the effective reproduction number using wastewater data. The wastewater virus concentration data, which were collected twice a week, were analyzed using daily COVID-19 incidence data obtained from Takamatsu, Japan between January 2022 and September 2022. We estimated the shedding load distribution (SLD) as a function of time since the date of infection, using a model employing the delay distribution, which is assumed to follow a gamma distribution, multiplied by a scaling factor. We also examined models that accounted for the temporal smoothness of viral load measurement data. The model that smoothed temporal patterns of viral load was the best fit model (WAIC = 2795.8), which yielded a mean estimated distribution of SLD of 3.46 days (95% CrI: 3.01-3.95 days). Using this SLD, we reconstructed the daily incidence, which enabled computation of the effective reproduction number. Using the best fit posterior draws of parameters directly, or as a prior distribution for subsequent analyses, we first used a model that assumed temporal smoothness of viral load concentrations in wastewater, as well as infection counts by date of infection. In the subsequent approach, we examined models that also incorporated weekly reported case counts as a proxy for weekly incidence reporting. Both approaches enabled estimations of the epidemic curve as well as the effective reproduction number from twice-weekly wastewater viral load data. Adding weekly case count data reduced the uncertainty of the effective reproduction number. We conclude that wastewater data are still a valuable source of information for inferring the transmission dynamics of COVID-19, and that inferential performance is enhanced when those data are combined with weekly incidence data.

Identifying the population susceptible to rubella in Japan, 2020: Fine-scale risk mapping.

BACKGROUND: Rubella remains a public health challenge in Japan, impeding the attainment of herd immunity. Despite vaccination efforts since 1976, persistent outbreaks reveal a susceptibility gap in male adults born before 1995. Seroepidemiological surveys are pivotal in evaluating population immunity and identifying at-risk groups. METHODS: This study aims to pinpoint high-risk areas for potential rubella outbreaks in Japan by merging seroepidemiological data from 2020 with population census information. Various data sources, including spatial demographic data, reported rubella and congenital rubella syndrome (CRS) cases, and traveler lodging statistics, were employed. Geospatial information for Japan's 230,300 small geographic areas was analyzed, and HI (hemagglutination inhibition) titers were examined by age and sex. Seroconversion was defined as an HI titer ≥ 1:32 or 1:16, indicating protective immunity. Geospatial maps illustrated the distribution of susceptible individuals per square kilometer, emphasizing high-risk urban areas like Tokyo and Osaka. Demographic shifts in the working-age population were assessed. RESULTS: Susceptible individuals cluster in densely populated urban centers, persisting despite demographic changes. The study highlights areas at risk of increased susceptibility, particularly with an HI titer cut-off of 1:16. Foreign travelers pose potential rubella importation risks as travel volume to Japan rises. To prevent epidemics and congenital rubella syndrome burden, achieving and sustaining herd immunity in high-risk areas is crucial. CONCLUSIONS: This study offers a comprehensive assessment of vulnerability in densely populated Japanese regions. Integrating population statistics with seroepidemiological data enhances our understanding of population immunity, guiding resource allocation for supplementary vaccination planning. To avert rubella epidemics, high-risk locations must bolster indirect protection through herd immunity, ultimately preventing congenital rubella syndrome.

Decomposing mechanisms of COVID-19 mortality in empirical datasets: A modeling study.

Our objective was to decompose mortality mechanisms during the coronavirus disease 2019 (COVID-19) pandemic to estimate direct, indirect, and associated deaths from COVID-19. Given the confirmatory diagnosis of COVID-19, a death event that was not necessarily caused by respiratory complications but stemmed from other complications was categorized as an indirect death from COVID-19. Associated deaths occurred in patients who did not have COVID-19 but died during the surge in COVID-19 cases when overwhelming pressure was exerted on the healthcare system. Analyzing the sixth wave (i.e., the first epidemic wave of the Omicron B.1.1.529 variant from January to May 2022), decomposition was achieved using the binomial and Poisson sampling process models fitted to two pieces of data (i.e., COVID-19 death certificate and excess data by major cause of death). The total numbers of direct, indirect, and associated deaths during the sixth wave in Osaka were estimated at 1,071; 948; and 2,157; respectively. The number of associated deaths was greater than the sum of direct and indirect deaths. We further observed that the composition of indirect and associated deaths differed by major cause of death, and deaths caused by circulatory disease included a greater proportion of indirect deaths compared with deaths by other causes. The goals of healthcare services for endemic COVID-19 include the sustainable provision of services to avoid preventable deaths. Therefore, gaining an in-depth understanding of mechanisms that lead to excess death is vital for improving future pandemic response efforts.

Public holidays increased the transmission of COVID-19 in Japan, 2020-2021: a mathematical modelling study.

OBJECTIVES: Although the role of specific holidays in modifying transmission dynamics of infectious diseases has received some research attention, the epidemiological impact of public holidays on the transmission of coronavirus disease 2019 (COVID-19) remains unclear. METHODS: To assess the extent of increased transmission frequency during public holidays, we collected COVID-19 incidence and mobility data in Hokkaido, Tokyo, Aichi, and Osaka from February 15, 2020 to September 30, 2021. Models linking the estimated effective reproduction number (Rt) with raw or adjusted mobility, public holidays, and the state of emergency declaration were developed. The best-fit model included public holidays as an essential input variable, and was used to calculate counterfactuals of Rt in the absence of holidays. RESULTS: During public holidays, on average, Rt increased by 5.71%, 3.19%, 4.84%, and 24.82% in Hokkaido, Tokyo, Aichi, and Osaka, respectively, resulting in a total increase of 580 (95% confidence interval [CI], 213 to 954), 2,209 (95% CI, 1,230 to 3,201), 1,086 (95% CI, 478 to 1,686), and 5,211 (95% CI, 4,554 to 5,867) cases that were attributable to the impact of public holidays. CONCLUSIONS: Public holidays intensified the transmission of COVID-19, highlighting the importance of considering public holidays in designing appropriate public health and social measures in the future.

Reconstructing the COVID-19 incidence in India using airport screening data in Japan.

BACKGROUND: A major epidemic of COVID-19 caused by the Delta variant (B.1.617.2) occurred in India from March to July 2021, resulting in 19 million documented cases. Given the limited healthcare and testing capacities, the actual number of infections is likely to have been greater than reported, and several modelling studies and excess mortality research indicate that this epidemic involved substantial morbidity and mortality. METHODS: To estimate the incidence during this epidemic, we used border entry screening data in Japan to estimate the daily incidence and cumulative incidence of COVID-19 infection in India. Analysing the results of mandatory testing among non-Japanese passengers entering Japan from India, we calculated the prevalence and then backcalculated the incidence in India from February 28 to July 3, 2021. RESULTS: The estimated number of infections ranged from 448 to 576 million people, indicating that 31.8% (95% confidence interval (CI): 26.1, 37.7) - 40.9% (95% CI: 33.5, 48.4) of the population in India had experienced COVID-19 infection from February 28 to July 3, 2021. In addition to obtaining cumulative incidence that was consistent with published estimates, we showed that the actual incidence of COVID-19 infection during the 2021 epidemic in India was approximately 30 times greater than that based on documented cases, giving a crude infection fatality risk of 0.47%. Adjusting for test-negative certificate before departure, the quality control of which was partly questionable, the cumulative incidence can potentially be up to 2.3-2.6 times greater than abovementioned estimates. CONCLUSIONS: Our estimate of approximately 32-41% cumulative infection risk from February 28 to July 3, 2021 is roughly consistent with other published estimates, and they can potentially be greater, given an exit screening before departure. The present study results suggest the potential utility of border entry screening data to backcalculate the incidence in countries with limited surveillance capacity owing to a major surge in infections.

Survey of exposure to stranded dolphins in Japan to investigate an outbreak of suspected infection with highly pathogenic avian influenza (H5N1) clade 2.3.4.4(b) in humans.

Background: A highly pathogenic avian influenza (HPAI) A (H5N1) virus has been detected in domestic and wild animals worldwide. The incidence of HPAI infections in sea mammals has been increasing, as is the number of stranded marine mammals linked to H5N1 viral clade 2.3.4.4(b). In this study, we investigated a stranding event involving dolphins and human-dolphin contact, and investigated the potential risk of animal-to-human H5N1 transmission with a survey of exposure on the Tsurigasaki coast, Japan. Methods: We performed a non-random, convenient-sample-based, survey on Tsurigasaki beach where around 30 melon-headed whales were stranded on April 3, 2023. Face-to-face (n = 25) and telephone (n = 1) interviews among surfers took place on April 7 and 8. A nasal swab for quick antigen testing was taken from those who wished to be tested (n = 13), to detect infections with influenza A virus. Results: Although there was no confirmatory diagnosis of H5N1 in either humans or dolphins (while n = 3 dolphins were autopsied), we found that a large number of surfers had touched the dolphins with their bare hands while attempting to rescue them, and that some surfers were directly exposed to dolphin blood and body fluids in the ocean. Conclusions: The adequate communication of risk is required to minimize the threat of viral transmission at this particular human-animal interface. Administrative and legal responses to cross-species transmission, including guidelines via one health frameworks, a rapid evaluation process of ethical approval, and the systematic involvement of experts in infectious disease, must be urgently formulated.

Reconstruction and analysis of the transmission network of African swine fever in People's Republic of China, August 2018-September 2019.

Introduction of African swine fever (ASF) to China in mid-2018 and the subsequent transboundary spread across Asia devastated regional swine production, affecting live pig and pork product-related markets worldwide. To explore the spatiotemporal spread of ASF in China, we reconstructed possible ASF transmission networks using nearest neighbour, exponential function, equal probability, and spatiotemporal case-distribution algorithms. From these networks, we estimated the reproduction numbers, serial intervals, and transmission distances of the outbreak. The mean serial interval between paired units was around 29 days for all algorithms, while the mean transmission distance ranged 332 -456 km. The reproduction numbers for each algorithm peaked during the first two weeks and steadily declined through the end of 2018 before hovering around the epidemic threshold value of 1 with sporadic increases during 2019. These results suggest that 1) swine husbandry practices and production systems that lend themselves to long-range transmission drove ASF spread; 2) outbreaks went undetected by the surveillance system. Efforts by China and other affected countries to control ASF within their jurisdictions may be aided by the reconstructed spatiotemporal model. Continued support for strict implementation of biosecurity standards and improvements to ASF surveillance is essential for halting transmission in China and spread across Asia.

Life-expectancy changes from 2019 to 22: A case study of Japan using provisional death count.

Many countries struggled with suppressing the incidence of COVID-19 caused by SARS-CoV-2 Omicron variant (B.1.1.529). As the epidemic size of COVID-19 in 2022 became bigger than earlier years in Japan, the present study aimed to estimate life expectancy at birth at the end of 2022, using provisional death datasets in Aichi and Fukui prefectures. We collected monthly death count from 2019 to the end of 2022, computing the period life table. While the life expectancy at birth in Aichi, 2019 was 84.6 years, it was very slightly extended to 84.7 years in 2020 and 2021, followed by a shortening for nearly 0.4 years in 2022. In Fukui, monotonous extension pattern was seen, i.e., 85.5 years in 2019, 85.6 in 2020, followed by 85.8 and 86.2 years in 2021 and 2022, respectively. Although decades-long trend of extending life expectancy at birth was partly discontinued from 2020 due to the pandemic at the national level, we have shown that the pandemic impact was still small in Japan by the end of 2022. First Omicron wave occurred shortly after primary series vaccination, and even real time booster program was underway during that wave. Different demographic consequences between Aichi and Fukui are explained by differential epidemic sizes prior to vaccination.

Epidemiological impact of travel enhancement on the inter-prefectural importation dynamics of COVID-19 in Japan, 2020.

Mobility restrictions were widely practiced to reduce contact with others and prevent the spatial spread of COVID-19 infection. Using inter-prefectural mobility and epidemiological data, a statistical model was devised to predict the number of imported cases in each Japanese prefecture. The number of imported cases crossing prefectural borders in 2020 was predicted using inter-prefectural mobility rates based on mobile phone data and prevalence estimates in the origin prefectures. The simplistic model was quantified using surveillance data of cases with an inter-prefectural travel history. Subsequently, simulations were carried out to understand how imported cases vary with the mobility rate and prevalence at the origin. Overall, the predicted number of imported cases qualitatively captured the observed number of imported cases over time. Although Hokkaido and Okinawa are the northernmost and the southernmost prefectures, respectively, they were sensitive to differing prevalence rate in Tokyo and Osaka and the mobility rate. Additionally, other prefectures were sensitive to mobility change, assuming that an increment in the mobility rate was seen in all prefectures. Our findings indicate the need to account for the weight of an inter-prefectural mobility network when implementing countermeasures to restrict human movement. If the mobility rates were maintained lower than the observed rates, then the number of imported cases could have been maintained at substantially lower levels than the observed, thus potentially preventing the unnecessary spatial spread of COVID-19 in late 2020.

Habitual Mask Wearing as Part of COVID-19 Control in Japan: An Assessment Using the Self-Report Habit Index.

Although the Japanese government removed mask-wearing requirements in 2023, relatively high rates of mask wearing have continued in Japan. We aimed to assess psychological reasons and the strength of habitual mask wearing in Japan. An Internet-based cross-sectional survey was conducted with non-random participant recruitment. We explored the frequency of mask usage, investigating psychological reasons for wearing masks. A regression analysis examined the association between psychological reasons and the frequency of mask wearing. The habitual use of masks was assessed in the participant's most frequently visited indoor space and public transport using the self-report habit index. The principal component analysis with varimax rotation revealed distinct habitual characteristics. Among the 2640 participants surveyed from 6 to 9 February 2023, only 4.9% reported not wearing masks at all. Conformity to social norms was the most important reason for masks. Participants exhibited a slightly higher degree of habituation towards mask wearing on public transport compared to indoor spaces. The mask-wearing rate was higher in females than in males, and no significant difference was identified by age group. Daily mask wearing in indoor spaces was characterized by two traits (automaticity and behavioral frequency). A high mask-wearing frequency has been maintained in Japan during the social reopening transition period. Mask wearing has become a part of daily habit, especially on public transport, largely driven by automatic and frequent practice.

Assessing the COVID-19 vaccination program during the Omicron variant (B.1.1.529) epidemic in early 2022, Tokyo.

BACKGROUND: Many countries, including high-income nations, struggled to control epidemic waves caused by the Omicron variant (B.1.1.529), which had an antigenically distinct evolution. Evaluating the direct and indirect effects of vaccination during the Omicron waves is essential to assess virus control policies. The present study assessed the population impacts of a vaccination program during the sixth wave caused by BA.1 and BA.2 from January to May 2022, in Tokyo. METHODS: We analyzed the primary series and booster vaccination coverages and the confirmed cases stratified by vaccination history. We estimated the number of COVID-19 cases that were directly and indirectly prevented by vaccination. To estimate the direct impact, we used a statistical model that compared risks between unvaccinated and vaccinated individuals. A transmission model employing the renewal process was devised to quantify the total effect, given as the sum of the direct and indirect effects. RESULTS: Assuming that the reporting coverage of cases was 25%, mass vaccination programs, including primary and booster immunizations, directly averted 640,000 COVID-19 cases (95% confidence interval: 624-655). Furthermore, these programs directly and indirectly prevented 8.5 million infections (95% confidence interval: 8.4-8.6). Hypothetical scenarios indicated that we could have expected a 19% or 7% relative reduction in the number of infections, respectively, compared with the observed number of infections, if the booster coverage had been equivalent to that of the second dose or if coverage among people aged 10-49 years had been 10% higher. If the third dose coverage was smaller and comparable to that of the fourth dose, the total number of infections would have increased by 52% compared with the observed number of infections. CONCLUSIONS: The population benefit of vaccination via direct and indirect effects was substantial, with an estimated 65% reduction in the number of SARS-CoV-2 infections compared with counterfactual (without vaccination) in Tokyo during the sixth wave caused by BA.1 and BA.2.

Evaluating the COVID-19 vaccination program in Japan, 2021 using the counterfactual reproduction number.

Japan implemented its nationwide vaccination program against COVID-19 in 2021, immunizing more than one million people (approximately 1%) a day. However, the direct and indirect impacts of the program at the population level have yet to be fully evaluated. To assess the vaccine effectiveness during the Delta variant (B.1.617.2) epidemic in 2021, we used a renewal process model. A transmission model was fitted to the confirmed cases from 17 February to 30 November 2021. In the absence of vaccination, the cumulative numbers of infections and deaths during the study period were estimated to be 63.3 million (95% confidence interval [CI] 63.2-63.6) and 364,000 (95% CI 363-366), respectively; the actual numbers of infections and deaths were 4.7 million and 10,000, respectively. Were the vaccination implemented 14 days earlier, there could have been 54% and 48% fewer cases and deaths, respectively, than the actual numbers. We demonstrated the very high effectiveness of COVID-19 vaccination in Japan during 2021, which reduced mortality by more than 97% compared with the counterfactual scenario. The timing of expanding vaccination and vaccine recipients could be key to mitigating the disease burden of COVID-19. Rapid and proper decision making based on firm epidemiological input is vital.

Possible adaptation measures for climate change in preventing heatstroke among older adults in Japan.

Introduction: Heatstroke mortality is highest among older adults aged 65 years and older, and the risk is even doubled among those aged 75 years and older. The incidence of heatstroke is expected to increase in the future with elevated temperatures owing to climate change. In the context of a super-aged society, we examined possible adaptation measures in Japan that could prevent heatstroke among older people using an epidemiological survey combined with mathematical modeling. Methods: To identify possible interventions, we conducted a cross-sectional survey, collecting information on heatstroke episodes from 2018 to 2019 among people aged 75 years and older. Responses were analyzed from 576 participants, and propensity score matching was used to adjust for measurable confounders and used to estimate the effect sizes associated with variables that constitute possible interventions. Subsequently, a weather-driven statistical model was used to predict heatstroke-related ambulance transports. We projected the incidence of heatstroke-related transports until the year 2100, with and without adaptation measures. Results: The risk factor with the greatest odds ratio (OR) of heatstroke among older adults was living alone (OR 2.5, 95% confidence interval: 1.2-5.4). Other possible risk factors included an inability to drink water independently and the absence of air conditioning. Using three climate change scenarios, a more than 30% increase in the incidence of heatstroke-related ambulance transports was anticipated for representative concentration pathways (RCP) 4.5 and 8.5, as compared with a carbon-neutral scenario. Given 30% reduction in single living, a 15% reduction in the incidence of heatstroke is expected. Given 70% improvement in all three risk factors, a 40% reduction in the incidence can be expected. Conclusion: Possible adaptation measures include providing support for older adults living alone, for those who have an inability to drink water and for those without air conditioning. To be comparable to carbon neutrality, future climate change under RCP 2.6 requires achieving a 30% relative reduction in all three identified risks at least from 2060; under RCP 4.5, a 70% reduction from 2050 at the latest is needed. In the case of RCP 8.5, the goal of heatstroke-related transports approaching RCP 1.9 cannot be achieved.

Beclin1 is essential for the pancreas development.

Beclin1 (Becn1) is a multifunctional protein involved in autophagy regulation, membrane trafficking, and tumor suppression. In this study, we examined the roles of Becn1 in the pancreas development by generating mice with conditional deletion of Becn1 in the pancreas using pancreatic transcriptional factor 1a (Ptf1a)-Cre mice (Becn1f/f; Ptf1aCre/+). Surprisingly, loss of Becn1 in the pancreas resulted in severe pancreatic developmental defects, leading to insufficient exocrine and endocrine pancreatic function. Approximately half of Becn1f/f; Ptf1aCre/+ mice died immediately after birth. However, duodenum and neural tissue development were almost normal, indicating that pancreatic insufficiency was the cause of death. These findings demonstrated a novel role for Becn1 in pancreas morphogenesis, differentiation, and growth, and suggested that loss of this factor leaded to pancreatic agenesis at birth.

Life-expectancy changes during the COVID-19 pandemic from 2019-2021: estimates from Japan, a country with low pandemic impact.

Background: The COVID-19 pandemic had a low impact on Japan in 2020, but the size of the epidemic increased considerably there in 2021. This study made a statistical analysis of life expectancy changes up to the end of 2021 in Japan. Objective: We aimed to estimate changes in life expectancy from 2019 to 2021 associated with the COVID-19 pandemic. To do so, we decomposed the life expectancy changes from 2020-2021 into age-specific and cause of death-specific contributions. Methods: We used the absolute number of deaths by age and prefecture in Japan to calculate life expectancy from 2019-21 at both national and prefectural levels, and also examined the correlation between life expectancy gap and annual number of COVID-19 cases, total person-days spent in intensive care, and documented deaths due to COVID-19. We used the Arriaga decomposition method to decompose national life expectancy changes from 2020 to 2021 into age and cause of death components. Results: From 2019-2020, Japan's national level life expectancy across the entire population was extended by 0.24 years. From 2020-2021, it shortened by 0.15 years. The life expectancy shortened more among women (0.15 years) than men (0.12 years). There was significant heterogeneity in life expectancy changes from 2020-2021 by prefecture. It ranged from the maximum shortening of 0.57 years in Tottori prefecture to the maximum extension of 0.23 years in Fukui. The regression analysis revealed the negative correlation between the life expectancy change and burden of COVID-19 at prefectural level. The decomposition of life expectancy changes at birth from 2020-2021 showed that losses in life expectancy were largely attributable to the mortality of the population over 70 years old. Changes in life expectancy among infants and working-age adults mostly contributed to lengthening overall life expectancy. Among leading major causes of death, deaths due to neoplastic tumor and cardiovascular diseases contributed to shortening life expectancy, whereas respiratory diseases did not. Conclusion: The decades-long increasing trend in life expectancy was suspended by the COVID-19 pandemic. However, life expectancy changes from 2019-2020 and 2020-2021 were small in Japan. This may be attributable to the small epidemiological impact of COVID-19 during this time period, but nonetheless, the negative impact of COVID-19 on life expectancy was indicated in the present study. The chance of death accelerated in older people in 2021, but a smaller number of deaths than usual among infants and working age adults contributed to extended life expectancy, and the change in the cause of death structure under the COVID-19 pandemic also significantly contributed to shortening life expectancy.

Night-time population consistently explains the transmission dynamics of coronavirus disease 2019 in three megacities in Japan.

Background: Mobility data are crucial for understanding the dynamics of coronavirus disease 2019 (COVID-19), but the consistency of the usefulness of these data over time has been questioned. The present study aimed to reveal the relationship between the transmissibility of COVID-19 in Tokyo, Osaka, and Aichi prefectures and the daily night-time population in metropolitan areas belonging to each prefecture. Methods: In Japan, the de facto population estimated from GPS-based location data from mobile phone users is regularly monitored by Ministry of Health, Labor, and Welfare and other health departments. Combined with this data, we conducted a time series linear regression analysis to explore the relationship between daily reported case counts of COVID-19 in Tokyo, Osaka, and Aichi, and night-time de facto population in downtown areas estimated from mobile phone location data, from February 2020 to May 2022. As an approximation of the effective reproduction number, the weekly ratio of cases was used. Models using night-time population with lags ranging from 7 to 14 days were tested. In time-varying regression analysis, the night-time population level and the daily change in night-time population level were included as explanatory variables. In the fixed-effect regression analysis, the inclusion of either the night-time population level or daily change, or both, as explanatory variables was tested, and autocorrelation was adjusted by introducing first-order autoregressive error of residuals. In both regression analyses, the lag of night-time population used in best fit models was determined using the information criterion. Results: In the time-varying regression analysis, night-time population level tended to show positive to neutral effects on COVID-19 transmission, whereas the daily change of night-time population showed neutral to negative effects. The fixed-effect regression analysis revealed that for Tokyo and Osaka, regression models with 8-day-lagged night-time population level and daily change were the best fit, whereas in Aichi, the model using only the 9-day-lagged night-time population level was the best fit using the widely applicable information criterion. For all regions, the best-fit model suggested a positive relationship between night-time population and transmissibility, which was maintained over time. Conclusion: Our results revealed that, regardless of the period of interest, a positive relationship between night-time population levels and COVID-19 dynamics was observed. The introduction of vaccinations and major outbreaks of Omicron BA. Two subvariants in Japan did not dramatically change the relationship between night-time population and COVID-19 dynamics in three megacities in Japan. Monitoring the night-time population continues to be crucial for understanding and forecasting the short-term future of COVID-19 incidence.

Reg family proteins contribute to inflammation and pancreatic stellate cells activation in chronic pancreatitis.

Chronic pancreatitis (CP) is a disease characterized by the inflammation and destruction of pancreatic tissue, leading to the replacement of functional tissue with fibrotic tissue. The regenerating gene (Reg) family proteins have recently been implicated in the repair and regeneration of inflamed pancreatic tissue, though the exact mechanisms of their involvement in the pathogenesis of CP are not yet fully understood. To investigate the role of Reg family proteins in CP, we generated global knockout mice (Reg-/-) for Reg1-3 (Reg1,2,3a,3b,3d,3g) genes using the CRISPR/Cas9 system. We then investigated the effect of Reg family protein deficiency in a genetic model of CP (X-SPINK1) mice by knocking out Reg1-3 genes. We examined pancreatic morphology, inflammatory cytokines expression, and activation of pancreatic stellate cells (PSCs) at different ages. Reg-/- mice showed no abnormalities in general growth and pancreas development. Deficiency of Reg1-3 in CP mice led to a reduction in pancreatic parenchymal loss, decreased deposition of collagen, and reduced expression of proinflammatory cytokines. Additionally, Reg proteins were found to stimulate PSCs activation. Overall, our study suggests that Reg1-3 deficiency can lead to the remission of CP and Reg family proteins could be a potential therapeutic target for the treatment of CP.

Age-dependent final size equation to anticipate mortality impact of COVID-19 in China.

Before reopening society in December 2022, China had not achieved sufficiently high vaccination coverage among people aged 80 years and older, who are vulnerable to severe infection and death owing to COVID-19. Suddenly ending the zero-COVID policy was anticipated to lead to substantial mortality. To investigate the mortality impact of COVID-19, we devised an age-dependent transmission model to derive a final size equation, permitting calculation of the expected cumulative incidence. Using an age-specific contact matrix and published estimates of vaccine effectiveness, final size was computed as a function of the basic reproduction number, R0. We also examined hypothetical scenarios in which third-dose vaccination coverage was increased in advance of the epidemic, and also in which mRNA vaccine was used instead of inactivated vaccines. Without additional vaccination, the final size model indicated that a total of 1.4 million deaths (half of which were among people aged 80 years and older) were anticipated with an assumed R0 of 3.4. A 10% increase in third-dose coverage would prevent 30,948, 24,106, and 16,367 deaths, with an assumed second-dose effectiveness of 0%, 10%, and 20%, respectively. With mRNA vaccine, the mortality impact would have been reduced to 1.1 million deaths. The experience of reopening in China indicates the critical importance of balancing pharmaceutical and non-pharmaceutical interventions. Ensuring sufficiently high vaccination coverage is vital in advance of policy changes.