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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.

Introduction: Several healthy euploid births have been reported following the transfer of mosaic embryos, including both euploid and aneuploid blastomeres. This has been attributed to a reduced number of aneuploid cells, as previously reported in mice, but remains poorly explored in humans. We hypothesized that mitochondrial function, one of the most critical factors for embryonic development, can influence human post-implantation embryonic development, including a decrease of aneuploid cells in mosaic embryos.Methods: To clarify the role of mitochondrial function, we biopsied multiple parts of each human embryo and observed the remaining embryos under in vitro culture as a model of post-implantation development (n = 27 embryos). Karyotyping, whole mitochondrial DNA (mtDNA) sequencing, and mtDNA copy number assays were performed on all pre- and post-culture samples.Results: The ratio of euploid embryos was significantly enhanced during in vitro culture, whereas the ratio of mosaic embryos was significantly reduced. Furthermore, post-culture euploid and culturable embryos had significantly few mtDNA mutations, although mtDNA copy numbers did not differ.Discussion: Our results indicate that aneuploid cells decrease in human embryos post-implantation, and mtDNA mutations might induce low mitochondrial function and influence the development of post-implantation embryos with not only aneuploidy but also euploidy. Analyzing the whole mtDNA mutation number may be a novel method for selecting a better mosaic embryo for transfer.

IntroductionAlthough the rapid plasma reagin (RPR) test is used to determine treatment efficacy for syphilis, animal studies show that it decreases gradually after an initial increase even without treatment. Pre-treatment changes in RPR titer in humans and its relationship with post-treatment changes in RPR titer are not well known.MethodsWe retrospectively analyzed the clinical records of syphilitic patients who underwent automated RPR (Mediace) testing twice before treatment (i.e., at diagnosis and treatment initiation) within 1-3 months at an HIV/AIDS referral hospital in Japan between 2006 and 2018. The RPR values were expressed as the ratio to the value at treatment initiation. The mean monthly relative change in the RPR after treatment was calculated on the log2 scale for each patient and analyzed by multivariable linear regression.ResultsSixty-eight patients were identified. The median age was 45 (interquartile range [IQR], 38-50), 98.5% (67/68) were men, and 97.1% (66/68) had HIV. The median RPR titer ratio at treatment initiation/diagnosis was 0.87 (IQR, 0.48-1.30). The RPR titer decreased more than twofold in 26.5% (18/68) and more than fourfold in 10.3% (7/68) before treatment. In the multivariable analysis, higher age (predicted monthly RPR relative change on the log2 scale 0.23/10 years [95% confidence interval [CI], 0.090-0.37]), history of syphilis (0.36 [95% CI, 0.07-0.65]), and a lower ratio of RPR at treatment initiation/diagnosis (-0.52/every 10-fold increase [95% CI, -0.81 to -0.22]) were associated with a slower RPR decrease after treatment.ConclusionsIn a mostly HIV patient population, RPR titer can show more than four-fold spontaneous increase or decrease within 1-3 months. Pre-treatment spontaneous decrease of RPR titer was associated with a slower decrease in post-treatment RPR titer.

Prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma is characterized by repeated cycles of remission followed by symptom recurrence, persistent detection of SARS-CoV-2, and profound humoral immunodeficiency. To the best of our knowledge, the present report is the first to describe dual antiviral therapy with remdesivir and ensitrelvir for prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma. A 59-year-old, female patient with a history of follicular lymphoma treated with obinutuzumab and bendamustine contracted COVID-19 despite receiving a single course of standard remdesivir therapy. She received dual antiviral therapy with remdesivir following a five-day course of oral ensitrelvir, which improved her clinical symptoms and chest radiology findings and cleared SARS-CoV-2 from respiratory samples. Dual antiviral therapy with remdesivir and ensitrelvir may be sufficient to stop viral replication and promote clinical resolution in prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma.

To the best of our knowledge, the present report is the first to describe immune reconstitution inflammatory syndrome (IRIS) in a case of Pneumocystis jirovecii (P. jirovecii) infection of the spleen. A 45-year-old, men who have sex with men patient presented with constipation, abdominal pain, nausea, fever, and weight loss. Human immunodeficiency virus infection and P. jirovecii pneumonia were diagnosed. Abdominal computed tomography revealed multiple, hypodense, cystic lesions in the spleen. Based on the histopathological findings of the lesion obtained from a percutaneous splenic biopsy, extrapulmonary P. jirovecii infection of the spleen was diagnosed. Trimethoprim/sulfamethoxazole was administered for 21 days, and antiretroviral therapy was initiated ten days after the former regimen was begun. Temporary enlargement of the splenic lesions and fever recurrence were observed after the trimethoprim/sulfamethoxazole regimen was completed. However, the clinical course was favorable, with no splenic rupture or splenic bleeding. Our investigation suggested that additional therapy, such as corticosteroid administration, may not be required for IRIS in a splenic P. jirovecii infection, but further research is needed for a definitive conclusion.

Abstract Physical properties of tritium (T) and deuterium (D) have been of great interest as a fuel for nuclear fusion. However, several kinds of the physical properties in a cryogenic environment have not been reported. Optical properties in liquid and solid phases are indispensable for the quality control of the DT fuel. We study the dependence of the refractive index of solid DT on temperature. A dedicated cryogenic system has been developed and forms a transparent solid DT in a prism cell. Refractive index measurements based on Snell’s law were conducted. The refractive indexes of solid DT are from 1.1618 ± 0.0002 to 1.1628 ± 0.0002 in the temperature range of 19.40 K to 17.89 K.

Waste incineration plants are complex dynamical systems that rely on expert human operators to maintain steady combustion, by observing real-time in-chamber video feeds. Real-time plant forecasting provides vital operational support in decision making, and applying machine learning to automatically learn dynamics forecast models from video feeds is an attractive means to realise this. However, learning complex dynamics in systems that requires cost-efficiency remains an open research problem. Specifically, modelling plant dynamics in real-time is challenging due to uncertainties caused by inhomogeneous waste inputs, requiring complex learning that impedes real-time modelling. To address this, this paper presents a real-time data-driven framework for generating video forecasts, by incorporating task-relevant domain-knowledge, during learning. Specifically, this method combines dynamics modelling and forecasting using dynamic mode decomposition, with Fourier transformations informed by expert operator heuristic knowledge for encoding task-relevant frequency information inside the learning process. Experiments in this paper demonstrate that the proposed framework captures intuitive physical aspects of the underlying physiochemical process, with a greatly reduced computational runtime in comparison to standard approaches, allowing for application in real-time domains. Forecasted video predictions are accurate over short time horizons, and capture important system characteristics over longer time periods.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan’s COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government’s role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Abstract To elucidate a mechanism for enhancing mung bean seedlings’ growth under microgravity conditions, we measured growth, gene expression, and enzyme activity under clinorotation (20 rpm), and compared data obtained to those grown under normal gravity conditions (control). An increase in fresh weight, water content, and lengths were observed in the clinostat seedlings, compared to those of the control seedlings. Real-time PCR showed that aquaporin expression and the amylase gene were upregulated under clinorotation. Additionally, seedlings under clinorotation exhibited a significantly higher amylase activity. Near-infrared image showed that there was no restriction of water evaporation from the seedlings under clinorotation. Therefore, these results indicate that simulated microgravity could induce water uptake, resulting in enhanced amylase activity and seedling growth. Upregulated aquaporin expression could be the first trigger for enhanced growth under clinorotation. We speculated that the seedlings under clinorotation do not use energy against gravitational force and consumed surplus energy for enhanced growth.

Stone tidal weirs are not just relics of the past; they also serve as a guide to future sustainable marine ecological conservation. They symbolize the ability of humans to adapt, use, and live in balance and harmony with the ocean environment. Situated along intertidal or coastal zones, these stone tidal weirs are on the frontline of climate impact and are often abandoned as the local community cannot afford the costs of repair. This has led to loss of this valuable traditional resource management system that contributes to tangible and intangible heritage of coastal communities, as well as to culture and biodiversity.

Objective: Pregnancy and lactation-associated osteoporosis (PLO) is a rare disease, which can lead to vertebral fractures in women of reproductive age. No treatment strategy for PLO has been established. Here we report a case of PLO treated with teriparatide followed by denosumab, in which remarkable improvement in bone mineral density (BMD) was achieved. Case report: A 27-year-old woman experienced severe back pain two weeks after her first delivery. PLO was diagnosed from her low BMD and multiple vertebral compression fractures. She was treated with teriparatide for 6 months, followed by denosumab. After 1 year, her BMD increase from baseline was 16.5% in L2∼4 and her pain had been relieved. Conclusion: In addition to weaning, administration of teriparatide followed by denosumab led to remarkable improvement in the patient's symptoms and BMD. Therefore, we regard this method as a promising choice for the treatment of PLO.

Evaluating the maturity of peach fruit is desirable during both the preharvest and postharvest periods, and flesh firmness (FF) is a representative maturity index. Although a non-destructive FF measurement technique using visible (VIS) and near-infrared (NIR) spectroscopy has been developed, the principle has been unclear. This study was conducted to examine the structure of the FF prediction model by comparing with that of the model for measuring water-soluble pectin (WSP) content. Those two prediction models have the same information regions related to the colors of pericarp and mesocarp (chlorophyll) and to a water band in the NIR region. Moreover, a statistical heterospectroscopy analysis between NIR and 1H nuclear magnetic resonance (NMR) spectra suggests the possibility that absorptions of methanol and succinate as well as galacturonic acid embedded in a water band play important roles in predicting FF. This approach would enhance the reliability of nondestructive VIS-NIR prediction models in many practical situations.

A 40-year-old male developed refractory acute promyelocytic leukemia (APL) after various treatments including all-trans retinoic acid, tamibarotene, arsenic trioxide (As2O3), conventional chemotherapy, and autologous peripheral blood stem cell transplantation. We attempted to use both tamibarotene and As2O3 as a combination therapy, and he achieved molecular complete remission. Grade 2 prolongation of the QTc interval on the electrocardiogram was observed during the therapy. The combination therapy of As2O3 and tamibarotene may be effective and tolerable for treating refractory APL cases who have no treatment options, even when they have previously been treated with tamibarotene and As2O3 as a single agent.

Foreign residents represent an increasing proportion of newly diagnosed human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) cases in Japan, though scant research has addressed this. This study aimed to estimate the diagnosed proportion of people living with HIV/AIDS (PLWHA) among foreign residents in Japan, covering 1990−2017 and stratifying by geographic region of the country of origin. A balance equation model was employed to statistically estimate the diagnosed proportion as a single parameter. This used published estimates of HIV incidence and prevalence, population size, visit duration, travel volume, as well as surveillance data on HIV/AIDS in Japan. The proportion varied widely by region: People from Western Europe, East Asia and the Pacific, Australia and New Zealand, and North America were underdiagnosed, while those from sub-Saharan Africa, South and South-East Asia, and Latin America were more frequently diagnosed. Overall, the diagnosed proportion of PLWHA among foreign residents in Japan has increased, but the latest estimate in 2017 was as low as 55.3%; lower than the estimate among Japanese on the order of 80% and far below the quoted goal of 90%. This finding indicates a critical need to investigate the underlying mechanisms, including disparate access to HIV testing.

Background: Convalescent plasma is a potential therapeutic option for patients with coronavirus disease 2019 (COVID-19). Despite its use for treating several viral infections, we lack comprehensive data on its efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We conducted a multicenter, open-label, randomized controlled trial of convalescent plasma therapy with high neutralizing activity against SARS-CoV-2 in high-risk patients within five days after the onset of COVID-19 symptoms. The primary endpoint was the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs from days 0-5., Results: Between February 24, 2021, and November 30, 2021, 25 patients were randomly assigned to either convalescent plasma (n = 14) or standard of care (n = 11) groups. Four patients discontinued their allocated convalescent plasma, and 21 were included in the modified intention-to-treat analysis. The median interval between the symptom onset and plasma administration was 4.5 days (interquartile range, 3-5 days). The primary outcome of the time-weighted average change in the SARS-CoV-2 viral load in nasopharyngeal swabs did not significantly differ between days 0-5 (1.2 log 10 copies/mL in the convalescent plasma vs. 1.2 log 10 copies/mL in the standard of care (effect estimate, 0.0 [95% confidence interval, -0.8-0.7]; P = 0.94)). No deaths were observed in either group., Conclusions: The early administration of convalescent plasma with high neutralizing activity did not contribute to a decrease in the viral load within five days compared with the standard of care alone., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

We report a case of a 63-year-old HIV-positive Japanese male with a CD4 cell count of 127/μL who was admitted to our hospital because of suspected malignant lymphoma. Initial blood tests revealed anemia, thrombocytopenia, hypoalbuminemia, and hypergammaglobulinemia. Imaging tests revealed a lung nodule, bilateral pleural effusion, hepatosplenomegaly and generalized lymphadenopathy. No evidence of malignant lymphoma or multicentric Castleman's disease was noted on biopsy specimens; however, Kaposi sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen-1-positive cells were observed as well as an elevated interleukin (IL)-6, IL-10 and KSHV viral load. He fulfilled the novel diagnostic criteria for KSHV-associated inflammatory cytokine syndrome (KICS). After initiating antiretroviral therapy, his symptoms and radiological abnormalities drastically improved. After 1-year follow-up, his HIV was well controlled without any relapsing symptoms.

Background: Kidney disease is a significant cause of morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). However, epidemiologic and clinical variables regarding kidney disease have not been determined among HIV-infected patients in Japan., Patients and Methods: A cross-sectional study of 788 HIV-infected outpatients including 706 men was conducted in 2009. The patient's mean age and CD4+ T cell count were 46.2 +/-11.8 years and 418 +/- 202/microL, respectively. Of them, 677 patients (86%) had an undetectable HIV-RNA level (<50 copies/mL). Random urine and blood samples were collected to study the coexistence of chronic kidney disease (CKD). In addition, serum cystatin C was measured since it is considered to be an alternative marker of early kidney dysfunction in the HIV population. The estimated glomerular filtration rate (eGFR) based on serum creatinine was calculated using the 3-variable equation, proposed by the Japanese Society of Nephrology [eGFR (mL/ min/1.73m2) = 194 x Serum creatinine (-1.094) x Age (-0.287 x 0.739 (if female)]. CKD stages were classified based on the National Kidney Foundation guidelines., Results: The prevalence of CKD and that of CKD > or = stage 3 was 14.9% and 9.4%, respectively. The pro-portion of each stage was as follows: stage 1, 15 patients (1.9%); stage 2, 28 patients (3.6%); stage 3, 66 patients (8.4%); stage 4, 1 patient (0.1%); stage 5, 1 patient (0.1%); and stage 5D, 6 patients (0.8%). Elevation of serum cystatin C (> or = 0.9 mg/L) was found in 23.3%. Comorbidities such as hypertension and diabetes were found in 55.4% and 27.0% in patients with CKD > or = stage 3, respectively. Urinalysis showed 71 patients (9.1%) with proteinuria and 44 patients (5.6%) with hematuria., Conclusion: CKD has become an important comorbidity for HIV-infected patients in Japan, a point that should be given more emphasis from public health perspective.