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Abstract Despite high vaccination rates globally, countries are still grappling with new COVID infections, and patients diagnosed as mild dying at home during outpatient treatment. Hence, this study aim to identify, then validate, biomarkers that could predict if newly infected COVID-19 patients would subsequently require hospitalization or could recover safely with medication as outpatients. Serum cytokine/chemokine data from 129 COVID-19 patients within 7 days after the onset of symptoms in Bangladesh were used as training data. The majority of patients were infected with the Omicron variant and over 88% were vaccinated. Patients were divided into those with mild symptoms who recovered, and those who deteriorated to moderate or severe illness. Using the Lasso method, 15 predictive markers were identified and used to classify patients into these two groups. The biomarkers were then validated in a cohort of 194 Covid patients in Japan with a predictive accuracy that exceeded 80% for patients infected with Delta and Omicron variants, and 70% for Wuhan and Alpha variants. In an environment of widespread vaccination, these biomarkers could help medical practitioners determine if newly infected COVID-19 patients will improve and can be managed on an out-patient basis, or if they will deteriorate and require hospitalization.

AbstractDeadwood, a vital component of forest ecosystems, constitutes a quintessential carbon reservoir that must be disclosed under the United Nations Framework Convention on Climate Change. This reservoir, comprising fallen logs, snags, and stumps, markedly affects carbon dynamics over decades. In this study, deadwood carbon stocks were quantified using data from 2674 sites in Japan surveyed between 2011 and 2015 via the National Forest Soil Carbon Inventory, and the deadwood carbon attributes in the country were explored. Deadwood were surveyed using the line intersect method for fallen logs and the belt transect method for stumps and snags. In Japan, the deadwood carbon stock (measured in t-C/ha) was quantified at 7.5 ± 9.74 (mean ± SD), with fallen logs at 3.26 ± 4.43, stumps at 2.45 ± 5.69, and snags at 1.80 ± 5.27, with significant differences detected among these stocks (p

Abstract The release of carbon dioxide from the soil to the atmosphere, known as soil respiration, is the second largest terrestrial carbon flux after photosynthesis, but the convergence of the data-driven estimates is unclear. Here we collate all historical data-driven estimates of global soil respiration to analyze convergence and uncertainty in the estimates. Despite the development of a dataset and advanced scaling techniques in the last two decades, we find that inter-model variability has increased. Reducing inter-model variability of global soil respiration is not an easy task, but when the puzzle pieces of the carbon cycle fit together perfectly, climate change prediction will be more reliable.

Abstract We address the nonperturbative calculation of the inclusive decay rate of semileptonic B (s)-meson decays from lattice QCD. Precise Standard-Model predictions are key ingredients in searches for new physics, and this type of computation may eventually provide new insight into the long-standing tension between the inclusive and exclusive determinations of the Cabibbo-Kobayashi-Maskawa (CKM) matrix elements |V cb | and |V ub |. We present results from a pilot lattice computation for B s → X c lν l , where the initial b quark described by the relativistic-heavy-quark (RHQ) formalism on the lattice and the other valence quarks discretised with domain-wall fermions are simulated approximately at their physical quark masses. We compare two different methods for computing the decay rate from lattice data of Euclidean n-point functions, namely Chebyshev and Backus-Gilbert approaches. We further study how much the ground-state meson dominates the inclusive decay rate and indicate our strategy towards a computation with a more comprehensive systematic error budget.

Abstract We present an ab initio study of inclusive semileptonic decays of heavy mesons from lattice QCD. Our approach is based on a recently proposed method, that allows one to address the study of these decays from the analysis of smeared spectral functions extracted from four-point correlators on the lattice, where the smearing is defined in terms of the phase-space integration relevant to the inclusive decays. We present results obtained from gauge-field ensembles from the JLQCD and ETM collaborations, and discuss their relation with theoretical predictions from the operator-product expansion.

Abstract A cytokine storm induces acute respiratory distress syndrome, the main cause of death in coronavirus disease 2019 (COVID-19) patients. However, the detailed mechanisms of cytokine induction due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To examine the cytokine production in COVID-19, we mimicked the disease in SARS-CoV-2-infected alveoli by adding the lysate of SARS-CoV-2-infected cells to cultured macrophages or induced pluripotent stem cell-derived myeloid cells. The cells secreted interleukin (IL)-6 after the addition of SARS-CoV-2-infected cell lysate. Screening of 25 SARS-CoV-2 protein-expressing plasmids revealed that the N protein-coding plasmid alone induced IL-6 production. The addition of anti-N antibody further enhanced IL-6 production, but the F(ab’)2 fragment did not. Sera from COVID-19 patients also enhanced IL-6 production, and sera from patients with severer disease induced higher levels of IL-6. These results suggest that anti-N antibody promotes IL-6 production in SARS-CoV-2-infected alveoli, leading to the cytokine storm of COVID-19.

Abstract After the accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), much of the wild and edible mushrooms and plants in the surrounding areas were contaminated with radiocesium (137Cs). To elucidate their concentration characteristics, we analyzed 137Cs radioactivity data in edible forest products brought in for food inspection by the residents of Kawauchi Village, 12–30 km away from the FDNPP, from 2012 to 2019. A Bayesian model to estimate 137Cs concentration was constructed. Parameters of the normalized concentration of species (NC sp) for mushrooms were similar to those of the same species obtained in a previous study. Although NC sp values were highly varied among species, mycorrhizal mushrooms tended to have high NC sp values, followed by saprotrophic mushrooms, and wild edible plants values were low. Also, half of mycorrhizal mushroom species (8 of 16) showed an increasing trend in concentration with time; however, saprotrophic mushrooms and wild plants generally demonstrated a decreasing trend (22 of 24). The model considering the sub-village location information decreased the error of individual samples by 40% compared to the model not considering any location information, indicating that the detailed geo-information improved estimation accuracy. Our results indicate that the radioactivity data from samples collected by local residents can be used to accurately assess internal exposure to radiation due to self-consumption of contaminated wild mushrooms and plants.

Abstract We perform a numerical computation of the anomalous magnetic moment (g − 2) of the electron in QED by using the stochastic perturbation theory. Formulating QED on the lattice, we develop a method to calculate the coefficients of the perturbative series of g − 2 without the use of the Feynman diagrams. We demonstrate the feasibility of the method by performing a computation up to the α 3 order and compare with the known results. This program provides us with a totally independent check of the results obtained by the Feynman diagrams and will be useful for the estimations of not-yet-calculated higher order values. This work provides an example of the application of the numerical stochastic perturbation theory to physical quantities, for which the external states have to be taken on-shell.

Abstract Background Mycobacterium tuberculosis is known to cause latent tuberculosis infection (LTBI) in 25–50% of the cases, of whom 10–20% develop active tuberculosis (TB). Notably, no marker currently exists for judging the therapeutic effect of TB; it is currently judged by chest X-ray and clinical symptoms. We attempted to establish a marker for distinguishing LTBI from active TB and to identify the probability of recurrence after TB treatment, using information on circulating miRNA expression. Methods In total, 32 patients were enrolled in this study: 16 with an onset or recurrence of active TB, and 16 with LTBI showing positive interferon-gamma release assays (IGRA) test and chest X-ray. Total RNA from serum in an exosome-rich fraction was first extracted, followed by miRNA expression analysis using a next-generation sequencer, then, this data were analyzed using miRDeep2. Results Using the expression information of eight miRNAs, LTBI and TB could be diagnosed with an accuracy of 71.8% (odds ratio: 6.16, p value = 3.20e-02). Conclusions A novel method for efficiently differentiating between LTBI and active TB was established. This method appears to be promising for evaluating the therapeutic effect of TB, as it can be performed in a minimally invasive manner.

Measurement(s) activity (of a radionuclide) • Cesium Cs 137 Technology Type(s) digital curation Factor Type(s) geographic location Sample Characteristic - Organism Cryptomeria japonica • Chamaecyparis obtusa • Pinus densiflora • Quercus serrata Sample Characteristic - Environment temperate evergreen needleleaf forest • temperate deciduous broadleaf forest • leaf • wood • litter layer • forest soil • mushroom (food source) • bark • pollen Sample Characteristic - Location Japan • Fukushima Prefecture Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13166462

In this study, we examined the composition of organic constituents of stem woody tissue together with tree growth in Quercus mongolica var. grosseserrata Blume seedlings raised under controlled CO2 and/or O3 concentrations in a Free-Air Concentration Enrichment system. After exposure to ambient air (control), elevated CO2 concentration (550 μmol mol–1 CO2), elevated O3 concentration (double that of the control), and a combination of elevated CO2 and O3 concentrations during a growing season, we measured the diameter and length of stem, and biomass of sampled seedlings and quantified the lignin, extractive, and holocellulose contents of the woody tissue of current-year stems. We confirmed that the growth of seedlings was enhanced under an elevated CO2 concentration condition. In line with this, the extractive content was lower in woody tissue formed under an elevated CO2 concentration than that formed under ambient air, whereas holocellulose content showed an inverse pattern. Elevated O3 concentration itself did not change the organic constituents of the woody tissue, but it reduced the influence of an elevated CO2 concentration. We thus assume that Q. mongolica formed woody tissue with a low extractive content under the high CO2 concentration condition, although this response was possibly mitigated by an elevated O3 concentration. Extractives contains antimicrobial components such as tannins, flavonoids, quinones, and terpenoids. The decrease in extractives within the widely distributed Q. mongolica in East Asia may have a non-negligible impact on C cycling in the future earth with high atmospheric CO2 concentration.

Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy remained unknown.Methods: In this retrospective study we evaluated the effects of tocilizumab monotherapy on the clinical characteristics, serum biomediator levels, viral elimination, and specific IgG antibody induction in 13 severely to critically ill patients and compared with those of dexamethasone monotherapy and dexamethasone plus tocilizumab.Results: A single tocilizumab administration led to a rapid improvement in clinical characteristics, inflammatory findings, and oxygen supply in 7 of 11 patients with severe COVID-19, and could recover from mechanical ventilation management (MVM) in 2 patients with critically ill COVID-19. Four patients exhibited rapidly worsening even after tocilizumab administration and required MVM and additional methylprednisolone treatment. Tocilizumab did not delay viral elimination or inhibit IgG production specific for the virus, whereas dexamethasone inhibited IgG induction. A multiplex cytokine array system revealed a significant increase in the serum expression of 54 out of 80 biomediators in patients with COVID-19 compared with that in healthy controls. Compared with those who promptly recovered in response to tocilizumab, patients requiring MVM showed a significantly higher ratio of basal level of ferritin/CRP and a persistent increase in the levels of CRP and specific cytokines and chemokines including IL-6, IFN-γ, IP-10, and MCP-1. The basal high ratio of ferritin/CRP was also associated with clinical deterioration even in patients treated with dexamethasone and tocilizumab.Conclusion: Tocilizumab as monotherapy has substantial beneficial effects in some patients with severe COVID-19, who showed a relatively low level of the ratio of ferritin/CRP and prompt reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1. The high ratio of ferritin/CRP is associated with rapid worsening of pneumonia. Further evaluation is warranted to clarify whether tocilizumab monotherapy or its combination with corticosteroid is preferred for severely to critically ill patients with COVID-19.

Spatiotemporal prediction of the response of planted forests to a changing climate is increasingly important for the sustainable management of forest ecosystems. In this study, we present a methodology for estimating spatially varying productivity in a planted forest and changes in productivity with a changing climate in Japan, with a focus on Japanese cedar (Cryptomeria japonica D. Don) as a representative tree species of this region. The process-based model Biome-BGC was parameterized using a plant trait database for Japanese cedar and a Bayesian optimization scheme. To compare productivity under historical (1996-2000) and future (2096-2100) climatic conditions, the climate scenarios of two representative concentration pathways (i.e., RCP2.6 and RCP8.5) were used in five global climate models (GCMs) with approximately 1-km resolution. The seasonality of modeled fluxes, namely gross primary production, ecosystem respiration, net ecosystem exchange, and soil respiration, improved after two steps of parameterization. The estimated net primary production (NPP) of stands aged 36-40 years under the historical climatic conditions of the five GCMs was 0.77 ± 0.10 kgC m-2 year-1 (mean ± standard deviation), in accordance with the geographical distribution of forest NPP estimated in previous studies. Under the RCP2.6 and RCP8.5 scenarios, the mean NPP of the five GCMs increased by 0.04 ± 0.07 and 0.14 ± 0.11 kgC m-2 year-1, respectively. The increases in annual NPP were small in the southwestern region because of the decreases in summer NPP and the small increases in winter NPP under the RCP2.6 and RCP8.5 scenarios, respectively. Under the RCP2.6 scenario, Japanese cedar was at risk in the southwestern region, in accordance with previous studies, and monitoring and silvicultural practices should be modified accordingly.

The effects of climate change on forest ecosystems take on increasing importance more than ever. Information on plant traits is a powerful predictor of ecosystem dynamics and functioning. We reviewed the major ecological traits, such as foliar gas exchange and nutrients, xylem morphology and drought tolerance, of Cryptomeria japonica and Chamaecyparis obtusa, which are major timber species in East Asia, especially in Japan, by using a recently developed functional trait database for both species (SugiHinokiDB). Empirically, C. obtusa has been planted under drier conditions, whereas C. japonica, which grows faster but thought to be less drought tolerant, has been planted under wetter conditions. Our analysis generally support the empirical knowledge: The maximum photosynthetic rate, stomatal conductance, foliar nutrient content and soil-to-foliage hydraulic conductance were higher in C. japonica than in C. obtusa. In contrast, the foliar turgor loss point and xylem pressure corresponding to 50% conductivity, which indicate drought tolerance, were lower in C. obtusa and are consistent with the drier habitat of C. obtusa. Ontogenetic shifts were also observed; as the age and height of the trees increased, foliar nutrient concentrations, foliar minimum midday water potential and specific leaf area decreased in C. japonica, suggesting that nutrient and water limitation occurs with the growth. In C. obtusa, the ontogenetic shits of these foliar traits were less pronounced. Among the Cupressaceae worldwide, the drought tolerance of C. obtusa, as well as C. japonica, was not as high. This may be related to the fact that the Japanese archipelago has historically not been subjected to strong dryness. The maximum photosynthetic rate showed intermediate values within the family, indicating that C. japonica and C. obtusa exhibit relatively high growth rates in the Cupressaceae family, and this is thought to be the reason why they have been selected as economically suitable timber species in Japanese forestry. This study clearly demonstrated that the plant trait database provides us a promising opportunity to verify out empirical knowledge of plantation management and helps us to understand effect of climate change on plantation forests by using trait-based modelling.

Abstract Background In our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies. Methods We enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016. Cancer and MTB treatments were administered according to the approved guidelines. Results Patient demographics included: men/woman: 24/6; median age: 66.5 years; Eastern Cooperative Oncology Group performance status 0–1/2/3–4: 24/4/2; Stage IIB–IIIC/IV/recurrence: 6/22/2; lung cancer (LC)/CRC/other: 15/10/5; and MTB diagnosis (before or during anti-CCT): 20/10 (LC: 8/7; CRC: 8/2; other: 4/1). For anti-CCT, 23 patients received two cytotoxic agents with or without targeted agents and 7 patients received a single cytotoxic or targeted agent. The overall response rate was 36.7%. Regarding anti-MTB chemotherapy, 22 patients received a daily drug combination containing isoniazid, rifampicin, and ethambutol, plus pyrazinamide in 15 of the 22 patients, followed by daily isoniazid and rifampicin; the remaining 8 patients received other combinations. Hematological adverse events of Grade ≥ 3 were observed in 19 (67.9%) of 28 patients; laboratory data were lost for the remaining 2. Grade 3 lymphopenia and higher were significantly more frequent in LC compared to other malignancies (P

Abstract This study assessed historical changes in emissions of nitrous oxide (N2O), a potent greenhouse gas and stratospheric ozone-depleting substance, from the soils of East Asia to the atmosphere. A process-based terrestrial ecosystem model (VISIT) was used to simulate the nitrogen cycle and associated N2O emissions as a function of climate, land use, atmospheric deposition, and agricultural inputs from 1901 to 2016. The mean regional N2O emission rate in the 2000s was estimated to be 2.03 Tg N2O year−1 (1.29 Tg N year−1; approximately one-third from natural ecosystems and two-thirds from croplands), more than triple the rate in 1901. A sensitivity analysis suggested that the increase of N2O emissions was primarily attributable to the increase of agricultural inputs from fertilizer and manure. The simulated N2O emissions showed a clear seasonal cycle and interannual variability, primarily in response to meteorological conditions and nitrogen inputs. The spatial pattern of the simulated N2O emissions revealed hot spots in agricultural areas of China, South Korea, and Japan. The average N2O emission factor (emission per unit nitrogen input) was estimated to be 1.38%, a value comparable to previous estimates. These biogeochemical modeling results will facilitate identifying ways to mitigate global warming and manage agricultural practices in this region.

Background: To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial. Methods: Japanese patients aged 5–65 years were eligible for the study, if they had HDM-induced allergic rhinitis (AR), allergic bronchial asthma (BA), or both. TO-204 was administered in a dose titration scheme, and the maintenance dose was determined according to the predefined criteria. The treatment period was 52 weeks, and patients who were willing to continue the treatment received TO-204 beyond 52 weeks. This clinical trial is registered at the Japan Pharmaceutical Information Center (Japic CTI-121900). Results: Between July 2012 and May 2015, 44 patients (28 with AR and 16 with allergic BA) were enrolled into the study. All patients were included in the analysis. The duration of treatment ranged from 23 to 142 weeks and the median maintenance dose was 200 Japanese allergy units (JAU). Adverse events occurred in 22 patients (50%). The most common adverse event was local reactions related to the injection sites. Four patients experienced anaphylactic reactions when they were treated with the dose of 500 JAU. Two patients experienced anaphylactic shock with the doses of 1000 JAU at onset. These 6 patients could continue the study with dose reduction. Conclusions: Safety profile of TO-204 was acceptable in Japanese patients with HDM-induced AR or allergic BA. Higher doses should be administered carefully, because the risk of anaphylaxis increased at doses of 500 or 1000 JAU. Keywords: Allergen immunotherapy, Allergic bronchial asthma, Allergic rhinitis, Clinical trial, House dust mite

Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a leading problem in health care facilities worldwide. Methods This single-center retrospective cohort study consisted of a derivation phase and a validation phase. The derivation phase included all patients admitted to Osaka University Hospital between May 2010 and April 2011. We proposed a provisional available, bed-sided, comprehensive (ABC) score, and evaluated its accuracy using the clinical diagnosis as a reference. We subsequently revised ABC scores based on k coefficient scores of each variable; this revision was validated by applying it to another patient population. Results A total of 172 patients and 154 cases were enrolled in the derivation and validation studies, respectively. The revised ABC score consisted of four simple variables: type of clinical specimen (1 to 3 points), Gram-staining result (1 point), presence of local inflammation (2 points), and a systemic inflammatory response (2 points). A revised score of ≥5 points was sensitive (93.8%) and specific (90.6%), and the area under the receiver-operating curve was 0.969 (95% CI; 0.957–1). Conclusions We developed a simple and comprehensive scoring system for diagnosis of nosocomial MRSA infections; this system is applicable in a wide variety of situations.

Abstract To elucidate the temporal changes in the radiocesium distribution in forests contaminated by the Fukushima Daiichi Nuclear Power Plant accident, we monitored the 137Cs concentration and inventory within forests from 2011 to 2015 across nine plots containing variable tree species and different contamination levels. The 137Cs concentrations in needles and branches decreased exponentially at all coniferous plots, with effective ecological half-lives of 0.45–1.55 yr for needles and 0.83–1.69 yr for branches. By contrast, the 137Cs concentration in deciduous konara oak leaves did not change over the five years. The concentration of 137Cs in oak wood increased by 37–75%, whereas that in Japanese red pine decreased by 63% over the five years. In Japanese cedar and hinoki cypress, the 137Cs concentration in wood showed an increasing trend in half of the plots. The changes in 137Cs in the organic and mineral soil layers were not strongly related to the tree species or contamination level. Our multi-site, multi-species monitoring results revealed that the pattern of temporal changes in radiocesium in the 9 forest plots was similar overall; however, changes in 137Cs in needles/leaves and wood differed among tree species.

A Correction to this paper has been published: https://doi.org/10.1038/s41597-021-00855-5.

Wine, a widely consumed beverage, comprises several biophenols that promote health. Flavonoids, majorly present in red wine, have been shown to have antioxidant, anti-inflammatory, anticancer, and immunomodulatory activities. Regular consumption of red wine (100 mL/day) is estimated to provide an average of 88 mg of flavonoids, whereas recent epidemiological studies indicate that wine is one of the major sources of flavonoid intake amongst wine lovers in European countries (providing an average intake of 291–374 mg/day of flavonoids). In addition to being antioxidants, in vitro studies suggest that flavonoids also have anti-allergic activities that inhibit IgE synthesis, activation of mast cells and basophils or other inflammatory cells, and production of inflammatory mediators, including cytokines. Furthermore, they affect the differentiation of naïve CD4+ T cells into effector T cell subsets. Moreover, several studies have reported the benefits of flavonoids in allergic models such as atopic dermatitis, asthma, anaphylaxis, and food allergy; however, evidence in humans is limited to allergic rhinitis and respiratory allergy. Although further evaluation is required, it is expected that an appropriate intake of flavonoids may be beneficial in preventing, and eventually managing, allergic diseases.

Soil greenhouse gas fluxes (particularly CO(2), CH(4), and N(2)O) play important roles in climate change. However, despite the importance of these soil greenhouse gases, the number of reports on global soil greenhouse gas fluxes is limited. Here, new estimates are presented for global soil CO(2) emission (total soil respiration), CH(4) uptake, and N(2)O emission fluxes, using a simple data-oriented model. The estimated global fluxes for CO(2) emission, CH(4) uptake, and N(2)O emission were 78 Pg C yr(-1) (Monte Carlo 95% confidence interval, 64-95 Pg C yr(-1)), 18 Tg C yr(-1) (11-23 Tg C yr(-1)), and 4.4 Tg N yr(-1) (1.4-11.1 Tg N yr(-1)), respectively. Tropical regions were the largest contributor of all of the gases, particularly the CO(2) and N(2)O fluxes. The soil CO(2) and N(2)O fluxes had more pronounced seasonal patterns than the soil CH(4) flux. The collected estimates, including both the previous and the present estimates, demonstrate that the means of the best estimates from each study were 79 Pg C yr(-1) (291 Pg CO(2) yr(-1); coefficient of variation, CV = 13%, N = 6) for CO(2), 21 Tg C yr(-1) (29 Tg CH(4) yr(-1); CV = 24%, N = 24) for CH(4), and 7.8 Tg N yr(-1) (12.2 Tg N(2)O yr(-1); CV = 38%, N = 11) for N(2)O. For N(2)O, the mean of the estimates that was calculated by excluding the earliest two estimates was 6.6 Tg N yr(-1) (10.4 Tg N(2)O yr(-1); CV = 22%, N = 9). The reported estimates vary and have large degrees of uncertainty but their overall magnitudes are in general agreement. To further minimize the uncertainty of soil greenhouse gas flux estimates, it is necessary to build global databases and identify key processes in describing global soil greenhouse gas fluxes.