Search

Introduction: Somatic or germline mutations in genes regulating Ras-MAPK pathway have been identified in majority of Juvenile myelomonocytic leukemia (JMML) cases. Mosaicism of KRAS and NRAS mutations in JMML were reported, with variation in the proportion of cells carrying these mutations across different organs. However, how this proportion is distributed across different organs had not been clarified whereas prevalence of somatic oncogenic KRAS mutations are known. Methods: Our study focused on one JMML patient with mosaic KRAS G12D mutation and uniparental disomy at the 12p locus, who developed aggressive transformation, invasion into multiple organs and subsequently died. DNA from FFPE biopsy samples of eighteen organs were analyzed using mutation-specific digital PCR (dPCR). The variant allele frequency (VAF) of KRAS G12D and hetero SNP at the 12p locus were analyzed in each samples to remove the impact of mutation by infiltrating tumor cells and to estimate the percentage of KRAS mutant cells. Results: KRAS G12D mutations were identified in samples from sixteen of eighteen analyzed tissues. The frequency of KRAS G12D mutated alleles varied among different tissue type and the median VAF was 5.9% (2.0% -29.3%). The VAF were relatively high in gastrointestinal tract (stomach, colon, ileum), liver and spleen, whereas the VAF were low or undetected in testis, heart and spinal cord. Conclusions: Our findings suggest that KRAS mosaic mutations can exhibit tissue specificity like somatic oncogenic mutations. These tissue distribution might be associated with pathogenesis of JMML and other types of cancer with mosaicism.

Intro: Detecting and responding to acute public health threats is one of the World Health Organization's (WHO) most important activities. Therefore, WHO established a unique approach for the global detection and verification of events of potential international public health concern and adopted an all-hazards approach as part of the International Health Regulations (2005), moving beyond a focus on infectious diseases only. Here, we analysed 20-year trends of acute public health events globally. Methods: We extracted data on acute public health events reported between 2002 and 2021 from the Event Management System (EMS). EMS is an internal WHO web-based platform used for tracking health threats globally. We examined the designation, source and hazard of events by WHO Region and over time by calculating descriptive statistics and trends using R. Findings: Between 2002 and 2021, 7572 events were recorded globally in EMS, ranging from 231 to 576 per year. Of these, 5466 (76%) were designated as substantiated, deemed true acute public health events, and only a small proportion (379, 5%) were unverifiable or had no designation. During the 20-year period, substantiated events were greatest in the WHO African Region (1684 events, 31%) and the WHO Region of the Americas (1312 events, 24%) and, similarly, by year, the burden was highest in those WHO regions. Globally, over time, two-thirds (3536, 65%) of substantiated events were initially reported by WHO and infectious diseases (4298, 79%) were the predominant cause of public health events. However, other causes, including animal origin or zoonoses were also important and disaster related events were on the rise in recent years, particularly in some WHO Regions. Conclusion: WHO has a robust system for global disease detection but health threats are continuously evolving. The impact of climate change and zoonoses is becoming more pronounced, emphasizing the importance of a One Health approach for disease detection.

The lead (Pb) in lead-acid batteries (LABs) accounts for up to 60% of their total weight and 80% of the metallic Pb produced worldwide. As a toxic substance but sought-after resource, developing a method to reclaim Pb from spent batteries, both safely and efficiently, is highly desirable. To this end, this paper explores the application of microwave heating to reduce Pb from PbO2, a component of LAB pastes, using a carbon (C) reductant. Various experiments were conducted between 200 and 1000 W to determine mass loss kinetics using a homemade thermogravimetric apparatus. The mechanisms and kinetics of the reactions, and their resultant phases, are discussed in comparison to differential thermal analyses (TG-DTA) of the same samples. Microwave heating was found to be highly effective, resulting in up to a 97% recovery of Pb metal at < 300 °C; however, complete reduction was unrealized due to crucible interference, microwave penetration depth, and the reflection of microwaves as Pb metal formed. The reduction and decomposition reactions were evaluated using X-ray diffraction (XRD).

Some mammal species exhibit pelage color change with seasonal molt. Seasonal molt and pelage color change are beneficial to thermoregulation and concealment, associated with seasonal environmental change. The Eurasian red squirrel Sciurus vulgaris Linnaeus, 1758 and the Siberian flying squirrel Pteromys volans (Linnaeus, 1758) are arboreal and sympatrically distributed in the subarctic northern Eurasian Continent and Sakhalin and Hokkaido islands. We expect that diurnal S. vulgaris may demonstrate more conspicuous difference between summer and winter pelages than nocturnal P. volans, because of its protective coloration in each season. To test this conjecture, we investigated their seasonal pelage color change. To diminish the effect of geographic variation in pelage color, we chose S. vulgaris orientis Thomas, 1906 and P. volans orii (Kuroda, 1921), which are endemic subspecies of Hokkaido Island, Japan. We used skin and stuffed specimens and frozen materials and categorized them into two pelage groups (summer and winter pelages) based on collection date. Pelage color characteristics were measured with a spectrophotometer for lightness, redness and yellowness. Countershading was examined by comparing dorsal and ventral lightness. Both subspecies showed lighter winter pelage than summer pelage, suggesting their greyish-white winter pelage was beneficial to concealment from predators during winter. As we expected, seasonal changes of redness and yellowness were more clearly recognized in S. vulgaris than in P. volans. As S. vulgaris is diurnal and vulnerable to attack by diurnal avian predators, reddish and yellowish pelage patterns may be important for concealment. Because it is nocturnal, P. volans may not need this reddish and yellowish pelage. Sciurus vulgaris also had a remarkably counter-shaded body, indicating that its body may reduce predation risk from daytime visual predators. Differences in seasonal pelage color change of these two arboreal squirrels may be caused by their different circadian rhythms.

The major chemical constituent contents of rice are moisture, protein and starch (amylose and amylopectin). Those constituent contents associate with eating quality of rice. Near-infrared (NIR) spectroscopy is one of the non-destructive methods for determining grain chemical contents. At grain elevator, moisture and protein contents can be measured with high accuracy using an NIR spectrometer by the effort of our research activities in Japan. However, the accuracy to determine amylose content is not sufficient. Thus, the objective of this study was to develop non-destructive method to determine rice amylose content for practical use at grain elevator. Milled rice amylose content measurement was performed using an auto-analyzer for reference (chemical) analysis. Spectra data of milled rice were obtained using an NIR spectrometer with a wavelength range of 850 to 1048 nm. Calibration model to determine amylose content was developed using non-waxy Japonica-type rice samples. Partial least squares (PLS) regression analysis was used to develop calibration model. The accuracy of the model was validated and the validation statistics were shown: coefficient of determination (r2) was 0.72, bias was -0.04%, standard error of prediction (SEP) was 0.92%, and ratio of SEP to standard deviation of reference data (RPD) was 1.90. Production year of the validation set (2017) was different from that of the calibration set (2008 to 2016). This means the same condition as practical use of this method at grain elevator. The result obtained in this study indicated that this calibration model enables non-destructive determination of rice amylose content at grain elevator.

Iron pyrite (FeS2) exhibits dynamic thermal stability and represents an ideal model system to probe complex phase transformations in materials. At elevated temperatures, the sublimation of S atoms from the FeS2 lattice results in a phase transformation to one of the many polymorphic forms of pyrrhotite, i.e., from Fe1-XS (where 0 ≤ X

Mucormycosis is a life-threatening infectious disease that occurs most commonly in immunocompromised patients such as those with hematological malignancies. Its clinical symptoms and associated radiological findings vary and specific biomarkers and culture characteristics have not been defined. An 85-year-old man who had been treated for myelodysplastic syndrome and tuberculosis for several months presented with subacute fever and worsening left-side chest pain. Contrast-enhanced computed tomography images depicted massive tumor-like consolidation without enhancement, expanding from the left lower lobe. Emboli that did not respond to anticoagulants were detected in the left descending pulmonary artery. Despite intensive treatment he developed multiple organ failure and died 47 days after hospitalization. Gross pathology of a lung autopsy specimen revealed left lower pulmonary arterial emboli and pulmonary infarction, which was concluded to be the direct cause of death. The emboli were histopathologically identified as invasive mycelia in vessels. Mucor sp. was detected via real-time polymerase chain reaction and immunohistopathological analyses revealed that the mold in the blood vessels of lung tissue was partially positive for the mucor antigen. In the present case of Mucor sp. pulmonary emboli in a patient with myelodysplastic syndrome, radiographic findings were hard to distinguish from those typical of a lung abscess.

We briefly review the current theoretical understanding of the light curves of novae. These curves exhibit a homologous nature, dubbed the universal decline law, and when time-normalized, they almost follow a single curve independently of the white dwarf (WD) mass or chemical composition of the envelope. The optical and near-infrared light curves of novae are reproduced mainly by free-free emission from their optically thick winds. We can estimate the WD mass from multiwavelength observations because the optical, UV, and soft X-ray light curves evolve differently and we can easily resolve the degeneracy of the optical light curves. Recurrent novae and classical novae are a testbed of type Ia supernova scenarios. In the orbital period versus secondary mass diagram, recurrent novae are located in different regions from classical novae and the positions of recurrent novae are consistent with the single degenerate scenario.

We identified a general course of classical nova outbursts in the B − V vs. U − B diagram. It has been reported that novae show spectra similar to A–F supergiants near optical light maximum. However, they do not follow the supergiant sequence in the color-color diagram, neither the blackbody nor the main-sequence sequence. Instead, we found that novae evolve along a new sequence in the pre-maximum and near-maximum phases, which we call the nova-giant sequence. This sequence is parallel to but Δ(U − B) ≈ −0.2 mag bluer than the supergiant sequence. After optical maximum, its color quickly evolves back blueward along the same nova-giant sequence and reaches the point of free-free emission (B − V = −0.03, U − B = −0.97) and stays there for a while, which is coincident with the intersection of the blackbody sequence and the nova-giant sequence. Then the color evolves leftward (blueward in B − V but almost constant in U − B) due mainly to development of strong emission lines. This is the general course of nova outbursts in the color-color diagram, which is deduced from eight well-observed novae including various speed classes. For a nova with unknown extinction, we can determine a reliable value of the color excess by matching the observed track of the target nova with this general course. This is a new and convenient method for obtaining color excesses of classical novae. Using this method, we redetermined the color excesses of nineteen well-observed novae.

Fabrication of fine TiN particle-dispersed dense Al2O3 composites with the compositions of Al2O3/TiN=100/0~90/10 vol% has been conducted from Al2O3/(Ti,TiN0.3) mixed powder compacts by capsule-free hot isostatic pressing (HIP) utilizing high-pressure N2 SHS. Fine Ti powders (φ ~ 0.3 μm) with TiN0.3 phase were prepared by thermal decomposition of planetary ball-milled fine TiH2 powders at 400 °C (673 K) for 1 h in a vacuum, followed by heating in N2 at 200°C (473 K) for 2 h. The Al2O3 powder compacts (relative densities of 57.2-57.8%) with homogeneously dispersed (Ti,TiN0.3) particles were prepared. The mixed powder compacts were hot isostatically pressed (HIPed) under the conditions of 1350 °C (1623 K) at 7 MPa N2 for 1 h, followed by the heating at the same temperature for 2 h under 196 MPa-N2. At the first stage of heating [1350°C (1623K)/7MPa/1h], solid/gas reaction of SHS between (Ti,TiN0.3) and N2 was introduced to form TiN and densification of the Al2O3 powder compacts up to the relative density of 92-93% with closed pores was performed. And at the sequent second stage [1350 °C (1623K)/196MPa/2h], densification of the most of pre-sintered composites consisting of Al2O3 and TiN reached higher relative densities than 98.5%. Dispersion of TiN particles (~φ 0.30 μm) in the composites suppressed the grain growth of Al2O3 during HIP-sintering. Mechanical properties, such as bending strength (σb), Vickers hardness (HV), fracture toughness (K1C), and electrical resistivity (ρ) of the composites were evaluated as a function of TiN content; the maximum values of σb=640 MPa, HV=19.5 GPa, and KIC=4.5 MPa・m1/2 were obtained in the Al2O3/TiN=97/3~95/5 vol% composites. Among the composites, the lowest ρ value of 2.6×103 Ω・m was attained at Al2O3/TiN=90/10 vol% composite.

The distribution of polymorphisms related to glutathione S-transferases (GST) has been described in different populations, mainly for white individuals. We evaluated the distribution of GST mu (GSTM1) and theta (GSTT1) genotypes in 594 individuals, by multiplex PCR-based methods, using amplification of the exon 7 of CYP1A1 gene as an internal control. In São Paulo, 233 whites, 87 mulattos, and 137 blacks, all healthy blood-donor volunteers, were tested. In Bahia, where black and mulatto populations are more numerous, 137 subjects were evaluated. The frequency of the GSTM1 null genotype was significantly higher among whites (55.4%) than among mulattos (41.4%; P = 0.03) and blacks (32.8%; P < 0.0001) from São Paulo, or Bahian subjects in general (35.7%; P = 0.0003). There was no statistically different distribution among any non-white groups. The distribution of GSTT1 null genotype among groups did not differ significantly. The agreement between self-reported and interviewer classification of skin color in the Bahian group was low. The interviewer classification indicated a gradient of distribution of the GSTM1 null genotype from whites (55.6%) to light mulattos (40.4%), dark mulattos (32.0%) and blacks (28.6%). However, any information about race or ethnicity should be considered with caution regarding the bias introduced by different data collection techniques, specially in countries where racial admixture is intense, and ethnic definition boundaries are loose. Because homozygous deletions of GST gene might be associated with cancer risk, a better understanding of chemical metabolizing gene distribution can contribute to risk assessment of humans exposed to environmental carcinogens.

The effects of human tumour necrosis factor-α (TNFα), or its mutein (F4168) having the cell adhesive Arg-Gly-Asp sequence at the N-terminus, on intestinal injury, were examined. Histopathological examination revealed that an intravenous injection of TNFα resulted in marked haemorrhage or oedema in the caecum of rats, whereas F4168 showed no such effects even at the same therapeutic dose. Moreover, the number of neutrophils that adhered to endothelial cells or infiltrated the mucosal tissue was much higher after TNFα injection compared with F4168 in vivo. The enhanced adhesion of neutrophils on to human umbilical vein endothelial cells also occurred when the latter were pre-stimulated with TNFα but not with F4168 in vitro. The expression of the cell adhesion molecules including endothelial leukocyte adhesion molecule-1 or intercellular adhesion molecule-1 on F4168- stimulated human umbilical vein endothelial ceils was significantly lower than that stimulated with TNFα. These results suggest that the Arg-Gly-Asp sequence introduced into the TNFα molecule abrogates the side effect of this cytokine such as tissue injury or shock, and that F4168 could be useful for systemic therapy.

The National Water Model (NWM) provides critical analyses and projections of streamflow that support water management decisions. However, the NWM performs poorly in lower-elevation rivers of the western United States (US). The accuracy of the NWM depends on the fidelity of the model inputs and the representation and calibration of model processes and water sources. To evaluate the NWM performance in the western US, we compared observations of river water isotope ratios (18O / 16O and 2H / 1H expressed in δ notation) to NWM-flux-estimated (model) river reach isotope ratios. The modeled estimates were calculated from long-term (2000–2019) mean summer (June, July, and August) NWM hydrologic fluxes and gridded isotope ratios using a mass balance approach. The observational dataset comprised 4503 in-stream water isotope observations in 877 reaches across 5 basins. A simple regression between observed and modeled isotope ratios explained 57.9 % (δ18O) and 67.1 % (δ2H) of variance, although observations were 0.5 ‰ (δ18O) and 4.8 ‰ (δ2H) higher, on average, than mass balance estimates. The unexplained variance suggest that the NWM does not include all relevant water fluxes to rivers. To infer possible missing water fluxes, we evaluated patterns in observation–model differences using δ18Odiff (δ18Oobs−δ18Omod) and ddiff (δ2Hdiff-8⋅δ18Odiff). We detected evidence of evaporation in observations but not model estimates (negative ddiff and positive δ18Odiff) at lower-elevation, higher-stream-order, arid sites. The catchment actual-evaporation-to-precipitation ratio, the fraction of streamflow estimated to be derived from agricultural irrigation, and whether a site was reservoir-affected were all significant predictors of ddiff in a linear mixed-effects model, with up to 15.2 % of variance explained by fixed effects. This finding is supported by seasonal patterns, groundwater levels, and isotope ratios, and it suggests the importance of including irrigation return flows to rivers, especially in lower-elevation, higher-stream-order, arid rivers of the western US.