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Metabolic dysfunction-associated steatohepatitis (MASH), previously called non-alcoholic steatohepatitis (NASH), is a growing concern worldwide, with liver fibrosis being a critical determinant of its prognosis. Monocyte-derived macrophages have been implicated in MASH-associated liver fibrosis, yet their precise roles and the underlying differentiation mechanisms remain elusive. In this study, we unveil a key orchestrator of this process: long chain saturated fatty acid-Egr2 pathway. Our findings identify the transcription factor Egr2 as the driving force behind monocyte differentiation into hepatic lipid-associated macrophages (hLAMs) within MASH liver. Notably, Egr2-deficiency reroutes monocyte differentiation towards a macrophage subset resembling resident Kupffer cells, hampering hLAM formation. This shift has a profound impact, suppressing the transition from benign steatosis to liver fibrosis, demonstrating the critical pro-fibrotic role played by hLAMs in MASH pathogenesis. Long-chain saturated fatty acids that accumulate in MASH liver emerge as potent inducers of Egr2 expression in macrophages, a process counteracted by unsaturated fatty acids. Furthermore, oral oleic acid administration effectively reduces hLAMs in MASH mice. In conclusion, our work not only elucidates the intricate interplay between saturated fatty acids, Egr2, and monocyte-derived macrophages but also highlights the therapeutic promise of targeting the saturated fatty acid-Egr2 axis in monocytes for MASH management., (© 2024. The Author(s).)

Despite the recognised risks of human exposure to mercury (Hg), the drivers of gaseous elemental mercury (GEM) emissions from the soil remain understudied. In this study, we aimed to identify the environmental parameters that affect the GEM flux from soil and derive the correlations between environmental parameters and GEM flux. Principal component analysis (PCA), factor analysis (FA), and structural equation modelling (SEM) were performed on samples from forest and non-forest sites. The associated results revealed the impact of each environmental parameter on GEM flux, either due to the interaction between the parameters or as a coherent set of parameters. An introductory correlation matrix examining the relationship between two components showed a negative correlation between GEM flux and atmospheric pressure at the two sites, as well as strong correlations between atmospheric pressure and soil temperature. In cases of non-forest open sites with no trees, the PCA and FA results were consistent, indicating that atmospheric pressure, solar irradiance, and soil moisture-defined as primary causality-are largely independent drivers of GEM flux. In contrast, the PCA and FA results for the forest areas with high humidity, tree coverage, and shade were inconsistent, confirming the hypothesis that primary causality affects GEM flux rather than consequent parameters driven by primary causality, such as air and soil temperature and atmospheric humidity. The SEM results provided further evidence for primary and consequent causality as crucial drivers of the GEM flux. This study demonstrates the importance of key primary parameters, such as atmospheric pressure, solar irradiance, and soil moisture content, that can be used to predict mercury release from soils, as well as the importance of consequent parameters, such as air and soil temperature and atmospheric humidity. Monitoring the magnitude of these environmental parameters alone may facilitate the estimation of mercury release from soils and be useful for detailed modelling of soil-air Hg exchange., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Monami Kondo reports financial support was provided by Japan Society for the Promotion of Science. Monami Kondo reports financial support was provided by Japan Science and Technology Agency., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of systemic vasculitis with eosinophilic inflammation. However, existing classification criteria are all designed to classify EGPA among vasculitis and there is no established method distinguishing EGPA from other eosinophilic disorders. The aim of the present study was to propose a scoring system to differentiate EGPA among eosinophilic disorders., Methods: Non-supervised hierarchical clustering using Ward's method and principal component analysis (PCA) were performed for 19 clinical parameters of 58 patients with eosinophilia-related diseases at a tertiary university hospital. The newly proposed scoring system was externally validated in 40 patients at another tertiary institution., Results: Two distinct clusters were identified, and clinical features including peripheral neuropathy, asthma, skin involvement, lung involvement, rheumatoid factor (RF) positivity, myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) positivity, IgE elevation, C-reactive protein (CRP) elevation, and vasculitis pathological findings were predominantly observed in one of these clusters (p < 0.05). Ten features defining the cluster with a high rate of vasculitis were weighted by PCA to create the E-CASE (EGPA classification among systemic eosinophilia) scoring system, on a 16-point scale. Based on the distribution of scores in the primary cohort, we defined an E-CASE score ≥12 as positive, ≤ 8 as negative, and 9-11 as undeterminable. The sensitivity and specificity of the E-CASE score in the validation cohort were 93.3% and 100%, respectively., Conclusions: We developed and verified a novel scoring system for differentiating EGPA from other types of eosinophilic disorders., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

The influence of flow channels on the leaching behavior of toxic elements in contaminated soil cannot be neglected in a column percolation test. This study presents a visualization of the flow channel formed in the soil and evaluated the relationship between the leaching behavior of soil components and flow. We conducted column percolation tests with two types of filling methods (Compaction and No compaction) and used X-ray computed tomography to visualize the soil structure and non-uniform flow. Additionally, the variations of flow in a cross section of water were evaluated using hydraulic conductivity based on differential pressure. Under No compaction, a flow occurred throughout the soil column at the beginning of the water passage, but a non-uniform flow emerged as the liquid-solid ratio increased; under Compaction, a non-uniform flow was formed from the beginning of water passage. The leaching behavior of the major components and toxic elements from soil with high adsorptive properties was significantly affected by the filling method up to a liquid-solid ratio of 2. These results suggest that the non-uniform flow formed in the column percolation test has a significant impact on the leaching of soil components., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Nawalparasi-West/Parasi is one of the severely affected districts in the Terai lowlands of Nepal by arsenic (As) contamination in groundwater, exceeding standards of 10 ppb (WHO) and 50 ppb (Nepal Drinking Water Standard). This study presents the spatial and temporal distribution of As across 6 km × 10 km region in Parasi via meteorological, hydrogeological, physio-chemical, and sedimentological investigations in 31 communities for about 5 years. In this study, water balance analysis was carried out for understanding the groundwater dynamics in the study area and its contribution to As elution. Gentle flow gradient and little to no infiltration was observed in the central region with relatively impervious silty clayey flood plain, where higher As concentrations were obtained compared to the northern Siwalik foothills and southern parts with coarser sediments. Similarly, higher As concentration (1048 ppb) was recorded in the drier pre-monsoon season than the wet season (529 ppb). The aquifer at 12 to 23 m depth feeding 73% wells in the study area exhibited higher As concentration in reduced environment as opposed to the oxidizing state at 5- to 6-m and 30- to 50-m deep aquifers. Other constituents such as Fe, B, and Cr and their relation with As were analyzed. The results of GERAS model analysis done for health risk assessment are also presented which show that under long-term exposure, the residents in Parasi were undertaking intolerable cancer risk of 1.1 to 6.4 × 10 -3 . This study further incorporates socio-economic sentiments vital to analyze, and propose sustainable and cheap countermeasures for immediate implementation to reduce As exposure and health risk in Nepal, which is also highly applicable for other affected regions in South Asian Region., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: To eliminate the disparity and maldistribution of physicians and medical specialty services, the development of diagnostic support for rare diseases using artificial intelligence is being promoted. Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a rare disorder often requiring special knowledge and experience to diagnose. In this study, we investigated the possibility of differential diagnosis of IgG4-RD based on basic patient characteristics and blood test findings using machine learning., Methods: Six hundred and two patients with IgG4-RD and 204 patients with non-IgG4-RD that needed to be differentiated who visited the participating institutions were included in the study. Ten percent of the subjects were randomly excluded as a validation sample. Among the remaining cases, 80% were used as training samples, and the remaining 20% were used as test samples. Finally, validation was performed on the validation sample. The analysis was performed using a decision tree and a random forest model. Furthermore, a comparison was made between conditions with and without the serum IgG4 concentration. Accuracy was evaluated using the area under the receiver-operating characteristic (AUROC) curve., Results: In diagnosing IgG4-RD, the AUROC curve values of the decision tree and the random forest method were 0.906 and 0.974, respectively, when serum IgG4 levels were included in the analysis. Excluding serum IgG4 levels, the AUROC curve value of the analysis by the random forest method was 0.925., Conclusion: Based on machine learning in a multicenter collaboration, with or without serum IgG4 data, basic patient characteristics and blood test findings alone were sufficient to differentiate IgG4-RD from non-IgG4-RD., (© 2022. The Author(s).)

Understanding the diffusive transport behavior of volatile organic compounds (VOCs) in near-surface soils is important because soil VOC emissions affect atmospheric conditions and climate. Previous studies have suggested that temperature changes affect the transport behavior; however, the effect of these changes are poorly understood. Indeed, under dynamic temperature conditions, the change in VOC flux is much larger than that expected from the temperature dependency of the diffusion coefficient of VOCs in air. However, the mechanism is not well understood, although water in soil has been considered to play an important role. Here, we present the results of experiments for the upward vertical vapor-phase diffusive transport of two VOCs (benzene and tetrachloroethylene) in sandy soil under sinusoidal temperature variations of 20-30 °C, as well as its numerical representation. The results clarify that the unexpectedly large changes in emission flux can occur as a result of changes in the VOC concentration gradient due to VOC release (volatilization) from/trapping (dissolution) into water, and that such flux changes may occur in various environments. This study suggests the importance of a global evaluation of soil VOC emissions by continuous measurements in various soil environments and/or predictions through numerical simulations with thorough consideration of the role of water in dynamic soil environments., (© 2022. The Author(s).)

Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease characterized by stiffness and aching mainly in the shoulders, neck and hip girdles. The underlying pathogenesis of PMR involves myeloid lineage activation with a high expression of pattern recognition receptors. In addition, vaccination against severe acute respiratory syndrome coronavirus 2 with mRNA-1273 functions as both an immunogen and intrinsic adjuvant. It leads to the activation of innate immunity, resulting in antibody production. We herein report the first case of PMR-like syndrome seven days after mRNA-1273 vaccination. Reassuringly, the symptoms, such as pain of the neck, shoulder girdle and pelvic girdle, as well as elevated inflammatory markers were resolved within a month without glucocorticoid or immunosuppressant administration.

Soil moisture is a key factor for mercury (Hg) emission from soil. Despite its significance for Hg emissions, the effect of soil moisture on Hg flux and fractions has not been thoroughly investigated. The objective of this study was to elucidate the influences of soil moisture and temperature on Hg fluxes from soils and Hg fractions. A kinetic study was performed to measure Hg emission fluxes of six soil samples under different temperature (T) (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) and moisture conditions (0%, 10%, and 20% added water). The results showed that the Hg fluxes increased with increases in T and soil moisture. A linear correlation was found between ln (Hg emission flux) and 1/T for the six soil samples at different moisture contents (R 2  = 0.73-0.99). The range of activation energy (Ea) values was 25.31-57.86 kJ/mol. The Hg fractions in soils of different moisture content were determined by a sequential extraction method. The results demonstrated that soil moisture affected the Hg fractions in soils. The Ea values had different relationships with soil moisture in different soils. There were correlations between Ea and the elemental and mercuric sulfide fractions for air-dried soils. However, for moist soils, Ea was negatively correlated with the water-soluble and acid-soluble fractions. Collectively, the combination of the Hg emission kinetics and Hg fraction measurement of different moist soils indicated that Hg emission was affected by both total Hg concentration and Hg fractions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Improving geothermal systems through hydraulic stimulation to create highly permeable fractured rocks can induce seismicity. Therefore, the technique must be applied at a moderate intensity; this has led to concerns of insufficient permeability enhancement. Adding chemical stimulation can mitigate these issues, but traditional methods using strong mineral acids have challenges in terms of achieving mineral dissolution over long distances and highly variable fluid chemistry. Here, we demonstrate a novel chemical stimulation method for improving the permeability of rock fractures using a chelating agent that substantially enhances the dissolution rate of specific minerals to create voids that are sustained under crustal stress without the challenges associated with the traditional methods. Applying this agent to fractured granite samples under confining stress at 200 °C in conjunction with 20 wt% aqueous solutions of sodium salts of environmentally friendly chelating agents (N-(2-hydroxyethyl)ethylenediamine-N, N', N'-triacetic acid and N, N-bis(carboxymethyl)-L-glutamic acid) at pH 4 was assessed. A significant permeability enhancement of up to approximately sixfold was observed within 2 h, primarily due to the formation of voids based on the selective dissolution of biotite. These results demonstrate a new approach for chemical stimulation., (© 2021. The Author(s).)

Landfill site selection is problematic in many countries, especially developing nations where there is rapid population growth, which leads to high levels of inadequate waste disposal. To find sustainable landfill sites in sprawling cities, this study presents an approach that combines geographic information system (GIS) with multi-criteria (social, environmental and, technical criteria) and the population growth projection. The greater Maputo area in Mozambique was selected as a representative city for the study, which is undergoing rapid urbanization. Six criteria, i.e., land use, transport networks, hydrology, conservation reserve, geology and slope, were considered and overlaid in the GIS using an analytic hierarchy process (AHP). The arithmetic projection of the population trend suggests that the greater Maputo area is experiencing a rapid and uncontrolled population growth, especially in Matola city. These pronounced changes in population then significantly change the landfill placement decision making. Dynamic and static scenarios were created, based on the analysis of multi-criteria and the areas likely to undergo future increased population growth. A comparative evaluation in a scenario of dynamic behavior considering future population showed that suitable areas for landfill sites have been drastically modified due to social and environmental factors affected by population distribution in some regions. The results indicate that some suitable areas can generate land use conflicts due to population growth with unplanned land use expansion. Finally, the western part of Matola city is recognized as the most recommendable landfill site, which can serve both Maputo and Matola city with affordable costs. This study provides an effective landfill placement decision making approach, which is possible to be applied anywhere, especially in developing countries to improve sustainable municipal solid waste management systems., Competing Interests: The authors declared that there is no conflict of interest with regards to research, authorship, and/or publication.

Among the CaCO 3 polymorphs, aragonite demonstrates a better performance as a filler material in the paper and plastic industries. Despite being ideal from the environmental protection perspective, the production of aragonite particles via CO 2 mineralization of rocks is hindered by the difficulty in achieving high production efficiencies and purities, which, however, can be mitigated by exploiting the potential ability of chelating agents on metal ions extraction and carbonation controlling. Herein, chelating agent N,N-dicarboxymethyl glutamic acid (GLDA) was used to enhance the extraction of Ca from calcium silicate and facilitate the production of aragonite particles during the subsequent Ca carbonation. CO 2 mineralization was promoted in the presence of 0.01-0.1 M GLDA at ≤ 80 °C, with the maximal CaCO 3 production efficiency reached 308 g/kg of calcium silicate in 60 min using 0.03 M GLDA, which is 15.5 times higher than that without GLDA. In addition, GLDA showed excellent effects on promoting aragonite precipitation, e.g., the content of aragonite was only 5.1% in the absence of GLDA at 50 °C, whereas highly pure (> 90%, increased by a factor of 18) and morphologically uniform aragonite was obtained using ≥ 0.05 M GLDA under identical conditions. Aragonite particle morphologies could also be controlled by varying the GLDA concentration and carbonation temperature. This study proposed a carbon-negative aragonite production method, demonstrated the possibility of enhanced and controlled aragonite particle production during the CO 2 mineralization of calcium silicates in the presence of chelating agents.

River sediments have the effect of aggregating geochemical environmental information, such as that related to geological and artificial pollution resulting from mine closure. This information comprises high-dimensional data and is related to the distribution and quantities of elements in river sediments. However, accessing and interpreting this geochemical information can be difficult. This study employed a data-driven analysis that can be mathematically and statistically reduced in dimension. Using high-dimensional geochemical and environmental information on river sediments, this study evaluated the environmental impact of closed mines. Sample for analysis were collected from three rivers. There are differences in the existence of mines and mine wastewater treatment methods in this river. A total of 33 elements were measured in river sediments. Frequency distribution analysis and Principal component analysis revealed that the elements had unique distribution and frequency characteristics in each river catchment. Four environmental factors could be extracted from the relationship of elements due to lower dimension. PC1 was influenced by the land use in the river area. PC2 captured the geological background. PC3 captured the mixing-diluting effect that occurs in rivers. PC4 effectively captured the effects of domestic wastewater and the effects of closed mines. The effects of the closed mines could be confirmed using the PC4 score for the Okawa River and the Akagawa River. By examining the elemental relationships obtained using these mathematical methods, it is possible to infer the effect of geological features and mines on sediment physiochemistry using existing data on river sediments., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Superhot geothermal environments in granitic crusts of approximately 400-500 °C are a frontier of geothermal energy. In the development of such environments, there is a concern of a reduction of permeability of fractured granite due to the formation of fine particles of amorphous silica induced by the phase change from subcritical water to supercritical water or superheated steam. However, the formation of silica particles and a resultant reduction in permeability have not been demonstrated to date. Therefore, experiments were conducted on the formation of amorphous silica particles with various combinations of temperature (430-500 °C) and pressure (20-30 MPa), in which the phase change of Si-containing water from liquid to either supercritical fluid or vapor was induced. Amorphous silica nanoparticles occurred under all conditions with smaller particles for higher temperature. The permeability of fractured granite was also observed to decrease significantly within several hours during injection of the particles into rock at 450 °C and 30 MPa under a confining stress of 40 MPa, with slower permeability reduction at a smaller number of particles or in the presence of larger aperture fractures. The present study suggests that the nanoparticles are likely to form and destroy the permeability in superhot geothermal environments, against which countermeasures should be investigated.

The Tohoku region of Japan is geologically diverse, with a long agriculture and mining history; however, little information about the origins and distribution mechanisms of elements in this region has been reported. This study aims to provide fundamental insights into the effects of geological features and anthropogenic activities on various elements, including toxic elements and rare-earth elements (REEs), in the Tohoku region. A geochemical database (2007, AIST) consisting of data for 53 elements in 485 river sediment samples from the region was used, and a data-driven method combining principal component analysis (PCA) was applied for analysis. GBs for numerous types of areas, including general areas (GGB), natural environments (NGB), high anthropogenic-influenced areas (AGB) and mineralised areas (MGB) were established; especially, MGB was newly proposed in this study to illuminate the role of ore deposits. Both PCA and GBs comparison results show that geological features (especially igneous rock distribution) were the most important factor affecting elemental distribution, rather than anthropogenic activities. In the PCA, the first principal component showed that REE resources were commonly associated with the distribution of granitic rocks and REE-bearing minerals. Anthropogenic contaminations from mining, urban, and anthropogenic areas played important roles as the origin of some toxic elements (e.g. Ni, Pb, Sb). Comparisons between these GBs effectively elucidated the enrichment of certain toxic elements (e.g., Hg, Sb) in ore deposit areas. This data-driven study not only clarified the origins of toxic elements, but also revealed the location of potential REE mineral resources in the Tohoku region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

ORAI1 constitutes the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, which is responsible for store-operated calcium entry into lymphocytes. It is known that ORAI1 is essential for the activation of T cells and mast cells and is considered to be a potent therapeutic target for autoimmune and allergic diseases. Here, we obtained a new humanized antibody, DS-2741a, that inhibits ORAI1 function. DS-2741a bound to human-ORAI1 with high affinity and without cross-reactivity to rodent Orai1. DS-2741a demonstrated suppression of CRAC-mediated human and mouse T-cell activation and mast cell degranulation in human ORAI1 knock-in mice. Furthermore, DS-2741a ameliorated house dust mite antigen-induced dermatitis in the human ORAI1 knock-in mouse. Taken together, DS-2741a inhibited T-cell and mast cell functions, thus improving skin inflammation in animal models of atopic dermatitis and reinforcing the need for investigation of DS-2741a for the treatment of allergic diseases in a clinical setting., (© 2020 Daiichi Sankyo Co., Ltd. FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)

Peptidylarginine deiminase 4 (PAD4), encoded by PADI4 , plays critical roles in the immune system; however, its contribution to the pathogenesis of lupus nephritis remains controversial. The pathological roles of PAD4 were investigated in lupus model mice. An imiquimod (IMQ)-induced lupus model was analyzed in wild-type (WT) and Padi4 -knockout (KO) mice. Proteinuria, serum anti-double stranded DNA (anti-dsDNA) antibody, and renal infiltrated cells were evaluated. Neutrophil migration and adhesion were assessed using adoptive transfer and adhesion assay. PAD4-regulated pathways were identified by RNA-sequencing of Padi4 KO neutrophils. Padi4 KO mice exhibited significant improvements in proteinuria progression compared with WT mice, whereas, serum anti-dsDNA antibody and immune complex deposition in the glomeruli showed no difference between both mice strains. Padi4 KO mice showed decreased neutrophil infiltration in the kidneys. Adoptively transferred Padi4 KO neutrophils showed decreased migration to the kidneys of IMQ-treated WT mice, and adhesion to ICAM-1 was impaired in Padi 4 KO neutrophils. Padi4 KO neutrophils exhibited reduced upregulation of p38 mitogen-activated protein kinase (MAPK) pathways. Toll-like receptor 7 (TLR7)-primed Padi4 KO neutrophils demonstrated reduced phosphorylation of p38 MAPK and lower expression of JNK-associated leucine zipper protein (JLP), a p38 MAPK scaffold protein. Neutrophils from heterozygous Jlp KO mice showed impaired adhesion to ICAM-1 and decreased migration to the kidneys of IMQ-treated WT mice. These results indicated a pivotal role of PAD4-p38 MAPK pathway in renal neutrophil infiltration in TLR7 agonist-induced lupus nephritis, and the importance of neutrophil-mediated kidney inflammation. Inhibition of the PAD4-p38 MAPK pathway may help in formulating a novel therapeutic strategy against lupus nephritis., (Copyright © 2020 Hanata, Shoda, Hatano, Nagafuchi, Komai, Okamura, Suzuki, Gunarta, Yoshioka, Yamamoto and Fujio.)

Background: SF3B1 (splicing factor 3B subunit-1) somatic mutation is specifically detected in myelodysplastic syndrome (MDS) with ring sideroblasts (MDS-RS). We investigated the sensitivity and utility of SF3B1 mutation analysis as a clinical laboratory test., Method: Detection limit for SF3B1 mutations by high-resolution melting (HRM) analysis was investigated by plasmid mixture. In 67 MDS patients, we examined the association between SF3B1 mutation and prognostic evaluation using the Revised International Prognostic Scoring System and revalidated MDS classifications based on the revised 4th edition of the WHO classification., Results: HRM analysis enabled mutation detection in the 12.5% SF3B1 mutant alleles. SF3B1 mutation was detected in 9 cases, mostly in the low-risk group. Cases of MDS with ring sideroblasts unrelated to SF3B1 mutation were detected in the high-risk group. Two cases were reclassified as MDS-RS after detecting SF3B1 mutation., Conclusions: SF3B1 mutation analysis as an initial screening at diagnosis increases the accuracy of prognostic prediction and disease classification., (© American Society for Clinical Pathology 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Superhot geothermal environments (above ca. 400 °C) represent a new geothermal energy frontier. However, the networks of permeable fractures capable of storing and transmitting fluids are likely to be absent in the continental granitic crust. Here we report the first-ever experimental results for well stimulation involving the application of low-viscosity water to granite at temperatures ≥400 °C under true triaxial stress. This work demonstrates the formation of a network of permeable microfractures densely distributed throughout the entire rock body, representing a so-called cloud-fracture network. Fracturing was found to be initiated at a relatively low injection pressure between the intermediate and minimum principal stresses and propagated in accordance with the distribution of preexisting microfractures, independent of the directions of the principal stresses. This study confirms the possibility of well stimulation to create excellent fracture patterns that should allow the effective extraction of thermal energy.

A new species of hermit crab, Pagurus fraserorum n. sp. (family Paguridae) is described from rocky subtidal reefs off KwaZulu-Natal, South Africa, and illustrated using both conventional drawings and colour photographs, and via three-dimensional (3D) X-ray micro-computed tomography (μCT). Because of the limitation μCT has in detecting very fine and soft structures, a novel approach of manually drawing setation and spinulation onto the two-dimensional images of the 3D visualizations was used to illustrate the pereopods. In addition, an interactive figure and rotation movie clips in the supplement section complement the species description, and the 3D raw data of the 3D type data are downloadable from the Gigascience Database repository. The new species is the sixth species of Pagurus Fabricius, 1775 reported from South Africa and is closely allied to the Indo-Pacific P. boriaustraliensis Morgen, 1990 and P. pitagsaleei McLaughlin, 2002, from which it differs by its shorter ocular peduncles, by the armature of the carpus of the right cheliped, and also in colouration. This study presents the first description of a hermit crab in which a majority of taxonomic details are illustrated through 3D volume-rendered illustrations. In addition, colour photographs and COI molecular barcodes are provided, and the latter compared to COI sequences of specimens from Western Australia previously identified as P. boriaustraliensis and of specimens of P. pitagsaleei from Taiwan, as well as to three additional South African members of the genus. The South African taxon was confirmed to be genetically distinct from all species tested., Competing Interests: The authors have declared that they have no competing interests.

A 76-year-old man complicated with end-stage renal disease had latent tuberculosis infection (LTBI), and isoniazid (INH) 300 mg daily was started to prevent reactivation of LTBI before using biologic agents for rheumatoid arthritis. On the 8th day after administration of INH, he presented with a fever, petechiae, and myalgia. Serological studies revealed elevated myogenic enzymes and creatinine level. Based on the exclusion of other etiologies, rapid improvement with cessation of INH, and the recurrence of the fever and myalgia with re-administration of a reduced dose of INH, we diagnosed him with INH-induced rhabdomyolysis. Physicians should be aware of rhabdomyolysis induced by INH at a therapeutic dose as an infrequent but potentially fatal adverse drug reaction.

Acute hemorrhagic rectal ulcer syndrome (AHRUS) can cause fatal gastrointestinal bleeding. However, there have been few epidemiological studies investigating risk factors of AHRUS. To determine the risk factors and predict one-year survival after onset of AHRUS, we conducted a retrospective density case-control study in a tertiary referral hospital. Patients with hematochezia, bloody stool, and rectal ulcer confirmed by colonoscopy between 2003 and 2011 were diagnosed as AHRUS ( n = 38). Patients with malignancies, infectious colitis, ulcerative colitis, or solitary rectal ulcer syndrome were excluded. Control subjects ( n = 123) without rectal ulcer were selected by risk set sampling for each AHRUS. Multivariate logistic regression analyses revealed that the significant adjusted odds ratio (95% confidence interval) of hospitalization, antithrombotic drug use, and one gram increase of serum albumin was 15.7 (2.25-108.9), 12.1 (1.53-94.4), and 0.11 (0.02-0.52), respectively. Endoscopic hemostasis for rectal bleeding was performed in 8 cases (21%). Seventeen percent of patients died within one year after the episode of AHRUS from non-AHRUS causes. This study revealed that hospitalization, antithrombotic drug use, and lower serum albumin value were significant risk factors for AHRUS, and that AHRUS was an unfavorable prognostic condition. This information could be helpful in recognizing high-risk patients of rectal bleeding and applying preventive measures.

Transforming growth factor (TGF)-βs are pluripotent cytokines with stimulatory and inhibitory properties for multiple types of immune cells. Analyses of genetic knockouts of each isoform of TGF-β have revealed differing expression patterns and distinct roles for the three mammalian isoforms of TGF-β. Considerable effort has been focused on understanding the molecular mechanisms of TGF-β1-mediated immune regulation, given its pivotal role in prohibiting systemic autoimmune disease. In recent years, functional similarities and differences between the TGF-β isoforms have delineated their distinct roles in the development of immunopathology and immune tolerance, with increased recent attention being focused on TGF-β3. In addition to the characteristic properties of each TGF-β isoform, recent progress has identified determinants of context-dependent functionality, including various cellular targets, cytokine concentrations, tissue microenvironments, and cytokine synergy, which combine to shape the physiological and pathophysiological roles of the TGF-βs in immunity. Controlling TGF-β production and signaling is being tested as a novel therapeutic strategy in multiple clinical trials for several human diseases. This review highlights advances in the understanding of the cellular sources, activation processes, contextual determinants, and immunological roles of TGF-β3 with comparisons to other TGF-β isoforms.