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Background The efficacy of rituximab (RTX) for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD) has not been fully established. This study compared the efficacy and safety of RTX and intravenous cyclophosphamide (CY) for SSc-ILD. Methods This retrospective study compared the efficacy and safety of RTX (20 patients) and CY (30 patients) after adjusting for the stabilised inverse probability of treatment weighting based on propensity scores. The efficacy endpoints were the absolute changes in forced vital capacity (FVC) and serum Krebs von den Lungen-6 (KL-6) levels from baseline to 6 and 12 months after treatment. The incidence of progression based on the definition of progressive pulmonary fibrosis was also recorded. The safety endpoint was the frequency of adverse events. Results The clinical characteristics of the two groups were well-balanced after adjusting for confounders (i.e., FVC, nintedanib use, and newly diagnosed cases). From baseline to 6 and 12 months after the start of treatment, the median FVC increased by 50 and 60 ml in the RTX group and 40 and 15 ml in the CY group, respectively, with no difference after adjustment. The changes in serum KL-6 levels and the incidences of progression were identical in both groups after adjustment. The overall adverse events were similar in both groups after adjustment. Conclusions RTX demonstrated comparable safety and efficacy as CY in patients with SSc-ILD. Thus, RTX may be an alternative to CY for the treatment of SSc-ILD.

The relative proportion of kynurenine aminotransferase (KAT) I–IV activities in the brain is similar between humans and rats. Moreover, KAT II is considered to be the main enzyme for kynurenic acid production in the brain. Taken together, human KAT II knock-in (hKAT II KI) rats will become a valuable tool for the evaluation of KAT II targeted drugs as a human mimetic model. Although we initially tried the approach by conventional gene-targeting via embryonic stem cells (ESCs) to generate them, we had to give up the production because of no recombinant ESCs. Accordingly, we developed a method to improve the efficiency of homologous recombination (HR) in ESCs by the combination with the CRISPR/Cas system. Co-electroporation of Cas9 plasmid, single guide RNA plasmid and hKAT II KI vector increased the number of drug-resistant colonies and greatly enhanced the HR efficiency from 0 to 36 %. All the clones which we obtained showed the same sequence as designed. These recombinant clones resulted in chimeras that transmitted the hKAT II KI allele to their offspring. hKAT II KI rats showed no reduction of KATs mRNA expression and the amount of kynurenic acid was similar between the hKAT II KI rats and the wild type in their brains. These results indicate that the methodology presented in this report can overcome the problem encountered in conventional gene-targeting that prevented production of humanized rats.

Plate impact test on medium carbon steel were carried out to the target plate by impacting the flyer plate with one-third and two-thirds thickness of the target plate. The spall damage within the target plate was evaluated non-destructively with a low frequency scanning acoustic microscope as well as ultrasonic velocity and backscattering intensity. We observed the spall damage distribution by the B-and Cscan images. The distribution of spall damage through the plate thickness depends on the tensile stress area within the target plate. The difference of spall damage distribution was investigated by the plate impact test by flyer plate with different thickness. In the plate impact test by the flyer plate with 1/3 target plate thickness, the spall damage was generated by tensile stress area which superposed in the back surface side. On the other hand, in the case of 2/3 target plate thickness, the spall damage was detected at the impact surface side. By generating the spall damage in the different position through the target thickness, it will be possible to evaluate the accumulation of spall damage by reflection and transmission of the stress wave at the internal damage subjected to repeated impact.

In order to clarify the collision phenomenon of the traffic machine in motion, such as automobile and aircraft, it is necessary to examine not only the deformation and the behavior of composed structural member but also the dynamic characteristic of friction coefficient and restitution coefficient in the collided contact surface. In this study, the restitution coefficient was estimated from the strain waveform measured by collision test using the Air Gun. The velocity and deformation dependence of the restitution coefficient was examined by carrying out the collision test at the different speed. As a result, in the metal test piece, restitution coefficient decreased by the plastic deformation with the increasing of the collision speed, and the velocity dependence was confirmed.

When a simple structure collides with inclined barrier, behavior and deformation of the structure after impact are different in the case in which the structure slides on a contact surface or the case in which it does not slide. In order to investigate the structural collapse behavior for oblique collided structure, therefore, it is important to clarify the sliding behavior of the structure on the contact surface. The sliding behavior of the structure during collision was estimated according to theoretically obtained the equation considering the equilibrium of change in the momentum and the impulse before and after the collision. For evaluating the sliding behavior of the simple structure, the impact test by the drop type impact testing machine was carried out to collide with inclined barrier. In the impact test, the circular plate of 60 mm diameter and 10 mm thickness was used as the simple structure, and impacted with various collision velocities (range from 2 to 6 m/s). The sliding behavior of the simple structure at the collided surface was observed by high speed camera, and evaluated by the image analysis. The theoretical result was compared to evaluate with experimental results.

The spread of Aedes albopictus (Skuse) eastward in the mid-1980s from its initial establishment in Houston, TX, was associated with rapid declines and local disappearances of Aedes aegypti (L.) in Gulf Coast states and Florida where annual larval surveillance during the early 1990s described temporal and spatial patterns of competitive displacements in cemeteries and tire shops. Approximately 20 yr later in 2013–2014, we re-visited former collection sites and sampled aquatic immatures of these two species from tire shops in 10 cities on State Route 441 and from 9 cemeteries from Lakeland to Miami in southwest Florida. In the recent samples Ae. aegypti was recovered from three central Florida cities where it had not been detected in 1994, but its northern limit on Rte. 441, Apopka, did not change. Other evidence, such as trends at a few cemeteries, suggested a moderate resurgence of this species since 1994. Cage experiments that exposed female progeny of Ae. aegypti from recent Florida collection sites to interspecific mating by Ae. albopictus males showed that females from coexistence sites had evolved resistance to cross-mating, but Ae. aegypti from sites with no Ae. albopictus were relatively susceptible to satyrization. Habitat classifications of collection sites were reduced by principal component (PC) analysis to four variables that accounted for > 99% of variances; PCs with strong positive loadings for tree cover and ground vegetation were associated with collection sites yielding only Ae. albopictus. Within the coexistence range of the two species, the numbers of Ae. aegypti among total Aedes collected were strongly correlated in stepwise logistic regression models with two habitat-derived PCs, distance from the coast, and annual rainfall and mean maximum temperatures at the nearest weather station. Subtle increases in the range of Ae. aegypti since its previous displacements are interpreted in the context of the evolution of resistance to mating interference, realized versus fundamental niches of the two species, and persisting competition with Ae. albopictus.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer’s disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

Mosquitoes have developed specialized oviposition strategies that allow them to develop in a wide variety of aquatic habitats. Environmentally cued hatching traits may also play an important role in the successful colonization of some larval habitats, but this subject has remained largely unexplored in Culicidae. Aedes atropalpus (Coquillett) is an autogenous rock pool specialist that may maintain unique adaptations for oviposition and egg hatching. We investigated the egg-laying strategies of Ae. atropalpus exposed to standard (non-diapausing) rearing conditions and diapause-inducing conditions and tested the impact of physical agitation on egg hatch rates by exposing floating and submerged eggs to physical agitation treatments. The results of the oviposition experiment indicate that Ae. atropalpus females primarily lay non-diapausing eggs directly onto the water surface and lay diapausing eggs directly on solid surfaces. The egg-hatching experiment demonstrated that physical agitation significantly increases Ae. atropalpus hatch rates. Floating and submerged eggs responded similarly to the agitation treatment. These data suggest that oviposition behaviors based on both egg diapause status and environmentally-cued hatching strategies may be important adaptations for Ae. atropalpus in riverine rock pools.

Native predators are postulated to have an important role in biotic resistance of communities to invasion and community resilience. Effects of predators can be complex, and mechanisms by which predators affect invasion success and impact are understood for only a few well-studied communities. We tested experimentally whether a native predator limits an invasive species' success and impact on a native competitor for a community of aquatic insect larvae in water-filled containers. The native mosquito Aedes triseriatus alone had no significant effect on abundance of the invasive mosquito Aedes albopictus. The native predatory midge Corethrella appendiculata, at low or high density, significantly reduced A. albopictus abundance. This effect was not caused by trait-mediated oviposition avoidance of containers with predators, but instead was a density-mediated effect caused by predator-induced mortality. The presence of this predator significantly reduced survivorship of the native species, but high predator density also significantly increased development rate of the native species when the invader was present, consistent with predator-mediated release from interspecific competition with the invader. Thus, a native predator can indirectly benefit its native prey when a superior competitor invades. This shows the importance of native predators as a component of biodiversity for both biotic resistance to invasion and resilience of a community perturbed by successful invasion.