Gifu University

Heart failure is a major cause of mortality worldwide. Accumulating evidence indicates that mitochondrial dysfunction, particularly excessive generation of reactive oxygen species (ROS) from the mitochondrial electron transport chain (ETC), plays a vital role in the onset and progression of heart failure. Importantly, mitochondrial dysfunction is believed to emerge at an early stage of heart failure development. However, due to the lack of noninvasive techniques to directly evaluate cardiac mitochondrial function in vivo, the timing and dynamics of mitochondrial functional alterations during the early phase of heart failure development remain unclear. Carbamoyl-PROXYL (CmP) is a membrane-permeable nitroxyl probe that mediates redox reactions within the mitochondrial ETC in the presence of reduced nicotinamide adenine dinucleotide, thereby sensitively indicating mitochondrial electron transfer dynamics. We applied in vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) to a mouse model of doxorubicin (DOX)-induced heart failure to validate its utility. In DOX-treated mice, the CmP reduction rate was significantly accelerated as early as 30 min after drug administration. However, no significant change was detected in epirubicin-treated mice compared with control animals. Considering that DOX induces ROS production through redox cycling at mitochondrial ETC complex I, these results demonstrate that in vivo DNP-MRI enables noninvasive visualization of ETC-associated mitochondrial redox imbalance in the living heart immediately after the onset of cardiotoxic stress, even when ROS generation has just begun and conventional functional changes are unapparent. Therefore, in vivo DNP-MRI represents a powerful noninvasive modality for the early diagnosis of heart failure.

Autoimmune cerebellar ataxia (ACA) is a potentially treatable cause of cerebellar dysfunction, but remains underrecognized because of diagnostic challenges, including limited access to autoantibody testing and heterogeneous clinical presentations. We aimed to describe the clinical and laboratory characteristics of patients with clinically diagnosed ACA (cdACA) in Japan, based on expert diagnoses, and evaluate associations between clinical factors and response to immunotherapy. This study was a retrospective, multi-center, descriptive study based on a two-step nationwide survey. We inquired at facilities accredited by the Japanese Society of Neurology about the number of patients with cdACA. Furthermore, we asked the facilities with cdACA experience for clinical information. Of 92 cdACA patients, 96.7% had isolated/predominant cerebellar symptoms. Autoantibodies associated with ACA were detected in 47 (51.1%) patients, with glutamic acid decarboxylase (GAD) antibodies being most frequent. 25 (27.2%) patients had concomitant cancer. Among 80 patients who received immunotherapy, 53 (66.2%) responded positively. Responders were more often female (p = 0.006), and had shorter median time to treatment (71 vs 344days, p = 0.010) and lower CSF protein (40.65 vs 71.05mg/dL, p = 0.003). Patients without malignancy responded more frequently (p = 0.006). This nationwide study provides the first real-world insights into the clinical characteristics and management of cdACA in Japan. Although these findings should be interpreted with caution due to diagnostic heterogeneity and the retrospective study design, some patients with concomitant cancer may also show functional improvement following immunotherapy. In the future, there should be further accumulation of ACA cases and the establishment of diagnostic criteria for ACA.

Multiple drivers of global change are causing rapid biodiversity loss worldwide. However, predicting species' trajectories remains challenging due to the dynamic and state-dependent nature of ecological responses in real-world ecosystems. Here, we leverage nonlinear time series analysis of a multi-decadal, high-resolution dataset encompassing climate, freshwater, and sediment variables, alongside estuarine macroinvertebrate abundance. Our analysis shows that key biological traits, including body size, mobility, and lifespan predict the mean and variability of the time-varying sensitivity of species to specific environmental drivers. Species with smaller body sizes or lower mobility exhibit consistently negative responses to warming. The temporal variability of species sensitivity, an aspect often overlooked in previous studies of species' environmental responses, is strongly associated with lifespan, with shorter-lived species showing greater fluctuations over time. These findings did not always align with results from controlled laboratory or short-term field experiments, highlighting the complex, state-dependent responses of species shaped by multiple drivers of global change. We introduce a framework that links biological traits to long-term environmental responses, providing a predictive basis for trait-sensitivity relationships.

Transorbital penetrating head trauma is rare but carries high mortality due to the risk of intracranial vascular injury and infection. Early vascular assessment and careful procedural planning are critical. A woman in her fifties sustained transorbital penetration by a chopstick that traversed the brainstem and extended to the posterior fossa. CT angiography demonstrated proximity to the cavernous segment of the right internal carotid artery and the posterior cerebral artery without active extravasation. Under endovascular standby with proximal balloon preparation, the foreign body was removed in a conventional angiography suite without craniotomy. Serial angiography and MRA revealed transient vascular irregularity that gradually resolved, documenting spontaneous vascular healing without the use of antithrombotic therapy. Post-treatment MRI demonstrated parenchymal injury along the penetrating trajectory without evidence of abscess formation. This case illustrates that in angiographically stable but anatomically high-risk transorbital penetrating injuries, planned extraction under endovascular standby may be a feasible option in carefully selected cases. Serial vascular follow-up is essential to detect delayed vascular changes and to confirm spontaneous vascular healing.

We aimed to examine the psychometric properties of the second version of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD-V2.0) and its correspondence with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity scale (CGI-S) scores. This cross-sectional study was conducted at 18 institutes in Japan. We performed correlational analyses to test the convergent and divergent validity of the BE-PSD-V2.0. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). The equipercentile equating method was employed to examine the linking of the BE-PSD-V2.0 with the PANSS and the CGI-S. A total of 353 patients with schizophrenia spectrum disorders were included. Spearman's rank correlation coefficients between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores ranged from 0.64 to 0.86, indicating sufficient convergent validity. These specific correlation coefficients were consistently the highest among all item-to-factor comparisons, indicating sufficient divergent validity. In 34 patients, ICCs for the BE-PSD-V2.0 itemand total scores ranged from 0.60 to 0.94, showing sufficient inter-rater reliability. Conversion tables were established between the BE-PSD-V2.0 total score and the PANSS total score, between the BE-PSD-V2.0 total score and the CGI-S score, and between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores. A correspondence between symptomatic remission criteria using the PANSS and BE-PSD-V2.0 was confirmed. The BE-PSD-V2.0 possesses sufficient psychometric properties and corresponds to the PANSS and CGI-S. It is a sound and reliable brief rating scale for assessing symptoms in schizophrenia spectrum disorders, and its established conversion correspondences facilitate score interpretation within existing clinical paradigms for both clinical practice and research.

While mixing of several liquid crystalline (LC) components is a good method to extract excellent properties, there have been no successful applications to bicontinuous cubic (Cubbi) LC materials of isotropically extended three-dimensional networks. We realized a Cubbi-phase eutectic mixture at around room temperature. Two kinds of binary mixtures of aryloylhydrazine-based compounds were examined, where one component was a nonazo Cubbi phase-forming compound and the other was two kinds of azo compounds with and without a methyl group at the 2-position of the outer ring in the azobenzene moiety. Both binary mixtures form a Cubbi phase in their middle composition ranges, but the temperature ranges are markedly different. In the case of the mixture with the azo compound without a methyl group, the Cubbi-phase temperature range is narrow and limited between 380 and 430 K. In contrast, the mixture with the 2-methyl azo compound is a eutectic mixture of the Cubbi phase around a molar ratio of 1:1, which expands from 435 K to below room temperature when cooled from the melt. The dynamic viscoelastic measurements revealed a high storage modulus of 2 MPa in the range 300-390 K. This finding encouraged us to examine the adhesion test for the mixture, which uncovered unprecedentedly strong adhesion to glass plates (showing a shear stress at a break of 7 MPa at 298 K). The obtained results indicate that both fluidic and elastic natures of the Ia3̅d Cubbi LC phase of isotropically extended 3D networks are important for the adhesion property.

The rapid synthesis of high-performance silicalite-1 membranes was systematically investigated by examining the effects of seed size, solution volume, and reactor configuration on membrane growth, microstructure, and gas separation performance. Silicalite-1 seeds (~100 nm and ~1 µm) were dip-coated onto capillary α-alumina supports, followed by secondary growth under controlled conditions. Small seeds (~100 nm) produced high nucleation density, uniform intergrowth, and defect-free membranes, yielding consistently high ideal separation factor for H2/SF6 (181-295) and low SF6 permeance (~10-9 mol m-2 s-1 Pa-1) after only 45 min of synthesis. In contrast, larger seeds (~1 µm) enabled faster growth but resulted in less uniform layers with inferior selectivity. Furthermore, a novel reactor design with enhanced heat transfer enabled the rapid silicalite-1 membrane synthesis on conventional large-diameter tubular supports, producing well-intergrown and uniform membranes with high H2 permeance (4.7 × 10-6 mol m-2 s-1 Pa-1) and high ideal separation factors of up to 349 for H2/SF6 and 223 for N2/SF6. Overall, this study demonstrates that optimization of seed properties, synthesis parameters, and reactor design enables rapid and scalable fabrication of silicalite-1 membranes with robust molecular sieving performance, highlighting their strong potential for SF6 purification applications.