Search

Abstract Understanding the physiological changes associated with aging and the associated disease risks is essential to establish biomarkers as indicators of biological aging. This study used the NMR-measured plasma metabolome to calculate age-specific metabolite indices. In doing so, the scope of the study was deliberately simplified to capture general trends and insights into age-related changes in metabolic patterns. In addition, changes in metabolite concentrations with age were examined in detail, with the period from 55–59 to 60–64 years being a period of significant metabolic change, particularly in men, and from 45–49 to 50–54 years in females. These results illustrate the different variations in metabolite concentrations by sex and provide new insights into the relationship between age and metabolic diseases.

Abstract In this study, we developed a new method of topology optimization for truss structures by quantum annealing. To perform quantum annealing analysis with real variables, representation of real numbers as a sum of random number combinations is employed. The nodal displacement is expressed with binary variables. The Hamiltonian H is formulated on the basis of the elastic strain energy and position energy of a truss structure. It is confirmed that truss deformation analysis is possible by quantum annealing. For the analysis of the optimization method for the truss structure, the cross-sectional area of the truss is expressed with binary variables. The iterative calculation for the changes in displacement and cross-sectional area leads to the optimal structure under the prescribed boundary conditions.

Abstract Lumbar spinal stenosis (LSS) is a degenerative disease characterized by intermittent claudication and numbness in the lower extremities. These symptoms are caused by the compression of nerve tissue in the lumbar spinal canal. Ligamentum flavum (LF) hypertrophy and spinal epidural lipomatosis in the spinal canal are known to contribute to stenosis of the spinal canal: however, detailed mechanisms underlying LSS are still not fully understood. Here, we show that surgically harvested LFs from LSS patients exhibited significantly increased thickness when transthyretin (TTR), the protein responsible for amyloidosis, was deposited in LFs, compared to those without TTR deposition. Multiple regression analysis, which considered age and BMI, revealed a significant association between LF hypertrophy and TTR deposition in LFs. Moreover, TTR deposition in LF was also significantly correlated with epidural fat (EF) thickness based on multiple regression analyses. Mesenchymal cell differentiation into adipocytes was significantly stimulated by TTR in vitro. These results suggest that TTR deposition in LFs is significantly associated with increased LF hypertrophy and EF thickness, and that TTR promotes adipogenesis of mesenchymal cells. Therapeutic agents to prevent TTR deposition in tissues are currently available or under development, and targeting TTR could be a potential therapeutic approach to inhibit LSS development and progression.

Abstract Quantitative sensory testing (QST) is useful when analysing musculoskeletal pain disorders. A handheld algometer is most commonly used for pressure pain threshold (PPT) tests. However, reference intervals for PPTs are not elucidated. We assessed reference intervals of PPTs for QST in 158 healthy adult Japanese with no history of musculoskeletal or neurological problems. A handheld algometer was used to record PPT at five different assessment sites on the body: lumbar paravertebral muscle, musculus gluteus maximus, quadriceps, tibialis anterior muscle, and anterior talofibular ligament. Multiple regression analysis was performed to explore sources of variation of PPT according to sex, age, body mass index, UCLA Activity Level Rating, and Tegner Activity Score. Reference intervals were determined parametrically by Gaussian transformation of PPT values using the two-parameter Box-Cox formula. Results of multiple regression analysis revealed that age was significantly associated with PPT of lumbar paravertebral muscle and musculus gluteus maximus. In females, body mass index showed significant positive correlation with PPT of anterior talofibular ligament, and UCLA Activity Level Rating also showed significant positive association with tibialis anterior muscle and anterior talofibular ligament. Site-specific reference intervals of PPTs for Japanese are of practical relevance in fields of pain research using a handheld algometer.

Abstract Malnutrition-inflammation-atherosclerosis (MIA) syndrome is a significant risk factor for mortality in patients undergoing hemodialysis. This study aimed to investigate the association between MIA syndrome and oral health status in hemodialysis patients. A cross-sectional study was conducted on 254 hemodialysis patients. Comprehensive medical and dental examinations were performed. Three components were included to define MIA syndrome: Geriatric Nutritional Risk Index, serum high-sensitivity C-reactive protein, and history of cardiovascular events as indicators of malnutrition, inflammation, and atherosclerosis, respectively. The association of MIA syndrome components with periodontitis and occlusal support was examined by multiple-ordered logistic regression analysis. Of 254 participants, 188 (74.0%) had at least one component of MIA syndrome. After adjusting for possible confounding factors, severe periodontitis was significantly associated with presence of more components of MIA syndrome (odds ratio [OR]: 2.64, 95% confidence interval [CI], 1.44–4.84, p = 0.002) and inflammation and malnutrition components (OR: 2.47 and 3.46, 95% CI 1.16–5.28 and 1.70–7.05, p = 0.020 and 0.001). On the other hand, occlusal support, evaluated by Eichner index, was not significantly associated with MIA syndrome or any of its components. In conclusion, periodontitis is associated with MIA syndrome, particularly with inflammation and malnutrition in hemodialysis patients, independent of occlusal support.

Abstract Flapping flight of animals has captured the interest of researchers due to their impressive flight capabilities across diverse environments including mountains, oceans, forests, and urban areas. Despite the significant progress made in understanding flapping flight, high-altitude flight as showcased by many migrating animals remains underexplored. At high-altitudes, air density is low, and it is challenging to produce lift. Here we demonstrate a first lift-off of a flapping wing robot in a low-density environment through wing size and motion scaling. Force measurements showed that the lift remained high at 0.14 N despite a 66% reduction of air density from the sea-level condition. The flapping amplitude increased from 148 to 233 degrees, while the pitch amplitude remained nearly constant at 38.2 degrees. The combined effect is that the flapping-wing robot benefited from the angle of attack that is characteristic of flying animals. Our results suggest that it is not a simple increase in the flapping frequency, but a coordinated increase in the wing size and reduction in flapping frequency enables the flight in lower density condition. The key mechanism is to preserve the passive rotations due to wing deformation, confirmed by a bioinspired scaling relationship. Our results highlight the feasibility of flight under a low-density, high-altitude environment due to leveraging unsteady aerodynamic mechanisms unique to flapping wings. We anticipate our experimental demonstration to be a starting point for more sophisticated flapping wing models and robots for autonomous multi-altitude sensing. Furthermore, it is a preliminary step towards flapping wing flight in the ultra-low density Martian atmosphere.

Abstract Although the scope of pharmacists’ work has expanded in Japan, people’s perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists’ opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding “collecting patient information” and “providing drug information to patients.” However, there were differences in perceptions regarding “medical collaboration” (nurses; 8/23 items, physicians; 11/23 items) and “community medicine” (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care.

Abstract Bone is one of the largest organ systems in humans and is considered to regulate whole-body homeostasis in cooperation with other organs. We have previously reported that a sympathetic or sensory nervous system inside bone regulates bone homeostasis. However, the detailed regulatory mechanism, including the distribution of nerves inside bone, remains unknown. Although a two-dimensional histological analysis has been widely used to evaluate the structure of nerves or blood vessels, the actual structure is more complex, suggesting that it should be evaluated three-dimensionally. Here, we established a novel bone tissue clearing technique (Osteo-DISCO) for murine bones which enabled us to visualize the detailed distribution of nerves or blood vessels inside bone. Interestingly, we found that there is a specific nerve entry site in each long bone and that surgical ablation of the specific nerve fibers entering bone tissue led to decreased bone formation and impaired bone regeneration. Furthermore, we revealed that the administration of calcitonin gene-related peptide (CGRP), which is primarily released from sensory nerves, suppressed the bone loss caused by surgical nerve ablation. An in vitro study also indicated that CGRP directly promotes osteoblast activity, suggesting that sensory nerves inside bone can regulate osteogenesis via the secretion of CGRP.

Abstract We aimed to quantitatively compare the choroid blood flow and choroid thickness at the periphery among eyes with central serous chorioretinopathy (CSC), fellow eyes and healthy eyes using ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA). Retrospective analysis of 49 patients with CSC (98 eyes, including unaffected fellow eyes) and 49 age and sex matched controls were included. We obtained 3-dimensional data of vertical 20 mm × horizontal 24 mm × scan depth 6 mm, comprising 9 subfields (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, lower, inferonasal regions). CSC eyes presented with greater density of large-vessel choroidal layer in all the 9 subfields compared with controls. Compared with normal eyes, CSC eyes had greater choroidal thickness (superotemporal, upper, superonasal, temporal, central, nasal, inferotemporal, and inferonasal subfields) and choroidal volume (superotemporal, upper, superonasal, temporal, central, and nasal subfields). Compared with control eyes, the choriocapillaris density in the superotemporal, inferotemporal and inferonasal subfields was greater in patients with CSC. Our study may provide further evidence for the congestion of vortex vein in the pathogenesis of CSC. UWF SS-OCTA can be used to evaluate the abnormalities of the choroidal structures even at the periphery in eyes with CSC.

Abstract A novel model to be applied to next-generation accelerators, Ising machines, is formulated on the basis of the phase-field model of the phase-separation structure of a diblock polymer. Recently, Ising machines including quantum annealing machines, attract overwhelming attention as a technology that opens up future possibilities. On the other hand, the phase-field model has demonstrated its high performance in material development, though it takes a long time to achieve equilibrium. Although the convergence time problem might be solved by the next-generation accelerators, no solution has been proposed. In this study, we show the calculation of the phase-separation structure of a diblock polymer as the equilibrium state using phase-field model by an actual Ising machine. The proposed new model brings remarkable acceleration in obtaining the phase-separation structure. Our model can be solved on a large-scale quantum annealing machine. The significant acceleration of the phase-field simulation by the quantum technique pushes the material development to the next stage.

Abstract The in vitro unconstrained Achilles tendon is nearly straight, while in vivo experiments reveal that the proximal region of the Achilles tendon, adjacent to Kager’s fat pad, bends ventrally during plantarflexion but remains nearly straight during dorsiflexion. Tendon bending is an important factor in determining the displacement of the foot compared to the shortening of the muscle fibers. The objective of this study was to elucidate the various mechanisms that could cause tendon bending, which currently remain unknown. Examination of Thiel-embalmed cadavers, with preservation of native articular joint mobility, revealed that the Achilles tendon still bent ventrally even when its surrounding tissues, including the skin surface, Kager’s fat pad, and distal portions of the soleus muscle were removed. Shear modulus and collagen fiber orientation were distributed homogeneously with respect to the longitudinal line of the tendon, minimizing their causative contributions to the bending. Given that tendon bending is not caused by either the nature of the deformations of the tissues surrounding the Achilles tendon or its physical properties, we conclude that it results from the geometric architecture of the Achilles tendon and its configuration with respect to the surrounding tissues.

Power system fault diagnosis is crucial for identifying the location and causes of faults and providing decision-making support for power dispatchers. However, most classical methods suffer from significant time-consuming, memory overhead, and computational complexity issues as the scale of the power system concerned increases. With rapid development of quantum computing technology, the combinatorial optimization method based on quantum computing has shown certain advantages in computational time over existing methods. Given this background, this paper proposes a quantum computing based power system fault diagnosis method with the quantum approximate optimization algorithm. The proposed method reformulates the fault diagnosis problem as a Hamiltonian by using Ising model, which completely preserves the coupling relationship between faulty components and various operations of protective relays and circuit breakers. Additionally, to enhance problem-solving efficiency under current equipment limitations, the symmetric equivalent decomposition method of multi-z-rotation gate is utilized. Furthermore, the small probability characteristics of power system events is utilized to reduce the number of qubits. Simulation results based on the test system show that the proposed methods can achieve the same optimal results with a faster speed compared with the classical higher-order solver provided by D-Wave., (© 2024. The Author(s).)

Ménière disease (MD) is an idiopathic inner ear disorder, and endolymphatic hydrops (EH) being considered to be its pathological basis. Currently, there is no gold standard for diagnosing MD. Previous study has reported visualized EH using MRI by intratympanic gadolinium-based contrast media (GBCM) administration (IT-Gd) in patients with MD, and this technique was gradually established for MD diagnosis. However, few studies reported their diagnostic sensitivity and specificity in clinical application. This prospective study aimed at investigating the clinical characteristics and magnetic resonance imaging (MRI) results of patients with MD, and analyzing the relationship between clinical results and MRI findings in MD patients. Our study shows that the diagnostic sensitivity and specificity of MRI were 79.2% and 80.7% respectively. Moreover, there was no significant correlation between hearing levels and cochlear grading scores, nor vestibular grading scores. The duration of disease was not significantly associated with cochlear or vestibular grading scores. These findings suggest that IT-Gd MRI offers reliable radiological diagnostic criteria for MD.

Anti-retroviral therapy (ART) can inhibit HIV proliferation but not achieve virus eradication from HIV-infected individuals. Under ART-based HIV control, virus-specific CD8 + T-cell responses are often reduced. Here, we investigated the impact of therapeutic vaccination inducing virus-specific CD8 + T-cell responses under ART on viral control in a macaque AIDS model. Twelve rhesus macaques received ART from week 12 to 32 after simian immunodeficiency virus (SIV) infection. Six of them were vaccinated with Sendai virus vectors expressing SIV Gag and Vif at weeks 26 and 32, and Gag/Vif-specific CD8 + T-cell responses were enhanced and became predominant. All macaques controlled viremia during ART but showed viremia rebound after ART cessation. Analysis of in vitro CD8 + cell ability to suppress replication of autologous lymphocytes-derived SIVs found augmentation of anti-SIV efficacy of CD8 + cells after vaccination. In the vaccinated animals, the anti-SIV efficacy of CD8 + cells at week 34 was correlated positively with Gag-specific CD8 + T-cell frequencies and inversely with rebound viral loads at week 34. These results indicate that Gag-specific CD8 + T-cell induction by therapeutic vaccination can augment anti-virus efficacy of CD8 + cells, which may be insufficient for functional cure but contribute to more stable viral control under ART.

The radio-frequency breakdown due to ultrahigh electric field strength essentially limits power handling capability of an individual high power microwave (HPM) generator, and this issue becomes more challenging for high frequency bands. Coherent power combining therefore provides an alternative approach to achieve an equivalent peak power of the order of ∼100 GW, which consequently provides opportunities to explore microwave related physics at extremes. The triaxial klystron amplifier (TKA) is a promising candidate for coherent power combing in high frequency bands owing to its intrinsic merit of high power capacity, nevertheless phase-locked long pulse radiation from TKA has not yet been obtained experimentally as the coaxial structure of TKA can easily lead to self-excitation of parasitic modes. In this paper, we present investigations into an X-band TKA capable of producing 1.1 GW HPMs with pulse duration of about 103 ns at the frequency of 9.375 GHz in experiment. Furthermore, the shot-to-shot fluctuation standard deviation of the phase shifts between the input and output microwaves is demonstrated to be less than 10°. The reported achievements open up prospects for accomplishing coherent power combining of X-band HPMs in the near future, and might also excite new development interests concerning high frequency TKAs.