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Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.

Gravity waves play essential roles in the terrestrial atmosphere because they propagate far from source regions and transport momentum and energy globally. Gravity waves are also observed in the Venus atmosphere, but their characteristics have been poorly understood. Here we demonstrate activities of small-scale gravity waves using a high-resolution Venus general circulation model with less than 20 and 0.25 km in the horizontal and vertical grid intervals, respectively. We find spontaneous gravity wave radiation from nearly balanced flows. In the upper cloud layer (~70 km), the thermal tides in the super-rotation are primary sources of small-scale gravity waves in the low-latitudes. Baroclinic/barotropic waves are also essential sources in the mid- and high-latitudes. The small-scale gravity waves affect the three-dimensional structure of the super-rotation and contribute to material mixing through their breaking processes. They propagate vertically and transport momentum globally, which decelerates the super-rotation in the upper cloud layer (~70 km) and accelerates it above ~80 km. Gravity waves are observed in Venus atmosphere, but their characteristics are not well-known. Here, the authors show spontaneous generation of gravity waves from the thermal tides in the Venus atmosphere as small-scale gravity waves are resolved in high-resolution general circulation model.

Formaldehyde (H 2 CO) is a critical precursor for the abiotic formation of biomolecules, including amino acids and sugars, which are the building blocks of proteins and RNA. Geomorphological and geochemical evidence on Mars indicates a temperate environment compatible with the existence of surface liquid water during its early history at 3.8–3.6 billion years ago (Ga), which was maintained by the warming effect of reducing gases, such as H 2 . However, it remains uncertain whether such a temperate and weakly reducing surface environment on early Mars was suitable for producing H 2 CO. In this study, we investigated the atmospheric production of H 2 CO on early Mars using a 1-D photochemical model assuming a thick CO 2 -dominated atmosphere with H 2 and CO. Our results show that a continuous supply of atmospheric H 2 CO can be used to form various organic compounds, including amino acids and sugars. This could be a possible origin for the organic matter observed on the Martian surface. Given the previously reported conversion rate from H 2 CO into ribose, the calculated H 2 CO deposition flux suggests a continuous supply of bio-important sugars on early Mars, particularly during the Noachian and early Hesperian periods.

Organic matter in the Martian sediments may provide a key to understanding the prebiotic chemistry and habitability of early Mars. The Curiosity rover has measured highly variable and 13 C-depleted carbon isotopic values in early Martian organic matter whose origin is uncertain. One hypothesis suggests the deposition of simple organic molecules generated from 13 C-depleted CO derived from CO 2 photochemical reduction in the atmosphere. Here, we present a coupled photochemistry-climate evolution model incorporating carbon isotope fractionation processes induced by CO 2 photolysis, carbon escape, and volcanic outgassing in an early Martian atmosphere of 0.5–2 bar, composed mainly of CO 2 , CO, and H 2 to track the evolution of the carbon isotopic composition of C-bearing species. The calculated carbon isotopic ratio in formaldehyde (H 2 CO) can be highly depleted in 13 C due to CO 2 -photolysis-induced fractionation and is variable with changes in atmospheric CO/CO 2 ratio, surface pressure, albedo, and H 2 outgassing rate. Conversely, CO 2 becomes enriched in 13 C, as estimated from the carbonates preserved in ALH84001 meteorite. Complex organic matter formed by the polymerization of such H 2 CO could explain the strong depletion in 13 C observed in the Martian organic matter. Mixing with other sources of organic matter would account for its unique variable carbon isotopic values.

Recent developments in artificial intelligence (AI) have introduced new technologies that can aid in detecting cognitive decline. This study developed a voice-based AI model that screens for cognitive decline using only a short conversational voice sample. The process involved collecting voice samples, applying machine learning (ML), and confirming accuracy through test data. The AI model extracts multiple voice features from the collected voice data to detect potential signs of cognitive impairment. Data labeling for ML was based on Mini-Mental State Examination scores: scores of 23 or lower were labeled as “cognitively declined (CD),” while scores above 24 were labeled as “cognitively normal (CN).” A fully coupled neural network architecture was employed for deep learning, using voice samples from 263 patients. Twenty voice samples, each comprising a one-minute conversation, were used for accuracy evaluation. The developed AI model achieved an accuracy of 0.950 in discriminating between CD and CN individuals, with a sensitivity of 0.875, specificity of 1.000, and an average area under the curve of 0.990. This voice AI model shows promise as a cognitive screening tool accessible via mobile devices, requiring no specialized environments or equipment, and can help detect CD, offering individuals the opportunity to seek medical attention.

Donepezil hydrochloride, used to treat Alzheimer's disease, is typically initiated at a low dose and titrated to minimize gastrointestinal side effects. Despite its favorable safety profile, the patient developed severe anorexia, dehydration, and electrocardiographic abnormalities. This case highlights the need for individualized dosing and careful monitoring of caregivers during pharmacotherapy.

Results of simulations with a new high-resolution Martian general circulation model (MGCM) (T106 spectral resolution, or ~67-km horizontal grid size) have been analyzed to reveal global distributions of gravity waves (GWs) during the solstice and equinox periods. They show that shorter-scale harmonics progressively dominate with height, and the body force per unit mass (drag) they impose on the larger-scale flow increases. Mean magnitudes of the drag in the middle atmosphere are tens of meters per second per sol, while instantaneously they can reach thousands of meters per second per sol. Inclusion of small-scale GW harmonics results in an attenuation of the wind jets in the middle atmosphere and in the tendency of their reversal. GW energy in the troposphere due to the shortest-scale harmonics is concentrated in the low latitudes for both seasons and is in a good agreement with observations. The vertical fluxes of wave horizontal momentum are directed mainly against the larger-scale wind. Orographically generated GWs contribute significantly to the total energy of small-scale disturbances and to the drag created by the latter. These waves strongly decay with height, and thus the nonorographic GWs of tropospheric origin dominate near the mesopause. The results of this study can be used to better constrain and validate GW parameterizations in MGCMs.

IntroductionFemoral localized periosteal thickening (LPT, also termed “beaking”) of the lateral cortex often precedes an atypical femoral fracture (AFF). Bisphosphonate (BP) use, glucocorticoid use, and Asian race are major risk factors for developing such fractures. The aim of this study was to determine whether the trabecular bone score (TBS) reflecting the lumbar trabecular microarchitecture was related to LPT in glucocorticoid-treated Japanese patients with autoimmune diseases.Materials and methodsWe retrospectively investigated 111 women with autoimmune diseases treated with prednisolone (PSL) who had undergone both femoral X-ray and dual-energy X-ray absorptiometry of the L1 − L4 lumbar vertebrae and for whom TBS could be evaluated for two or more of these.ResultsFemoral LPT was evident in the X-rays of 18 of 111 patients (16.2%). Higher body mass index (BMI), longer duration of PSL use and longer duration of BP use were significant in patients with LPT compared to those without. The TBS was significantly lower in patients with LPT than in those without (1.314 ± 0.092 vs. 1.365 ± 0.100, p = 0.044); however, the lumbar bone mineral density did not differ significantly (0.892 ± 0.141 vs. 0.897 ± 0.154 g/cm2, p = 0.897). TBS was significantly associated with LPT (odds ratio, 0.004; 95% CI, 0 − 0.96; p = 0.048), but not in the multivariate analysis including BMI, duration of PSL use and duration of BP use.ConclusionsThe TBS was lower in glucocorticoid-treated Japanese women with autoimmune diseases with LPT than in those without LPT, and deteriorated trabecular microarchitecture influenced by longer use of BP and glucocorticoid might be associated with the development of LPT.

Parkinson's disease (PD) is associated with various cognitive impairments. However, the nature of cognitive modification in patients with PD remains to be elucidated. In the present study, we examined whether patients with PD could correct and maintain subjective time duration and line length estimation. After training sessions, in which participants repeatedly memorized either a duration or a length, we compared a learning performance in 20 PD patients with 20 healthy controls. In the case of duration in the PD patients, the learned durations immediately returned to baseline of pre-training within a few minutes. However, the patients' ability to learn length estimation remained unimpaired. In contrast, healthy controls were able to retain the learned duration and length estimations. Time compression in PD's internal clock may become entrained to their altered duration estimation even after learning of accurate time duration. These deficits may be associated with disrupting cognitive modification in PD.