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Defect generation and recovery at the interface of a silicon dioxide/silicon ( SiO 2 /Si) stack are studied in oxygen ( O 2) or argon (Ar) plasma processing and post-annealing. Defect generation is recognized to be dependent on the processing gas and the SiO 2 layer thickness. O 2 plasma processing shows a strong incident-ion energy dependence, where ion's implantation, diffusion, and reactions in the SiO 2 layer play important roles in defect generation. A similar dependence is observed for Ar plasma processing; however, it also shows the photon effects in defect generation for a thick SiO 2 layer. Defect recovery is demonstrated by annealing, where recovery depends on the annealing temperature as well as the amount of defects generated at the interface. [ABSTRACT FROM AUTHOR]

A method for preparing important building blocks for natural product synthesis has been developed using singlet oxygen generated from 5,10,15,20-tetraphenylporphyrin under blue LED irradiation. Using this method, the allylic oxidation of dicyclopentadiene proceeded smoothly in air atmosphere with an 87% yield. The conditions, using TPP under blue LED irradiation, were expanded to include the oxidation of cyclopentadiene. The approach offers a simple and cost-effective method of synthesizing important building blocks for natural product synthesis. [ABSTRACT FROM AUTHOR]

With the rapid spread of telecommuting since the COVID-19 pandemic, companies have been relocating to high-end business centers, thereby enhancing the workplace experience for employees, a phenomenon called the "flight to quality." However, this trend's impact on rents and vacancy rates in individual office buildings has not been extensively studied. To determine the effects of the flight-to-quality phenomenon on individual buildings, we examine the impact of modern amenities, which directly influence employee lifestyles, on rents and vacancy rates in the Tokyo office market. Using a propensity score-based quasi-experimental method, we find that commercial properties with such modern amenities command higher rents and experience lower vacancy rates than those without. The difference in vacancy rates has increased since 2020. However, the significance of these amenities diminishes for properties less competitive in age, size, and location. The results indicate that the "flight to quality" may further polarize the office real estate market into two categories: one for high-end buildings experiencing increasing demand, and another for those with modest amenities experiencing decreasing demand. The findings have implications for office building owners/investors and the government, make educated decisions as to whether to invest in modern amenities, join the quality competition, or encourage urban restructuring. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) and rotavirus infections are long-standing infectious diseases that affect children worldwide. RSV and rotavirus were first discovered in clinical specimens in 1955 and 1973, respectively. From their discovery to the present day, significant progress has been made in understanding these two infections. The introduction of a simple and rapid antigen diagnostic test into clinical settings in the 1990s offered new insight into the clinical characteristics and epidemiology of these infections. Regarding therapeutics, symptomatic treatments have remained the mainstay; however, prophylactic humanized anti-RSV monoclonal antibodies have been developed and advances in structural biology may allow for more effective human anti-RSV monoclonal antibodies and novel RSV vaccines to be developed soon. For rotavirus, two vaccines have been licensed and broadly applied over the past 10 years, which have been successful clinically and have changed the epidemiology of rotavirus infections in Japan. [ABSTRACT FROM AUTHOR]

The use of prenatal testing in Japan is expected to increase. However, there are ethical concerns regarding pregnancy termination upon the detection of fetal chromosomal abnormalities, such as Down syndrome. Furthermore, factors associated with decision-making following a positive result of Down syndrome after prenatal screening remain unclear. Therefore, we aimed to evaluate the association between decision-making among university students following a hypothetical positive result of Down syndrome in prenatal screening and their perception of their future career development defined as vocational identity. This cross-sectional study included 256 individuals (109 men, 143 women, and four who preferred not to answer). Self-anonymous semi-structured questionnaires were distributed to collect information regarding socio-demographic characteristics, vocational identity, and decision-making following a positive prenatal screening result of Down syndrome. Vocational identity was assessed using the Vocational Identity Measure. Women students were more likely to intend to continue the pregnancy (76.9%, p < 0.05); however, students without siblings (68.2%, p < 0.01) and men and women students with higher scores for vocational identities who were raised in an academically oriented family were more likely to intend to terminate the pregnancy (p < 0.05). Therefore, gender and vocational identity were associated with decision-making following a positive result of Down syndrome. Further qualitative and quantitative studies on factors associated with decision-making following a positive result of Down syndrome are necessary to eliminate the burden and social barrier, including gender division of labor and the effect of vocational career for people wishing to parent a child with Down syndrome. [ABSTRACT FROM AUTHOR]

Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head–neck junction. Despite anatomical consensus regarding the femoral head–neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head–neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head–neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p‐value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology. [ABSTRACT FROM AUTHOR]

The meniscal position within the knee is critical to maintain normal knee function. The joint capsule might dynamically coordinate the medial meniscus (MM) by transmitting a semimembranosus action. However, their interrelationships in vivo are unclear. We aimed to determine relationships among the MM, joint capsule, and semimembranosus during passive tibial external-internal and isometric tibial internal rotation at the medial and posteromedial knees of 10 healthy individuals in vivo using ultrasound. We analyzed images of the MM and joint capsule locations at the medial and posteromedial knee and the velocity waveform similarity of each structure during rotational tasks. Both isometric internal rotation with semimembranosus action and passive tibial external rotation displaced the MM inward at the medial knee. The MM and joint capsule during these MM displacements coordinately moved with more than moderate cross-correlation coefficients (passive external and isometric internal rotations, ≥ 0.54 and ≥ 0.90, respectively). The movements of the MM and joint capsule to the semimembranosus during isometric internal rotation also coordinated with moderate cross-correlation coefficients (≥ 0.62). Therefore, the joint capsule might dynamically coordinate the MM by transmitting semimembranosus action. Whether increased tibial internal rotation or semimembranosus shortening causes MM extrusion awaits further investigation. [ABSTRACT FROM AUTHOR]

Deficiencies in the ING4 tumor suppressor are associated with advanced stage tumors and poor patient survival in cancer. ING4 was shown to inhibit NF-kB in several cancers. As NF-kB is a key mediator of immune response, the ING4/NF-kB axis is likely to manifest in tumor-immune modulation but has not been investigated. To characterize the tumor immune microenvironment associated with ING4-deficient tumors, three approaches were employed in this study: First, tissue microarrays composed of 246 primary breast tumors including 97 ING4-deficient tumors were evaluated for the presence of selective immune markers, CD68, CD4, CD8, and PD-1, using immunohistochemical staining. Second, an immune-competent mouse model of ING4-deficient breast cancer was devised utilizing CRISPR-mediated deletion of Ing4 in a Tp53 deletion-derived mammary tumor cell line; mammary tumors were evaluated for immune markers using flow cytometry. Lastly, the METABRIC gene expression dataset was evaluated for patient survival related to the immune markers associated with Ing4-deleted tumors. The results showed that CD68, CD4, CD8, or PD-1, was not significantly associated with ING4-deficient breast tumors, indicating no enrichment of macrophages, T cells, or exhausted T cell types. In mice, Ing4-deleted mammary tumors had a growth rate comparable to Ing4-intact tumors but showed increased tumor penetrance and metastasis. Immune marker analyses of Ing4-deleted tumors revealed a significant increase in tumor-associated macrophages (Gr-1loCD11b+F4/80+) and a decrease in granzyme B-positive (GzmB+) CD4+ T cells, indicating a suppressive and/or less tumoricidal immune microenvironment. The METABRIC data analyses showed that low expression of GZMB was significantly associated with poor patient survival, as was ING4-low expression, in the basal subtype of breast cancer. Patients with GZMB-low/ING4-low tumors had the worst survival outcomes (HR = 2.80, 95% CI 1.36–5.75, p = 0.0004), supportive of the idea that the GZMB-low immune environment contributes to ING4-deficient tumor progression. Collectively, the study results demonstrate that ING4-deficient tumors harbor a microenvironment that contributes to immune evasion and metastasis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the primary sites, clinical characteristics, and treatment outcomes of patients with metastatic tumors in the eye and ocular adnexa. This retrospective case series consisted of 42 patients diagnosed with intraocular metastasis (IM) or ocular adnexal metastasis (OAM) at a tertiary center between January 2001 and June 2023. The patients comprised 18 men and 24 women; 24 (57%) and 18 (43%) patients were diagnosed with IM and OAM, respectively. In the IM group, the primary tumors originated from the lungs (79%), followed by the breasts (17%). In the OAM group, the primary tumors originated from the breasts (33%). Previously, 57% of the patients had been diagnosed with cancer. In the IM group, 38% exhibited bilateral involvement. Only 6% of the patients with OAM had bilateral diseases. The 1-, 3-, and 5-year overall survival (OS) was 42%, 18%, and 7%, respectively. The median OS since metastasis diagnosis in the lungs and breast was 11.8 and 10.5 months, respectively. Lung cancer remains the predominant primary cancer in IM, whereas breast cancer is the major cancer in OAM. Despite poor OS, early detection will facilitate the prompt treatment of primary cancer and metastatic sites. [ABSTRACT FROM AUTHOR]

Purpose: The chordae Willisii (CWs), trabecular projections into the lumen of the dural sinuses, are not well understood. We aimed to explore them using magnetic resonance imaging (MRI). Methods: Eighty-five patients underwent volumetric contrast-enhanced MRI, while another 30 underwent a fluid-attenuated inversion recovery (FLAIR) sequence in the coronal section. Results: The CWs were detected as linear filling defects lying in the dural sinuses, adjacent to the surrounding dura mater. They were found in the superior sagittal sinus (SSS) in 68.2% of the patients, most frequently in the middle third, with laminar appearance. In 27.1% of the patients, the CWs divided the SSS lumen into separate channels. The CWs were identified in the transverse sinus, transverse-sigmoid sinus junctional area and sigmoid sinus, and straight sinus in 54.1, 47.1, and 8.2%, respectively. On the FLAIR images, dural septi partially dividing the SSS lumen were identified in all patients. In addition, in 73.3% of the patients, fine linear structures were observed in the lumen with inconstant arrangements. Conclusions: The CWs may be constant structures distributed over the lumen of the intracranial dural sinuses. Contrast-enhanced MRI may be useful for detecting laminar CWs. The FLAIR sequence may be advantageous for delineating the dural septi projecting into the lumen of the dural sinuses. [ABSTRACT FROM AUTHOR]

Next‐generation "Beyond 5G (B5G)/6G" wireless network systems have been researched and developed for meeting the rapid growth of mobile traffic. A high‐yield fabrication process of InP‐based transistors and tera‐hertz monolithic integrated circuits with 300 GHz operation is reported, which is a candidate frequency for "Beyond 5G/6G" network systems. The main focus is on a high‐yield and reproductive fabrication process of InP‐based high electron mobility transistors (HEMTs) while revisiting previous studies. The DC and radio frequency characteristics of fabricated InP‐HEMTs from the viewpoint of integrating circuits are described. Then, high‐frequency performances of ft = 280 GHz and fmax = 860 GHz in the bias conditions of Vgs/Vds = 0.2/1.1 V with good uniformity are obtained. Finally, InP‐based 300 GHz‐band mixer and power amplifiers are introduced, to which a backside process is also applied for ensuring their stability and enhancing output power. [ABSTRACT FROM AUTHOR]

Summary: Aims: A multi‐stakeholder consensus has proposed MASLD (metabolic dysfunction‐associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid‐term mortality of patients with biopsy‐proven MASLD in Japan. Methods: We enrolled 1349 patients with biopsy‐proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data‐mining analysis. Results: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty‐five patients with MASLD died. Of these, liver‐related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9‐fold and 1.8‐fold risk of mortality, respectively. In the decision‐tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid‐term prognosis of patients with MASLD. Conclusions: In patients with biopsy‐proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver‐related events. Hepatic inflammation and fibrosis were significant factors influencing mid‐term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD. [ABSTRACT FROM AUTHOR]

Vernal keratoconjunctivitis is a persistent allergic ocular disease predominantly mediated by the T-helper 2 lymphocyte-associated immune response. The standard therapeutic approaches for vernal keratoconjunctivitis include topical corticosteroids and immunosuppressive eye drops. However, managing vernal keratoconjunctivitis with only topical treatments becomes challenging during seasonally exacerbated periods. Systemic treatments such as oral corticosteroids or cyclosporine may be alternative options. Recently, dupilumab's efficacy in refractory vernal keratoconjunctivitis treatment has been documented. Here, we report a case of refractory vernal keratoconjunctivitis coexisting with atopic dermatitis that rapidly improved after upadacitinib administration. An 18-year-old Japanese woman presented with atopic dermatitis, vernal keratoconjunctivitis, and hay fever. In winter, the patient experienced widespread erythema and escalated itching, leading to significant discomfort and insomnia. Owing to the difficulty in maintaining her current regimen, upadacitinib (15 mg), a Janus kinase inhibitor was initiated. After upadacitinib administration, the treatment-resistant vernal keratoconjunctivitis and erythema improved. Upadacitinib is beneficial in severe cases of atopic dermatitis. Consequently, in our case, upadacitinib may offer therapeutic benefits for refractory vernal conjunctivitis by improving the T-helper 1/2 type immune response, autoimmunity, and oxidative stress. To our knowledge, this is the first report suggesting the potential utility of upadacitinib in managing severe vernal conjunctivitis. [ABSTRACT FROM AUTHOR]

The use of fibrin glue for inguinal hernia mesh fixation has been suggested to be effective in preventing hematomas and reducing postoperative pain compared to tacks and sutures.. The effect of fibrin glue can vary significantly based on the device used. This study assessed the efficacy of fibrin glue based on the type of devices used in an ex vivo system. The rabbit's abdominal wall was trimmed to a size of 3.0 × 6.0 cm and was secured at the edges with metal fixtures. To measure the maximum tensile strength at the point of adhesion failure, the hernia mesh was fixed to the rabbit's abdominal wall using fibrin glue in a 2 cm square area, left for 3 min, and then pulled at a speed of 50 cm/min. The test was conducted 10 times for each group. The median (minimum–maximum) tensile strength values using the spraying, two-liquid mixing, and sequential layering methods were 3.58 (1.99–4.95), 0.51 (0.27–1.89), and 1.32 (0.63–1.66) N, respectively. The spraying method had predominantly higher tensile strength values than the two-liquid mixing and sequential layering methods (P < 0.01). In conclusion, in hernia mesh fixation, the spraying method can be adopted to achieve appropriate adhesive effects. [ABSTRACT FROM AUTHOR]

Aim: Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers. Methods: We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA– central memory T cells (TCM), CCR7– CD45RA– effector memory T, and CCR7– CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS). Results: Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning). Conclusions: Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD. [ABSTRACT FROM AUTHOR]

Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157, 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori et al., J. Am. Soc. Nephrol. 28, 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic et al., Proc. Natl. Acad. Sci. U.S.A. 93, 4229-4234 (1996)], and other illnesses. [ABSTRACT FROM AUTHOR]

The photorefractive properties of triphenylamine polymer-based composites with various composition ratios were investigated via optical diffraction, response time, asymmetric energy transfer, and transient photocurrent. The composite consisted of a photoconductive polymer of poly((4-diphenylamino)benzyl acrylate), a photoconductive plasticizer of (4-diphenylamino)phenyl)methanol, a sensitizer of [6,6]-phenyl-C61-butyric acid methyl ester, and a nonlinear optical dye of (4-(azepan-1-yl)-benzylidene)malononitrile. The photorefractive properties and related quantities were dependent on the composition, which was related to the glass transition temperature of the photorefractive polymers. The quantum efficiency (QE) of photocarrier generation was evaluated from the initial slope of the transient photocurrent. Transient photocurrents were measured and showed two unique peaks: one in the range of 10−4 to 10−3 s and the other in the range of 10−1 to 1 s. The transient photocurrents was well simulated (or reproduced) by the expanded two-trapping site model with two kinds of photocarrier generation and recombination processes and two different trapping sites. The obtained photorefractive quantity of trap density was significantly related to the photoconductive parameters of QE. [ABSTRACT FROM AUTHOR]

Meta‐analyses examining dichotomous outcomes often include single‐zero studies, where no events occur in intervention or control groups. These pose challenges, and several methods have been proposed to address them. A fixed continuity correction method has been shown to bias estimates, but it is frequently used because sometimes software (e.g., RevMan software in Cochrane reviews) uses it as a default. We aimed to empirically compare results using the continuity correction with those using alternative models that do not require correction. To this aim, we reanalyzed the original data from 885 meta‐analyses in Cochrane reviews using the following methods: (i) Mantel–Haenszel model with a fixed continuity correction, (ii) random effects inverse variance model with a fixed continuity correction, (iii) Peto method (the three models available in RevMan), (iv) random effects inverse variance model with the treatment arm continuity correction, (v) Mantel–Haenszel model without correction, (vi) logistic regression, and (vii) a Bayesian random effects model with binominal likelihood. For each meta‐analysis we calculated ratios of odds ratios between all methods, to assess how the choice of method may impact results. Ratios of odds ratios <0.8 or <1.25 were seen in ~30% of the existing meta‐analyses when comparing results between Mantel–Haenszel model with a fixed continuity correction and either Mantel–Haenszel model without correction or logistic regression. We concluded that injudicious use of the fixed continuity correction in existing Cochrane reviews may have substantially influenced effect estimates in some cases. Future updates of RevMan should incorporate less biased statistical methods. [ABSTRACT FROM AUTHOR]

A succinct synthetic approach to mugineic acids and 2'‐hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring‐opening reactions to form two C−N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'‐hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'‐hydroxy group. The dansyl‐labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA‐probe through these transporters. [ABSTRACT FROM AUTHOR]

A succinct synthetic approach to mugineic acids and 2'‐hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring‐opening reactions to form two C−N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'‐hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'‐hydroxy group. The dansyl‐labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA‐probe through these transporters. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study was to compare the efficacy of intravenous immunoglobulin (IVIG) therapy for obstetric antiphospholipid syndrome (APS) refractory to conventional treatment. Methods: We conducted a single-arm, open-label multicentre clinical intervention trial. The enrolled criteria were patients with refractory APS who had a history of still or premature birth before 30 weeks of gestational age, even though they had been treated with conventional treatment, i.e. heparin and low-dose aspirin. After confirming the foetal heartbeats, a single course of IVIG (0.4 g/kg body weight daily for 5 days) was added to conventional treatment. The primary outcome was a live birth ratio of >30 weeks of gestational period, and the secondary outcome included improving pregnancy outcomes compared to previous pregnancy. Results: Twenty-five per cent of patients (2 of 8 cases) achieved a live birth after the 30th week of pregnancy by IVIG-only add-on treatment, which is the same prevalence as the historical control. However, by adding other second-line therapy to IVIG and conventional treatment, further three patients (37.5%) achieved improvements in pregnancy outcome compared to previous treatments. In total, five patients (62.5%) were able to achieve preferable pregnancy outcomes through combination treatment including IVIG. Conclusions: This clinical trial could not demonstrate the efficacy of IVIG-only add-on therapy at improving the pregnancy outcomes of patients with obstetric APS refractory to conventional treatment. However, the combination of IVIG with rituximab or statins adding to conventional treatment improved pregnancy outcomes and resulted in more live births. Further studies are needed to investigate the efficacy of multi-targeted therapy to treat obstetric refractory APS. [ABSTRACT FROM AUTHOR]

Recently, we proposed a new orbital analysis method, natural reaction orbital (NRO), which automatically extracts orbital pairs that characterize electron transfer in reaction processes by singular value decomposition of the first-order orbital response matrix to the nuclear coordinate displacements [Ebisawa et al., Phys. Chem. Chem. Phys. 24, 3532 (2022)]. NRO analysis along the intrinsic reaction coordinate (IRC) for several typical chemical reactions demonstrated that electron transfer occurs mainly in the vicinity of transition states and in regions where the energy profile along the IRC shows shoulder features, allowing the reaction mechanism to be explained in terms of electron motion. However, its application has been limited to single configuration theories such as Hartree–Fock theory and density functional theory. In this work, the concept of NRO is extended to multiconfigurational wavefunctions and formulated as the multiconfiguration NRO (MC-NRO). The MC-NRO method is applicable to various types of electronic structure theories, including multiconfigurational theory and linear response theory, and is expected to be a practical tool for extracting the essential qualitative features of a broad range of chemical reactions, including covalent bond dissociation and chemical reactions in electronically excited states. In this paper, we calculate the IRC for five basic chemical reaction processes at the level of the complete active space self-consistent field theory and discuss the phenomenon of electron transfer by performing MC-NRO analysis along each IRC. Finally, issues and future prospects of the MC-NRO method are discussed. [ABSTRACT FROM AUTHOR]

Recently, surface‐hopping ab initio molecular dynamics (SH‐AIMD) simulations have come to be used to discuss the mechanisms and dynamics of excited‐state chemical reactions, including internal conversion and intersystem crossing. In dynamics simulations involving intersystem crossing, there are two potential energy surfaces (PESs) governing the motion of nuclei: PES in a spin‐pure state and PES in a spin‐mixed state. The former gives wrong results for molecular systems with large spin‐orbit coupling (SOC), while the latter requires a potential gradient that includes a change in SOC at each point, making the computational cost very high. In this study, we systematically investigate the extent to which the magnitude of SOC affects the results of the spin‐pure state‐based dynamics simulations for the hydride MH2 (M = Si, Ge, Sn, Pb) by performing SH‐AIMD simulations based on spin‐pure and spin‐mixed states. It is clearly shown that spin‐mixed state PESs are indispensable for the dynamics simulation of intersystem crossing in systems containing elements Sn and Pb from the fifth period onward. Furthermore, in addition to the widely used Tully's fewest switches (TFS) algorithm, the Zhu‐Nakamura (ZN) global switching algorithm, which is computationally less expensive, is applied to SH for comparison. The results from TFS‐ and ZN‐SH‐AIMD methods are in qualitative agreement, suggesting that the less expensive ZN‐SH‐AIMD can be successfully utilized to investigate the dynamics of photochemical reactions based on quantum chemical calculations. [ABSTRACT FROM AUTHOR]

Oncocytoma arising from the parotid gland and extending into the parapharyngeal space (PPS) has not been previously reported. A 64-year-old woman presented with a large slowly growing mass extending from the parotid to the submandibular area, expanding medially to displace the pharynx across the midline. Core-needle biopsy revealed an oncocytoma in the PPS measuring 120 × 88 × 60 mm in size. Although the tumor was of an unprecedentedly large size and extended into multiple spaces, it could be removed via a cervical–parotid approach without osteotomy. The resected tumor was again diagnosed as oncocytoma. A postoperative complication was weakness of the ipsilateral facial nerve, which almost completely resolved in 6 months. No recurrence has been noted on 1 y follow-up. We were able to resect an extremely large oncocytoma arising from the parotid gland without osteotomy. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME. Methods: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients. Results: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3− M-MDSCs and were abundant in treatment-resistant GC patients. Conclusions: The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME. [ABSTRACT FROM AUTHOR]

Progress in evolutionary developmental biology (evo‐devo) has deepened our understanding of how intrinsic properties of embryogenesis, along with natural selection and population genetics, shape phenotypic diversity. A focal point of recent empirical and theoretical research is the idea that highly developmentally stable phenotypes are more conserved in evolution. Previously, we demonstrated that in Japanese medaka (Oryzias latipes), embryonic stages and genes with high stability, estimated through whole‐embryo RNA‐seq, are highly conserved in subsequent generations. However, the precise origin of the stability of gene expression levels evaluated at the whole‐embryo level remained unclear. Such stability could be attributed to two distinct sources: stable intracellular expression levels or spatially stable expression patterns. Here we demonstrate that stability observed in whole‐embryo RNA‐seq can be attributed to stability at the cellular level (low variability in gene expression at the cellular levels). We quantified the intercellular variations in expression levels and spatial gene expression patterns for seven key genes involved in patterning dorsoventral and rostrocaudal regions during early development in medaka. We evaluated intracellular variability by counting transcripts and found its significant correlation with variation observed in whole‐embryo RNA‐seq data. Conversely, variation in spatial gene expression patterns, assessed through intraindividual left–right asymmetry, showed no correlation. Given the previously reported correlation between stability and conservation of expression levels throughout embryogenesis, our findings suggest a potential general trend: the stability or instability of developmental systems—and the consequent evolutionary diversity—may be primarily anchored in intrinsic fundamental elements such as the variability of intracellular states. Research highlights: We investigated the precise origins of developmental stability that was previously determined by whole‐embryo RNA‐seq, given its significance in indicating the potential for phenotypic conservation during evolution.Our findings suggest that the developmental stability can be primarily attributed to stability in gene expression at the cellular level, rather than stability in spatial gene expression patterns.The result provides further insight into how embryogenesis introduces bias in phenotypic evolution, and thus paves the way for a deeper understanding of developmental stability that would enable the prediction of phenotypic evolution. [ABSTRACT FROM AUTHOR]

BACKGROUND: Foot arch dynamics play an important role in dynamic postural control. Association between foot arch dynamics and postural control among adolescent athletes remains poorly explored. OBJECTIVE: To examine the relationship between foot arch dynamics, intrinsic foot muscle (IFM) morphology, and toe flexor strength and dynamic postural stability after jump landing and repetitive rebound jump performance in competitive adolescent athletes. METHODS: Based on foot arch dynamics, evaluated from relative change in the foot arch height in sitting and standing positions, 50 adolescent athletes were classified as stiff, normal, or flexible. IFM morphology was evaluated by ultrasonography. Dynamic postural stability index (DPSI) was measured as participants jumped and landed with the right leg onto a force plate, whereas repetitive rebound jumping performance was assessed using the jump height and reactive jump index. RESULTS: The stiff group had a significantly worse DPSI and vertical stability index than the normal group (p = 0.26, p = 0.44, respectively), and worse anteroposterior stability index (APSI) values than the flexible group (p = 0.005). Multivariate regression models of the relationship between the APSI and foot arch dynamics showed adequate power (probability of error = 0.912). CONCLUSIONS: Increased foot arch stiffness negatively affects dynamic balance during jump-landing, which may deteriorate their performance. [ABSTRACT FROM AUTHOR]

Background: We investigated the outcomes of postoperative radiation therapy for olfactory neuroblastoma (ONB) and our cross‐departmental collaboration to enhance the effectiveness of cancer treatment. Methods: We retrospectively evaluated 22 patients with ONB who underwent postoperative radiotherapy after tumor resection. En bloc resection was performed; pathology specimens were prepared in coronal sections; and irradiation fields were determined after discussion with radiation oncologists, head and neck surgeons, and pathologists. Results: The overall survival and local control rates were 95.5% and 100%, respectively, at a median 37‐month follow‐up. The 3‐ and 5‐year disease‐free survival (DFS) rates were 64.4% and 56.3%, respectively. Of the 22 patients, 9 (8 Kadish C and 1 Kadish B) had disease recurrence. Of the nine patients, five had positive margins and two had closed margins; cervical lymph node recurrence occurred in six, and distant metastasis with or without cervical lymph node recurrence occurred in three. DFS analysis of risk factors showed no statistically significant differences, but positive margins were a significant recurrence factor in multivariate analysis. Conclusions: The local control rate of ONB treated with postoperative radiation therapy was 100%. This may be attributed to cross‐departmental cooperation between head and neck surgeons, pathologists, and radiation oncologists, which resulted in accurate matching of CT images for treatment planning with the location of the tumor and positive margins. Longer follow‐up periods are required to evaluate the effectiveness of our strategy. [ABSTRACT FROM AUTHOR]

Background: Appendicitis is an inflammatory condition that requires timely and effective intervention. Despite being one of the most common surgically treated diseases, the condition is difficult to diagnose because of atypical presentations. Ultrasound and computed tomography (CT) imaging improve the sensitivity and specificity of diagnoses, yet these tools bear the drawbacks of high operator dependency and radiation exposure, respectively. However, new artificial intelligence tools (such as machine learning) may be able to address these shortcomings. Methods: We conducted a state-of-the-art review to delineate the various use cases of emerging machine learning algorithms for diagnosing and managing appendicitis in recent literature. The query ("Appendectomy" OR "Appendicitis") AND ("Machine Learning" OR "Artificial Intelligence") was searched across three databases for publications ranging from 2012 to 2022. Upon filtering for duplicates and based on our predefined inclusion criteria, 39 relevant studies were identified. Results: The algorithms used in these studies performed with an average accuracy of 86% (18/39), a sensitivity of 81% (16/39), a specificity of 75% (16/39), and area under the receiver operating characteristic curves (AUROCs) of 0.82 (15/39) where reported. Based on accuracy alone, the optimal model was logistic regression in 18% of studies, an artificial neural network in 15%, a random forest in 13%, and a support vector machine in 10%. Conclusions: The identified studies suggest that machine learning may provide a novel solution for diagnosing appendicitis and preparing for patient-specific post-operative complications. However, further studies are warranted to assess the feasibility and advisability of implementing machine learning-based tools in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the diameters of the optic sheath (OSD) and superior ophthalmic vein (SOVD) in response to positional changes using magnetic resonance imaging (MRI). Materials and methods: Fifty adult outpatients who presented to the hospital underwent thin-slice coronal T2-weighted MRI in the supine position followed by the prone position. Results: The OS and SOV were well delineated in all the patients. The OSD in the anterior orbit was measured in the supine and prone positions on both sides. In addition, the SOVD in the anterior and posterior orbits was measured in the supine and prone positions on both sides. The OSD demonstrated an increase on both sides in 100% of the cases. The SOVD demonstrated an increase on both sides in 94% of the cases, whereas the remaining 6% demonstrated a decrease. The OSD measured at the anterior orbit and the SOVD at the anterior and posterior orbits significantly increased on both sides with positional changes from the supine to the prone position. Conclusion: OSD and SOVD may expand and contract in response to alterations in the intracranial pressure and venous flow patterns. MRI examination in the supine position combined with positional changes can help to better understand the OS and SOV as dynamic structures. [ABSTRACT FROM AUTHOR]

Background: The flexion adduction internal rotation (FADIR) test is performed by the combined motions of hip flexion (with knee flexion), adduction, and internal rotation, and can often reproduce anterior hip pain consistent with an individual's presenting pain. Since it has high sensitivity for intraarticular pathology diagnosis but low specificity, understanding the extraarticular pathology that can induce anterior hip pain in the FADIR test may also be essential. This study hypothesized that the interrelationships between the joint capsule and gluteus minimus differ in individuals with and without FADIR-positive pain and aimed to elucidate the in vivo interrelationships at hip internal rotation in 90°-flexion, which is also often restricted in individuals with FADIR-positive pain. Methods: Ten hips were included in the FADIR-positive group, and ten hips without hip pain in the FADIR test were included in a control group. Based on the ultrasound images at the four hip rotation conditions (20° and 10° external rotations, 0° external/internal rotation, and 10° internal rotation), orientation measurements of the gluteus minimus (muscle belly portion) and joint capsule were performed and quantitatively compared between the FADIR-positive and control groups. Additionally, 3 hips of 3 participants were randomly selected from each of the control and FADIR-positive groups for magnetic resonance imaging analysis. Results: At 0°-external/internal and 10°-internal rotation, on ultrasound images, fibers of the gluteus minimus and joint capsule in the FADIR-positive group were significantly more oriented in the same direction than those in the control group. Magnetic resonance imaging showed that the loose connective tissue between the gluteus minimus and joint capsule was prominent at 10°-internal rotation in the control group, although this was not apparent in the FADIR-positive group. Conclusions: At hip internal rotation in 90° flexion, the muscular belly portion of the gluteus minimus and joint capsule were oriented in the same direction to a greater extent in the FADIR-positive group than in the control group owing to a morphological change in the loose connective tissue between them. The pathological changes in the loose connective tissue may inhibit smooth movement of the gluteus minimus relative to the joint capsule in individuals with FADIR-positive pain. [ABSTRACT FROM AUTHOR]

Background: Early surgery is recommended for patients with hip fractures. Average time to surgery in Japan is 3.8 days. Such delay could be caused by the burden of preoperative assessment and management of geriatric comorbidities upon orthopedic surgeons. Hospitalist co-management has potential benefits in comprehensive perioperative care that could positively affect time to surgery in patients with hip fractures. We compare clinical outcomes of patients with hip fractures managed by orthopedic surgeon-led care (conventional group) vs. those of patients with hip fractures managed by hospitalist co-management.Methods: In this single-center retrospective cohort study, time to surgery was assessed with interrupted time series analyses. Whole length of hospital stay, length of hospital stay after surgery, complications during hospitalization, 30-day readmission, initiation of osteoporosis treatment and adherence to guidelines for deep vein thrombosis prophylaxis were also evaluated with Chi-square or Fisher's exact tests.Results: The conventional group comprised 332 patients and the co-management group 418 patients. Interrupted time series analyses revealed an immediate reduction of time to surgery by 1.2 days (95%CI, -1.9 to -0.4, P = 0.003) with the start of co-management. Whole length of hospital stay and length of hospital stay after surgery tended to be shorter, but without statistical significance. Intermediate to severe complications and 30-day readmission were not significantly different between the groups. In the co-management group, the rate of initiation of osteoporosis treatment (46.4% vs. 6.3%, P < 0.001) and adherence rate to guidelines for deep vein thrombosis prophylaxis (99.3% vs. 88%, P < 0.001) were significantly higher than those in the conventional group.Conclusions: Hospitalist co-management for elderly patients with hip fractures led to significantly shorter time to surgery than conventional orthopedic surgeon-led care, and had advantages in other clinical indicators. [ABSTRACT FROM AUTHOR]

Idealized numerical simulations of the Kuroshio western boundary current flowing over the Hirase seamount were conducted to examine the mechanisms of phenomena observed by shipboard and mooring measurements. Along the Kuroshio, enhanced mixing [vertical diffusivity, Kρ = O(10−2) m2 s−1] was observed in a low-stratification layer between high-shear layers around low tide, and a V-shaped band of the negative vertical component of relative vorticity (ζz) was also observed. Those features were reproduced in simulations of the Kuroshio that included the D2 tide. In the simulation, a streak of negative ζz detached from the Hirase turned into vertically tilted 10-km-scale vortices. The buoyancy frequency squared (N2) budget at the mooring position showed that the low stratification was caused by vertical and horizontal advection and horizontal tilting. The Kρ tended to increase when the Ertel potential vorticity (PV) < 0, as expected given the inertial instability. However, the magnitude of Kρ also depended on the tidal phase near Hirase, and Kρ was increased in the high vertical shear zones at the periphery of vortices where a strain motion is large. These results indicate that not only inertial instability but also tidal and vertical shear effects are important for driving turbulent mixing. Significance Statement: A basin-scale distribution of wind stress drives a strong surface-intensified current in the western part of each ocean basin, such as the Gulf Stream and the Kuroshio. This western boundary current is regarded as a place where the kinetic energy and vorticity generated by winds are dissipated, allowing the basin-scale circulation to keep a steady state, but its dissipation mechanisms are not well understood. To understand the mechanisms, we conducted idealized numerical simulations that isolate the interactions between a seamount and the current as well as tidal currents, and compared results with observations. Our findings provide insights into how the current transfers kinetic energy to smaller scales when it flows over a seamount. [ABSTRACT FROM AUTHOR]

Anomalies, unexpected events, and model inaccuracies have detrimental effects on satellite operations. High-fidelity models are required, but these models quickly become large and expensive. Cheap or low-fidelity models speed up computation but lack accuracy. To compromise these requirements, this study proposes a multifidelity framework based on cokriging. The proposed multifidelity framework is compared against three other standard methods often used in satellite simulations: a standalone gated recurrent unit, Gaussian process regression, and the autoregressive integrated moving average with explanatory variables model. The robustness of high-fidelity data point placement is also examined. Moreover, the real-time aspect of the simulation is considered by applying the sliding window technique. This multifidelity framework is demonstrated using temperature data obtained from thermal vacuum testing of Small Demonstration Satellite 4: a 50-kg-class satellite. The multifidelity framework provided higher accuracy and robustness than the other methods, however, having a higher computational cost as compared to a purely low-fidelity model. Up to 92% reduction of the error was achieved by the proposed framework. [ABSTRACT FROM AUTHOR]

We report a case of FLT3-mutated APL who developed disease relapse despite all-trans retinoic acid (ATRA) + chemotherapy, and re-induction chemotherapy with arsenic trioxide (ATO) and high-dose (HD) cytarabine (Ara-C) therapy failed to yield complete remission. Because the leukemic cells were resistant to all the aforementioned therapies, we started the patient on monotherapy with gilteritinib, a selective FLT3-inhibitor, as an alternative re-induction treatment option rather than further intensive chemotherapy. The patient showed complete hematologic remission in response to this therapy. This case serves as supporting evidence for the use of single-agent therapy with gilteritinib as a bridge to transplantation in patients with refractory FLT3-mutated APL. [ABSTRACT FROM AUTHOR]

Total and orbital electron densities of molecules are explored for the effect of the long‐range correction (LC) for density functional theory (DFT) exchange functionals by comparing to the effect of the ab initio coupled cluster singles and doubles (CCSD) method. Calculating the LC effect on the total electron densities shows that the LC stabilizes the electrons around the long‐range interaction regions of kinetic energy density, which are assumed to be electrons other than free electrons and self‐interacting electrons, while the CCSD method stabilizes the electrons in the long‐range interaction regions in the vertical molecular planes. As a more precise test, the LC effect on orbital densities are compared to the CCSD effect on Dyson orbital densities. Surprisingly, these effects are similar for the unoccupied orbitals, indicating that the LC covers the effects required to reproduce the CCSD Dyson unoccupied orbitals. For exploring the discrepancies between these effects on the occupied orbitals, the photoionization cross sections are calculated as a direct test for the shapes of the HOMOs to investigate the differences between these effects on the occupied orbitals. Consequently, the LC clearly produces the canonical HOMOs close to the CCSD Dyson and experimental ones, except for the HOMO of benzene molecule that mixes with the HOMO−1 for the CCSD Dyson orbitals. This indicates that the orbital analyses using the photoionization cross sections are available as a direct test for the quality of DFT functionals. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) clinically includes autoimmunity as indicated by antinuclear antibody (ANA) positivity and overlap of autoimmune hepatitis (AIH). Discriminating AIH-overlap NASH from NAFLD/NASH is required for proper treatment, and typically involves pathological diagnosis by invasive liver biopsy. Differential patterns of peripheral lymphocytes in NAFLD and AIH were assessed to noninvasively indicate risk factors of AIH-overlap NASH by flow cytometry (FCM). Methods: We assessed the differential frequencies of peripheral lymphocytes in 115 patients: 70 NASH (ANA negative:positive:AIH-overlap = 36:20:14), 18 NAFL, and 27 AIH (acute:chronic = 12:15) patients diagnosed by FCM. We focused on the following populations of lymphocytes: T cells, B cells, natural killer (NK) cells, NKT cells, helper T cell (Th) subsets (Th1, Th2, and Th17), and regulatory T cells; we also examined programmed cell death (PD) 1 and cytotoxic T-lymphocyte antigen levels. Results: Several significant differences in laboratory parameters and peripheral lymphocyte frequencies were found among the NAFLD and AIH subgroups. In univariate and multivariate analyses, hyaluronic acid level, liver stiffness, and the frequencies of Th17 and CD8+ PD1+ T cells were independent risk factors of NASH in NAFLD. Regarding overlap of AIH, only the frequency of CD8+ PD1+ T cells (odds ratio, 0.01; 95% CI 0.00–38.9, p = 0.004) was an independent risk factor in NASH and significantly decreased in AIH. Conclusions: The decreased frequency of peripheral CD8+ PD1+ T cells is an independent risk factor of NASH overlapping with AIH in the present cohort. Our findings will facilitate development of a new noninvasive FCM method for indicating risk factors of NASH, including autoimmunity. [ABSTRACT FROM AUTHOR]

Purpose: The prospective study aimed to examine the central retinal artery (CRA) using computed tomography (CT). Materials and methods: Seventy adult outpatients comprising 32 men and 38 women, at a mean age of 60.6 ± 13.3 years, were enrolled in the study. The patients underwent contrast-enhanced CT. The scan timing was set to start 5.0 s after the circle of Willis began to be delineated. Results: The ophthalmic arteries (OphAs) were comfortably delineated in all. In 97% of the patients, the CRA was delineated from the original site on the OphA to a more distal segment coursing on the optic sheath. Unilateral and bilateral CRA delineations were observed in 44% and 53% of cases, respectively. The delineated CRAs demonstrated highly variable morphologies in terms of the course and length on the optic sheath. In addition, the distance between the original site of the CRA and the posterior limit of the bulb was measured. The mean distance was 18.6 ± 5.0 mm on the right and 17.8 ± 4.3 mm on the left, respectively. No significant right-to-left differences in the measurements (p > 0.05) were observed. Conclusions: If optimal scan timing is adopted, the CRA segments coursing on the optic sheath can be delineated using contrast-enhanced CT. CT may be a useful diagnostic modality for the CRAs and associated pathological conditions. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to explore age-related atrophy of the mammillary bodies (MBs) based on their temporal change using magnetic resonance imaging (MRI). Materials and methods: The study included 30 adult outpatients who presented to the hospital and were followed for more than 100 months with annual MRIs. The bi-ventricular width (BVW), third ventricle width (TVW), and bi-mammillary dimension (BMD) were measured on axial T2-weighted imaging and analyzed. Results: The 30 patients comprised 1 in their 40s, 5 in their 50s, 6 in their 60s, 11 in their 70s, 5 in their 80s, and 2 in their 90s. The MBs were consistently detected with left-to-right symmetry. The mean BVW was 32 ± 2.2 mm on the initial (BVW1) and 32 ± 2.4 mm on the last (BVW2) MRI. The mean TVW was 7.0 ± 2.3 mm on the initial (TVW1) and 7.6 ± 2.7 mm on the last (TVW2) MRI. Furthermore, the mean BMD was 9.9 ± 1.3 mm on the initial (BMD1) and 10 ± 1.3 mm on the last (BMD2) MRI. Statistically, no age ranges had a large dimension for BVW1, BVW2, TVW1, TVW2, BMD1, or BMD2. Changes between TVW1 and TVW2 were significantly different in the patients in their 80s; changes between BMD1 and BMD2 were not different for any age range or between sexes. Conclusions: Aging alone does not seem to promote MB atrophy. In healthy brains, the MBs may be stationary structures throughout life. [ABSTRACT FROM AUTHOR]

Vertebral compression fractures are common in elderly people and most are due to osteoporosis. Osteoporosis treatment is effective for secondary prophylaxis, so initiation is recommended. Despite the clear benefits, the rate of initiation of osteoporosis treatment is very low. It is reported to be due to several factors including insufficient systems-based approaches for hospitals and post-acute care. Hospitalists, who are physicians dedicated to the treatment of patients in hospital and whose activity is generalist rather than specialized, are reported to be associated with higher-quality inpatient care because of, among other things, closer adherence to guidelines. Co-management by hospitalists for patients with vertebral compression fractures has potential benefits towards improving the outcomes. We compared the rate of initiation of osteoporosis treatment for patients with vertebral compression fractures between conventional orthopedic surgeon-led care (conventional group) and hospitalist co-management care (co-management group). This is a single-center retrospective cohort study to evaluate the rate of initiation of osteoporosis treatment and reasons for non-initiation of osteoporosis treatment. Other clinical indicators were also evaluated, including length of hospital stay, preventable complications during hospitalization, and rate of 30-day readmission. We identified 55 patients in the conventional group and 93 patients in the co-management group. The rate of initiation of osteoporosis treatment was higher in the co-management group (45.2% vs. 3.6%, OR 21.5; 95%CI 5.12–192.0; P < 0.01). Most of the patients with non-initiation in the co-management group had reasons for it described in the medical records, but in the conventional group the reasons were unknown. There was no significant difference in length of hospital stay, preventable complications during hospitalization, or 30-day readmission between the groups. Hospitalist co-management of patients with vertebral compression fractures showed significantly higher rate of initiation of osteoporosis treatment than conventional orthopedic surgeon-led care. [ABSTRACT FROM AUTHOR]

Cerebellar climbing fibers convey diverse signals, but how they are organized in the compartmental structure of the cerebellar cortex during learning remains largely unclear. We analyzed a large amount of coordinate-localized two-photon imaging data from cerebellar Crus II in mice undergoing 'Go/No-go' reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue. Changes in neural activities during learning of the first two components were correlated with corresponding changes in timing control and error learning across animals, indirectly suggesting causal relationships. Spatial distribution of these components coincided well with boundaries of Aldolase-C/zebrin II expression in Purkinje cells, whereas several components are mixed in single neurons. Synchronization within individual components was bidirectionally regulated according to specific task contexts and learning stages. These findings suggest that, in close collaborations with other brain regions including the inferior olive nucleus, the cerebellum, based on anatomical compartments, reduces dimensions of the learning space by dynamically organizing multiple functional components, a feature that may inspire new-generation AI designs. [ABSTRACT FROM AUTHOR]

Iron-sulfur clusters are prosthetic groups of proteins involved in various biological processes. However, details of the immature state of the iron-sulfur cluster into proteins have not yet been elucidated. We report here the first structural analysis of the Zn-containing form of a Rieske-type iron-sulfur protein, PetA, from Thermochromatium tepidum (TtPetA) by X-ray crystallography and small-angle X-ray scattering analysis. The Zn-containing form of TtPetA was indicated to be a dimer in solution. The zinc ion adopts a regular tetra-coordination with two chloride ions and two cysteine residues. Only a histidine residue in the cluster-binding site exhibited a conformational difference from the [2Fe-2S] containing form. The Zn-containing structure indicates that the conformation of the cluster binding site is already constructed and stabilized before insertion of [2Fe-2S]. The binding mode of ZnCl2, similar to the [2Fe-2S] cluster, suggests that the zinc ions might be involved in the insertion of the [2Fe-2S] cluster. Iron–sulfur clusters are important cofactors involved in a wide range of protein functions, however, the incorporation of FeS clusters into proteins remains underexplored. Here, the authors report the crystal structure of a Zn-containing form of a Rieske protein, in which ZnCl2 binds in an FeS-binding site, representing a putative immature form of a Rieske protein prior to FeS insertion. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to evaluate the fall characteristics of wheelchair basketball players by sex and impairment classification using the official videos of the Tokyo 2020 Summer ParalympicGames. Design: Thiswas a video-based observational study. In total, 42 men's and 31 women's wheelchair basketball game videos were obtained from the official International Paralympic Committee. The videos were analyzed to assess the number of falls, playing time of the fall, playing phase, contact, foul judgment, fall location/direction, and the body part that first impacted the floor. Results: A total of 1269 falls (men, n = 944; and women, n = 325) occurred. The analysis of men demonstrated significant differences in rounds, playing phase, location of fall, and body part first impacted. Women demonstrated significant differences in all categories except in rounds. Comparisons by functional impairment showed different trends for men and women. Conclusions: The detailed observation of videos suggested that men aremore likely to have dangerous falls. There is a necessity for discuss the prevention measures based on sex and impairment classification. [ABSTRACT FROM AUTHOR]

Head impacts during blind football are common and have high injury rates; however, their characteristics and impact are still underreported. We compared head impact characteristics in blind football players with and without falls on all 18 official blind football match videos from the Tokyo 2020 Paralympic games. The rate of head impacts with falls was significantly higher in the preliminary phase, offense phase, and during dribbling. Significant differences in the region of the head impacted were also observed among the impact subjects/objects. The findings in this study would contribute to the development of injury prevention measures to minimize head injuries from head impact in blind football. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the contribution of L-menthol administration to endurande exercise capacity. Thirteen male runners (age, 35.8 ± 7.8 years; peak oxygen uptake, 62.7 ± 6.8 mL kg−1 min−1) ran on treadmills at fixed intensities of their anaerobic thresholds to exhaustion. All participants underwent three trials—water ingestion (W-IG), L-menthol mouth rinsing (M-MR), and L-menthol ingestion (M-IG)— in a random order every 5 min while running. Breathing comfort (BC) was measured immediately after fluid intake. Dyspnea threshold against external inspiratory resistance was examined before and after the running test. The running time with M-IG (1683.9 ± 520.3 s) was longer than that with W-IG (1410.2 ± 465.9 s, effect size [ES] = 0.55). BC with M-IG (2.00 ± 0.74) was higher than that with W-IG (0.42 ± 0.79) at exhaustion (ES > 2.00). The dyspnea threshold after running decreased to 19.2 ± 7.6 cm H₂O L−1 s−1 with W-IG, whereas that with M-MR (26.2 ± 6.5 cm H₂O L−1 s−1) and M-IG (29.2 ± 2.8 cm H₂O L−1 s−1) remained high (p for interaction < 0.001). M-IG facilitated BC during running, improved endurance capacity, and prevented decreases in the dyspnea threshold against external inspiratory resistance after exhaustive running. Highlights L-menthol ingestion facilitated breathing comfort during high intensity endurance running and improved exhaustive endurance running capacity. Even after exhaustion, L-menthol solution relieved dyspnea sensitivity against external inspiratory resistance. L-menthol ingestion might help athletes improve their endurance running capacity. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the origin, course, and distribution of the branches of the posterior femoral cutaneous nerve, considering the segmental and dorsoventral compositions of the sacral plexus, including the pudendal nerve. The buttocks and thighs of five cadavers were analyzed bilaterally. The branches emerged from the sacral plexus, which was divided dorsally to ventrally into the superior gluteal, inferior gluteal, common peroneal, tibial, and pudendal nerves. It descended lateral to the ischial tuberosity and comprised the thigh, gluteal, and perineal branches. As for the thigh and gluteal branches, the dorsoventral order of those originating from the sacral plexus corresponded to the lateromedial order of their distribution. However, the dorsoventral boundary was displaced at the inferior margin of the gluteus maximus between the thigh and gluteal branches. The perineal branch originated from the ventral branch of the nerve roots. In addition, the pudendal nerve branches, which ran medially to the ischial tuberosity, were distributed in the medial part of the inferior gluteal region. These branches should be distinguished from the gluteal branches; the former should be classified as the medial inferior cluneal nerves and the latter as the lateral ones. Finally, the medial part of the inferior gluteal region was distributed by branches of the dorsal sacral rami, which may correspond to the medial cluneal nerves. Thus, the composition of the posterior femoral cutaneous nerve is considered necessary when considering the dorsoventral relationships of the sacral plexus and boundaries of the dorsal and ventral rami. [ABSTRACT FROM AUTHOR]

Membrane receptor guanylyl cyclases play a role in many important facets of human physiology, from regulating blood pressure to intestinal fluid secretion. The structural mechanisms which influence these important physiological processes have yet to be explored. We present the 3.9 Å resolution cryo-EM structure of the human membrane receptor guanylyl cyclase GC-C in complex with Hsp90 and its co-chaperone Cdc37, providing insight into the mechanism of Cdc37 mediated binding of GC-C to the Hsp90 regulatory complex. As a membrane protein and non-kinase client of Hsp90-Cdc37, this work shows the remarkable plasticity of Cdc37 to interact with a broad array of clients with significant sequence variation. Furthermore, this work shows how membrane receptor guanylyl cyclases hijack the regulatory mechanisms used for active kinases to facilitate their regulation. Given the known druggability of Hsp90, these insights can guide the further development of membrane receptor guanylyl cyclase-targeted therapeutics and lead to new avenues to treat hypertension, inflammatory bowel disease, and other membrane receptor guanylyl cyclase-related conditions. [ABSTRACT FROM AUTHOR]

Proprioceptive sensory information from muscle spindles is essential for the regulation of motor functions. However, little is known about the motor control regions in the cerebellar cortex that receive proprioceptive signals from muscle spindles distributed throughout the body, including the orofacial muscles. Therefore, in this study, we investigated the pattern of projections in the rat cerebellar cortex derived from the supratrigeminal nucleus (Su5), which conveys orofacial proprioceptive information from jaw-closing muscle spindles (JCMSs). Injections of an anterograde tracer into the Su5 revealed that many bilateral axon terminals (rosettes) were distributed in the granular layer of the cerebellar cortex (including the simple lobule B, crus II and flocculus) in a various sized, multiple patchy pattern. We could also detect JCMS proprioceptive signals in these cerebellar cortical regions, revealing for the first time that they receive muscle proprioceptive inputs in rats. Retrograde tracer injections confirmed that the Su5 directly sends outputs to the cerebellar cortical areas. Furthermore, we injected an anterograde tracer into the external cuneate nucleus (ECu), which receives proprioceptive signals from the forelimb and neck muscle spindles, to distinguish between the Su5- and ECu-derived projections in the cerebellar cortex. The labeled terminals from the ECu were distributed predominantly in the vermis of the cerebellar cortex. Almost no overlap was seen in the terminal distributions of the Su5 and ECu projections. Our findings demonstrate that the rat cerebellar cortex receives orofacial proprioceptive input that is processed differently from the proprioceptive signals from the other regions of the body. [ABSTRACT FROM AUTHOR]

Medial meniscal extrusion (MME) is a structural abnormality that leads to early knee osteoarthritis; however, its formation remains debated. For anatomical consideration of the mechanism underlying MME formation, we examined the capsular attachment on the posteromedial tibia and its layered association with the semimembranosus. Fourteen knees of eight body donors were analyzed in this study; six knees were grouped for macroscopic analysis, whereas four knees each were grouped for histological and phosphotungstic acid-enhanced micro-computed tomography analyses. The capsular attachment varied in width according to location and was not distant from the articular cartilage and posterior root. A portion of the posteromedial joint capsule formed the semimembranosus tendinous sheath. The dense fibrous membrane superficial to the semimembranosus, which was continuous from its tendinous sheath, existed as one of the layers of the joint capsule. The aforementioned findings were confirmed in all specimens. Based on the capsular attachment and its layered association with the semimembranosus, the conventional posteromedial knee ligaments may be only a part of the joint capsule divided into two layers by the semimembranosus. If the coordinated action of the joint capsule and semimembranosus partially contributes to the medial meniscus stability, such a structural problem may affect MME formation. [ABSTRACT FROM AUTHOR]

Shape measurements are crucial for evolutionary and developmental biology; however, they present difficulties in the objective and automatic quantification of arbitrary shapes. Conventional approaches are based on anatomically prominent landmarks, which require manual annotations by experts. Here, we develop a machine-learning approach by presenting morphological regulated variational AutoEncoder (Morpho-VAE), an image-based deep learning framework, to conduct landmark-free shape analysis. The proposed architecture combines the unsupervised and supervised learning models to reduce dimensionality by focusing on morphological features that distinguish data with different labels. We applied the method to primate mandible image data. The extracted morphological features reflected the characteristics of the families to which the organisms belonged, despite the absence of correlation between the extracted morphological features and phylogenetic distance. Furthermore, we demonstrated the reconstruction of missing segments from incomplete images. The proposed method provides a flexible and promising tool for analyzing a wide variety of image data of biological shapes even those with missing segments. [ABSTRACT FROM AUTHOR]