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Objective. The purpose of the study was to estimate, using an isotemporal substitution model, the effect of replacing sedentary behavior (SB) with physical activity on the incidence of disability in community-dwelling older adults. Methods. This 2-year longitudinal cohort study enrolled 3691 community-dwelling older adults (57.2% women; mean age = 74.0 [SD = 5.0] years). Individuals with dementia, stroke, Parkinson disease, depression, low Mini-Mental State Examination scores, dependence on basic activities of daily living, and missing data were excluded. Physical activity and potential confounding factors were investigated as a baseline survey of disability incidence, defined by Japanese long-term care insurance certification, for 2 years in 2 regions. Physical activity data (SB, light-intensity physical activity, and moderateto vigorous-intensity physical activity [MVPA]) were measured using triaxial accelerometers for 14 days, and daily mean time spent in each physical activity parameter was computed in increments of 10 minutes. The relationship between baseline physical activity and disability incidence adjusted for potential confounders was analyzed using multilevel Cox proportional hazards regression analyses with an isotemporal substitution model. Results. The disability incidence rate was 3.8%, excluding individuals who could not be followed-up. Replacing 10 minutes of SB per day with MVPA was associated with a decreased disability incidence (hazard ratio = 0.870; 95% CI = 0.766-0.988), whereas no evidence was found for replacing SB with light-intensity physical activity (hazard ratio = 0.980; 95% CI = 0.873-1.10). Conclusions. Replacing SB with MVPA was associated with a lower risk of disability. These findings are helpful for establishing disability prevention strategies. Impact. These results suggest that feasible changes in daily behavior, such as replacing 10 minutes of SB with MVPA daily, might have a protective effect on disability incidence. Clarifying these associations is useful for developing disability prevention strategies and may help reduce the incidence of disability in community-dwelling older adults. Keywords: Epidemiology, Geriatrics, Physical Disability, Introduction Physical inactivity is prevalent worldwide and is a significant risk factor for noncommunicable diseases. (1) Physical inactivity is associated with a higher risk of mortality, poor quality of life, [...]

The periosteum is the layer of cells that covers nearly the entire surface of every bone. Upon infection, injury or malignancy the bone surface undergoes new growth—the periosteal reaction—but the mechanism and physiological role of this process remain unknown1,2. Here we show that the periosteal reaction protects against cancer invasion into the bone. Histological analyses of human lesions of head and neck squamous cell carcinomas (HNSCCs) show that periosteal thickening occurs in proximity to the tumour. We developed a genetically dissectible mouse model of HNSCC and demonstrate that inducible depletion of periosteal cells accelerates cancerous invasion of the bone. Single-cell RNA sequencing reveals that expression of the gene encoding the protease inhibitor TIMP1 is markedly increased in the periosteum at the pre-invasive stage. This increase is due to upregulation of HIF1α expression in the tumour microenvironment, and increased TIMP1 inactivates matrix-degrading proteases, promoting periosteal thickening to inhibit cancer invasion. Genetic deletion of Timp1impairs periosteal expansion, exacerbating bone invasion and decreasing survival in tumour-bearing mice. Together, these data show that the periosteal reaction may act as a functional stromal barrier against tumour progression, representing a unique example of tissue immunity mediated by stromal cells.

Due to the large proliferation of electrical devices combined with the ecological transition for carbon neutrality in various modern countries, the demand for compact and efficient portable energy sources is continuously increasing. In this research work, we have developed electrochemical energy storage heterostructures based on graphene oxides (GOs) and titanium disulfide (TiS2) nanosheets of different lateral sizes through a facile colloidal association thanks to the opposite electric charges of the two types of nanosheets. Large GO (LGO) served as a template system to organize TiS2nanosheets at different loadings, of which incorporation prevented any restacking of the layered graphitic structure. While large nanosheets led to the decoration of TiS2aggregates including Li+cations on LGO, the association of the nanosheets of different compositions but equivalent sizes drove the formation of an interstratified organization of the nanosheets. The singular organization within GO and TiS2nanosheets remained after a hydrothermal reduction process, leading to heterostructure materials with a large specific surface area and capacitance of 113 F/g obtained in 6 M KOH aqueous solution. These outstanding electrochemical performances, drastically enhanced by about 41% from those of the individual reduced GO (capacitance of 80 F/g) used as a collector for the electric carriers, suggest that the developed heterostructures present a possible application as electrochemical energy storage technology materials for supercapacitor applications.

Purpose: Nasal colonization with methicillin-resistant Staphylococcusaureus(MRSA) is a known risk factor for periprosthetic joint infection (PJI). In our facility, preoperative prophylaxis with mupirocin without the chlorhexidine soap scrub or vancomycin was consistently implemented for more than 15 years. This study aimed to evaluate the current screening and treatment of intranasal MRSA colonization in our elective primary THA patient population. Methods: All patients who underwent primary THA between April 2011, and March 2021 were included in this analysis. All patients were screened preoperatively for nasal MRSA approximately 1 month before surgery. Patients with nasal MRSA contamination are treated with topical mupirocin to eradicate the bacteria before surgery. The patients were examined again approximately two weeks before surgery. We evaluated the current screening and treatment of intranasal colonization with MRSA in our elective primary total hip arthroplasty (THA) patient population. Results: Out of 6251 patients, 106 (1.7%) had nasal MRSA contamination. The bacteria were not eradicated in three (3.6%) patients at the second screening. Twenty-two joints (0.35%) out of the 6251 had deep infections. Only 1 patient out of the 106 MRSA nasal carriers suffered from PJI. Twenty-one of the 6145 non-carriers had PJI. The difference between the prevalence of nasal MRSA contamination and the incidence of deep infections was not statistically significant. Conclusion: Our findings suggest that screening of all patients for nasal MRSA before THA followed by mupirocin calcium treatment if needed is sufficient PJI prophylaxis.

Although several recent meta-analyses have investigated the clinical influence of the addition of lateral lymph node dissection (LLND) on oncologic outcomes in patients with mid-low rectal cancer (RC) undergoing mesorectal excision (ME), most studies included in such meta-analyses were retrospectively designed. Therefore, this study aimed to explore the clinical influence of prophylactic LLND on oncologic outcomes in patients with mid-low RC undergoing ME.

Study design: A prospective case series. Objective: To investigate the possible associations of multi-directional cervical kyphoscoliosis (CKS) with substance abuse and evaluate treatment outcomes. Summary of background data: CKS is a rare medical situation without a well-established pathology. Still there are many obscurities in treatment paradigms and outcomes. To our knowledge, there is no published report on the association between CKS with addiction. Besides the novel report of such a rare etiology for CSK, the complexity of the neurosurgical treatment makes this report the first of its kind. Methods: In this series, we presented three patients with a history of crack cocaine addiction who suffered CKS due to prolonged hand-over-neck posture and treated all of them with a complex neurosurgical protocol. Results: All cases were operated on and restored their normal spine alignment. Their long-term outcomes showed independent neurological status with no major surgical complications. Conclusion: Crack cocaine addiction might be associated with CKS in long-term cocaine abuse. A complex neurosurgical approach can achieve a sustainable clinical outcome.

Zetekitoxin AB (ZTX), a member of the saxitoxin (STX) family isolated from the Panamanian golden frog Atelopus zeteki, shows extremely potent NaV-inhibitory activity. Here, we investigate the synthesis of 12-membered ring structure with the C11 tertiary hydroxyl group in ZTX by means of the Mislow-Evans rearrangement reaction and subsequent ring-closing metathesis reaction. Although this approach did not provide access to the 12-membered macrocycle, we obtained a new STX analog with an 18-membered macrolactam structure as a synthetic mimic of ZTX.

Objective markers which can reliably predict psychosis transition among individuals with at-risk mental state (ARMS) are warranted. In this study, sixty-five ARMS subjects [of whom 17 (26.2%) later developed psychosis] were recruited, and we performed supervised linear support vector machine (SVM) with a variety of combinations of.modalities (clinical features, cognition, structural magnetic resonance imaging, eventrelated.potentials, and polyunsaturated fatty acids) to predict future psychosis onset. While single-modality SVMs showed a poor to fair accuracy, multi-modal SVMs revealed better predictions, up to 0.88 of the balanced accuracy, suggesting the advantage of multi-modal machine-learning methods for forecasting psychosis onset in ARMS.

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The H–+ C2H2→ H2+ C2H–reaction is important in understanding the production mechanisms of anionic molecules in interstellar environments. Herein, the rate coefficients for the H–+ C2H2→ H2+ C2H–reaction were calculated using ring-polymer molecular dynamics (RPMD), classical molecular dynamics (MD), and quasi-classical trajectory (QCT) approaches on a newly developed ab initio potential energy surface (PES) in full dimensions. PES was constructed by fitting a large number of ab initio energy points and their gradients using the permutationally invariant polynomial basis set method. There was no barrier in the reaction coordinates, which was a collinear-dominated reaction, and the reaction proceeded exothermically. It is found that the fitted PES provides the appropriate thermal rate coefficients based on all RPMD, classical MD, and QCT simulations at higher temperatures. The evaluation of the rate coefficients at lower temperatures should be conducted carefully because the fitting of the PES associated with the long-range interaction should be further improved. The spatial distribution of the nucleus allows a more effective attraction between the reactants.

Objective Neuroendovascular procedures rely on successful navigation and stable access to the target vessel. The Stabilizer is a 300 cm long exchange wire with a 0.014 diameter and a soft, flexible stent at the distal end designed to assist with navigation and device delivery. This study aims to assess the efficacy of the Stabilizer for navigation in a variety of challenging environments.Methods The efficacy of the Stabilizer was evaluated using three challenging vascular models: a giant aneurysm model, a severe tortuosity model, and an M1 stenosis model. The Stabilizer was compared with a conventional wire during navigation in each model.Results In the giant aneurysm model, there was no significant difference of success during straightening of a looped wire and significantly higher success rates when advancing an intermediate catheter with the Stabilizer beyond the aneurysm neck compared to a conventional guidewire. The Stabilizer also significantly increased success rates when advancing an intermediate catheter through a model with severe tortuosity compared to a conventional guidewire, as well as exchange maneuver for intracranial stenting in a stenosis model compared to an exchange wire.Conclusions In our experimental model, the Stabilizer significantly improved navigation and device delivery in a variety of challenging settings compared to conventional wires.

Aiming to understand how Maasai women use informal learning and literacy to access to health information and improve well-being of their family at the village level, this qualitative study explores the significance of village based informal learning and literacy in maintain good health among village women and girls in the male-dominated community in rural Kenya. Data were collected through semi-structured interviews, informal conversations and observations. 15 Village women, 12 women’s group leaders and 10 government officials were interviewed during an intensive six-month field study in Kenya. The information obtained from the interviews was analysed thematically and as narrative case studies. Results indicate that the village women initiate manageable health promotion activities to improve the well-being of their family and community via informal learning and literacy approaches. The study also concludes that the interviewed Maasai women developed their own effective communication mechanism to improve the situation of gender inequality in their community.

ABSTRACTIn the Japan Proton Accelerator Research Complex, the purpose of the 3 GeV rapid cycling synchrotron (RCS) is to accelerate a 1 MW, high-intensity proton beam. To achieve beam operation at a repetition rate of 25 Hz at high intensities, the RCS was elaborately designed. After starting the RCS operation, we carefully verified the validity of its design and made certain improvements to establish a reliable operation at higher power as possible. Consequently, we demonstrated beam operation at a high power, namely, 1 MW. We then summarized the design, actual performance, and improvements of the RCS to achieve a 1 MW beam.

Fibroblasts, the most abundant structural cells, exert homeostatic functions but also drive disease pathogenesis. Single-cell technologies have illuminated the shared characteristics of pathogenic fibroblasts in multiple diseases including autoimmune arthritis, cancer and inflammatory colitis. However, the molecular mechanisms underlying the disease-associated fibroblast phenotypes remain largely unclear. Here, we identify ETS1 as the key transcription factor governing the pathological tissue-remodeling programs in fibroblasts. In arthritis, ETS1 drives polarization toward tissue-destructive fibroblasts by orchestrating hitherto undescribed regulatory elements of the osteoclast differentiation factor receptor activator of nuclear factor-κB ligand (RANKL) as well as matrix metalloproteinases. Fibroblast-specific ETS1 deletion resulted in ameliorated bone and cartilage damage under arthritic conditions without affecting the inflammation level. Cross-tissue fibroblast single-cell data analyses and genetic loss-of-function experiments lent support to the notion that ETS1 defines the perturbation-specific fibroblasts shared among various disease settings. These findings provide a mechanistic basis for pathogenic fibroblast polarization and have important therapeutic implications.

OBJECTIVE--To examine the association between self-reported physical activity (PA) and diabetes-related quantitative traits. RESEARCH DESIGN AND METHODS--The observational cohort was 1,152 Mexican American adults with dual-energy X-ray absorptiometry, oral and [...]

OBJECTIVE--To identify physiological and clinical variables associated with development of type 2 diabetes up to 12 years after pregnancies complicated by gestational diabetes. RESEARCH DESIGN AND METHODS--Seventy-two islet cell antibody-negative nondiabetic Hispanic women had oral (oGTT) and intravenous (ivGTT) glucose tolerance tests, glucose clamps, and body composition assessed between 15 and 30 months after pregnancies complicated by gestational diabetes mellitus (GDM). They returned for oGTTs at 15-month intervals until they dropped out, developed diabetes, or reached 12 years postpartum. Cox regression analysis was used to identify baseline predictors and changes during follow-up that were associated with development of type 2 diabetes. RESULTS--At baseline, relatively low insulin sensitivity, insulin response, and G-cell compensation for insulin resistance were independently associated with development of diabetes. During follow-up, weight and fat gain and rates of decline in G-cell compensation were significantly associated with diabetes, while additional pregnancy and use of progestin-only contraception were marginally associated with diabetes risk. CONCLUSIONS--In Hispanic women, GDM represents detection of a chronic disease process characterized by falling β-cell compensation for chronic insulin resistance. Women who are farthest along at diagnosis and/or deteriorating most rapidly are most likely to develop type 2 diabetes within 12 years after the index pregnancy. Weight gain, additional pregnancy, and progestin-only contraception are potential modifiable factors that increase diabetes risk. Diabetes 59:2625-2630, 2010, The diagnosis of gestational diabetes mellitus (GDM) identifies relatively young women without known diabetes who have circulating glucose concentrations in the upper end of the population distribution during pregnancy. Those [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ijlp.2009.10.005 Byline: Yoji Nakatani (a), Miwa Kojimoto (b), Saburo Matsubara (c), Isao Takayanagi (d) Keywords: Offender; Mental disorder; Treatment; Supervision; Rehabilitation; Japan Abstract: This article describes the recent law reform on forensic mental health and its background in Japan, focusing on the enactment of the Medical Treatment and Supervision Act in 2005. The new system -- under which a person who commits a serious criminal offence in a state of insanity or diminished responsibility shall be referred by the public prosecutor to the District Court -- aims to provide intensive psychiatric treatment to offenders with mental disorders, attaching great importance to their reintegration into society. The court panel, which consists of a judge and a specially qualified psychiatrist, plays a key role in the treatment procedure. Upon the agreement of the two panel members, the panel delivers a verdict that takes into account the outcome of psychiatric evaluation; possible verdicts are inpatient treatment order, outpatient treatment order (mental health supervision), and no treatment order. Designated facilities are currently being established for inpatient and outpatient treatment. Referring to the published data on outcomes of enforcement, this article discusses particularities, current problems, and future prospects of the system, drawing comparisons between the German and Japanese systems. Author Affiliation: (a) University of Tsukuba, School of Comprehensive Human Sciences, 1-1-1 Tennodai, Tsukuba-City, Ibaraki 305-8577, Japan (b) Faculty of Contemporary Policy Studies, University of Josai, Tokyo, Japan (c) Matsubara Hospital, Kanazawa, Japan (d) Arisawabashi Psychiatric Hospital, Toyama, Japan

OBJECTIVE--To identify novel type 2 diabetes gene variants and confirm previously identified ones, a three-staged genomewide association study was performed in the Japanese population. RESEARCH DESIGN AND METHODS--In the stage 1 scan, we genotyped 519 case and 503 control subjects with 482,625 single nucleotide polymorphism (SNP) markers; in the stage 2 panel comprising 1,110 case subjects and 1,014 control subjects, we assessed 1,456 SNPs (P < 0.0025, stage 1); additionally to direct genotyping, 964 healthy control subjects formed the in silico control panel. Along with genome-wide exploration, we aimed to replicate the disease association of 17 SNPs from 16 candidate loci previously identified in Europeans. The associated and/or replicated loci (23 SNPs; P < 7 x [10.sup.-5] for genome-wide exploration and P < 0.05 for replication) were examined in the stage 3 panel comprising 4,000 case subjects and 12,569 population-based samples, from which 4,889 nondiabetic control subjects were preselected. The 12,569 subjects were used for overall risk assessment in the general population. RESULTS--Four loci--1 novel with suggestive evidence (PEPD on 19q13, P = 1.4 x [10.sup.-5]) and three previously reported--were identified; the association of CDKAL1, CDKN2A/CDKN2B, and KCNQ1 were confirmed (P < 10-19). Moreover, significant associations were replicated in five other candidate loci: TCF7L2, IGF2BP2, SLC30A8, HHEX, and KCNJ11. There was substantial overlap of type 2 diabetes susceptibility genes between the two populations, whereas effect size and explained variance tended to be higher in the Japanese population. CONCLUSIONS--The strength of association was more prominent in the Japanese population than in Europeans for more than haft of the confirmed type 2 diabetes loci. Diabetes 58: 1690-1699, 2009, The predisposition to and the course of type 2 diabetes vary according to ethnic group (1-3). In Japan, the incidence of type 2 diabetes has increased recently and is now [...]

Radical polymerization is an economic and practical polymerization method over ionic and coordination polymerizations and is widely used for polymer production. Although many efforts have been made to improve the convenience and controllability of radical polymerization, it is still a challenge to directly observe the microbehaviors of propagation, which may provide inspiration for the development of polymerization processes. In this study, we focused on the tacticity of polystyrene produced by bulk radical polymerization since there is a debate over the temperature dependence. The propagation process is simulated viaRed Moon methodology, which is a cost-effective method for handling complex chemical reaction systems. By the multiple pathway analysis for the propagation reaction model composed of the dimer radical and the monomer using density functional theory, we obtained the relative energies in multiple transition states, whose energy differences are partly explained by the π–π stacking interactions. Viaperforming Red Moon simulations from 30 to 190 °C, we confirmed that meso contents moderately increase as the temperature increases, which is explained by the influence of temperature on the probability density of the reaction conformations of each pathway. The successful prediction and explanation for tacticity demonstrate the potential of Red Moon methodology in unveiling the microbehaviors of propagation.

OBJECTIVE--Dietary patterns in Western populations have been linked to type 2 diabetes, but the role of diet in Japanese remains unclear. We investigated the association between major dietary patterns and [...]

Background: Inflammation may be involved in the pathogenesis of atherosclerosis, type 2 diabetes mellitus, and cancer. Many studies have reported the relation of specific foods and nutrients to inflammation, but few studies have examined the relation of dietary patterns to inflammatory markers. Objective: We investigated the relation between dietary patterns and circulating high-sensitivity C-reactive protein (hs-CRP) in Japanese men and women. Design: The subjects were participants in the baseline survey of an ongoing cohort study of lifestyle-related diseases between February 2004 and July 2006. We excluded persons with life-limiting or possible inflammation-related diseases and those using analgesics. After further exclusion of subjects with a CRP concentration > 3 mg/L, 7802 subjects remained in the analysis. The dietary patterns were derived from principal component analysis of the frequency of consumption of 49 food items ascertained by the food-frequency questionnaire. Results: We identified 4 dietary patterns: healthy, high-fat, seafood, and Westernized breakfast patterns. The healthy dietary pattern, characterized by high intakes of vegetables, fruit, soy products, and fish, was significantly and inversely related to hs-CRP concentrations, even after adjustment for age, body mass index, smoking, alcohol consumption, and physical activity in both men and women. Although hs-CRP concentrations were slightly elevated in persons with a high score for the seafood pattern, multivariate-adjusted means did not show a significant trend. Neither the high-fat dietary pattern nor the Westernized breakfast pattern was related to hs-CRP concentrations. Conclusion: The healthy dietary pattern may be related to suppression of inflammation.

This study examines the effects of three response styles when faced with distress—rumination, problem-solving, and distraction—on unhealthy eating behaviors. In this study, we looked at how these coping strategies are linked to unhealthy eating behaviors in 24,883 students in grades four to eight in Japan between 2015 and 2019. We checked again at year-long intervals to see if the coping strategies had any effect on the students’ unhealthy eating behaviors. In addition, we considered depressive symptoms and body mass index in our analysis because these variables might also be related to unhealthy eating behaviors. We found that more rumination (i.e., a repetitive negative thinking pattern) predicted the severity of unhealthy eating behaviors and depressive symptoms in the following year across all the grades. In addition, greater depressive symptoms also contributed to an increase in unhealthy eating behaviors in the following year. Therefore, we suggest that rumination is a key factor that influences mental health during adolescence.

Clinical studies have shown that Aggregatibacter actinomycetemcomitans(A. actinomycetemcomitans) is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis (RA). However, the mechanism is poorly understood. Here, we show that systemic infection with A. actinomycetemcomitanstriggers the progression of arthritis in mice anti-collagen antibody-induced arthritis (CAIA) model following IL-1β secretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in macrophages. The administration of polymyxin B (PMB), chloroquine, and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice, suggesting that the recognition of lipopolysaccharide (LPS) in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in macrophages. These data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with A. actinomycetemcomitans. This work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with A. actinomycetemcomitans.

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNA-sequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

Background: Artificial intelligence-based computer-aided detection (AI–CAD) for tuberculosis (TB) has become commercially available and several studies have been conducted to evaluate the performance of AI–CAD for pulmonary tuberculosis (TB) in clinical settings. However, little is known about its applicability to community-based active case-finding (ACF) for TB. Methods: We analysed an anonymized data set obtained from a community-based ACF in Cambodia, targeting persons aged 55 years or over, persons with any TB symptoms, such as chronic cough, and persons at risk of TB, including household contacts. All of the participants in the ACF were screened by chest radiography (CXR) by Cambodian doctors, followed by Xpert test when they were eligible for sputum examination. Interpretation by an experienced chest physician and abnormality scoring by a newly developed AI–CAD were retrospectively conducted for the CXR images. With a reference of Xpert-positive TB or human interpretations, receiver operating characteristic (ROC) curves were drawn to evaluate the AI–CAD performance by area under the ROC curve (AUROC). In addition, its applicability to community-based ACFs in Cambodia was examined. Results: TB scores of the AI–CAD were significantly associated with the CXR classifications as indicated by the severity of TB disease, and its AUROC as the bacteriological reference was 0.86 (95% confidence interval 0.83–0.89). Using a threshold for triage purposes, the human reading and bacteriological examination needed fell to 21% and 15%, respectively, detecting 95% of Xpert-positive TB in ACF. For screening purposes, we could detect 98% of Xpert-positive TB cases. Conclusions: AI–CAD is applicable to community-based ACF in high TB burden settings, where experienced human readers for CXR images are scarce. The use of AI–CAD in developing countries has the potential to expand CXR screening in community-based ACFs, with a substantial decrease in the workload on human readers and laboratory labour. Further studies are needed to generalize the results to other countries by increasing the sample size and comparing the AI–CAD performance with that of more human readers.

Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer, a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits. Because HMW adiponectin may be biologically active, we measured it in serum using a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration chromatography that the ELISA detected mainly adiponectin with 12-18 subunits, and we compared HMW with total adiponectin concentration in patients with type 2 diabetes. We next investigated the relationship between serum HMW and coronary artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59 patients with angiographically confirmed CAD. Total adiponectin was measured in serum by a commercially available ELISA. Like serum total adiponectin, HMW adiponectin correlated positively with HDL cholesterol and negatively with triglyceride, insulin sensitivity, creatinine clearance, and circulating inflammatory markers. Total and HMW adiponectin were significantly higher in women than in men, as was the HMW-to-total adiponectin ratio. Serum HMW and the HMW-to-total adiponectin ratio were significantly lower in men with than without CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW adiponectin, tended to be lower when CAD was present. In conclusion, determination of HMW adiponectin, especially relative to total serum adiponectin, is useful for evaluating CAD in type 2 diabetic patients., Adiponectin, also known as Acrp30 (1), AdipoQ (2), gelatin-binding protein of 28 kDa (GBP28) (3), and apM1 (4), is an adipocyte-specific protein that enhances insulin sensitivity and promotes lipid metabolism [...]

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, manifesting as the progressive development of fluid-filled renal cysts. In approximately half of all patients with ADPKD, end-stage renal disease results in decreased renal function. In this study, we used CRISPR-Cas9 and somatic cell cloning to produce pigs with the unique mutation c.152_153insG (PKD1insG/+). Pathological analysis of founder cloned animals and progeny revealed that PKD1insG/+pigs developed many pathological conditions similar to those of patients with heterozygous mutations in PKD1. Pathological similarities included the formation of macroscopic renal cysts at the neonatal stage, number and cystogenic dynamics of the renal cysts formed, interstitial fibrosis of the renal tissue, and presence of a premature asymptomatic stage. Our findings demonstrate that PKD1insG/+pigs recapitulate the characteristic symptoms of ADPKD.

ABSTRACTThe present study aimed to investigate the test-retest reliability of the Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) in a sample of 138 children with autism spectrum disorder (ASD) from a child psychiatric clinic in Tokyo, Japan. The stability coefficient of the Full Scale Intelligence Quotient (FSIQ), which is composed of four indices, was very high at .83, while those of the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) individually were moderate to high, ranging from .62 to .79. Comparisons among three age groups revealed that the coefficients for children aged 5 to 7 years tended to be lower than those for children aged 11 years and older. With respect to relative strengths and weaknesses between index scores, approximately half of children did not exhibit the same trend in the second test. These results revealed that the FSIQ and index scores are stable in the long term in children with ASD aged 11 years and older, and that the PSI and discrepancies in index scores are less stable. Thus, practitioners should take into account ecological information and the test-taking behaviors of children when interpreting WISC-IV results for children with ASD.Abbreviations:ASD: autism spectrum disorder; WISC-IV: wechsler intelligence scale for children – fourth edition; FSIQ: full scale intelligence quotient; VCI: verbal comprehension index; PRI: perceptual reasoning index; WMI: working memory index; PSI: processing speed index

BaSi2is a promising absorber material for next-generation thin-film solar cells (TFSCs). For high-efficiency TFSCs, a suitable interlayer should be found for every light absorber. However, such an interlayer has not been studied for BaSi2. In this study, we investigated amorphous Zn1–xGexOyfilms as interlayers for BaSi2. The Zn/Ge atomic ratio in the Zn1–xGexOyfilm and the optical band gap depend on the substrate temperature during sputtering deposition. A suitable i-Zn1–xGexOy/BaSi2heterointerface with spike-type conduction band offset was achieved when Zn1–xGexOywas deposited on BaSi2at 50 °C. Furthermore, photoresponsivity measurements revealed that Zn1–xGexOyhas an excellent surface passivation effect on BaSi2. When the thickness of Zn1–xGexOywas 2 nm, a high photoresponsivity of 0.9 A/W was obtained for a 500 nm thick BaSi2layer at a wavelength of 780 nm under an applied bias voltage of 0.5 V between the front and rear electrodes, where the photoresponsivity in the short-wavelength region was significantly improved compared with that of BaSi2capped with an amorphous Si layer. X-ray photoelectron spectroscopy revealed that the Zn1–xGexOyfilms suppressed the oxidation of the BaSi2surface, decreasing the carrier recombination rate. This is the first demonstration of passivation interlayers for BaSi2with suitable band alignment for carrier transport and surface passivation effects.

OBJECTIVE -- To investigate the association between carotid atherosclerosis, measured as intima-media thickness (IMT), and cardiovascular morbidity in type 2 diabetic patients. RESEARCH DESIGN AND METHODS -- We investigated the [...]

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2associated with the risk allele in these younger patients. DOCK2expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n= 61 individuals) identified cell-type-specific downregulation of DOCK2and a COVID-19-specific decreasing effect of the risk allele on DOCK2expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.

Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup.

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The demand for the autonomous adaptive control of manufacturing lines has been growing to realize productivity improvement and carbon neutrality. We propose a methodology to realize the autonomous control of product quality under the existence of effects from non-measurable parameters. By local linear regression modeling with temporal neighborhood data, a single manufacturing parameter is selected by the obtained regression coefficients. Simulation results demonstrated that the straightforward multiple regression modeling often resulted in unstable control behavior with vibrations in product quality. We tested three approaches (scaling the amount of control, introduction of control interval, and semiparametric regression modeling for regression) to cope with the unstable behavior. The semiparametric regression model exhibited the best performance in realizing the stable control by correctly selecting the control target parameter with the additional non-linear term, that compensates the time-dependent non-measurable parameters.

The reaction between H3+and CO is important in understanding the H3+destruction mechanism in the interstellar medium. In this work, thermal rate coefficients for the H3++ CO and D3++ CO reactions are calculated using ring-polymer molecular dynamics (RPMD) on a high-level machine-learning potential energy surface. The RPMD results agree well with the classical molecular dynamics results, where nuclear quantum effects are completely ignored, whereas the agreement between the RPMD results and the previous quasi-classical trajectory is good only at low temperatures. The calculated [HCO+]/[HOC+] product branching ratios decrease as the temperature increases, and the product branching is exclusively determined by the initial collisional orientation, which governs the formation of an ion–dipole complex, H3+···CO or H3+···OC, that dissociates into H2+ HCO+or H2+ HOC+, respectively, via a direct mechanism. However, the contribution of the indirect mechanism via the rearrangement between H3+···CO and H3+···OC increases as the temperature increases, although its absolute fraction is small.

Background and Aims: Little information is available for investigating the effect of the direction of sperm injected into the cytoplasm on clinical results for human oocytes following intracytoplasmic sperm injection (ICSI). This study aimed to examine the impact of the direction of sperm (head-first or tail-first) injected into the cytoplasm on fertilization and embryo development for high-elasticity or low-elasticity human oocytes following the Piezo-ICSI.Methods: We retrospectively investigated 2717 high-elasticity oocytes and 907 low-elasticity oocytes between May 2016 and December 2022. Of 2717 high-elasticity oocytes, 1148 were injected sperm head-first, and 1569 were injected sperm tail-first into the cytoplasm by Piezo-ICSI. Of 907 low-elasticity oocytes, 480 were injected head-first, and 427 were injected sperm tail-first into the cytoplasm. The membrane of high-elasticity oocytes was robust and was ruptured artificially by the piezo-pulse. The membrane of low-elasticity oocytes was weak and spontaneously ruptured without the piezo-pulse. The rates of degeneration, fertilization (2PN), 0PN, 1PN, ≥3PN, abnormal cleavage, and good-quality day-3 embryos were evaluated in both groups.Results: Table 1 shows the effect of sperm direction on fertilization and embryo development for high-elasticity oocytes. The fertilization rate of tail-first group was significantly higher than the head-first group. The 0PN rate of tail-first group was significantly lower than the head-first group. The good quality Day-3 embryo rate of tail-first group was significantly higher than the head-first group.Table 2 shows the effect of sperm direction on fertilization and embryo development for low-elasticity oocytes. The fertilization rate of the tail-first group was significantly higher than the head-first group. However, no significant difference was observed in other comparable items.Conclusions: Tail-first sperm injection significantly improved the fertilization rates more than the head-first sperm injection regardless of the elasticity of the oocyte membrane following Piezo-ICSI.

We investigated the oxidation of oxygen vacancies at the surface of anatase TiO2(001) using a supersonic seeded molecular beam (SSMB) of oxygen. The oxygen vacancies at the top surface and subsurface could be eliminated by the supply of oxygen using an SSMB. Oxygen vacancies are present on the surface of anatase TiO2(001) when it is untreated before transfer to a vacuum chamber. These vacancies, which are stable in the as-grown condition, could also be effectively eliminated by using the oxygen SSMB.

A new single-chip video LSI for the high-band 8mm camcorder has been developed. This newly-developed LSI includes all of the luminance(y) and chrominance(c) signal processor with the controller for EVR(electric Variable Resistor) system. This paper describes how new LSI has succeeded in reducing the number of ICs and peripheral components and the power consumption drastically by using only bipolar technology.

Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of “from population to neuron”, combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.