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A incidência de acidente vascular cerebral embólico na cardiopatia chagásica crônica foi avaliada a partir de duas séries consecutivas de casos: a primeira compreendendo 63 pacientes com cardiopatia chagásica crônica e, a segunda, 84 pacientes com acidentes cerebrovasculares, 59 dos quais de tipo não hemorrágico. Em relação aos casos de cardiopatia chagásica crônica a incidência de acidente vascular cerebral embólico mostrou-se da ordem de 3,17%; em relação aos acidentes cerebrovasculares, da ordem de 4,76% e quando considerados apenas aqueles de tipo não hemorrágico, da ordem de 6,78%.Mural thrombi in the cavities of the heart are commonly found in chronic Chagas' cardiopathy and embolic phenomena may result from them. Acute cerebrovascular insults resulting from embolic occlusion of cerebral arteries are described in Chagas' disease since 1953. The purpose of this investigation was to evaluate the incidence of this type of cerebrovascular embolic insult. Two groups of patients successively admitted to a general hospital were studied: the first of 63 cases of chronic Chagas' cardiopathy; the second of 84 cases of acute cerebrovascular disease. The brain insult was non-hemorrghagic type in 59 cases of the second group. The evaluation pertinent to the first series showed that embolic cerebrovascular insult occurred in 3.17% of the cases. Concerning the second series the incidence of embolic cerebrovascular insult secondary to chronic Chagas' cardiopathy was 4.76% when all cerebrovascular insults were considered, and 6.78% when only non hemorrhagic cerebrovascular insults were considered.

Nas amostras de líqüido cefalorraqueano (LCR) de 200 pacientes com afecções do sistema nervoso central (SNC) foi efetuada pesquisa de anticorpos a Trypanosama cruzi (T. cruzi) mediante: reação de fixação do complemento (RFC) em 69, reação de imunofluorescência (IgG) indireta (RIF) em 118, ambas em 13. Em 50 casos, para a RIF, o LCR foi também previamente concentrado 20 vezes. Os resultados foram avaliados em relação às patologias que acometiam o SNC, ao comportamento das células e proteínas do LCR e ao resultado de investigações imunológicas no LCR para outras infecções do SNC (sífilis, cisticercose, esquistossomíase e toxoplasmose) para as quais técnicas semelhantes foram adotadas. Anticorpos a T. cruzi foram demonstrados em três pacientes: em um com reagudização da moléstia de Chagas na vigência da síndrome de imunodeficiência adquirida; em um paciente com epilepsia e em um paciente com acidente vascular cerebral, ambos com moléstia de Chagas comprovada pela presença de anticorpos a T. cruzi no soro.

The total and partial charge-changing cross sections of28Si on carbon targets at 736 and 723 A MeV are studied by CR-39 plastic nuclear track detectors using the HSP-1000 microscope system and the PitFit track measurement software. The values of the total charge-changing cross section areandat 736 and 723 A MeV, respectively. The result is compared with the ones obtained by other experimental and theoretical results. The odd–even effect of the partial charge-changing cross section is observed. [ABSTRACT FROM AUTHOR]

The Japanese Virtual Observatory (JVO) is a web portal to various kinds of astronomical resources distributed all over the world. We have started its official operation of the JVO portal since March 2008. The JVO provides seamless access to the Virtual Observatory (VO) compliant data services, and also access to the reduced data observed with Subaru telescope and on-line data reduction system for Suprime-Cam instrument of the Subaru telescope. The system implements standards of the International Virtual Observatory Alliance (IVOA) to communicate with the VO components in the world.

The Virtual Observatory (VO) for Astronomy is a framework that empowers astronomical research by providing standard methods to find, access, and utilize astronomical data archives distributed around the world. VO projects in the world have been strenuously developing VO software tools and/or portal systems. Interoperability among VO projects has been achieved with the VO standard protocols defined by the International Virtual Observatory Alliance (IVOA). As a result, VO technologies are now used in obtaining astronomical research results from a huge amount of data. We describe typical examples of astronomical research enabled by the astronomical VO, and describe how the VO technologies are used in the research.

Background: The aim of this study was to examine the effects of long-term (10 months) volleyball training on biochemical responses in adolescent female athletes since the cumulative effects of chronic training on this population are not yet clear., Methods: Twenty-one adolescent female volleyball players competing at the national level served as the participants. All athletes carried out volleyball training, which consisted of ball handling, specialized drills, and practical game-style exercises, including physical training in the school gymnasium. The average training cycle consisted of 6 days per week, with a total of about 2 to 2.5 hours of volleyball training per day. In order to determine the cumulative effects on autonomic, immune, renal function and bone resorption, salivary and urinary samples were collected before volleyball training on 3 consecutive days (days 1, 3 and 5) at months 0 and 10, respectively., Results: No significant changes in body mass, salivary secretion rate, urinary albumin, L-type fatty acid binding protein and type I collagen cross-linked N-telopeptide concentration were found. In contrast, significant decreases were noted in salivary α-amylase activity (% change: -22.9), total protein (%change: -21.4), and immunoglobulin A concentration (% change: -20.1)., Conclusions: The results of this study imply that the autonomic function after chronic volleyball training in adolescent female athletes may be enhanced due to training adaptation, although the immune function may be attenuated as a result of cumulative overtraining. Moreover, long-term volleyball training in adolescent female athletes appears to suppress bone resorption and not to induce cumulative damage to renal function.

A 69-year-old man with a history of thymoma resection was diagnosed with COVID-19 pneumonia. Initially, the patient responded well to molnupiravir, but he experienced a relapse. Subsequent steroids for COVID-19-related organizing pneumonia (OP) led to temporary improvement, but his condition deteriorated when the steroids were tapered off. Further investigation revealed hypogammaglobulinemia, and Good's syndrome (GS) was diagnosed. Immunoglobulin replacement therapy was administered, significantly improving the pulmonary shadows, and no subsequent relapse occurred. GS is an immunodeficiency condition associated with thymoma. If COVID-19 recurs or is refractory despite steroid therapy for OP, COVID-19 itself may not be resolved due to immunodeficiency., Competing Interests: Conflict of interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Given the opposing properties of uric acid (UA), which are intracellular prooxidant action and extracellular antioxidant action, the association of circulating UA levels with dementia remains controversial. We aimed to ascertain whether both lower and higher plasma UA levels are associated with the risk of incident dementia among middle-aged and older population., Methods: 1685 participants (530 men and 1155 women) aged 40-69 years at baseline (1990-1993) were randomly selected for plasma UA measurement from base cohort participants who responded to the baseline questionnaire and provided blood samples. They were followed for dementia (disabling dementia requiring care; hereinafter dementia) from 2006 to 2016 using certification records for national long-term care insurance in Japan. A Cox proportional hazards model adjusted for various lifestyle factors and past medical history (cardiometabolic disease) was applied for overall participants and sex., Results: Dementia was diagnosed in 240 participants (14.2 % overall: 16.0 % in men and 13.4 % in women). No statistically significant association with plasma UA was found in overall participants. Compared to participants with UA of 5.1-6.0 mg/dL, men with ≥6.1 mg/dL showed fully adjusted hazard ratios of 1.46 (95 % confidence interval: 0.78-2.75) for 6.1-7.0 mg/dL and 1.89 (0.97-3.66) for ≥7.1 mg/dL, while women with ≥6.1 mg/dL showed 1.13 (0.54-2.38)., Conclusions: No statistically significant association between plasma UA level and risk of dementia was found in overall participants or by sex., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Baicalein, a flavone derived from Scutellaria baicalensis Georgi, exhibits potent anti-inflammatory, antiviral, and anticancer properties. Its derivative, known as 8-bromobaicalein (BB), has been found to have strong cytotoxic effect on MCF-7 human breast cancer cells. However, its limited solubility in water has hindered its potential for wider applications. To address this issue, we investigated the use of cyclodextrins specifically βCD, 2,6-di-O-methyl-β-cyclodextrin (DMβCD), and hydroxypropyl-β-cyclodextrin (HPβCD) to improve the solubility of BB through inclusion complexation. During 250 ns molecular dynamics simulations, it was found that BB can form inclusion complexes with all βCDs. These complexes exhibit two distinct orientations: chromone group insertion (C-form) and phenyl group insertion (P-form). The formation of these complexes is primarily driven by van der Waals interactions. DMβCD has the highest number of atom contacts with BB and the lowest solvent accessibility in the hydrophobic cavity. These results coincide with the highest binding affinity from the MM/GBSA-based free energy calculation method. Experimental phase solubility diagrams revealed a 1:1 stoichiometric ratio (A L type) between BB and βCDs, in which BB/DMβCD showed the highest stability. The formation of inclusion complexes was confirmed by differential scanning calorimetry and scanning electron microscope methods. Additionally, the BB/DMβCD inclusion complex demonstrated significantly higher anticancer activity against MCF-7 human breast cancer cells compared to BB alone. These findings underscore the potential of DMβCD for formulating BB in pharmaceutical and medical applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The utility of synthetic ECV, which does not require hematocrit values, has been reported; however, high-quality CT images are essential for accurate quantification. Second-generation Deep Learning Reconstruction (DLR) enables low-noise and high-resolution cardiac CT images. The aim of this study is to compare the differences among four reconstruction methods (hybrid iterative reconstruction (HIR), model-based iterative reconstruction (MBIR), DLR, and second-generation DLR) in the quantification of synthetic ECV., Methods: We retrospectively analyzed 80 patients who underwent cardiac CT scans, including late contrast-enhanced CT (derivation cohort: n = 40, age 71 ± 12 years, 24 males; validation cohort: n = 40, age 67 ± 11 years, 25 males). In the derivation cohort, a linear regression analysis was performed between the hematocrit values from blood tests and the CT values of the right atrial blood pool on non-contrast CT. In the validation cohort, synthetic hematocrit values were calculated using the linear regression equation and the right atrial CT values from non-contrast CT. The correlation and mean difference between synthetic ECV and laboratory ECV calculated from actual blood tests were assessed., Results: Synthetic ECV and laboratory ECV showed a high correlation across all four reconstruction methods (R ≥ 0.95, p < 0.001). The bias and limit of agreement (LOA) in the Bland-Altman plot were lowest with the second-generation DLR (hybrid IR: bias = -0.21, LOA: 3.16; MBIR: bias = -0.79, LOA: 2.81; DLR: bias = -1.87, LOA: 2.90; second-generation DLR: bias = -0.20, LOA: 2.35)., Conclusions: Synthetic ECV using second-generation DLR demonstrated the lowest bias and LOA compared to laboratory ECV among the four reconstruction methods, suggesting that second-generation DLR enables more accurate quantification.

Surgical treatment of infected aneurysms is problematic due to their high complication and mortality rates. Infected aortic aneurysms are at high risk of rupture and should be operated on as soon as possible after diagnosis. A 72-year-old female patient with a medical history of diabetes mellitus, hyperlipidemia, and hypertension presented with a fever of 38°C and back pain, without any apparent cause, in 2021. Her C-reactive protein (CRP) level increased to 20 mg/dL. Further evaluation with contrast-enhanced computed tomography (CT) revealed a low-density area with air pockets surrounding the abdominal aorta. The patient was diagnosed with native abdominal aortic infection and transferred to our hospital for treatment. The next day, endovascular aortic repair (EVAR) was performed using an Endurant stent graft (161682). Postoperatively, the patient was treated with antibiotics, and subsequently, blood infection was alleviated. Moreover, the CRP levels normalized. Follow-up contrast-enhanced CT showed resolution of the air pockets surrounding the abdominal aorta. The patient was discharged home on postoperative day 33. During her three-year follow-up as an outpatient, no recurrence of the infection was detected. While open surgical repair with prosthetic graft replacement is often the preferred treatment for infected abdominal aortic aneurysms, in select cases, as demonstrated by our patient, EVAR can be employed to prevent rupture, followed by antibiotic therapy to achieve infection control., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nakajima et al.)

An 83-year-old woman was suspected to have lung cancer in the right lung. However, diffuse opacities only appeared in the left lung, and she was urgently hospitalized due to severe respiratory failure. The opacities in the left lung deteriorated, and she died despite treatments including antibiotics and steroids. An autopsy revealed pleomorphic carcinoma in the right upper lobe, stenosis of the right pulmonary artery due to compression of the right hilar lymph nodes, and diffuse alveolar damage (DAD) throughout the left lobes. Acute respiratory distress syndrome (ARDS), of which a histological feature is DAD, consists of bilateral opacities in the lungs according to the definition. Unilateral ARDS is extremely rare and has reportedly developed in patients with unilateral pulmonary artery agenesis. The unilateral absence of pulmonary perfusion might be involved in the pathogenesis of unilateral ARDS. In patients with lung cancer, compression of the pulmonary artery may result in unilateral ARDS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Experimental animal models of ischemic spinal cord injury (iSCI) are essential for studying its pathogenesis and for developing new therapeutic strategies to improve functional recovery in humans. Many existing models, however, exhibit high variability or early lethality. A reliable experimental iSCI model would significantly advance novel treatment approaches for these severe neurological disorders. To this end, we have established a rat model of persistent iSCI with an extended lifespan., Methods: We have developed a novel iSCI model that induces localized ischemic lesions in the spinal cord of male Sprague-Dawley rats. This is achieved by cross clamping the descending aorta just rostral the azygos vein using an atraumatic bulldog clamp., Results: The experimental iSCI model consistently demonstrated symptoms specific to spinal cord ischemia at the lumbar level. The procedure takes approximately 50 min and does not require specialized surgical equipment. It has a survival rate of 84%, a recovery rate of 40%, and a complication rate of 16%., Conclusions: We have successfully developed a rat model of persistent iSCI. This protocol proves to be highly reliable and holds promise for evaluating new therapeutic strategies aimed at promoting functional recovery in patients suffering from spinal cord ischemia., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The activation of the antitumor immune responses of T cells and natural killer (NK) cells is important to induce breast tumor shrinkage via preoperative chemotherapy. We evaluated how antitumor immune responses contribute to the effects of such therapy., Methods: Forty-three patients with stages I - IV breast cancer who underwent surgery between August 2018 and Jun 2023 after preoperative chemotherapy were enrolled. Peripheral natural killer (pNK) cell activity was assessed by 51 Cr-release assay, and the counts and percentages of CD4 + , CD8 + , and NK cells and their subsets in peripheral blood were measured before and after chemotherapy by two-color flow cytometry. Associations of cell population changes with chemotherapy responses were analyzed., Results: On univariate analysis, relative to grade (G) ≤ 1 effects, G ≥ 2 therapeutic effects were associated significantly with human epidermal growth factor receptor 2 (HER-2) + breast cancer (P = 0.024) and post-chemotherapy CD56 + CD16 - NK cell accumulation (8.4% vs. 5.5%, P = 0.042), and tended to be associated with increased pre-chemotherapy CD56 + CD16 - NK cell percentages (5.4% vs. 3.3%, P = 0.054) and pNK cell activity (42.0% vs. 34.5%, P = 0.057). The accumulation and increased percentage of CD56 + CD16 - NK cells in patients with G ≥ 2 effects were not associated with changes in pNK cell activity or the disappearance of axillary lymph-node metastases. On multivariate analysis, G ≥ 2 therapeutic effects tended to be associated with higher pre-chemotherapy pNK levels (odds ratio = 0.96; 95% confidence interval: 0.921 - 1.002; P = 0.067)., Conclusions: The accumulation of the immunoregulatory CD56 + CD16 - NK cell subset in the peripheral blood before and after chemotherapy may lead to the production of cytokines that induce an antitumor immune response. Activation of the immune response mediated by CD56 + CD16 - pNK cells after chemotherapy and their high counts before chemotherapy may contribute to the improvement of therapeutic effects against breast cancer., Competing Interests: None to declare., (Copyright 2024, Kim et al.)

Background: Monitoring the progression of idiopathic pulmonary fibrosis (IPF) using CT primarily focuses on assessing the extent of fibrotic lesions, without considering the distortion of lung architecture., Objectives: To evaluate three-dimensional average displacement (3D-AD) quantification of lung structures using deformable registration of serial CT images as a parameter of local lung architectural distortion and predictor of IPF prognosis., Materials and Methods: Patients with IPF evaluated between January 2016 and March 2017 who had undergone CT at least twice were retrospectively included ( n = 114). The 3D-AD was obtained by deformable registration of baseline and follow-up CT images. A computer-aided quantification software measured the fibrotic lesion volume. Cox regression analysis evaluated these variables to predict mortality., Results: The 3D-AD and the fibrotic lesion volume change were significantly larger in the subpleural lung region (5.2 mm (interquartile range (IQR): 3.6-7.1 mm) and 0.70% (IQR: 0.22-1.60%), respectively) than those in the inner region (4.7 mm (IQR: 3.0-6.4 mm) and 0.21% (IQR: 0.004-1.12%), respectively). Multivariable logistic analysis revealed that subpleural region 3D-AD and fibrotic lesion volume change were independent predictors of mortality (hazard ratio: 1.12 and 1.23; 95% confidence interval: 1.02-1.22 and 1.10-1.38; p = 0.01 and p < 0.001, respectively)., Conclusions: The 3D-AD quantification derived from deformable registration of serial CT images serves as a marker of lung architectural distortion and a prognostic predictor in patients with IPF.

Background: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations., Methods: We used data from the baseline survey (2011-2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40-74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression., Results: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000 g (males 3.7%: females 0.8%). Among 88,653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500 g was associated with a higher prevalence of CVD (aPR 1.76; 95% CI, 1.37-2.26), hypertension (aPR 1.29; 95% CI, 1.17-1.42), and diabetes (aPR 1.53; 95% CI, 1.26-1.86) when a birth weight of 3,000-3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1,500-2,499 grams and 2,500-2,999 grams, while no significant associations were observed for birth weight at or over 4,000 grams. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout., Conclusion: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women., Purpose: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation., Methods: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40-74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture., Results: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 - 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture., Conclusions: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Fruits and vegetables contain abundant amounts of antioxidant vitamins such as vitamin C, α-carotene, and β-carotene. Few prospective observational studies have investigated the effects of fruit and vegetable intake on the risk of dementia, and the results are inconsistent., Objectives: Our aim was to examine associations between fruit and vegetable intake and the risk of disabling dementia., Methods: We conducted a follow-up survey within the Japan Public Health Center-based Prospective Study involving 42,643 individuals aged 50-79 y at baseline (2000-2003). Dietary fruit and vegetable intakes and related antioxidant vitamin intakes (i.e., α-carotene, β-carotene, and vitamin C) were determined using a food frequency questionnaire. The diagnosis of disabling dementia was made based on the daily living disability status related to dementia under the Japanese long-term care insurance program from 2006 to 2016. Hazard ratios and 95% confidence intervals for disabling dementia were estimated using area-stratified Cox proportional hazard models adjusted for potential confounding factors., Results: A total of 4994 cases of disabling dementia were recorded. We observed an inverse association between total fruit and vegetable intake and the risk of dementia among males and females: the multivariate hazard ratios (95% confidence intervals) for the highest compared with lowest quartiles of intake were 0.87 (0.76, 0.99) (P- trend = 0.05) among males and 0.85 (0.76, 0.94) (P- trend = 0.006) among females. Among antioxidant vitamins, vitamin C intake was inversely associated with the risk of dementia among males and females: the multivariate hazard ratios (95% confidence intervals) for the highest compared with lowest quartiles of intake were 0.71 (0.61, 0.84) (P- trend < 0.0001) among males, and 0.76 (0.67, 0.86) (P- trend < 0.0001) among females., Conclusions: Fruit and vegetable intake and dietary intake of vitamin C may contribute to reducing the risk of disabling dementia among males and females., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Diffuse-type gastric cancer (DGC) is a subtype of gastric cancer that is prone to peritoneal dissemination, with poor patient prognosis. Although intercellular adhesion loss between cancer cells is a major characteristic of DGCs, the mechanism underlying the alteration in cell-to-extracellular matrix (ECM) adhesion is unclear. We investigated how DGCs progress and cause peritoneal dissemination through interactions between DGC cells and the tumour microenvironment (TME). P53 knockout and KRAS G12V -expressing (GAN-KP) cells and Cdh1-deleted GAN-KP (GAN-KPC) cells were orthotopically transplanted into the gastric wall to mimic peritoneal dissemination. The GAN-KPC tumour morphology was similar to that of human DGCs containing abundant stroma. RNA sequencing revealed that pathways related to Rho GTPases and integrin-ECM interactions were specifically increased in GAN-KPC cells compared with GAN-KP cells. Notably, we found that Rac Family Small GTPase 1 (RAC1) induces Integrin Subunit Alpha 6 (ITGA6) trafficking, leading to its enrichment on the GC cell membrane. Fibroblasts activate the FAK/AKT pathway in GC cells by mediating extracellular matrix (ECM)-Itga6 interactions, exacerbating the malignant phenotype. In turn, GC cells induce abnormal expression of fibroblast collagen and its transformation into cancer-associated fibroblasts (CAFs), resulting in DGC-like subtypes. These findings indicate that Cdh1 gene loss leads to abnormal expression and changes in the subcellular localization of ITGA6 through RAC1 signalling. The latter, through interactions with CAFs, allows for peritoneal dissemination., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose. Takatsugu Ishimoto is a member of the Editorial Board of the British Journal of Cancer., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background & Aims: Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample., Methods: We studied individuals without a history of cancer, myocardial infarction, stroke, diabetes, or depression at baseline in 2011-2016, with a five-year follow-up. We used Poisson regression models and the g-formula, thereby calculating the risk difference (RD) for depression. Multiple sensitivity analyses were conducted. Missing data were handled using random forest imputation. We also examined effect heterogeneity based on sex, age, and body mass index by analyzing the relative excess risk due to interaction and the ratio of risk ratios., Results: In total, 94,873 individuals were evaluated, and 80,497 completed the five-year follow-up survey for depression. Of these, 18,172 showed depression. When comparing the high consumption group with the no consumption group, the fully adjusted RD (95% CI) was 3.6% (2.8% to 4.3%) for total sugary drinks, 3.5% (2.1% to 4.7%) for carbonated beverages, 2.3% (1.3% to 3.4%) for vegetable juice, 2.4% (1.1% to 3.6%) for 100% fruit juice, and 2.6% (1.9% to 3.5%) for sweetened coffee. In contrast, the fully adjusted RD (95% CI) was -1.7% (-2.6% to -0.7%) for black coffee. The fully adjusted RD for green tea did not reach statistical significance. The results were robust in multiple sensitivity analyses. We did not find substantial effect heterogeneity based on sex, age, and body mass index., Conclusions: Total sugary drinks, carbonated beverages, vegetable and fruit juices, and sweetened coffee may increase the risk of depression, whereas black coffee may decrease it., Competing Interests: Conflict of interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: As infrequent social interaction is a potential risk of dementia, oral malodor may increase the risk of dementia, including Alzheimer's disease., Objective: This study investigated the association between malodor and dementia., Methods: We used the Japan Public Health Center-based Prospective Study data obtained at Yokote City. A total of 1,493 individuals aged 56 to 75 years underwent a dental examination and self-reported survey from May 2005 to January 2006. Follow-up for the onset of dementia was conducted using long-term care insurance data from 2006 to 2016. Hazard ratios of oral malodor on dementia were estimated by the Cox proportional hazards model. The inverse probability-weighted Cox model was used as a sensitivity analysis., Results: The study comprised 1493 participants (53.6% women) with a mean age of 65.6 (SD = 5.8) years old; at the end of the follow-up, 6.4% ( n  = 96) developed dementia, and the percentage was 20.7 in severe malodor group. Throughout 15274.133 person-years of follow-up, the average incidence rate for the onset of dementia per 1000 person-years was 6.29. The highest incidence rate was seen in participants with severe malodor (22.4 per 1000 person-years). After adjusting for confounders, compared to those with no malodor, there was a 3.8 (95% confidence interval: 1.5 to 9.4) times greater hazard of developing dementia in participants with severe malodor. The inverse probability weighted Cox model confirmed the same trend with an adjusted marginal hazard ratio of 4.4 (1.2 to 16.4)., Conclusions: A significant association between oral malodor and the onset of dementia exists., Competing Interests: The authors have no conflict of interest to report., (© 2024 – The authors. Published by IOS Press.)

Competing Interests: Disclosures None.

The objective of this study was to clarify whether there are sex-specific differences in salivary α-amylase and immunoglobulin A responses following acute endurance exercise in adolescent males and females with equivalent cardiorespiratory fitness levels. Twenty-six aerobically trained adolescent males and females with similar training status were enrolled in this study. Each individual executed a 1-h prolonged cycling exercise corresponding to a constant power output at 65% of peak oxygen uptake. Unstimulated whole salivary samples were taken with the passive drooling method at the 10-min period before and after exercise for the determination of salivary responses [α-amylase, immunoglobulin A, total protein and flow rate]. Salivary α-amylase activity, immunoglobulin A concentration and total protein concentration were significantly augmented immediately after acute endurance exercise. Regarding sex differences, only the salivary flow rate was significantly lower in females than in males. The findings of the present study imply that adolescent males and females appear to have similar salivary responses after acute endurance exercise, as represented by salivary α-amylase activity and immunoglobulin A concentration in connection with total protein concentration and salivary flow rate, when they are matched for peak oxygen uptake relative to fat-free body mass., (© 2023 The Authors. European Journal of Oral Sciences published by John Wiley & Sons Ltd on behalf of Scandinavian Division of the International Association for Dental Research.)

Nystagmus is a well-known side effect of antiseizure medicines (ASMs), but it is often underestimated and overlooked. Here, we describe a case in which nystagmus during eye closure was identified early using routine electroencephalography (EEG). A 34-year-old man developed focal epilepsy after head trauma at the age of 25 years. The patient was treated with carbamazepine but liver dysfunction was observed; therefore, treatment was attempted with lacosamide (LCM) and lamotrigine. With an increase in the LCM dose, steep potential changes suggestive of horizontal nystagmus were observed in the electrooculogram, F7, and F8 on EEG, and the patient complained of eye shaking during eye closure. These symptoms and EEG findings improved with LCM dose reduction. If the presence of nystagmus is identified on EEG coincidentally and a patient's subjective symptoms with ASM are confirmed, it is advisable to taper and/or discontinue the causative agent., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sasaki et al.)

Objective: Previous findings on the association between sleep duration, changes in sleep duration, and long-term dementia risk were mixed. Thus, we aimed to investigate the association between midlife sleep duration, its change, and dementia., Methods: We recruited 41,731 Japanese (40-71 years) and documented their habitual sleep duration at baseline (1990-1994) and a 5-year follow-up survey. Changes in sleep duration were calculated as differences between baseline and 5-year measurements. We identified dementia using the Long-Term Care Insurance system (2007-2016). Hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia were calculated using the area-stratified Cox model., Results: During 360,389 person-years, 4621 participants exhibited dementia. The multivariable HRs of dementia compared with 7 h of sleep were 1.13 (95% CI: 0.98-1.30) for 3-5 h, 0.93 (0.85-1.02) for 6 h, 1.06 (0.99-1.14) for 8 h, 1.13 (1.01-1.27) for 9 h, and 1.40 (1.21-1.63) for 10-12 h with a J-shaped fashion (p for linear < 0.001 and quadratic < 0.001). For its change, the HRs compared with no change were 1.02 (0.90-1.16) for decreased ≥2 h, 0.95 (0.88-1.03) for decreased 1 h, 1.00 (0.91-1.09) for increased 1 h, and 1.37 (1.20-1.58) for increased ≥2 h. The positive association for decreased sleep duration was observed in individuals with an initial sleep duration of ≤7 h, but not in those with ≥8 h (p for interaction = 0.007)., Conclusions: Long and increased sleep duration was associated with a higher risk of dementia., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

GABA (Gamma-aminobutyric acid) is a non-protein amino acid widely known as major inhibitory neurotransmitter. It is synthesized from glutamate via the enzyme glutamate decarboxylase (GAD). GAD is ubiquitous in all organisms, but only plant GAD has ability to bind Ca 2+ /calmodulin (CaM). This kind of binding suppresses the auto-inhibition of Ca 2+ /calmodulin binding domain (CaMBD) when the active site of GAD is unfolded resulting in stimulated GAD activity. OsGAD4 is one of the five GAD genes in rice genome. It was confirmed that OsGAD4 has ability to bind to Ca 2+ /CaM. Moreover, it exhibits strongest expression against several stress conditions among the five OsGAD genes. In this study, CRISPR/Cas9-mediated genome editing was performed to trim the coding region of CaMBD from the OsGAD4 gene, to remove its autoinhibitory function. DNA sequence analysis of the genome edited rice plants revealed the truncation of CaMBD (216 bp). Genome edited line (#14-1) produced 11.26 mg GABA/100 g grain, which is almost nine-fold in comparison to wild type. Short deletion in the coding region for CaMBD yielded in mutant (#14-6) with lower GABA content than wild type counterpart. Abiotic stresses like salinity, flooding and drought significantly enhanced GABA accumulation in #14-1 at various time points compared to wild-type and #14-6 under the same stress conditions. Moreover, upregulated mRNA expression in vegetative tissues seems correlated with the stress-responsiveness of OsGAD4 when exposed to the above-mentioned stresses. Stress tolerance of OsGAD4 genome edited lines was evidenced by the higher survival rate indicating the gene may induce tolerance against abiotic stresses in rice. This is the first report on abiotic stress tolerance in rice modulated by endogenous GABA., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01460-1., Competing Interests: Competing interestsThe authors have no conflicts of interest to declare., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness., Methods and Analysis: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs., Results: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88)., Conclusions: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The coexistence of 2 Mahaim pathways represents a diagnostic challenge. We present a case in which the SH/HA intervals were useful for identifying concealed nodoventricular or His-ventricular pathways., Competing Interests: This study was supported by departmental resources only. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Malignant ascites accompanied by peritoneal dissemination contain various factors and cell populations as well as cancer cells; however, how the tumor microenvironment is shaped in ascites remains unclear. Single-cell proteomic profiling and a comprehensive proteomic analysis are conducted to comprehensively characterize malignant ascites. Here, we find defects in immune effectors along with immunosuppressive cell accumulation in ascites of patients with gastric cancer (GC) and identify five distinct subpopulations of CD45(-)/EpCAM(-) cells. Mesothelial cells with mesenchymal features in CD45(-)/EpCAM(-) cells are the predominant source of chemokines involved in immunosuppressive myeloid cell (IMC) recruitment. Moreover, mesothelial-mesenchymal transition (MMT)-induced mesothelial cells strongly express extracellular matrix (ECM)-related genes, including tenascin-C (TNC), enhancing metastatic colonization. These findings highlight the definite roles of the mesenchymal cell population in the development of a protumorigenic microenvironment to promote peritoneal dissemination., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Modulating autophagy and mitophagy, vital cellular quality control systems, offer therapeutic potential for critical illnesses. However, limited drug screening options hinder progress. We present a novel assay using the photoswitchable fluorescent reporter, mito-Kaede, to quantify mitophagy flux. Mito-Kaede's superior UV-induced photoconversion and brightness post-conversion make it ideal for prolonged mitochondrial dynamics tracking. Its specificity in responding to mitophagy, confirmed by parkin-knockout cells, adds value. When coupled with a custom fluid exchange system, enabling efficient medium changes, precise mitophagy observations become feasible. This mitophagy assay, alongside our methodological insights, can decipher mitophagy's role in pathology and supports drug screening efforts.

The long interspersed nuclear element-1 (LINE-1) retrotransposons are a major family of mobile genetic elements, comprising approximately 17% of the human genome. The methylation state of LINE-1 is often used as an indicator of global DNA methylation levels and it regulates the retrotransposition and somatic insertion of the genetic element. We have previously reported the significant relationship between LINE-1 hypomethylation and poor prognosis in upper gastrointestinal (GI) cancers. However, the causal relationships between LINE-1 hypomethylation, retrotransposition, and tumor-specific insertion in upper GI cancers remain unknown. We used bisulfite-pyrosequencing and quantitative real-time PCR to verify LINE-1 methylation and copy number in tissue samples of 101 patients with esophageal and 103 patients with gastric cancer. Furthermore, we analyzed the LINE-1 retrotransposition profile with an originally developed L1Hs-seq. In tumor samples, LINE-1 methylation levels were significantly lower than non-tumor controls, while LINE-1 copy numbers were markedly increased. As such, there was a significant inverse correlation between the LINE-1 methylation level and copy number in tumor tissues, with lower LINE-1 methylation levels corresponding to higher LINE-1 copy numbers. Of particular importance is that somatic LINE-1 insertions were more numerous in tumor than normal tissues. Furthermore, we observed that LINE-1 was inserted evenly across all chromosomes, and most often within genomic regions associated with tumor-suppressive genes. LINE-1 hypomethylation in upper GI cancers is related to increased LINE-1 retrotransposition and tumor-specific insertion events, which may collectively contribute to the acquisition of aggressive tumor features through the inactivation of tumor-suppressive genes., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: To evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX)., Methods: Active RA patients with an inadequate response to MTX were randomly assigned to the E6011 or placebo group and received the study drug subcutaneously every 2 weeks during a 24-week double-blind study period. Subjects who completed evaluations at Week 24 were rolled over into the extension phase and received open-label E6011 (200 or 400 mg) every 2 weeks until Week 102. The safety analysis was conducted up to Week 104, and the efficacy analysis was conducted up to Week 84., Results: A total of 169 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 167 (98.8%) subjects experienced any adverse events, and the incidence of treatment-related adverse events was 56.2%. The American College of Rheumatology 20 response rates were observed between 40 and 70% during the extension phase., Conclusions: E6011 was safe and well tolerated with no notable safety concerns up to 102 weeks in RA patients with an inadequate response to MTX., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The objective of the study is to evaluate the long-term safety and efficacy of E6011, a humanized anti-fractalkine monoclonal antibody, in patients with rheumatoid arthritis with an inadequate response to biological disease-modifying antirheumatic drugs., Methods: In the double-blind treatment phase (24 weeks), placebo or E6011 400 mg was administered until Week 10. Thereafter, E6011 200 mg or 400 mg was administered to Week 22. Subjects who completed the evaluation at Week 24 of the treatment phase were rolled over into the extension phase. The extension phase lasted until Week 104, and all subjects received E6011 400 mg or 200 mg every 2 weeks in an open-label manner until Week 102., Results: A total of 47 subjects completed the double-blind treatment phase and were rolled over into the extension phase. In total, 46 (97.9%) subjects experienced any adverse events, and the incidence of treatment-related adverse events was 57.4%. No clear efficacy trend in the American College of Rheumatology 20% response rates was observed., Conclusions: E6011 was well tolerated in active rheumatoid arthritis patients who had shown an inadequate response to biologic disease-modifying antirheumatic drugs, but no clear benefit in the American College of Rheumatology 20% response rates was observed. Further studies are needed to clarify the clinical benefit of E6011., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with cancer are at an increased risk of developing coronavirus disease 2019 (COVID-19) infection. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) against epidermal growth factor receptor 2 (HER2)-positive cancer, known to cause drug-induced interstitial lung disease (DILD), including drug-induced pneumonitis. A 60-year-old woman with breast cancer developed a fever during treatment with T-DXd and was diagnosed with COVID-19. The fever persisted for approximately 3 weeks, and chest computed tomography showed multiple consolidations with bilateral peripheral predominance. Since the clinical course was atypical for COVID-19 due to the long duration of the fever and the CT pattern was frequently seen in T-DXd-induced ILD, the patient was diagnosed with T-DXd-induced ILD, following which, prednisolone was started, leading to improvement in the symptoms and fading of shadows. Even in patients suspected of COVID-19 pneumonia, physicians should consider the possibility of DILD, particularly in patients undergoing cancer treatment., Competing Interests: The authors declare no conflict of interests., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Life enjoyment, linked to the ability to engage pleasurably with one's environment, may be related to the risk of developing dementia. This prospective cohort study examined the association between level of life enjoyment and disabling dementia incidence among Japanese community residents., Methods: The participants were Japanese, aged 45-74 years old at 5-years follow-up, in the Japan Public Health Center-based Study (N = 38,660). Psychological conditions and other confounding variables were identified through self-administered questionnaires. Incident disabling dementia registered based on the Japan's Long-Term Care Insurance system from 2006 to 2016. Hazard ratios [95% confidence intervals] were assessed using Cox proportional hazards models., Results: Over a median follow-up period of 9.4 years, a total of 4,642 cases of disabling dementia developed. Level of life enjoyment was inversely associated with the risk of disabling dementia: the multivariable hazard ratios were 0.75 [0.67-0.84] (p < .001) and 0.68 [0.59-0.78] (p < .001) with medium and high life enjoyment, respectively, compared to low life enjoyment. Furthermore, the association between greater life enjoyment and low risk for disabling dementia was strongest in the subgroup with low-medium mental stress. In the high mental stress group, this association was evident for poststroke disabling dementia, but not for disabling dementia without a history of stroke., Discussion: A higher level of life enjoyment was associated with a lower risk of disabling dementia, particularly in the low-medium mental stress group. This finding suggests the importance of having life enjoyment by managing mental stress for reducing risk of disabling dementia., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anion binding and ion pairing of dipyrrolyldiketone Pt II complexes as anion-responsive π-electronic molecules resulted in photophysical modulations, as observed in solid-state phosphorescence properties. Modifications to arylpyridine ligands in the Pt II complexes significantly impacted the assembling behaviour and photophysical properties of anion-free and anion-binding (ion-pairing) forms. The Pt II complexes, in the presence of guest anions and their countercations, formed various anion-binding modes and ion-pairing assembled structures depending on constituents and forms (solutions and crystals). The Pt II complexes emitted strong phosphorescence in deoxygenated solutions but showed extremely weak phosphorescence in the solid state owing to self-association. In contrast, the solid-state ion-pairing assemblies with tetraalkylammonium cations exhibited enhanced phosphorescence owing to the formation of hydrogen-bonding 1D-chain Pt II complexes dispersed by stacking with aliphatic cations. Theoretical studies revealed that the enhanced phosphorescence in the solid-state ion-pairing assembly was attributed to preventing the delocalisation of the electron wavefunction over Pt II complexes., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Insufficient evidence exists on the sex-specific associations of body mass index (BMI) and weight change through midlife with dementia incidence, especially in Asian populations., Methods: For 37,414 Japanese residents aged 40 to 59 years, BMIs at baseline (year 1990 or 1993) and 10-year follow-ups were obtained. Weight changes between baseline and 10-year follow-ups were determined. Disabling dementia incidence from 2006 to 2016 was ascertained using long-term care insurance (LTCI) certifications. Hazard ratios (HRs) were computed., Results: Increased dementia risk was observed with obesity at baseline and with underweight at 10-year follow-ups. Weight loss after baseline was at greater risk than weight gain. No sex difference was observed., Discussion: In both sexes, obesity in midlife increased the risk of developing dementia with increasing impacts of weight loss after midlife. A healthy body weight throughout adulthood is beneficial for dementia prevention., Highlights: Obesity in midlife is a risk factor for incident dementia.Weight loss is a bigger risk factor than weight gain in later midlife.Association of BMI and weight change in midlife with dementia does not vary by sex., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information, (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Glycolysis is highly enhanced in pancreatic ductal adenocarcinoma (PDAC) cells; thus, glucose restrictions are imposed on nontumor cells in the PDAC tumor microenvironment (TME). However, little is known about how such glucose competition alters metabolism and confers phenotypic changes in stromal cells in the TME. Here, we report that cancer-associated fibroblasts (CAFs) with restricted glucose availability utilize lactate from glycolysis-enhanced cancer cells as a fuel and exert immunosuppressive activity in the PDAC TME. The expression of lactate dehydrogenase A (LDHA), which regulates lactate production, was a poor prognostic factor for patients with PDAC, and LDHA depletion suppressed tumor growth in a CAF-rich murine PDAC model. Coculture of CAFs with PDAC cells revealed that most of the glucose was taken up by the tumor cells and that CAFs consumed lactate via monocarboxylate transporter 1 to enhance proliferation through the TCA cycle. Moreover, lactate-stimulated CAFs upregulated IL-6 expression and suppressed cytotoxic immune cell activity synergistically with lactate. Finally, the LDHA inhibitor FX11 reduced tumor growth and improved antitumor immunity in CAF-rich PDAC tumors. Our study provides insight regarding the crosstalk among tumor cells, CAFs, and immune cells mediated by lactate and offers therapeutic strategies for targeting LDHA enzymatic activity in PDAC cells.