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Purpose: The aim of this study was to retrospectively compare bone substitute fracture patterns and outcomes in patients who underwent open wedge high tibial osteotomy (OWHTO) with OSferion60 or OSferion60 Marvelous bone substitutes. Patients with and without bone substitute fractures were compared and risk factors for bone substitute fracture were identified. Methods: Included patients were physically active non-smokers with knee osteoarthritis and deformity in the proximal tibia, persistent pain, and

Adrenocorticotropic hormone (ACTH) therapy is effective for infantile epileptic spasms syndrome (IESS) but can induce immunosuppression. In Japan, Bacille Calmette-Guérin (BCG) vaccination, modified in 2013 to reduce osteitis/osteomyelitis risk, coincides with the peak onset age of IESS. This raises concerns about infection risks when administering ACTH therapy post-vaccination. To evaluate the impact of BCG vaccination timing on treatment decisions, we retrospectively reviewed the medical records of 86 IESS patients at our hospital (1996–2020). Infants who received ACTH therapy within eight weeks of BCG vaccination experienced no serious adverse events. Four patients deferred or opted out of ACTH therapy, with seizure remission taking 2–15 weeks. The overlap between IESS onset and BCG vaccination period presents clinical challenges in determining the appropriate timing for ACTH therapy. Further epidemiological and immunological research is needed to clarify the relationship between ACTH therapy and BCG-associated adverse events and to optimize treatment strategies and vaccination schedules.

We demonstrate that the recently announced signal for a stochastic gravitational wave background (SGWB) from pulsar timing array (PTA) observations, if attributed to new physics, is compatible with primordial GW production due to axion-gauge dynamics during inflation. More specifically we find that axion-U(1) models may lead to sufficient particle production to explain the signal while simultaneously source some fraction of sub-solar mass primordial black holes (PBHs) as a signature. Moreover there is a parity violation in GW sector, hence the model suggests chiral GW search as a concrete target for future. We further analyze the axion-SU(2) coupling signatures and find that in the low/mild backreaction regime, it is incapable of producing PTA evidence and the tensor-to-scalar ratio is low at the peak, hence it overproduces scalar perturbations and PBHs.

This study focuses on the accurate evaluation of carbon dioxide capture in cementitious materials, a critical factor in reducing the carbon footprint of the concrete industry. Currently, there is no standardized method accurately quantifying fixed CO2 in carbonated cementitious materials. Additionally, since cementitious materials may contain organic carbon (TOC), which can lead to an overestimation of total inorganic carbon (TIC), separating and quantifying TIC and TOC is essential but remains challenging. We introduce a novel, straightforward approach for separately quantifying TIC and TOC based on total carbon measurement. Experiments were conducted using carbonated cement paste and a mixture containing polypropylene powder at various mass ratios. The optimal dissolution method for measuring TIC via acid solution and subsequent pretreatment was validated using X-ray diffraction analysis. This study proposes a subtraction method for determining TIC and TOC content in cementitious materials, providing a practical solution for environmental assessments in the concrete industry.

Studies on intestinal cell differentiation, particularly in dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD), have predominantly focused on the disruption of intestinal crypts and suppressive effects on the intestinal microbiota; however, repeated administration of DSS is required to induce inflammatory pathology, and there is a lack of observation of early responses and consideration of differentiation stages. Although colonic adenocarcinoma (Caco-2) cells can be used as intestinal cell models, research on these cells in an immature state is limited. We, therefore, investigated the relationship between Caco-2 cell culture duration and immunological differentiation using α-defensin5 (DEFA5) as an indicator of intestinal immunity and differentiation. Changes in protein and gene expression levels in response to DSS were examined at each differentiation stage. Expression of immune- and differentiation-related proteins, including DEFA5 and lysozyme, was evident from Day 8 of culture. Immune responses to DSS varied with the differentiation stage, affecting cell viability and cytokine expression. • Caco-2 cell culture duration correlates with the differentiation stage of Paneth cells. • DSS exposure elicits different effects depending on the differentiation stage. • Our in-vitro model of IBD facilitates the characterization of the cell differentiation process and provides a methodology to help elucidate the causal mechanisms of IBD.

In this study, the expansion behavior of cement materials after high-temperature heating and water immersion was observed experimentally. Two experiments were conducted using mortar specimens with different sand-to-cement ratios subjected to different high-temperature histories up to 1000 °C. In Case 1, the specimens were immersed in water after high-temperature heating and then cooled naturally; in Case 2, the specimens were immersed in water at high temperatures without the cooling process. Based on the results, it was confirmed that lime expansion due to the rehydration of CaO by heating occurred in Case 1. In contrast, dynamic continuous explosive spalling occurred in Case 2 because of water penetration into the specimen at a high temperature. The explosive spalling in water observed in Case 2 is a phenomenon that has not been reported to date. Possible failure mechanisms for lime expansion and continuous expansive spalling in water are suggested.

Whether all obesity-related variants contribute to the onset of obesity or one or a few variants cause obesity in genetically heterogeneous populations remains obscure. Here, we investigated the genetic architecture of obesity by clustering the Japanese and British populations with obesity using obesity-related factors. In Step-1, we conducted a genome-wide association study (GWAS) with body mass index (BMI) as the outcome for eligible participants. In Step-2, we assigned participants with obesity (BMI ≥25 kg/m2) to five clusters based on obesity-related factors. Subsequently, participants from each cluster and those with a BMI

Many plants can produce essential oils (EOs), having various biological properties. This study evaluated the antioxidant, anti-enzymatic and antimicrobial effects of the EOs derived from leaves of Eucalyptus cladocalyx, E. angulosa, E. microcorys, E. ovata, E. diversicolor, E. saligna, E. sargentii and E. resinifera. The antioxidant activity of the EOs was carried out with three different methods (ABTS, DPPH and FRAP). In addition, their anti-colinesterases, anti α-amylase and anti α-glucosidase effects were assessed by spectrophotometric assays. The antimicrobial activities were tested against six phytopathogenic bacterial strains, including two G + ve (Bacillus mojavensis and Clavibacter michiganensis) and four G-ve (Pseudomonas fluorescence, P. syringae, Xanthomonas campestris and E. coli). The current study has also investigated the inhibition of biofilm formation and the possible effect on bacterial cells biofilm metabolism of three Gram-negative (Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii) and two Gram-positive pathogenic bacteria (Staphylococcus aureus and Listeria monocytogenes). The ABTS and DPPH tests indicated that E. diversicolor and E. saligna EOs showed high antioxidant activities, whereas FRAP test suggested that E. diversicolor EO exhibited the better antioxidant activity. E. resinifera and E. ovata EOs were the most active against cholinesterases instead E. ovata and E. sargentii EOs were more active against enzymes involved in diabetes. Antibacterial assays revealed that E. ovata and E. saligna EOs possess significant activity closely to tetracycline. Whereas, the antifungal assay revealed that all EOs have effectively suppressed the tested fungal growth. E. saligna EO showed substantial efficacy inhibiting both the mature biofilm (85.40 %) and metabolic activities (89.80 %) of L. monocytogenes. These results demonstrate the wide range of possible uses for Eucalyptus EOs in both agriculture and medicine fields, suggesting potential uses as strong antibiofilm agents and for biocontrol of phytopathogens.

Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Introduction: Clinical trials confirmed the beneficial effects of adding pertuzumab (P) to the combination of trastuzumab-chemotherapy (TC) in the (neo)adjuvant setting of high-risk HER2-positive early breast cancer (HER2+BC). We evaluated the clinical, economic and societal impact of adding pertuzumab to neoadjuvant TC combination (TPC) in Italy. Methods: A cost-consequence analysis comparing TPC vs. TC was performed developing a cohort-based multi-state Markov model to estimate the clinical, societal and economic impact of the neoadjuvant therapy of TPC versus TC in HER2+BC at high-risk of recurrence. The model works on a cycle length of 1 month and 5-years-time horizon. Literature review-based data were used to populate the model. The following clinical and economic outcomes were estimated: cumulative incidence of loco-regional/distant recurrences, life of years and QALY and both direct and indirect costs (€). Finally, sensitivity analyses were performed. Results: TPC was associated with a 75,630 € saved of direct costs. Specifically, it was associated with an initial increase of treatment costs (+4.8%) followed by reduction of recurrence management cost (−20.4%). TPC was also associated with an indirect cost reduction of 1.40%, as well as decreased incidence of distant recurrence (−20.14%), days of work lost (−1.53%) and days lived with disability (−0.50%). Furthermore, TPC reported 10,47 QALY gained (+2.77%) compared to TC. The probability to achieve the pathological complete response (pCR) was the parameter that mostly affected the results in the sensitivity analysis. Conclusion: Our findings suggested that TPC combination could be a cost-saving option in patients with HER2+BC at high-risk of recurrence.

Purpose: To investigate the relationship between retinal traction force and impairment of the inner retinal layer in patients with epiretinal membrane (ERM). Design: Nonrandomized, retrospective consecutive case series. Participants: Two hundred nine eyes of 201 patients with idiopathic ERM who underwent vitrectomy for idiopathic ERM were enrolled. Methods: Retinal folds caused by ERM were visualized using en face OCT, and the maximum depth of retinal folds within the parafovea (MDRF) was measured. Focal macular electroretinogram (ERG) was used to measure the amplitude and implicit time of each component for the ERM eyes and the normal fellow eyes. B-scan OCT images were used to measure the thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) + outer plexiform layer (OPL). Expression of α-smooth muscle actin (α-SMA) in surgically removed ERM specimens was quantified by reverse-transcription polymerase chain reaction. Main Outcome Measures: We analyzed the relationship between MDRF and the relative amplitudes of focal macular ERG (affected eye/fellow eye), the relationships between MDRF and the mean INL thickness and ONL+OPL thickness, comparison of INL thickness and ONL+OPL thickness for each area when cases were classified according to MDRF localization in the ETDRS chart, and the relationship between MDRF and the relative expression of α-SMA in the ERM specimens. Results: The MDRF significantly correlated with the relative amplitudes (affected eye/fellow eye) of b-waves and oscillatory potentials (r = −0.657, P = 0.015; r = −0.569, P = 0.042, respectively) and the mean INL thickness and ONL+OPL thickness (r = 0.604, P

Objectives: Previous studies ruled out the benefits of azithromycin for treatment of patients with COVID-19 who are hospitalized. However, the effects of azithromycin for treatment of patients with positive SARS-CoV-2 test results in the community remains a matter of debate. This study aimed to assess whether azithromycin, when used in subjects with positive test results for SARS-CoV-2, is associated with a reduced risk of hospitalization, in-hospital COVID-19 outcomes, and death. Methods: Two study cohorts were selected. Cohort A included subjects with positive test results for SARS-CoV-2 between February 20, 2020 and December 10, 2020; cohort B included subjects infected with SARS-CoV-2 and hospitalized between February 20, 2020 and December 31, 2020. We compared the risk of hospitalization, intensive care unit access, need for mechanical ventilation, and death in azithromycin users versus nonusers. A clustered Fine-Gray analysis was employed to assess the risk of hospitalization; logistic and Cox regressions were performed to assess the risk of intensive care unit access, mechanical ventilation, and death. Results: In cohort A, among 4861 azithromycin users and 4861 propensity-matched nonusers, azithromycin use was associated with higher risk of hospitalization (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.45-1.75) compared with nonuse. In cohort B, among 997 subjects selected in both groups, azithromycin use was not significantly associated with intensive care unit access (odds ratio [OR] 1.22, 95% CI 0.93-1.56), mechanical ventilation (OR 1.30, 95% CI 0.99-1.70), 14-day mortality (HR0.88, 95% CI 0.74-1.05), or 30-day mortality (HR 0.89, 95% CI 0.77-1.03). Conclusion: Our findings confirm the lack of benefits of azithromycin treatment among community patients infected with SARS-CoV-2, raising concern on potential risks associated with its inappropriate use.

Background: Atrial fibrillation (AF) is the most common arrhythmia in patients undergoing hemodialysis (HD); AF lowers quality of life (QoL) and increases the risk of dialysis-related complications. The present study aimed to evaluate the effectiveness of AF ablation on the QoL in patients undergoing HD. Methods: Nineteen patients undergoing HD (14 men, age 68 ± 8 years; 15 with paroxysmal AF) who underwent catheter ablation (CA) of AF were enrolled in the study. The Kidney Disease Quality of Life Short Form (KDQOL-SF) was assessed to evaluate the QoL of the HD patients at baseline and 6 months after the ablation. Ablation outcomes and procedural complications were evaluated and compared to those of 1053 consecutive non-HD patients who underwent AF ablation. Results: The KDQOL-SF of the HD patients 6 months after the ablation showed an improvement in physical functioning (54 ± 23 to 68 ± 28, P < 0.01), general health perceptions (38 ± 17 to 48 ± 15, P < 0.01), and symptoms/problems (75 ± 21 to 84 ± 13, P = 0.02), compared to baseline. For intradialytic symptoms, dyspnea during HD significantly improved after the CA in the HD patients without AF recurrence (43% to 7%, P = 0.04), whereas the atrial tachyarrhythmias and hypotension during HD remained unchanged. During the follow-up period of 17 ± 13 months after the last procedure, the incidence of being arrhythmia-free was similar (HD patients, 79% vs non-HD patients, 86%, log-rank P = 0.82). No life-threatening complications occurred in any of the patients. Conclusions: CA of AF improves QoL in patients undergoing chronic HD therapy. Résumé: Contexte: La fibrillation auriculaire (FA), la forme d’arythmie la plus fréquente chez les patients sous hémodialyse (HD), entraîne une diminution de la qualité de vie (QdV) et une augmentation des risques de complications liées à la dialyse. La présente étude visait à évaluer l’effet de l’ablation de la FA sur la QdV des patients sous HD. Méthodologie: Dix-neuf patients sous HD (âgés de 68 ± 8 ans, dont 14 étaient des hommes et 15 étaient atteints de FA paroxystique) ayant subi une ablation par cathéter de la FA ont été admis dans l’étude. Le questionnaire KDQOL-SF (Kidney Disease Quality of Life Short Form) a été utilisé pour évaluer la QdV des patients sous HD avant l’intervention et six mois après l’ablation. L’issue de l’ablation et les complications liées à l’intervention ont été évaluées et comparées à celles de 1 053 patients consécutifs n’étant pas hémodialysés et ayant subi une ablation de la FA. Résultats: La comparaison des résultats initiaux au KDQOL-SF des patients hémodialysés avec les résultats obtenus six mois après l’ablation a montré des améliorations de la fonction physique (de 54 ± 23 à 68 ± 28, p < 0,01), de la perception de l’état de santé global (de 38 ± 17 à 48 ± 15, p < 0,01), et des symptômes/problèmes de santé (de 75 ± 21 à 84 ± 13, p = 0,02). En ce qui concerne les symptômes survenant lors des séances d’HD, une amélioration significative de la dyspnée a été observée après l’ablation par cathéter chez les patients sous HD sans récurrence de la FA (de 43 % à 7 %, p = 0,04), alors qu’aucun changement n’a été constaté pour les tachyarythmies auriculaires et l’hypotension. Durant la période de suivi de 17 ± 13 mois après la dernière intervention, le nombre de patients sans arythmie était comparable dans les deux groupes (79 % chez les patients hémodialysés et 86 % chez les patients non hémodialysés, test du log-rank = 0,82). Aucun patient n’a subi de complication menaçant le pronostic vital. Conclusions: L’ablation par cathéter de la FA permet d’améliorer la QdV des patients qui subissent un traitement par HD de longue durée.

The antibody titers of volunteers, including elderly people, were investigated after the second dose of the BNT162b2 vaccine (Pfizer-BioNTech) as an mRNA vaccine against the coronavirus disease 2019 (COVID-19). Serum samples were collected from 105 volunteers (44 healthcare workers and 61 elderly people) 7–14 days after the second vaccine dose, and antibody titers were measured. The antibody titers of study participants in their 20s were significantly higher than those of other age groups. Furthermore, the antibody titers of participants aged

Background: Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) improve survival in castration-resistant prostate cancer (CRPC). However, which agent is better for patients with CRPC remains unclear. Objective: To evaluate whether ENZ or ABI is better as first-line treatment for CRPC. Design, setting, and participants: An investigator-initiated, multicenter, randomized controlled trial was conducted in Japan. The study enrolled 203 patients with CRPC before chemotherapy between February 20, 2015, and July 31, 2019. Patients were randomly assigned 1:1 to the ENZ or ABI arm. Outcome measurements and statistical analysis: The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included the PSA response rate (≥50% decline from baseline), overall survival, and safety. A log-rank test was used for comparison of survival analyses between arms. Results and limitations: After randomization, 92 patients in each arm were treated and analyzed. Time to PSA progression did not significantly differ between the arms (median 21.2 mo for ENZ and 11.9 mo for ABI; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.51–1.27; p = 0.1732). There was a significant difference in the PSA response rate between the arms (72% for ENZ and 57% for ABI; p = 0.0425). There was no significant difference in overall survival (median 32.9 mo for ENZA and 35.5 mo for ABI; HR 1.17, 95% CI 0.72–1.88; p = 0.5290). Grade ≥3 adverse events were observed in 11% of patients in the ENZA arm and 21% in the ABI arm (p = 0.1044). Conclusions: ENZ did not show any survival benefit in comparison to ABI, but showed a better PSA response rate with a low rate of severe adverse events in CRPC. Patient summary: Results from our study suggest that use of enzalutamide before abiraterone may have potential clinical benefits for patients with castration-resistant prostate cancer.

This study focused on rivers as an urban blue space and investigated how urban residents perceive the biodiversity of rivers around their homes to understand whether people’s evaluation of biodiversity changes depended on the extent of their nature experiences. Quantitative data measured by the environmental DNA method were used as an indicator of biodiversity, while urban residents' perceptions of the river and their experiences of nature were ascertained by conducting a social survey. A regression analysis of 312 responses of people living in the catchment areas around 20 rivers showed that for participants with more childhood nature experiences, their satisfaction with their neighborhood waterfront areas tended to increase as river biodiversity increased. However, for those who have had fewer childhood experiences with nature, an increase in biodiversity resulted in lower satisfaction with waterfront areas. These results indicate that modern urban residents with little experience with nature tend to prefer concrete paved rivers for their recreational value and walkability rather than rivers with high biodiversity.

Background: The Japanese apricot (Prunus mume Sieb. et Zucc.) is popularly known as ume in Japan, and the heated concentrate of ume juice, called ume extract, is commonly consumed as food. A neutralized, diluted ume extract (dUE) reported as MK615 solution exhibits hepatoprotective properties. However, the active substance contributing to its hepatoprotective efficacies has not been explored. We aimed to identify and characterize the active substance underlying the hepatoprotective potential of ume extract. Our results are described in two parts and whereas the objective of this part (Part 1) was to identify the active substance, in Part 2, we elucidated its chemical structure. Methods: The components of ume extract were fractionated stepwise, and their hepatoprotective activities were evaluated using a D-galactosamine-induced liver injury rat model. The fractionated components were characterized qualitatively and quantitatively using high-performance liquid chromatography (HPLC) analysis and were dosed to rats, equalizing the content of the main components. Finally, a purified active substance was isolated by crystallization, and its hepatoprotective activity was verified. The molecular mass and formula of the active substance were elucidated by high-resolution mass spectrometry. Results: The dUE, but not the components from unheated ume juice concentrate, showed hepatoprotective activity. Focusing on the components peculiar to the ume extract, a fraction rich in a water-soluble substance, tentatively named unknown 1 (UK1), was found to have hepatoprotective activity. It was observed that both the UK1-rich fraction and dUE suppressed the hepatic expression of nitric oxide synthase 2 (Nos2). Furthermore, the purified UK1 (≥93.88% purity, containing 6.11% hydrate water) was demonstrated to have hepatoprotective activity comparable to that of dUE. UK1 has the molecular formula C10H11NO9, with a molecular weight of 289, corresponding to a novel compound. Conclusions: Our findings revealed that UK1, which is likely to be a previously unknown, bioactive component in ume extract, is the major hepatoprotective substance in dUE.

Background: This report represents the second part (Part 2) of a two-part report on investigating a novel hepatoprotective substance in ume extract. The heated juice concentrate of Japanese apricot (Ume, Prunus mume Sieb. et Zucc.), popularly called ume extract, is known for its health benefits. In Part 1 of this study (presented in this issue together), we reported the identification of the active substance underlying the hepatoprotective potential of ume extract for the first time. The substance, tentatively referred to unknown 1 (UK1), was shown to have the molecular formula C10H11NO9 with a molecular weight of 289. Here (in Part 2), we aimed to decipher the structure of UK1. Moreover, we show that UK1 is formed by heating the components of ume juice. Methods: The purified UK1 (≥93.88% purity, containing 6.11% hydrate water) was subjected to nuclear magnetic resonance (NMR) spectroscopic analysis. The structure of UK1 was elucidated by one-dimension (1D)-NMR (1H, 13C, and DEPT135) and 2D-NMR (COSY, HSQC, and HMBC) experiments. Further, the artificial synthesis of UK1 was attempted by heating aqueous solutions containing citric acid and L-asparagine (L-Asn) or L-aspartic acid (L-Asp). The synthetic experiments were performed using a series of solutions of varying concentrations (1-fold, 5-fold, 10-fold, and 15-fold) of citric acid and L-Asn (molar ratio 5: 1). The molar ratio of citric acid and L-Asn (5: 1) was specified to mimic that in ume juice. Results: The chemical structure of UK1 was determined as 2-[3-(carboxymethyl)-3-hydroxy-2,5-dioxopyrrolidin-1-yl]butanedioic acid. More simply, UK1 was identified as an imide in which citric acid was bound to Asp. UK1 could be synthesized by heating (110 °C for 4 h) a solution containing citric acid and L-Asn, or citric acid and L-Asp. The yield of UK1 was dependent on the concentrations of citric acid and L-Asn. Conclusions: The findings of this study further validate the conclusions made in Part 1 that UK1 is a novel hepatoprotective substance in ume extract. Based on the structure, UK1 is referred to as “ASP citrimide.” This study demonstrates that ASP citrimide is formed by the association of citric acid and L-Asn (or L-Asp) during the heat concentration of ume juice.

IntroductionThe licensure exam in nursing has always focused on the curricula used in universities. ‘Tuning’ was the first project that sought to harmonize training purposes regarding competences and learning outcomes in Europe. The Tuning educational structures have been offered in various disciplines, including nursing with the development of the Tuning Nursing Project.The study describes which of 47 Tuning Nursing Competences were evaluated during the licensure exam in nursing degree courses, and what types of trials were used for their assessment.MethodsA multicentric observational study was conducted in 4 universities in Italy. Data were collected in academic years 2017–2019, using two grids: one for cognitive and one for psychomotor tests.ResultsThe Tuning competences were requested 7522 times. The most frequently demanded were those associated with domain number two, “Nursing practice and clinical decision making”. The level of performance most required in cognitive tests was the autonomy of judgement, and both tests concerned the fields of non-communicable diseases and the hospitalized adult patient.ConclusionsThe competences most often assessed coincided with those deemed core for the first cycle of studies at the European level. Unfortunately, it has been detected a high degree of discrepancy in the types of tests used in different schools.

Background: Driving cessation is a major negative life event that has been associated with a decline in health conditions including dementia. The increase in activity owing to the expansion of life space is a possible explanation for the positive relationship between driving and brain health. The present study examined the association between driving, life space, and structural brain volume in older individuals. Methods: High-resolution magnetic resonance imaging was employed to examine the brain volume in 1063 older adults. Participants were classified as non-drivers, those who drove

Introduction: Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking. Methods: We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models. Results: Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7–87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%–95%) and mean tumor mutational burden was 7.06 (range: 0–18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767–771, 83.1%) and the far loop (codons 771–775, 13%) and only in 3.9% within the C helix (codons 761–766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03). Conclusions: EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.

To identify the impact of drying rate on mechanisms of drying shrinkage, two hardened cement paste (hcp) samples were prepared. Mature samples were dried directly at the target relative humidity (RH), “rapid drying”, or at RH decreasing from 95% step by step till 11%, “gradual drying”. When comparing the relation of mass change versus drying shrinkage, at high RH range over 80%, gradually dried samples showed less mass change for same amount of shrinkage comparing to rapid drying samples. For the range of RH of 80%-40%, the incremental values of both mass change and drying shrinkage were same for two drying methods. The specimens were characterized by XRD, TG-DTA and water vapor sorption isotherms. By combining the results with findings in the literature, we postulated that an additional part of drying shrinkage is activated when dried at high relative humidity for a longer time and we attributed this additional part to gel pores of calcium silicate hydrates.

Summary: Brown adipose tissue (BAT) has critical roles in thermogenesis and systemic metabolism. Capillary rarefaction was reported to develop in BAT with dietary obesity, and previous studies showed that suppression of vascular endothelial growth factor A (VEGF-A) reduced capillary density in BAT, promoting the functional decline of this organ. Capillarization is regulated through the balance between angiogenesis and vasculogenesis on the one hand and apoptosis of endothelial cells (ECs) on the other; however, the role of EC apoptosis in BAT remained to be explored. In studies testing the role of boysenberry polyphenols (BoyP) in BAT, we found that BoyP decreased EC apoptosis, enhanced capillarization in BAT, and ameliorated dietary BAT dysfunction, which was associated with the upregulation of nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin 1 (SIRT-1) in ECs. Our studies suggest that EC SIRT-1 would be one of the potential targets of BoyP that contributes to BAT capillarization and function.

Without a current standard of care, patients with rare malignancy are subjected to precision oncology with next-generation sequencing to identify a course of treatment. We sought to establish the clinical relevance of comprehensive genomic profiling (CGP) among patients with rare malignancy. Rare malignancy was defined using the Rare Cancers in Europe definition (

This paper revisits the competitive environment of the banking system in Latin America and the Caribbean and investigates the early impact of fintech development in the region thus far. Against the backdrop of high net interest margins (NIMs) and limited financial depth in the region, panel regressions broadly confirm the results of existing literature on the association of NIMs with the changes in financial sector structure, including market concentration, administrative costs, and foreign banks, although differences between domestic and foreign banks narrowed after the 2008-09 global financial crisis. Difference-in-difference regressions and case studies on Brazil and Mexico suggest that fintech is associated with reductions in NIMs and defensive responses by incumbent banks, both of which benefit consumers. The case studies also shed light on regulatory approaches and prudential considerations in fostering financial innovation and banking sector competition.

Summary: Brown adipose tissue (BAT) is a metabolically active organ that contributes to the thermogenic response to cold exposure. In addition, other thermogenic cells termed beige adipocytes are generated in white adipose tissue (WAT) by cold exposure. Although activation of brown/beige adipose tissue is associated with mobilization of both glucose and lipids, few studies have focused on the role of glycolytic enzymes in regulating adipose tissue function. We generated mouse models with specific deletion of the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) from adipose tissue. Deletion of Pgam1 from both BAT and WAT promoted whitening of BAT with beiging of visceral WAT, whereas deletion of Pgam1 from BAT alone led to whitening of BAT without beiging of WAT. Our results demonstrate a potential role of glycolytic enzymes in beiging of visceral WAT and suggest that PGAM1 would be a novel therapeutic target in obesity and diabetes.

Infected aortic aneurysm (IAA) is a rare, life-threatening disease with rapid progression and a high mortality rate. An 84-year-old man developed IAA caused by urosepsis owing to extended-spectrum β-lactamase–producing Escherichia coli infection. Considering surgical risk and perioperative mortality, the patient underwent computed tomography–guided percutaneous abscess drainage and continuous irrigation with optimal antibiotic therapy. We controlled his systemic inflammation without surgery; thus, he was discharged. Six months later, we confirmed that the abscess had almost disappeared in the follow-up computed tomography scan. Percutaneous abscess drainage and irrigation may be an effective therapeutic option for surgical high-risk patients with IAA. Résumé: L’anévrisme aortique infecté (AAI) est une affection rare menaçant le pronostic vital, qui évolue rapidement et est associée à un taux de mortalité élevé. Nous exposons le cas d’un homme de 84 ans présentant un AAI secondaire à un urosepsis, lui-même causé par une infection à Escherichia coli productrice de bêta-lactamases à spectre étendu. Compte tenu du risque associé à une intervention chirurgicale et du risque de mortalité périopératoire, nous avons procédé à un drainage percutané de l’abcès guidé par tomographie assistée par ordinateur et sous irrigation continue, puis prescrit une antibiothérapie optimale. Nous avons ainsi réussi à maîtriser l’inflammation générale sans intervention chirurgicale, et le patient a pu recevoir son congé de l’hôpital. Six mois plus tard, une tomodensitométrie de suivi a permis de confirmer la disparition presque complète de l’abcès. Le drainage et l’irrigation d’un abcès par voie percutanée peuvent donc être une option thérapeutique efficace dans le cas des patients présentant un AAI les exposant à un risque chirurgical élevé.

Background: CXCR5+ T follicular helper (TFH) cells primarily promote B cells to produce an antigen-specific antibody through germinal centers (GCs). TFH cells exist in circulation, and circulating(c) TFH2 cells, a subset of cTFH cells, are able to help naïve B cells produce IgE in healthy individuals. Conversely, IL-10-producing regulatory B (Breg) cells inhibit an accelerated immune response. Methods: We investigated the roles of cTFH cells and cBreg cells based on a TH2 response in patients with atopic asthma (AA). Thirty-two patients with AA and 35 healthy volunteers (HV) were enrolled. We examined cTFH cells including their subsets, their expression of ICOS and PD-1, and cBreg cells by flow cytometry and their associations with clinical biomarkers. Plasma levels of CXCL13, which is a counterpart of CXCR5, were also measured using ELISA. Results: In patients with AA, cTFH2 cells were increased and cTFH1 cells were decreased compared with those in HV. The expression levels of ICOS on cTFH and their subset cells were elevated and Breg cells were greatly decreased. The plasma levels of CXCL13 in patients with AA were significantly elevated and correlated well with the cTFH2/cBreg ratio. These cells were examined in 10 patients AA before and after inhaled corticosteroid (ICS) treatment. Interestingly, the percentages and numbers of TFH2 and ICOS+ cTFH cells declined after ICS treatment together with improvements in symptoms and clinical biomarkers. Conclusions: The percentages and numbers of cTFH2 and ICOS+ cTFH cells might be useful as biomarkers of TH2 typed airway inflammation in patients with AA. Keywords: CXCL13, ICS, IgE, Regulatory B cell, T follicular helper cell

Aberrant hyperactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) has been reported in non-small cell lung cancer through overexpression of the p62/sequestosome1 protein, resulting in the acquisition of malignancy and drug resistance. We previously discovered compounds termed K67 and KOA153 that overcome chemotherapy resistance in human hepatocellular carcinoma cell lines by inhibiting the protein–protein interactions between p62 and Kelch-like ECH-associated protein 1 (Keap1), an Nrf2 suppressor. Herein, we synthesized analogs of K67 and KOA153 and investigated their potential as doxorubicin sensitizers against a human non-small cell lung cancer A549 cell line that is addicted to Nrf2 via overexpression of p62. KOA153 and the newly synthesized amide compounds exhibited significant doxorubicin-sensitizing activity without cytotoxicity. In addition, dimethylamide derivatives activated Nrf2 in HEK293 cells expressing normal levels of p62. Therefore, dimethylamide derivatives are likely novel type of anticancer agents.

Objectives: The purpose of this study is to evaluate the efficacy of annual zoledronic acid treatment in Japanese patients with nonmetastatic prostate cancer during androgen deprivation therapy (ADT). Methods: This is a single institution 12-month study. Between 2016 and 2019, patients aged 70 years or older on ADT for nonmetastatic prostate cancer had bone mineral density (BMD) measured and 10-year probability of fracture calculated using fracture risk assessment tool (FRAX). Patients who showed osteopenia or had a 10-year hip fracture risk ≥ 3% or a 10-year probability of major osteoporotic fracture ≥ 20% were offered treatment with zoledronic acid 5 mg intravenously (ZA group). The patients who did not receive treatment were set as the control group. Lumbar and hip BMD were measured 6 and 12 months after treatment in the ZA group and 12 months after baseline in the control group. The yearly BMD change of both groups was compared. Results: The mean ages of the ZA group (n = 26) and control group (n = 12) were 80.5 ± 9.1 and 76.1 ± 6.7 years, respectively. In the ZA group, lumbar and hip BMD changes at 12 months were +2.1% and +0.8%, respectively. In the control group, lumbar and hip BMD changes were −0.9% and −4.9%, respectively. There were statistically significant differences between the 2 groups in BMD percent changes (P

As of October 2020, there is still no specific drug to treat COVID-19 as it rages worldwide. Favipiravir, indicated for the treatment of new and re-emerging influenza infections, has been suggested to be effective against SARS-CoV-2, although this is not yet fully validated. We administered favipiravir to a 64-year-old female patient with COVID-19. Her symptoms resolved quickly after the start of treatment, with reduction of SARS-CoV-2 viral load, but she developed a fever again on day 12. Since the fever was relieved by discontinuation of favipiravir, and based on positive results with a drug-induced lymphocyte stimulation test, we diagnosed her with favipiravir-induced drug fever. A decrease in the serum concentration of favipiravir was observed along with resolution of the fever. The present case suggests that drug fever should be considered in the differential diagnosis of relapsing fever episodes in COVID-19 patients receiving favipiravir.

Summary: The suppressors of cytokine signaling (SOCS) proteins are negative regulators of cytokine signaling required to prevent excessive cellular responses. In particular, SOCS3 is involved in the regulation of metabolic syndromes, such as obesity and diabetes, by suppressing leptin and insulin signals. SOCS3 also suppresses the inflammatory response associated with metabolic stress, but this specific role remains undefined. Wild-type mice on a high-fat diet (HFD) exhibited only fatty liver, whereas systemic deletion of SOCS3 resulted in excessive myeloid hematopoiesis and hepatic inflammation. In addition, depletion of the gut microbiota resulted in considerable improvement in excess granulopoiesis and splenomegaly, halting the progression of systemic inflammation in SOCS3KO mice on the HFD. This result suggests that intestinal dysbiosis is involved in inflammation associated with SOCS3KO. Although contributing to diet-induced obesity and fatty liver, SOCS3 is nevertheless critical to suppress excess myeloid hematopoiesis and severe systemic inflammation associated with intestinal dysbiosis on HFD.

Backgrounds: Some patients who undergo implantation of cardiac resynchronization therapy with defibrillator (CRT-D) survive long enough, thus requiring CRT-D battery replacement. Defibrillator therapy might become unnecessary in patients who have had significant clinical improvement and recovery of left ventricular ejection fraction (LVEF) after CRT-D implantation. Methods: Forty-nine patients who needed replacement of a CRT-D battery were considered for exchange of CRT-D for cardiac resynchronization therapy with pacemaker (CRT-P) if they met the following criteria: LVEF >45%; the indication for an implantable cardioverter defibrillator was primary prevention at initial implantation and no appropriate implantable cardioverter defibrillator therapy was documented after initial implantation of the CRT-D. Results: Seven patients (14.2%) were undergone a downgrade from CRT-D to CRT-P without any complications. No ventricular tachyarrhythmic events were observed during a mean follow-up of 39.7 ± 21.1 months and there was no significant change in LVEF between before and 1 year after device replacement (53.5% ± 6.2% vs. 56.4% ± 7.3%, P = 0.197). Conclusions: This study confirmed mid-term feasibility and safety of downgrade from CRT-D to CRT-P alternative to conventional replacement with CRT-D. Keywords: Cardiac resynchronization therapy, Cardioverter defibrillator, Downgrade, Primary prevention, Ventricular tachyarrhythmia

Summary: Immunogenic tumor cell death enhances anti-tumor immunity. However, the mechanisms underlying this effect are incompletely understood. We established a system to induce tumor cell death in situ and investigated its effect on dendritic cell (DC) migration and T cell responses using intravital photolabeling in mice expressing KikGR photoconvertible protein. We demonstrate that tumor cell death induces phagocytosis of tumor cells by tumor-infiltrating (Ti)-DCs, and HMGB1-TLR4 and ATP-P2X7 receptor signaling-dependent Ti-DC emigration to draining lymph nodes (dLNs). This led to an increase in anti-tumor CD8+ T cells of memory precursor effector phenotype and secondary tumor growth inhibition in a CD103+ DC-dependent manner. However, combining tumor cell death induction with lipopolysaccharide treatment stimulated Ti-DC maturation and emigration to dLNs but did not improve tumor immunity. Thus, immunogenic tumor cell death enhances tumor immunity by increasing Ti-DC migration to dLNs where they promote anti-tumor T cell responses and tumor growth inhibition.

As cognitive dysfunction due to schizophrenia is strongly associated with patients' social rehabilitation, cognitive functions have been examined as a therapeutic target. Although the Brief Assessment of Cognition in Schizophrenia (BACS) has been used to evaluate cognitive function, it is difficult to administer in routine clinical practice due to its time-consuming nature. Therefore, a novel tool is needed to facilitate the assessment of cognitive function. In the present study, we examined whether cognitive function can be assessed effectively by testing psychomotor function in patients with schizophrenia. Test batteries consisting of choice reaction time (CRT) and compensatory tracking task (CTT) and the BACS were examined in 20 schizophrenic patients to evaluate the correlation between the scales by Pearson correlation coefficient. Of the test batteries, the CRT was significantly correlated with attention functions, a subtest of the BACS (r = -0.506, p = 0.023), and the CTT was strongly correlated with attention functions (r = -0.716, p < 0.001) and working memory (r = -0.633, p = 0.003). A multiple regression analysis was performed to clarify the association between psychomotor function tests and the total BACS score, and peripheral awareness task, a component of CTT, was independently associated with the total BACS score (β = -0.59, p = 0.004) with an R2 of 0.37. Thus, of the psychomotor function tests, the CRT and the CTT are highly useful in assessing cognitive functions in schizophrenic patients. However, no having large sample size in this study is a limitation.

Background: Respiratory management during catheter ablation of atrial fibrillation (AF) is important for the efficacy and safety of the procedure. Obstructive apnea due to an upper airway obstruction might cause serious complications including air embolisms and cardiac tamponade. However, real time monitoring of upper airway obstructions during catheter ablation has not been established. The purpose of the present study was to evaluate esophageal pressure monitoring for respiratory management during catheter ablation of AF. Methods and Results: Twenty-four consecutive patients (20 men and 4 women; mean age, 61 ± 13 years) with AF who underwent esophageal pressure monitoring during catheter ablation of AF were retrospectively analyzed. The patients were divided into 2 groups. One was the obstructive apnea (OA) group (n = 17), which required airway management tools including nasal airways and/or non-invasive positive airway pressure (NPPV) and the other was the control group (n = 7), which did not require airway management. Esophageal pressure measurements were obtained in all patients, and the OA group exhibited a substantial negative esophageal pressure as compared to the control group (−41.48 ± 19.58 vs. −12.42 ± 5.77 mmHg, p

The distribution of compressive strength in thick concrete members exposed to various environments in a nuclear power plant undergoing decommissioning is investigated. X-ray diffraction data, scanning electron microscopy analysis, and chemical analysis data reveal that rock-forming minerals in the aggregate had reacted and portlandite had been consumed to form calcium alumino silicate hydrates (C-A-S-H) when evaporable water content was sufficient. In addition, the study confirms Al-tobermorite formation in modern concrete after 16.5 years of elevated temperature conditions ranging from 40 to 55 °C. It is concluded that an appropriate aggregate and binder combination for the concrete enhances the compressive strength of thick concrete members thanks to the reaction of rock-forming minerals with portlandite, and also strengthens the chemical stability through the formation of Al-tobermorite under elevated temperature conditions and sufficient evaporable water content.

Beta-band (15–30 ​Hz) corticomuscular and intermuscular coherences are important markers of the corticospinal interaction. The purpose of this study was to investigate whether amount of visual feedback during an isometric pinch grip contraction would influence these coherences in young and elderly adults. Thirty-three healthy young and elderly subjects performed pinch grip force-matching task with right thumb and index finger, while scalp electroencephalogram (EEG) and electromyogram (EMG) from the first dorsal interosseous (FDI) and abductor pollicis brevis (APB) muscles were recorded. The amount of visual feedback was altered by manipulation of visual gain (low and high). Beta-band corticomuscular coherence was computed between EEG over the sensorimotor cortex and EMG from the FDI muscle and between EEG and EMG from the APB muscle (EEG-FDI and EEG-APB coherences). Also, beta-band intermuscular coherence was computed between EMG signals from the FDI and APB muscles (EMG-EMG coherence). Task performance was quantified as standard deviation (SD) of force and mean force error (MFE). EEG-FDI coherence was larger at high than low visual gain in the elderly but not in the young subjects, whereas there was no effect of age or visual gain on EEG-APB coherence. EMG-EMG coherence was smaller at high than low visual gain in the young and elderly subjects. The MFE was smaller at high than low visual gain in the young and elderly subjects, but the SD of force was smaller at high than low visual gain only in the young subjects. These results suggest that the effect of aging on beta-band coherence depends on the amount of visual feedback and further that visual feedback modulates beta-band corticomuscular and intermuscular coherences differently.