Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.

Objectives: This study validated the Japanese version of O’Donovan et al.’s (2020) composite measure of psychological safety scale and examined the associations of psychological safety with mental health and job-related outcomes. Methods: Online surveys were administered twice to Japanese employees with teams of more than three members. Internal consistency and test-retest reliability was tested using Cronbach’s α and intra-class correlation coefficient (ICC). Structural validity was examined using confirmatory factor analysis (CFA) and exploratory factor analysis (EFA). Convergent validity was tested. Multiple linear regression analyses were conducted to examine the relationship between psychological safety and psychological distress, work engagement, job performance, and job satisfaction. Results: Two hundred healthcare workers and 200 non-healthcare workers were analyzed. The Cronbach’s alpha of the total score was 0.92 - 0.96 and ICC was 0.88 - 0.92. CFA demonstrated poor fit, and EFA yielded a two-factor structure, suggesting one factor combined with peers and team. The scale showed good convergent validity. The total score of the scale showed significant associations with all outcomes in adjusted model in all workers. Conclusions: The Japanese version of the measure of the psychological safety scale presented good reliability and validity. Psychological safety is important for employees’ mental health and performance.

Epithelial-mesenchymal transition (EMT) networks are essential in acquiring the drug resistance and cancer malignant features in cancer stem cells (CSCs). In this regard, gene expression profiles in diffuse- and intestinal-type gastric cancer (GC) have been analyzed to reveal the network pathways in EMT and CSCs, since the diffuse-type GC has much more mesenchymal features than intestinal-type GC that has the intestinal features. The study results revealed that the activation state of several canonical pathways related to cell cycle regulation was altered. The canonical pathway on Cell cycle: G1/S checkpoint regulation was activated in diffuse-type GC, and canonical pathways on Cell cycle control of chromosomal replication and Cyclins and cell cycle regulation were activated in intestinal-type GC. Canonical pathway related to Role of BRCA1 in DNA damage response was activated in intestinal-type GC, where BRCA1, which is related to G1/S phase transition was up-regulated in intestinal-type GC. Several microRNAs (miRNAs), including mir-10, mir-17, mir-19, mir-194, mir-224, mir-25, mir-34, mir-451, and mir-605, were identified to have direct relationships of RNA-RNA interaction in Cell cycle: G1/S checkpoint regulation pathway. Additionally, cell cycle regulation may be altered in EMT conditions. The alterations in activation states of the pathways related to cell cycle regulation in diffuse- and intestinal-type GC would indicate the significance of cell cycle regulation in EMT.

Epithelial-mesenchymal transition (EMT) plays an important role in the acquisition of cancer stem cell (CSC) feature and drug resistance, which are the main hallmarks of cancer malignancy. Although previous findings have shown that several signaling pathways are activated in cancer progression, the precise mechanism of signaling pathways in EMT and CSCs are not fully understood. In this study, we focused on the intestinal and diffuse-type gastric cancer (GC), and analyzed the gene expression of public RNAseq data to understand the molecular pathway regulation in different subtypes of gastric cancer. Network pathway analysis was performed by Ingenuity Pathway Analysis (IPA). Total 2815 probe set IDs were significantly different between intestinal- and diffuse-type GC data in cBioPortal Cancer Genomics. The 10 genes including male-specific lethal 3 homolog (Drosophila) pseudogene 1 (MSL3P1), CDC28 protein kinase regulatory subunit 1B (CKS1B), DEAD-box helicase 27 (DDX27), golgi to ER traffic protein 4 (GET4), chromosome segregation 1 like (CSE1L), translocase of outer mitochondrial membrane 34 (TOMM34), YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), ribonucleic acid export 1 (RAE1), par-6 family cell polarity regulator beta (PARD6B), and MRG domain binding protein (MRGBP) were found to have difference in gene expression in intestinal- and diffuse-type GC. Total 463 direct relationships with 3 molecules (MYC, NTRK1, UBE2M) were found in the biomarker-filtered network generated by network pathway analysis. The networks and features in intestinal- and diffuse-type GC have been investigated and profiled in bioinformatics. Our results revealed the signaling pathways networks in intestinal- and diffuse-type GC, bringing new light for the elucidation of drug resistance mechanisms in CSCs.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

The integration of robotics and image processing has led to the realization of robot autonomy in dynamic environments through the provision of visual feedback. This paper presents the application of parallel and open-link robots in palletizing and shape drawing tasks as enhanced by visual feedback from image processing. In determining the set of joint angles that could be used to reach the desired position and orientation of the end effector, the geometric approach in which the spatial geometry of the robotic arms was decomposed into several plane geometry problems was employed. Image processing techniques were used to enhance the performance of the robotic manipulators. In one approach, Color-based segmentation was used to distinguish between different objects in the workspace by using predefined color markers as references in the L*a*b color space. Classification of each pixel in the workspace image was then done by calculating the Euclidean distance between that pixel and a predefined color marker. A second approach employed Edge detection to identify the boundaries of objects within the workspace image by employing the Hough Transform mathematical model to detect the abrupt changes in the image brightness pixel-wise. The pixel locations from Hough were then sorted sequentially to outline the detected object. The integration of image processing with the robotic tasks was expected to improve the precise detection of the position of objects as well as the outline of geometric shapes. The incorporation of visual feedback allowed for dynamic robot manipulation in which prior knowledge of the workspace was not requisite. This led to improved pick and place as well as shape detection as applied in palletizing and shape drawing tasks actuated by the parallel and serial link manipulators, respectively.

Carthamin potassium salt isolated from Carthamus tinctorius L. was purified by an improved traditional Japanese method, without using column chromatography. The 1H and 13C nuclear magnetic resonance (NMR) signals of the pure product were fully assigned using one- and two-dimensional NMR spectroscopy, while the high purity of the potassium salt and deprotonation at the 3’ position of carthamin were confirmed by atomic adsorption spectroscopy and nano-electrospray ionization mass spectrometry.

As Automated Driving Systems (ADS) technology gets assimilated into the market, the driver’s obligation will be changed to a supervisory role. A key point to consider is the driver’s engagement in the secondary task to maintain the driver/user in the control loop. The paper’s objective is to monitor driver engagement with a game and identify any impacts the task has on hazard recognition. We designed a driving simulation using Unity3D and incorporated three tasks: No-task, AR-Video, and AR-Game tasks. The driver engaged in an AR object interception game while monitoring the road for threatening road scenarios. From the results, there was less than 1 second difference between the means of gaming task (mean = 2.55s, std = 0.1002s) to no-task (mean = 2.55s, std = 0.1002s). Game scoring followed three profiles/phases: learning, saturation, and decline profile. From the profiles, it is possible to quantify/infer drivers’ engagement with the game task. The paper proposes alternative monitoring that has utility, i.e., entertaining the user. Further experiments AR-Game focusing on real-world car environment will be performed to confirm the performance following the recommendations derived from the current test.

Almost contact complex Riemannian manifolds, known also as almost contact B-metric manifolds, are equipped with a pair of pseudo-Riemannian metrics that are mutually associated with each other using the tensor structure. Here we consider a special class of these manifolds, those of the Sasaki-like type. They have an interesting geometric interpretation: the complex cone of such a manifold is a holomorphic complex Riemannian manifold (also called a Kähler–Norden manifold). The basic metric on the considered manifold is specialized here as a soliton, i.e. has an additional curvature property such that the metric is a self-similar solution of an intrinsic geometric flow. Almost solitons are more general objects than solitons because they use functions rather than constants as coefficients in the defining condition. A β -Ricci-Bourguignon-like almost soliton ( β is a real constant) is defined using the pair of metrics. The introduced soliton is a generalization of some well-known (almost) solitons (such as those of Ricci, Schouten, Einstein), which in principle arise from a single metric rather than a pair of metrics. The soliton potential is chosen to be pointwise collinear to the Reeb vector field, or the Lie derivative of any B-metric along the potential to be the same metric multiplied by a function. The resulting manifolds equipped with the introduced almost solitons are characterized geometrically. Appropriate examples for two types of almost solitons are constructed and the properties obtained in the theoretical part are confirmed.

The causal networks are important for understanding the signaling alterations in diseases. To reveal the network pathways affected in epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) have been analyzed. The network pathways in GC were analyzed in Ingenuity Pathway Analysis (IPA). The analysis of the probe sets of which gene expression has significant differences between diffuse- and intestinal-type GC in RNA Sequencing publicly available data identified 1099 causal networks in diffuse- and intestinal-type GC. Master regulators of the causal networks included lenvatinib, pyrotinib, histone deacetylase 1 (HDAC1), mir-196, and erb-b2 receptor tyrosine kinase 2 (ERBB2). The analysis of the HDAC1-interacting network identified the involvement of regulation of EMT by growth factors pathway, coronavirus pathogenesis pathway, and vorinostat. The network had RNA-RNA interactions with microRNAs such as mir-10, mir-15, mir-17, mir-19, mir-21, mir-217, mir-223, mir-25, mir-27, and mir-34. These molecular networks revealed in the study may lead to the identification of drug targets for GC.

Nonlinear rheological properties of chiral crystal cholesteryl oleyl carbonate (COC) in blue phase III are investigated under different shear deformations; large amplitude oscillatory shear, step shear deformation, and continuous shear flow. Rheology of the liquid crystal is significantly affected by structural rearrangement of defects under shear flow. One of the examples on the defect-mediated rheology is the blue phase rheology. Blue phase is characterized by three dimensional network structure of the disclination lines. It has been numerically studied that the rheological behavior of the blue phase is dominated by destruction and creation of the disclination networks. In this study, we find that the nonlinear viscoelasticity of BPIII is characterized by the fracture of the disclination networks. Depending on the degree of the fracture, the nonlinear viscoelasticity is divided into two regimes; the weak nonlinear regime where the disclination network locally fractures but still show elastic response, and the strong nonlinear regime where the shear deformation breaks up the networks, which results in a loss of the elasticity. Continuous shear deformation reveals that a series of the fracture process delays with shear rate. The shear rate dependence suggests that force balance between the elastic force acting on the disclination lines and the viscous force determines the fracture behavior.

This paper describes the development of a controller that enables trajectory control and vibration control. The controller performance was verified the using a 3D 2-link, flexible manipulator. On trajectory control using inverse kinematics, it was confirmed that the deflection due to its own weight deteriorated the track following performance. The vibration component of the resonance frequency of the flexible manipulator was generated, and the tip position accuracy is deteriorated. Using the results of control experiments based on the inverse kinematics, the system is identified and then created an inverse system for simultaneous control of trajectory control and vibration control. The target trajectories were the three joint angles. Finally, it was demonstrated through experiments on actual manipulator, that the system could sufficiently follow the ideal trajectory and suppress link vibrations.

Background and Objectives: The trends in metabolic dysfunction-associated steatotic liver disease (MASLD) and related metabolic dysfunctions in Japan is unknown. Thus, we aimed to clarify the trends of these before the novel coronavirus disease 2019 pandemic in Japan. Materials and Methods: We included Japanese individuals aged 25-79 years who underwent health examinations at our center. We analyzed anthropometry, lifestyle-related disease, and nutritional intake in relation to MASLD trends from 2010-2019. Results: The prevalence of MASLD increased in all ages and body mass index (BMI) classes, reaching 30.3% in males and 16.1% in females, with MASLD accounting for 75% of steatotic liver cases and more than half of all type 2 diabetes mellitus (T2DM) and high waist circumference (HWC) cases. The increase in the prevalence of MASLD was due to an increase in that of steatotic liver itself, and there was no increase in the prevalence of other factors, such as overweight, T2DM, hypertension, and dyslipidemia. The prevalence of glucose metabolic disorders (GMDs) and hypertension decreased. National nutritional data showed an increase in energy intake, total fat, saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids, which correlated with a decrease in GMDs. Salt intake also decreased, which correlated with hypertension. The MASLD group had a higher prevalence of all related metabolic factors than the non-MASLD group, especially HWC, T2DM, and hyperlipidemia. Conclusion: The prevalence of MASLD increased with that of steatotic liver, regardless of age or BMI. A relationship between increased dietary fat, increased steatotic liver, and decreased GMDs was suggested.

In this study, we developed a lightweight shoe sensor system equipped with four high-capacity, compact triaxial force sensors and an inertial measurement unit. Remarkably, this system enabled measurements of localized three-directional ground reaction forces (GRFs) at each sensor position (heel, first and fifth metatarsal heads, and toe) and estimations of stride length and toe clearance during walking. Compared to conventional optical motion analysis systems, the developed sensor system provided relatively accurate results for stride length and minimum toe clearance. To test the performance of the system, 15 older and eight young adults were instructed to walk along a straight-line while wearing the system. The results revealed that compared to the young adults, older adults exhibited lower localized GRF contributions from the heel and greater localized GRF contribution from the toe and fifth metatarsal locations. Furthermore, the older adults exhibited greater variability in their stride length and smaller toe clearance with greater variability compared to the young adults. These results underscore the effectiveness of the proposed gait analysis system in distinguishing the gait characteristics of young and older adults, potentially replacing traditional motion capture systems and force plates in gait analysis.

Activation of the EGFR pathway plays an important role in the progression of cancer and is associated with a poor prognosis in patients. The monoclonal antibody cetuximab, which displays EGFR extracellular domain-specific binding, has proven effective in the treatment of locally advanced disease and relapsed/metastatic disease. However, the effects of cetuximab are weaker than those of EGFR tyrosine kinase inhibitors (TKIs). This study investigates differences in the effects on cell growth of cetuximab and EGFR TKI AG1478 at the molecular level using oral squamous cell carcinoma (OSCC) cell lines. First, we found that there were EGFR-inhibitor sensitive (EIS) and EGFR-inhibitor resistant cell lines. The EIS cell lines expressed not only EGFR but also ErbB3, and both were clearly phosphorylated. The levels of phosphorylated ErbB3 were unaffected by cetuximab but were reduced by AG1478. EGFR ligand treatment increased the levels of phosphorylated EGFR but not phosphorylated ErbB3. Moreover, when EIS cell lines that were only capable of anchorage-dependent growth were grown in suspension, cell growth was suppressed and the levels of phosphorylated FAK, Src, and ErbB3 were significantly reduced. The levels of phosphorylated ErbB3 were unaffected by the FAK inhibitor PF573228, but were reduced by Src inhibition. Finally, combining cetuximab and a Src inhibitor produced an additive effect on the inhibition of EIS cell line growth.

This paper proposes a contact force controller for a constrained flexible manipulator in three-dimensional motion. This controller used the conversion formula obtained empirically and experimental results showed the effectiveness of the proposed contact force controller. First, the manipulator was operated with the tip of the second link restrained, then, time response of the root strain, joint angles and contact force were used to derive the relational between the three quantities. The effectiveness of the relational expression was verified by conducting a target contact force tracking experiment by inputting the angle from the relational expression. The contact force control using the strain feedback method was proposed with the strain amount estimated from the target contact force as the target value, and its effectiveness was verified by experiments. From the results obtained, controller using the strain feedback method was designed for the purpose of controlling the contact force at the tip of a flexible manipulator with two links and three degrees of freedom that performs three-dimensional spatial motion, and its effectiveness was shown by comparison with the contact force feedback method.

Introduction: Atrial fibrillation (AF) is a common cardiac arrhythmia whose prevalence rises with age and is linked to increased morbidity and mortality due to the risk of thromboembolism. Management typically involves anticoagulation and rhythm control, but the treatment of elderly patients with multiple comorbidities requires careful consideration of drug side effects and interactions. Cibenzoline, a Vaughan-Williams class IA antiarrhythmic, is effective against AF but has risks of toxicity, especially in older people and those with renal impairment, due to its renal excretion and prolonged half-life in these populations. Discussion: This paper presents a case of an 80-year-old woman with paroxysmal AF who suffered cardiac arrest due to cibenzoline toxicity despite receiving standard adjusted dosages. The patient's cibenzoline blood concentration was significantly higher than the therapeutic range, leading to cardiotoxicity, which was exacerbated by drug interactions with bisoprolol and edoxaban, both metabolized by the CYP3A4 enzyme. Venoarterial extracorporeal membrane oxygenation (V-A ECMO) and intra-aortic balloon pump (IABP) successfully managed the cardiac arrest. This case emphasizes the unpredictable pharmacokinetics of cibenzoline in elderly patients with renal impairment and the need for vigilant therapeutic drug monitoring to avoid adverse events. Conclusions: Cibenzoline can pose a significant risk of severe toxicity in elderly patients with renal impairment, and drug interactions may potentiate this risk. The paper underscores the importance of careful dose adjustment and monitoring of drug levels in this population. In cases of cibenzoline-induced cardiac arrest, V-A ECMO and IABP are effective treatment modalities. The case study serves as a critical reminder for clinicians to remain vigilant for drug-induced complications and to apply aggressive supportive treatments when necessary.

Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for biological research, but also are candidate drugs for treatment of various diseases, including diabetes and allergy, although no RXR antagonist has yet been approved for clinical use. In this review, we describe currently available RXR antagonists, their structural classification, and their evaluation, focusing on the latest research.

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, and which does not allow protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, we perfused these membranes with bovine blood. Pure water permeability before and after bovine blood perfusion was measured using the dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference despite protein fouling, leading to low values of albumin SC. This is due to the mechanism that protein fouling occurs on the membrane surface, while there is little internal pore blocking. Therefore, controlling the fouling is essential for membranes in medical use. These characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.

The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC₅₀) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

Photovoltaic power generation has high variability and uncertainty because it is affected by uncertain factors such as weather conditions. Therefore, probabilistic forecasting is useful for optimal operation and risk hedging in power systems with large amounts of photovoltaic power generation. However, deterministic forecasting is the mainstay of photovoltaic generation forecasting; there are few studies on probabilistic forecasting and feature selection from weather or time-oriented features in such forecasting. In this study, prediction intervals were generated by the lower upper bound estimation using neural networks with two outputs to make probabilistic predictions. The objective was to improve prediction interval coverage probability (PICP), mean prediction interval width (MPIW), and loss, which is the integration of these two metrics, by removing unnecessary features through feature selection. When features with high gain were selected by random forests (RF), in the forecast of 14.7-kW PV systems, loss improved by 1.57 kW, PICP by 0.057, and MPIW by 0.12 kW on average over two weeks compared to the case where all features were used without feature selection. Therefore, the low gain features from RF act as noise in LUBE and reduce the prediction accuracy.

Beyond plasma glucose-lowering in patients with type 2 diabetes, sodium- glucose cotransporter 2 inhibitors (SGLT2i) significantly reduced the hospitalization for heart failure (HF) and retarded the progression of chronic kidney disease (CKD). Endothelial dysfunction is not only involved in the development and progression of cardiovascular disease (CVD), and is also associated with the progression of CKD. In patients with type 2 diabetes, hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia induce the development of endothelial dysfunction. SGLT2i have shown an improvement in endothelial dysfunction, as assessed by flow-mediated vasodila-tion, in individuals at high risk for CVD. Along with an improvement of endothelial dysfunction, SGLT2i showed improvements in oxidative stress, inflammation, mitochondrial dysfunction, glucotoxicity such as advanced glycation end products signaling and nitric oxide bioavailability. The improvements in endothelial dysfunc-tion and such endothelium-derived factors may play an important role in preventing the development of coronary artery disease, coronary microvascular dysfunction and diabetic cardiomyopathy which cause HF and in retarding CKD. The suppression of the development of HF and the progression of CKD achieved by SGLT2i might have been largely induced by the improvement of vascular endothelial function by SGLT2i.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

The injury causes resistance in human gastric cancer (GC). This Adverse Outcome Pathway (AOP) entitled “Increases in cellular reactive oxygen species (ROS) and chronic ROS leading to human treatment-resistant gastric cancer (GC)” consists of molecular initiating event (MIE) as “Increases in cellular ROS” and “Chronic ROS”, followed by series of key events (KEs); “porcupine-induced Wnt secretion and Wnt signaling activation”, “beta-catenin activation”, “epithelial-mesenchymal transition (EMT), and adverse outcome (AO) as “human treatment-resistant GC” in the sequence. ROS has multiple roles in disease such as development and progression of cancer, or apoptotic induction causing anti-tumor effects. In this AOP, we focus on the role of sustained levels of chronic ROS to induce the therapy-resistance in human GC. EMT, which is cellular phenotypic change from epithelial to mesenchymal-like features, demonstrates cancer stem cell (CSC)-like characteristics in human GC. EMT is induced by Wnt/beta-catenin signaling, providing the rationale to have Wnt secretion and beta-catenin activation as KEs in the AOP.

The activation of halogen bonding by the substitution of the pentafluorosulfanyl (SF5) group was studied using a series of SF5-substituted iodobenzenes. The simulated electrostatic potential values of SF5-substituted iodobenzenes, ab initio molecular orbital calculations of intermolecular interactions of SF5-substituted iodobenzenes with pyridine, and the 13C NMR titration experiments of SF5-substituted iodobenzenes in the presence of pyridine or tetra (n-butyl) ammonium chloride (TBAC) indicated the obvious activation of halogen bonding, although this was highly dependent on the position of SF5-substitution on the benzene ring. 3,5-Bis-SF5-iodobenzene was the most effective halogen bond donor followed by o-SF5-substituted iodobenzene, while the m- and p-SF5 substitutions did not activate the halogen bonding of iodobenzenes. The 2:1 halogen bonding complex of 3,5-bis-SF5-iodobenzene and 1,4-diazabicyclo[2.2.2]octane (DABCO) was also confirmed. Since SF5-containing compounds have emerged as promising novel pharmaceutical and agrochemical candidates, the 3,5-bis-SF5-iodobenzene unit should be an attractive fragment of rational drug design capable of halogen bonding with biomolecules.

Metabolic-dysfunction associated steatotic liver disease (MASLD) is a chronic liver disease that affects more than a quarter of the global population, and is increasing worldwide, due to the pandemic of obesity. Insulin resistance is closely associated with the development and progression of MASLD. Hepatic entry of increased fatty acids (FA) released from adipose tissue, increase in FA synthesis and reduced FA oxidation in the liver, and hepatic overproduction of triglyceride (TG)-rich lipoproteins may induce the development of MASLD. Since insulin resistance also induces atherosclerosis, the leading cause for death in MASLD patients is cardiovascular disease (CVD). Considering that the development of CVD determines the prognosis of MASLD patients, the ideal therapeutic interventions for MASLD should reduce body weight, improve coronary risk factors, in addition to an improvement in liver functiom. Lifestyle modification such as diet and exercise and surgical interventions such as bariatric surgery and intragastric balloons have shown to improve MASLD by reducing body weight. Sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have been shown to improve coronary risk factors and to suppress the occurrence of CVD. Both SGLT2i and GLP-1 have been reported to improve liver enzymes, hepatic steatosis and fibrosis. We recently reported that the selective peroxisome proliferator-activated receptor-alpha (PPARα) modulator, pemafibrate, improved liver function. PPARα agonists have multiple anti-atherogenic properties. Here, we consider the pathophysiology of MASLD and the mechanisms of action of such drugs, and consider whether such drugs and the combination therapy of such drugs could be the ideal treatments for MASLD.

Long read sequencers, known for their effectiveness in detecting genomic structural variations (SV), are becoming a standard in comprehensive genetic analysis. In preimplantation genetic testing (PGT) for SV carriers, information on breakpoint junctions is required for the determination of carrier status in embryo selection. These sequencers are employed for challenging cases involving SVs that are difficult to analyze with conventional cytogenetical methods or detailed junctions of chromosomal translocations, providing valuable insights. They also play a crucial role in acquiring simultaneous information on surrounding single-nucleotide polymorphisms (SNPs) around causative variants in PGT. Despite their advantages, challenges related to sequencing accuracy and testing costs exist. Thus, understanding long read sequencers’ characteristics is essential for their effective utilization. This review summarizes the advanced applications of long read sequencers in preclinical workups and their integration into PGT. It also highlights in-house clinical cases, showing the implementation of long-read sequencing and discussing prospects in the field.

Rotavirus is a major cause of diarrhea globally in animals and young children under 5 years. Here, molecular detection and genetic characterization of porcine rotavirus in smallholder and commercial pig farms in the Lusaka Province of Zambia were con-ducted. Screening of 148 stool samples by RT-PCR targeting the VP6 gene revealed a prevalence of 22.9 % (34/148). Further testing of VP6-positive samples with VP7-specific primers produced 12 positives, which were then Sanger-sequenced. BLASTn of the VP7 positives showed sequence similarity to porcine and human rota-virus strains with identities ranging from 87.5% to 97.1%. By next-generation se-quencing, the full-length genetic constellation of the representative strains RVA/pig-wt/ZMB/LSK0137 and RVA/pig-wt/ZMB/LSK0147 were determined. Geno-typing of these strains revealed a known Wa-like genetic backbone and their genetic constellations were G4-P[6]-I5-R1-C1-M1-A8-N1-T1-E1-H1 and G9-P[13]-I5-R1-C1-M1-A8-N1-T1-E1-H1, respectively. Phylogenetic analysis revealed that these two viruses might have their ancestral origin from pigs, though some of their gene segments were related to human strains. The study shows evidence of reas-sortment and possible interspecies transmission between pigs and humans in Zambia. Therefore, the “One Health” surveillance approach for rotavirus A in animals and humans is recommended to inform the design of effective control measures.

In Japan, bariatric surgical treatment was started in 1982. The Japanese Society for Treatment of Obesity (JSTO) was established in 2007 and then JSTO started national registry of bariatric surgery cases and multidisciplinary educational program. 44 facilities registered 4055 bariatric surgical cases until 2021. In this study, the purpose is to clarify the indication, the safety and the effectiveness of the sleeve gastrectomy using national registry data base compiled by JSTO. Preoperative BMI was ranged from 27.6 to 90.7kg/m², and the mean value was 42.7. As gender, men/women was 1/1.3. Age was 42.2 as mean.　As preoperative comorbidities, DM ratio was 54.4% of the patients, Hypertension 64.5%, dyslipidemia 65.1%, and sleep apnea syndrome 69.8%. As operation method, laparoscopic method were taken in 99.7% of the cases. The intra operative incidents rate was 0.9 %. Conversion rate to open method was 1.1%. Postoperative morbidity ratio was 5.6% and mortality was 0 %. Reoperations were performed in 1.5 % of the cases. Postoperative hospital stay was 5 days in Median value. Body weight loss was 27.6 kg in the mean value after follow up days of 279±245. As the effect on the preoperative metabolic comorbidities, DM has improved in 82.9 % of the cases, hypertension 67.9 % and Dyslipidemia 66.6%. In conclusion, using JSTO database, we evaluated the indication, postoperative complications and weight loss effect of sleeve gastrectomy in Japan. Regarding the evaluation of the effect on preoperative comorbidities, future follow-up based on more detailed criteria was considered to be necessary.

Ophthalmological services face global inadequacies, especially in low- and middle-income countries, which are marked by a shortage of both practitioners and equipment. This study employed a portable slit-lamp microscope with video capabilities and cloud storage for a more equitable global diagnostic resource distribution. To enhance accessibility and quality of care, this study targeted corneal opacity, a global cause of blindness. To boost the online diagnosis efficiency, an AI pipeline was developed using anterior segment videos to detect corneal opacity. First, we extracted image frames from videos and learned them using a Convolutional Neural Network(CNN) model. Second, we manually annotated to extract only the corneal margins, adjusted the contrast with CLAHE, and learned using the CNN model. Finally, we performed semantic segmentation of the cornea using the annotated data. The results showed an accuracy of 0.8 for image frames, and 0.96 for corneal margins. Dice and IoU were 0.94 for semantic segmentation of corneal margins. While corneal opacity detection from video frames seemed challenging in the early stages of this study, manual annotation, corneal extraction, and CLAHE contrast adjustment significantly improved accuracy. Integrating manual annotation into the AI pipeline through semantic segmentation achieved a high accuracy in detecting corneal opacity.

The fluctuation of the conditions on Lake Limboto affects people's activities around the lake. They try to survive by facing the problem of the lake, which is shallowing and narrowing. Yet the lake is predicted will be disappeared in 2030. This means that the productivity of the lake also diminishes. This article aims to analyze how the communities around the lake respond to the evolution and shocking prediction toward the lake into their daily activities. This study uses an interdisciplinary approach by integrating some fields of study to understand and solve the problems. One of the approaches involves interviewing people around the lake. Nevertheless, the base of the study is socio-cultural studies, which uses also old texts and oral literature as the support of the study. The research needs the theory of cultural studies to look at the survival and resilience of the people of lake so that they form their special daily activity. The results of the study show that some people know that there is a prediction of disappearing of the lake, but they have not anticipated it, as if this problem is only a government affair. They still live at the lake bank, try to survive and to be resilience even in poor conditions.

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component, C1q. To provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for quantitative visualization of the interaction between IgG and the C1 complex composed of C1q, C1r, and C1s. Results showed that C1q in the C1 complex is restricted regarding internal motion and has a stronger binding affinity for on-membrane IgG assemblages than C1q alone, presumably because of smaller conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG variant that lacks the entire CH1 domain in the absence of antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the CL domain that is cryptic in the presence of the CH1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Amid urgent global climate and biodiversity crises, the strategic restoration of degraded forests stands as a vital countermeasure. This study pioneers a novel approach for the identification and prioritization of potential degraded forest areas suitable for restoration (PDFR), utilizing the advancements in Earth observation data. Utilizing Landsat data within the Google Earth Engine, our PDFR method applies a nuanced, phenology-based threshold classification to accurately map forest covers at a 30-m resolution, distinguishing prime restoration areas such as evergreen, semi-evergreen, deciduous, and flooded forests, and categorizing them into varying levels of degradation using Siem Reap, a province in Cambodia as a case study. The projections indicate a promising potential for carbon sequestration through restoration of the critically (~96,693 ha), highly (48,878 ha), moderately (46,487 ha), and slightly degraded (75,567 ha) forests, estimating a capture of 193.73 TgCO2 in Siem Reap from 2021 to 2030 upon comprehensive restoration initiatives. As Earth observation technologies continue to evolve, the PDFR method emerges as a strategic blueprint for data-driven policy formulation, fostering sustainable forest management and aligning with the global commitments delineated in the Glasgow Forests Declaration for 2030.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

Membranes based on sulfonated synditoactic polystyrene were thoroughly characterized by contrast variation SANS over a wide Q-range in dry and hydrated states. The film samples were prepared by solid-state sulfonation that allowed a uniform sulfonation of only the amorphous phase while preserving the crystallinity of the membrane. The samples were loaded with different guest molecules in either the amorphous (fullerenes) or the crystalline (toluene) regions, in order to vary the neutron contrast or to reproduce the conditions enabling an increased resistance of the membranes to chemical decomposition. The use of uni-axially deformed film samples and contrast variation with different H2O/D2O mixtures allowed for the identification and characterization of different structural levels with sizes between nm and μm, which form and evolve in the membrane morphology in dry and hydrated states and produce scattering features on different detection sectors and at different detection distances after the sample, depending on their size and orientation.

United Nations Framework Conventions on Climate Change (UNFCC) conventions in their conference of parties (COPs) has continuously considered and agreed reducing emission level in order to minimize the impact of global climate change. Reducing emission due to deforestation and degradation (REDD) ,was considered as one of the major activities in this regard during Kyoto protocol in 2009 which laid foundation for the participating countries to be compensated financially for reduced carbon emission. Mexico convention -2012 required the countries to develop and implement a transparent and consistent monitoring, reporting and verification (MRV) process. Later in Paris agreement-2015, the parties agreed to limit the global warming to 2 degree centigrade and with further efforts to 1.5-degree centigrade furthering entailing the parties to prepare and communicate nationally determined contributions (NDCs) every five years. Nepal aimed to decrease the average annual deforestation rate by 0.05 percent from existing 0.44 percent in the terai region and 0.1 percent in the Chure. Nepal decided to develop its forest reference level (FRL) in national level for the historical period 2000-2010 considering Carbon dioxide and carbon pools above and below ground. As per the Forestry Sector Strategy, Nepal aims to increase carbon stock growth by at least 5% by 2025 as compared to 2015 and decrease mean annual deforestation rate to 0.05. After major change in administrative division in Nepal, forest management responsibility has shifted down to the Sub-national level. But forest resource studies have not been conducted yet in these levels. Despite a small country, Nepal has at least four clear physiological regions. The amount of carbon stock stored by different forest type are different depending upon species distribution, carbon volume and density for each species, and their distribution along ecological and physiological regions. Sal (shorea Robusta), for example, having one of the highest carbon densities, is a major forest types in Nepal. The purpose of this study was to generate forest map of the country, calculate carbon stock, gain and loss, and their rate in each province due to deforestation/afforestation using remote sensing data. Further Sal forest map was generated and its contribution in carbon stock was calculated using averaged national carbon density as well as using regional density method. According to the study, around 5.1 million hectares of Nepali land was forest in 2015 increasing from 4.2 million hectares in 2005. However, Sal forest has decreased during the same period. Province 1 contributed the maximum (130 Tg) and Province 2 the minimum (40Tg) of Carbon stock in 2015. Using the conventional method of calculation with national average density (108.08 t/ha), a total of 36.7T CO2 yr-1 carbon sink was observed in the Country. Whereas, with the new approach of calculation, a total of 44.7 T CO2 e of carbon sink per year was estimated during the same period. This approach holds potential for qualifying as an MRV process of Nepal. The subnational level forest and carbon statistics produced during this study can be important assets for the better forest governance. This can also pave way for policy formation and preparation of action plan for sustainable forest management and intervention strategy and obtaining better financial incentives participating in the reduction of emission due to deforestation and forest degradation (REDD) plus programs.

Various types of electroconductive additives were evaluated for high C-rate capability in an attempt to extend practical application of high-areal-capacity lithium–sulfur batteries that employ an aluminum-foam current collector. Carbon nanofibers (CNFs) were found to be the most effective additive, with the ability to attain a high-sulfur-loading of 40 mg cm−2. A CNF-containing cell exhibited gravimetric capacities of 1094 and 758 mAh gsulfur−1 (46.8 and 32.4 mAh cm−2) at 0.05 and 0.1 C-rate, respectively, in an ether-based electrolyte. Because a CNF-containing slurry exhibits low viscosity even at a high solid ratio, it could be filled into the aluminum foam. Additionally, a lithium–sulfur battery with high-sulfur-loading had an energy density of ~120 Wh kg−1, a value that was calculated from the weight of the components of the cathode, anode, current collectors, electrolyte, and separator. Assuming that the amount of electrolyte decreases and that the energy density of cells accumulate, a theoretical energy density of 522 Wh kg−1 was estimated. Moreover, it was found that even if a high-areal-capacity was achieved, the discharge capacity converged at a high C-rate, unless there was an improvement in ion diffusion in the bulk electrolyte. This is considered a limitation of sulfur cathodes with high-sulfur-loading.

The outdoor field test of the 4-terminal on Si tandem photovoltaic module (specifically, InGaP/GaAs on Si) was investigated and performance model, considering spectrum change affected by fluctuation of atmospheric parameters, was developed and validated. The 4-terminal on Si tandem photovoltaic module had about 40 % advantage in seasonal performance loss compared with standard InGaP/GaAs/InGaAs 2-terminal tandem photovoltaic module. This advantage is expanded in (subarctic zone) < (temperate zone) < (subtropical zone). The developed and validated model used all-climate spectrum model and considered fluctuation of atmospheric parameters, and can be applied every type of on-Si tandem solar cells.

Monolayer graphene absorbs 2.3 percent of the incident visible light. This “small” absorption has been used to emphasize the visual transparency of graphene, but it in fact means that multilayer graphene absorbs a sizable fraction of incident light, which causes non-negligible fluorescence. In this paper, we formulate the light emission properties of multilayer graphene composed of tens to hundreds of layers using a transfer matrix method and confirm the method’s validity experimentally. We could quantitatively explain the measured contrasts of multilayer graphene on SiO2/Si substrates and found sizable corrections, which cannot be classified as incoherent light emissions, to the reflectance of visible light. The new component originates from coherent emission caused by absorption at each graphene layer. Multilayer graphene thus functions as a partial coherent light source of various wavelengths, and it may have surface-emitting laser applications.

Bats are of significant interest as reservoirs for various zoonotic viruses with high diversity. During the past two decades, many herpesviruses have been identified in various bats worldwide by genetic approaches, whereas there have been few reports on the isolation of infectious herpesviruses. Herein, we report the prevalence of herpesvirus infection of bats captured in Zambia and genetic characterization of novel gammaherpesviruses isolated from Macronycteris vittatus bats. By our PCR screening, herpesvirus genomes were detected in 29.2% (7/24) of Rousettus aegyptiacus, 78.1% (82/105) of Macronycteris vittatus, and 100% (1/1) of Hipposideros caffer bats in Zambia. Phylogenetic analyses of the detected herpesvirus genomes revealed that the Zambian bat herpesviruses were divided into seven betaherpesvirus groups and five gammaherpesvirus groups. Two infectious strains of a novel gammaherpesvirus, tentatively named Macronycteris gammaherpesvirus 1 (MaGHV1), were successfully isolated from Macronycteris vittatus bats, and their complete genomes were sequenced. The genome of MaGHV1 encoded 79 open reading frames, and phylogenic analyses of the DNA polymerase and glycoprotein B demonstrated that MaGHV1 formed an independent lineage sharing a common origin with other bat-derived gammaherpesviruses. Our findings provide new information regarding the genetic diversity of herpesviruses maintained in African bats.

In recent years, more attention has been paid to behavioral problems in children. However, for the most part, risk factors for these problems have yet to be determined. The current prebirth cohort study investigated the relationship between maternal calcium consumption during pregnancy and behavioral problems in five-year-old Japanese children. Subjects were 1199 mother-child pairs. Dietary intake was assessed using a diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, and peer problems were assessed using the Strengths and Difficulties Questionnaire. Logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for four behavioral problems under study according to the quartile of calcium intake, with the lowest quartile as the reference. Adjustment was made for maternal age, gestation at baseline, region of residence at baseline, number of children at baseline, maternal and paternal education, household income, maternal depressive symptoms during pregnancy, maternal alcohol intake during pregnancy, maternal smoking during pregnancy, child's age, child's birth weight, postnatal secondhand smoke exposure at home during the first year of life, and breastfeeding duration. Higher maternal calcium intake during pregnancy was independently associated with a decreased risk of childhood emotional and hyperactivity problems; the adjusted ORs between extreme quartiles (95% CIs, P for trend) were 0.46 (0.27–0.79, 0.01) and 0.60 (0.37–0.97, 0.046). No such inverse associations were observed for childhood conduct problems or peer problems. Maternal calcium intake during pregnancy may decrease the risk of childhood emotional and hyperactivity problems.

The effects of statin use for primary prevention in reducing mortality among older adults in Asian populations are unknown. This study aimed to determine whether use of statins for primary prevention was associated with a decreased risk of all-cause mortality in a Japanese older adult population. A regional, population-based, longitudinal cohort study was conducted using the Shizuoka Kokuho Database (SKDB). Data were compared between the statin-treated group and a non-statin-treated (control) group using the inverse probability of treatment weighting (IPTW) method. In the SKDB cohort aged ≥65 years, new statin use was associated with a decreased risk of all-cause mortality (hazard ratio, 0.40; 95% confidence interval [CI], 0.33–0.48) after IPTW adjustment. The risk difference for mortality at 5 years in the statin-treated group (7.9%) compared with that in the control group (92.1%) was 0.05 (95% CI, 0.04–0.06), and the number needed to treat was 21.20 (95% CI, 18.10–24.70). In conclusion, statin use for primary prevention in older adults may reduce the risk of all-cause mortality in the population without atherosclerotic disease. Furthermore, statin use for primary prevention is feasible in patients aged 75 to &lt;85 years and in patients with comorbidities such as diabetes, or dementia.

Background: The safety and effectiveness of factor-Xa (FXa) inhibitors for nonvalvular atrial fibrillation (NVAF) remains inconclusive. We investigated the current dosing of rivaroxaban, apixaban and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity. Methods and Results: This multicenter clinical study monitored the drug PC levels and two coagulation biomarkers (fibrinogen: FIB, and fibrin monomer complex: FMC) at peak and trough timing in 268 outpatients receiving rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted according to the dose adjustment criteria of each drug. Based on our previous study, each peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (three on rivaroxaban, two on apixaban and three on edoxaban) in whom bleeding events occurred; among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels remained within the normal range (< 6.1 µg/ml) regardless of PC variation. These finding suggested that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and frequency of dosing. Regarding the change in peak drug PC levels over time, rivaroxaban tended to accumulate more than edoxaban (p

Diet modification may be a potential contributor in the prevention of age-related cognitive decline. The association between dairy product consumption and cognitive function remains unknown in older people. We investigated whether cheese intake is associated with lower cognitive function (LCF) in community-dwelling older adults. This cross-sectional study included 1503 adults aged over 65 years. Analyzed data were obtained from face-to-face interviews and functional ability measurement. Cognitive function was assessed using mini-mental state examination (MMSE), and a score ≤ 23 was defined as LCF. The prevalence of LCF was 4.6% and this group had smaller calf circumference, slower usual walking speed, and more frequent history of anemia than subjects with MMSE scores ≥ 24. After adjusting for confounding factors, logistic regression analysis revealed cheese intake (odds ratio (OR) = 0.404, 95% confidence interval (CI) = 0.198-0.824), age (OR = 1.170, 95% CI = 1.089-1.256), usual walking speed (OR = 0.171, 95% CI = 0.062-0.472) and calf circumference (OR = 0.823, 95% CI = 0.747-0.908) as significant factors associated with LCF. Although the present study was an analysis of cross-sectional data of Japanese community-dwelling older adults, the results suggest that cheese intake is inversely associated with LCF.

In the process of transcription initiation by RNA polymerase, promoter DNA sequences affect multiple reaction pathways determining the productivity of transcription. However, the question of how the molecular mechanism of transcription initiation depends on sequence properties of promoter DNA remains poorly understood. Here, combining the statistical mechanical approach with high-throughput sequencing results, we characterize abortive transcription and pausing during transcription initiation by Escherichia coli RNA polymerase at a genome-wide level. Our results suggest that initially transcribed sequences enriched with thymine bases represent the signal inducing abortive transcription. On the other hand, certain repetitive sequence elements broadly embedded in promoter regions constitute the signal inducing pausing. Both signals decrease the productivity of transcription initiation. Based on solution NMR and in vitro transcription measurements, we also suggest that repetitive sequence elements of promoter DNA modulate the rigidity of its double-stranded form, which profoundly influences the reaction coordinates of the productive initiation via pausing.

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n=12) and CKD-aP (mild, moderate, or severe pruritus; n=11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8，and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in expression of ion channels at the skin tissue including specific for cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

The effects of psychological pressure on perceiving the height of a jump bar just before starting a high jump run was investigated. University students (N = 14) training for a high jump event performed 15 trials (3 practice, 6 pressure, and 6 non-pressure) in counterbalanced order in their daily practice environment. The height of the bar was judged as significantly higher on pressure trials compared to non-pressure trials. A regression analysis indicated that participants who reported increased subjective perceived pressure tended to judge the bar to be higher. There was no significant difference between pressure and non-pressure trials for the performance index, defined as the success rate. This study provides the first evidence that environmental perceptions prior to executing a motor task under pressure may make performance of the task appear to be more difficult.

Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2.　RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Mangrove creeks adjoining typical riverine mangrove forests is known to be a net source of CO2 and dissolved inorganic carbon (DIC) to the ocean due to the decomposition of rich organic carbon in the soil; such information is limited in fringe mangroves. This study aims to clarify the difference in carbonate processes between the two types of mangrove forests. We conducted continuous monitoring of the partial pressure of carbon dioxide (pCO2) and measured carbonate chemistry parameters (total alkalinity (TA) and DIC) in two types of mangrove areas located in Okinawa, Japan. The result showed that the maximum pCO2 reached 5242 µatm in the Fukido River estuary (a riverine mangrove), whereas it was only 765 µatm on the Yubu coast (a fringe mangrove). The measured maximum TA and DIC values were 3285 µM and 3283 µM in the Fukido River estuary and 3162 µM and 2977 µM on the Yubu coast. These indicate that pCO2 on the Yubu coast was maintained at low values by the carbonate buffering capacity even when TA and DIC increased rapidly. The mangroves on the Yubu coast grow on dead corals and coral soils. It was suggested that the DIC/TA ratio was constantly kept at approximately 0.9 due to TA production by the dissolution of calcium carbonate (CaCO3), which resulted in lower pCO2.

The aim of this study is to describe a research protocol of a multi-country randomized controlled trial to investigate the effect of a smartphone CBT stress management program on improving depression and other health- and work-related outcomes among hospital nurses in Vietnam and Thailand during the COVID-19 epidemic as a part of the COCONATS project. The study is a two-arm, parallel randomized control trial. Hospital nurses (N = 1,500) will be recruited in Vietnam and Thailand, and those who meet the criteria will be randomly allocated to the intervention or control (treatment as usual) group. A seven-week, seven-module smartphone-based stress management program will be developed to teach CBT skills. The intervention group will participate in the program for 10 weeks. Depression as the primary outcome will be measured using the DASS21 at baseline and in 3- and 6-month follow-up surveys. A mixed model repeated measures analysis will be used to test the intervention effect in the total combined sample, on an intention-to-treat basis. This is the first study to investigate the effectiveness of a self-guided smartphone CBT program on improving depression among hospital nurses using a RCT design in South-East Asian middle-income countries during the COVID-19 pandemic.

Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodelling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We previously demonstrated that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in osteoblast-like MC3T3-E1 cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase positively regulates the OPG synthesis. The present study is aimed to investigate the effect of OSM on BMP-4-stimulated OPG synthesis in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells.  Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK affected by OSM. On the other hand, the BMP-4-stimulated phosphorylation of p70 S6 kinase was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblasts.

Shales are well known for their strong anisotrophic properties. The classical Athy’s model on the exponential porosity reduction with the depth commonly uses based on localities only. Shale compaction curve affects the results of the basin modeling as it is important input data, thus the standard compaction curve of shales needs to be established. This study provided a new data and complies available data of Thailand shales to propose the new empirical relationship among porosity, burial depth, and geological age. The numerical data of the geological time were estimated by the application from the relationship of velocity and depth in each geological ages. The variation of the Thailand shale data due to the different geological ages was found in this study. Finally, the standard curve of shale compaction proposed by Puttiwongrak et al. [9] was examined and confirmed by this research findings.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Digital Microfluidic Biochips (DMFBs), used in various kinds of fields like DNA analysis, clinical diagnosis, and PCR testing, have made biochemical experiments more compact, efficient, and user-friendly than previous ways. However, their reliability is often compromised by their inability to adapt to all kinds of errors. All errors in biochips can be categorized into two types: known errors and unknown errors. Known errors are detectable before the start of the routing process through sensors or cameras. Unknown errors, in contrast, become apparent only during the routing process and remain undetected by sensors or cameras, which is the biggest issue to unexpectedly stop the routing process and diminishes the reliability of biochips. This paper introduces a deep reinforcement learning-based routing algorithm designed to manage not only known errors but also unknown errors. Our experiments demonstrate that our algorithm outperforms previous ones in terms of the success rate of the routing in the scenario including both known errors and unknown errors. Additionally, our algorithm contributes to detecting unknown errors during the routing process and identifying the most efficient routing path with high probability.

Exercise can be hypothesized to play an important role in NAFLD treatment by changing the oral bacterial flora and in the mechanism underlying periodontal disease. We performed salivary component analysis before and after an exercise regimen, and genome analysis of the oral bacterial flora to elucidate the underlying mechanism. Obese middle-aged men with NAFLD and periodontal disease were allocated to 12-week exercise (n=49) or dietary restriction (n=21) groups. We collected saliva to compare the oral microflora; performed predictive analysis of metagenomic functions; and measured the salivary immunoglobulin A, cytokine, bacterial lipopolysaccharide (LPS), and lactoferrin concentrations. The exercise group showed improvements in clinical indices of oral environment. Salivary component analysis revealed significant reductions in LPS, and lactoferrin during the exercise regimen. Diversity analysis of oral bacterial flora revealed higher alpha- and beta-diversity after the exercise regimen. Analysis of the microbial composition revealed that the numbers of Campylobacter (+83.9%), Corynebacterium (+142.3%), Actinomyces (+75.9%), and Lautropia (+172.9%) were significantly higher and that of Prevotella (−28.3%) was significantly lower. The findings suggest that an exercise regimen improves the oral environment of NAFLD patients by increasing the diversity of the oral microflora and reducing the number of periodontal bacteria that produce LPS and its capability.

The highest efficiency solar cell won in the efficiency race does not always give the most excellent annual energy yield in the real world solar condition that the spectrum is ever-changing. The study of the radiative coupling of the concentrator solar cells implied that the efficiency could increase by the recycle of the radiative recombination generated by the surplus current in upper junction. Such configuration is called by a super-multi-junction cell. We expanded the model in the concentrator solar cell to non-concentrating installation. It was shown that this super-multi-junction cell configuration was found robust and can keep the maximum potential efficiency (50 % in realistic spectrum fluctuation) up to 10 junctions. The super-multi-junction cell is also robust in the bandgap engineering of each junction. Therefore, the future multi-junction may not be needed to tune the bandgap for matching the standard solar spectrum, as well as relying upon artificial technologies like ELO (Epitaxial lift-off), wafer-bonding, mechanical-stacking, and reverse-growth, but merely uses up-right and lattice-matching growth technologies. We have two challenging techniques; one is the optical cap layer that may be the directional photon coupling layer in the application of the photonics technologies, and another is the high-quality epitaxial growth with almost 100 % of the radiative efficiency.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Understanding tumor attachments and management of feeding arteries are very important factors to achieve safe resection of skull base meningioma. We examined the distributions and frequencies of feeding arteries in skull base meningioma by cerebral angiography, and also assessed relationships to tumor attachment for skull base meningioma. We enrolled patients with skull base meningioma who underwent MRI and cerebral digital subtraction angiography (DSA), from September 2015 to October 2022. Subjects comprised 115 patients (32 males, 83 females; mean age, 52.7 years) with 117 meningiomas showing tumor attachments around the “cavernous sinus to upper part of the clivus” (Area 1), “lower part of the clivus to foramen magnum” (Area 2), and “tentorium around the petrous bone” (Area 3). We examined feeding arteries based on cerebral angiography and counted the number of related feeding arteries. Particularly frequent arteries, such as the dorsal meningeal artery (DMA), ascending pharyngeal artery (APA), tentorial artery (TA), and petrosal branch (PB) of the middle meningeal artery (MMA) were analyzed for associations of tumor attachment to Areas 1–3. DMA, APA, TA, and PB are very frequent feeding arteries among skull base meningiomas. In some cases, the artery of the foramen rotundum, posterior ethmoidal artery, recurrent meningeal artery, posterior meningeal artery, etc., supply blood to the skull base meningioma. Meningiomas with DMA as a feeding artery correlated strongly with tumor attachment to Area 1 (p&lt;0.001). Meningiomas with APA correlated strongly with tumor attachment to Area 2 (p&lt;0.001). Meningiomas with TA correlated strongly with tumor attachment to Area 3 (p&lt;0.001). PB correlated with Area 3 (p&lt;0.05). Visualization of these arteries suggests tumor attachments to the correlated areas. An accurate anatomical understanding of tumor attachment and feeding arteries is essential to determine appropriate surgical strategies for skull base meningioma. Pre-operative DSA can provide further understanding of the feeding arteries and attachments of skull base meningioma.

The thermal properties of novel nanomaterials play a significant role in determining the performance of the material in technological applications. Herein, direct measurement of the temperature diffusivity of cellulose nanocomposite films was carried out by the micro-contact method. Polymer films containing up to 2%wt. of nanocellulose were synthesised by a simple chemical process. Films of a high optical transmittance T ≈ 80 % (for a 200- μ m-thick film), which were up to 44% crystalline, were characterised. Two different modalities of temperature diffusivity based on: 1) a resistance change and 2) micro-thermocouple detected modulation of a heat wave, were used for the polymer films with cross-sections of ∼ 100 μ m thickness. Twice different in-plane α ‖ and out-of-plane α ⊥ temperature diffusivities were directly determined with high fidelity: α ‖ = 2 . 12 × 10 − 7 m 2 /s and α ⊥ = 1 . 13 × 10 − 7 m 2 /s. An amorphous polyethylene terephthalate (PET) fiber was measured for comparison α ‖ = 1 . 15 × 10 − 7 m 2 /s. This work provides an example of a direct contact measurement of thermal properties of nanocellulose composite films. The thermal diffusivity, which is usually high in strongly interconnected networks and crystals, was investigated for the first time in this composite.

Severe cases of SARS-CoV-2 infection are characterized by an immune response that leads to the overproduction of pro-inflammatory cytokines, resulting in damage to the lungs and other organs. This remarkable increase in cytokines and other inflammatory molecules is primary caused by viral proteins, in particular ORF8, a unique accessory protein specific to SARS-CoV-2. In addition to its role in cytokine induction, ORF8 is attributed with various other functions, including its ability to evade type I interferon responses. Despite the evidence, the mechanisms through which ORF8 exerts these functions remains a subject of controversy. In this mini review, we discuss the multifaceted roles of ORF8 as a modulator of cytokine response, focusing on type I interferon and IL-6. We also discuss data from our studies indicating that ORF8 augments production of IL-6 induced by Poly(I:C) in human embryonic kidney (HEK)-293 and monocyte-derived dendritic cells (mono-DCs).

To examine the hydrophobicity of torrefied wood fuel, the water resistances of torrefied pellets prepared by two different methods were evaluated using exposure tests under indoor and outdoor conditions. Torrefied pellets from the xylem of Japanese cedar (Sugi, Cryptomeria japonica) and oak (Konara, Quercus serrata) were prepared by two methods: the torrefaction of wood chips followed by pelletization and the pelletization of wood chips followed by torrefaction. It was found that the pellets prepared by pelletization followed by torrefaction had much lower moisture levels than those prepared by the other method and they showed almost no change in diameter after an outdoor weathering test. These characteristics are unique and indicate that the pellets can be applied not only for industrial use but also for residential and commercial purposes.

Recent advancements in semiconductor photonic and electronic devices such as Uni-travelling-carrier photodiodes (UTC-PDs), have played a significant role in the development of Terahertz communication technology. However, a major challenge that still persists is the limited output power from a single UTC-PD required for practical transmission distances. To enhance the output power, we propose and demonstrate a novel Terahertz wave power combining technique using a photomixer device that comprises of two arrayed UTC-PDs monolithically integrated with a microstrip line-based 2 × 1 Wilkinson power combiner and a rectangular patch antenna on a Silicon Carbide (SiC) substrate at 300 GHz. At photocurrents of 8 mA and 10 mA from the two UTC-PDs, the device experimentally exhibited a 7.3 dB increase in power relative to the power obtained with 8 mA UTC-PD and a 4.4 dB increase in power relative to the power obtained with 10 mA UTC-PD, when both UTC-PDs were irradiated. This implies that power can be enhanced by a factor of N2 if the photocurrent is multiplied by a factor of N. This technology presents a holistic and cutting edge platform for further power multiplication by further increasing the number of arrayed UTC-PDs.

Background Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who previously received platinum-based chemotherapy and immune checkpoint inhibitors. The EV-301 phase III trial demonstrated a significantly improved overall survival and response rates compared with standard chemotherapy. However, more data, especially from larger real-world studies, are needed to assess its effectiveness in Japanese patients. Methods A total of 6,007 urothelial cancer patients treated with pembrolizumab as second-line treatment were analyzed. Among them, 619 patients received enfortumab vedotin after pembrolizumab, while 394 received docetaxel or paclitaxel after pembrolizumab. Results The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p=0.013, hazard ratio: 0.71). In the multivariate analysis, enfortumab vedotin induction was an independent risk factor for the overall survival (p=0.013, hazard ratio: 0.70). There were no significant differences in the cancer-specific survival. Conclusions Enfortumab vedotin prolonged the overall survival in Japanese patients with advanced or metastatic urothelial carcinoma compared with paclitaxel or docetaxel after pembrolizumab treatment.

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Background. Many anticancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (compound B) showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds, in comparison with 4 popular anticancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one-order of magnitude higher TSM as compared with newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two order of magnitude lower TSE than compounds A and B. Compounds A and B showed higher TSM, TSE and TSN values than doxorubicin, 5-FU and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

Background Late-onset hypogonadism (LOH) is a condition caused by the decline of testosterone with aging, and is associated with various symptoms, including lower urinary tract symptoms (LUTS). Although some reports have shown that testosterone replacement treatment for LOH improved LUTS, no large study has revealed a correlation between LUTS and LOH. This study investigated the correlation between the severity of LOH and LUTS in Asian Japanese males of >40 years of age using a web-based questionnaire. Methods We asked a total of 2,000 Japanese male individuals to answer both the AMS and IPSS/QOL questionnaires using a web-based survey. Among these 2,000 individuals, 500 individuals were assigned to each of the following age groups: 40-49, 50-59, 60-69, and ≥70 years. LOH symptoms were assessed by AMS score as no/little (17-26 points), mild (27-36 points), moderate (37-49 points), and severe (≥50 points). To compare the risk of voiding and storage dysfunction according to the severity of AMS, voiding dysfunction was assessed by the sum of IPSS Q1, Q3, Q5, and Q6, while storage dysfunction was assessed by the sum of IPSS Q2, Q4, and Q7. Results The IPSS total score was positively correlated with the severity of AMS (shown as median [mean±SD]): no/little group, 2 (3.67±5.36); mild group, 6 (7.98±6.91); moderate group, 11 (12.49±8.63); and severe group, 16 (14.83±9.24) (p<0.0001). The prevalence of an IPSS total score of ≥8 in the AMS severity groups was as follows: no/little group, 13.3% (111 of 834); mild group, 38.3% (225 of 587); moderate group, 64.2% (244 of 380); severe group, 72.4% (144/199). The prevalence of nocturia in the AMS severity groups was as follows: no/little group, 19.8% (165 of 834); mild group, 31.5% (185 of 587); moderate group, 43.9% (167 of 380); and severe group, 50.8% (101 of 199). Conclusions Individuals with higher AMS values, which represents severe LOH symptoms, showed a higher risk of nocturia and LUTS.

Although sarcopenia is characterized by a loss of muscle strength and skeletal muscle mass, few studies have evaluated the effect of muscle strength on hepatocellular carcinoma (HCC) patients. We separately evaluated the impact of sarcopenia-related factors (grip strength [GS] and the skeletal muscle index [SMI]) on the survival among lenvatinib-treated unresectable HCC (u-HCC) patients. This single-center cohort study was conducted at a university hospital. The study population included 63 lenvatinib-treated u-HCC patients managed between April 2018 and April 2020. A decreased GS and decreased SMI were found in 21 (33.3%) and 22 (34.9%) patients, respectively. The overall survival (OS) of the normal GS group was significantly higher than that of the decreased GS group, while that of the normal and decreased SMI groups did not differ markedly. There were no significant differences in the progression-free survival between the normal GS and decreased GS groups or the normal SMI and decreased SMI groups. A multivariate Cox proportional hazards model showed that ALBI2b (hazard ratio [HR] 4.39) and a decreased GS (HR 3.55) were independently associated with an increased risk of poor prognosis. In addition to the hepatic functional reserve, a decreased GS was a poor prognostic factor in lenvatinib-treated u-HCC patients.

Abstract: Congenital cytomegalovirus (cCMV) infection poses significant risks to fetal development, particularly affecting the nervous system. This study reports a fetal autopsy case, examining cCMV infection and focusing on CMV DNA measurements in various fetal organs before formalin fixation, a novel approach for comprehensive CMV DNA evaluations in fetal organs affected by cCMV. A 20-week-old male fetus was diagnosed with cCMV following the detection of CMV DNA in ascites obtained via abdominocentesis in utero. After termination of pregnancy, multiple organs of the fetus, including the cerebrum, thyroid gland, heart, lungs, liver, spleen, kidneys, and adrenal glands, were extracted and examined for CMV DNA loads using real-time polymerase chain reaction. Histopathological examination involved hematoxylin-eosin and CMV-specific immunostaining. A correlation was found between CMV DNA loads and pathology, with higher CMV-infected cell numbers observed in organs positively identified with both staining methods, exhibiting CMV DNA levels of ≥1.0 × 104 copies/mL, compared to those detected solely by CMV-specific immunostaining, where CMV DNA levels ranged from 1.0 x 103 to 1.0 x 104 copies/mL. These results highlight a quantifiable relationship between organ infection extent and CMV DNA concentration, providing insights into cCMV pathogenesis and potentially informing future diagnostic and therapeutic strategies for cCMV infection.

Background: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. Methods: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate for up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA group. We compared the remission maintenance rates in AZA and ADA groups for up to 5 years after TAC discontinuation. Results: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA group (n=16) exhibited a significantly higher relapse-free rate than the AZA group (n=26) (p<0.05; log-rank test). Conclusion: Switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

While many studies have described the association between cognitive decline and eating habits, little attention has been paid to its association with cheese intake. In this cross-sectional study of 1,035 community-dwelling women aged ≥ 65, we investigated the association between intake/type of cheese and cognitive function. The anthropometry, functional ability, and the frequency of food intake, including cheese, were assessed. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a score of 20–26 was defined as mild cognitive decline (MCD). We found that MMSE score was significantly different between the presence of cheese intake (cheese intake: 28.3±1.9; non-cheese intake: 27.8±2.2) and between the type of cheese consumed (Camembert cheese: 28.7±1.3; others: 28.3±1.9). After adjusting for confounders, multiple logistic regression revealed four significant independent variables for MCD: Camembert cheese intake (odds ratio [OR] = 0.448, 95% confidence interval [CI] = 0.214–0.936), age (OR = 1.114, 95% CI = 1.059–1.171), usual walking speed (OR = 0.2620, 95% CI = 0.109–0.621), and repetitive saliva swallowing test scores (OR = 0.865, 95% CI = 0.750–0.995). Our results, while based on cross-sectional data from Japanese community-dwelling older women, demonstrated that Camembert cheese intake is significantly associated with MCD.

Several epidemiological studies and intervention trials have demonstrated that flavanols present in grapes and blueberries can lower the risk of cardiovascular disease. However, the mechanisms of action of these compounds remain unclear due to their low bioavailability. A polyphenol-rich grape and blueberry extract (PEGB) contained about 16% flavanol, of which 11% was monomer and 4% was dimer. A sensory test investigated the oral perception of a PEGB. At concentrations where quercetin had almost no detectable taste, PEGB exhibited significant astringency. Furthermore, in comparing the redox properties against O2･- using a luminescence method, PEGB acted as a prooxidant at low concentrations, promoting O2･-production and scavenging O2･-at high concentrations under pH conditions similar to oral cavity and intestine. In contrast, quercetin showed antioxidant activity at any concentration. A single oral administration of PEGB to rats showed a significant increase in skeletal muscle arteriolar blood flow. According to these results, PEGB containing flavanols displays a potent astringent flavor, increases O2･-production at low concentrations in a neutral pH environment as well as oral and intestine, and considerably enhances blood flow to skeletal muscles after a single dose in rats. The results of this study indicate a need to investigate the causal relationship between oral perception, redox properties, and bioactivity of polyphenols.

Copper (Cu) is a critical element for cancer cell proliferation and considerably accumulates in the nucleus. 64Cu2+ is an anticancer radiopharmaceuticals targeting the copper requirement of cancer cells. However, intravenously injected 64Cu2+ ions primarily accumulate in the liver. Ligand complexation of 64Cu2+ would be a promising method for increasing tumor delivery by reducing liver uptake. Herein, we used three tripodal amine ligands [tris(2-aminoethyl)amine (Tren), diethylenetriamine (Dien), and tris(2-pyridylmethyl)amine (TPMA)] to enclose 64Cu2+ ions and compared their in vivo tumor and liver uptake using a tumor-bearing xenograft mouse model of the extrahepatic bile duct carcinoma cell line TFK-1. We examined intracellular Cu distribution using microparticle-induced X-ray emission (micro-PIXE) analysis for these compounds. 64Cu2+-Tren and 64Cu2+-Dien showed higher tumor uptake than 64Cu2+-TPMA and 64Cu2+ ions in TFK-1 tumors. Among the three 64Cu2+ complexes and 64Cu2+ ions, liver uptake was inversely correlated with tumor uptake. Micro-PIXE analysis showed that in vitro cellular uptake was similar to in vivo tumor uptake and nuclear delivery was the highest for 64Cu2+-Tren. Conclusively, an inverse correlation between tumor and liver uptake was observed using three 64Cu2+ complexes of tripodal amine ligands and 64Cu2+ ions. These results provide useful information for the future development of anticancer 64Cu radiopharmaceuticals.

Evidence of the efficacy and safety of colorectal stent placement for palliation remains insufficient. This single-arm, prospective, multicenter study with WallFlex enteral colonic stent included 200 consecutive patients with malignant large bowl obstruction in the palliation cohort. The technical and clinical success, as well as stent patency and complications as short-term (≤ 7 days) and long-term (&gt; 7days) outcomes, of high axial force self-expandable metal stent (SEMS) placement was evaluated. The technical and clinical success rates were 98.5% and 94.5%, respectively. Non recurrent colorectal obstruction at 1 year was 63.9%, and 71.2% of the patients remained free of recurrent colorectal obstruction until death or the last follow-up. Fifty-six patients (28.0 %) received chemotherapy and five patients were administered bevacizumab after stent placement. The overall complication rate was 47%, including four (2.0%) early-onset and ten (5.0%) late-onset perforations, mostly due to stent-edge injury. Only the use of a long SEMS was a risk factor for perforation. In conclusion, endoscopic colorectal stenting using high axial force SEMS is an effective and safe procedure for palliation in patients with malignant colorectal obstruction. However, care should be taken to avoid perforation at the stent edge when using a long SEMS.

INTRODUCTION AND OBJECTIVES: Osteoporosis is a common consequence of androgen deprivation therapy (ADT) for prostate cancer. Up to 20% of men on ADT have suffered from fracture within 5 years. The WHO Fracture Risk Assessment Tool (FRAX) has been utilized to predict the 10-year probability of major osteoporotic and hip fracture. However, no large studies assessing the utility of FRAX with versus without dual-energy X-ray absorptiometry (DEXA) in prostate cancer patients have been performed. We validated the usefulness of FRAX combined with DEXA in men with prostate cancer. METHODS: FRAX was done in a total of 1,220 prostate cancer patients including those who underwent brachytherapy (n=547), radical prostatectomy (n=200), external beam radiation therapy (n=264), hormonal therapy only (n=187), and definitive treatment along with hormonal therapy (n=645) in Yokohama City University Hospital. Of these, 109 patients received DEXA. RESULTS: In men without receiving DEXA, the median (mean ± SD) risks for major osteoporotic and hip fracture were 8.5% (9.3 ± 4.8) and 3.2% (4.2 ± 3.9), respectively. One hundred sixteen (9.5%) and 634 (52.0%) of these patients had the major osteoporotic risk of more than 15% and hip fracture risk of more than 3%, respectively. In contrast, in men with DEXA, the median (mean ± SD) risks for major osteoporotic and hip fracture were 5.3% (5.4 ± 2.1) and 0.85% (1.3 ± 1.2), respectively. Two (0.2%) and 4 (8.0%) of these patients had the major osteoporotic risk of more than 15% and hip fracture risk of more than 3%, respectively [Table1]. In the same cohort who received DEXA, the risks for major osteoporotic (p < 0.001) and hip (p < 0.001) fracture were significantly lower in men with DEXA than in those without DEXA. CONCLUSIONS: Our results suggest that FRAX combined with DEXA might prevent unnecessary osteoporosis medication in prostate cancer patients.

Abstract: Appetite loss is common in older patients and an independent risk factor for sarcopenia, which is associated with high mortality. However, few studies have explored the phenomenon of appetite loss after discharge from the intensive care unit (ICU). Therefore, we aimed to describe the prevalence of appetite loss and the relationship between appetite loss and depression in patients living at home 12 months after intensive care. We conducted a post hoc analysis, which was a published ambidirectional study examining post-intensive care syndrome at 12 months after discharge. We included patients aged > 65 years. The Short Nutritional Assessment Questionnaire (SNAQ) and Hospital Anxiety Depression Scale (HADS) were used for the analysis. Descriptive statistics and a multilevel generalized linear model were used to clarify the relationship between appetite loss and depression. Data from 468 patients were analyzed. The defined appetite loss was 25.4% (95%CI, 21.5–29.4). High severity of depression was an independent factor for high probability of appetite loss (OR, 1.2; 95%CI, 1.14–1.28; p=0.00). Poor appetite is common 12 months after intensive care and is associated with the severity of depression.

Human-elephant conflict has become a conservation challenge in Asia and Africa resulting in considerable human fatalities annually. We deployed an AI-embedded camera-alert system in a conflict hotspot in West Bengal, India to determine if AI algorithms could accurately detect elephants and if real-time alerts that triggered a rapid response could prevent serious incidents. The system successfully detected elephants near villages (266 events) and transmitted real-time alerts (x̄ = 42 seconds) permitting quick response by field personnel to prevent conflict (x̄ = 18.2, SD = 12.4 min to arrival). Matriarch herds of elephants were detected mostly at night when human traffic was minimal; lone adult bulls, the class most prone to conflict, were detected day and night. Frequent detections of humans (33,217 events) on routes used by elephants highlighted the value of real-time monitoring especially during daytime. Twelve human fatalities and eighteen serious injuries occurred in the study area between 2019-2023 but none during deployment of the AI system, supporting the hypothesis that alerts integrated with rapid response can reduce conflict. Loss of lives and livelihoods underscore the urgency of applying this approach to other elephant ranges and adapting AI models to conflict-prone species to provide early warning and promote coexistence.

Background: The patients with cancer, especially pancreas cancer, are frequently associated with thrombosis which is one of causes for poor outcome, and hypercoagulability exists in cancer patients. Hypercoagulability is considered to be caused by thrombin burst. Methods: Activated partial thromboplastin time (APTT), small amount of tissue factor induced FIX activation (sTF/FIXa) assays and thrombin time (TT) using clot waveform analysis (CWA) were performed in 138 patients with malignant neoplasm including pancreas cancer and 66 non-cancer patients. Results: Thrombosis was frequently associated in pancreas cancer and was observed in stage I. CWA-APTT showed that the peak times and heights were markedly long and heigh, respectively, in cancer patients, and the peak times were significantly longer in pancreas cancer patients than benign pancreas diseases, and the 1st DPH was significantly higher in pancreas cancers than other cancers or benign pancreas diseases. CWA-sTF/FIXa showed that the peak times and heights were longer and higher, respectively, in patients with cancer than those without cancers, and that the 1st DPH was significantly higher in pancreas cancers than in other cancers. CWA-TT showed that the peak times were significantly shorter in cancer patients than in healthy volunteers and that the peak heights were significantly higher in cancer than in benign pancreas diseases. Conclusions: Cancer patients including pancreas cancer were frequently associated with thrombosis due to hypercoagulability with thrombin burst detected by CWA.

Background: The COVID-19 pandemic has exacerbated existing healthcare disparities among American Indian/Alaska Native (AI/AN) populations, rooted in historical traumas and systemic marginalization. Methods: This study conducted at a single Indian Health Service (IHS) clinic in central Michigan examines the effectiveness of educational interventions in enhancing COVID-19 knowledge and attitudes among AI/AN populations. Utilizing a pre/post prospective study design, participants received either a video or infographic educational intervention, followed by a survey assessing COVID-19 knowledge and attitudes. Results: The results indicate significant improvements in knowledge and attitudes post-intervention, with both modalities proving effective. However, specific factors such as gender, political affiliation, and place of residence influenced COVID-19 attitudes and knowledge, emphasizing the importance of tailored interventions. Conclusions: Despite limitations, this study highlights the critical role of educational interventions in addressing vaccine hesitancy and promoting health equity within AI/AN communities. Moving forward, comprehensive strategies involving increased Indian Health Service funding, culturally relevant interventions, and policy advocacy are crucial in mitigating healthcare disparities and promoting health equity within AI/AN communities.

High-grade gliomas present a significant challenge in neuro-oncology because of their aggressive nature and resistance to current therapies. Boron neutron capture therapy (BNCT) is a potential treatment method; however, the boron carrier compounds used — such as 4-borono-L-phenylalanine (L-BPA) — have limitations. This study evaluated the use of boron-conjugated 4-iodophenylbutanamide (BC-IP), a novel boron compound in BNCT, for the treatment of glioma. Using in vitro drug exposure experiments and in vivo studies, we compared BC-IP and BPA, with a focus on boron uptake and retention characteristics. The results showed that although BC-IP had a lower boron uptake than BPA, it exhibited superior retention. Furthermore, despite lower boron accumulation in tumors, BC-IP showed significant survival improvement in glioma-bearing rats compared to controls. These results suggest that BC-IP, with its unique properties, may be an alternative boron carrier for BNCT. Further research is required to optimize this potential treatment modality, which could significantly contribute to advancing the treatment of high-grade gliomas.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p &lt; 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

Background In SILIUS (NCT01214343), combination of sorafenib and hepatic arterial infusion chemotherapy did not significantly improve overall survival in patients with advanced hepatocellular carcinoma (HCC) compared with sorafenib alone. In this study, we explored the relationship between objective response by mRECIST and overall survival (OS) in the sorafenib group, in the combination group and in all patients in the SILIUS trial. Methods Association between objective response and OS in patients treated with sorafenib (n=103), combination (n=102) and all patients (n=205) were analyzed. The median OS of responders was compared with that of non-responders. Landmark analyses were performed according to objective response at several fixed time points, as sensitivity analyses, and the effect on OS was evaluated by Cox regression analysis with objective response as a time-dependent covariate, with other prognostic factors was performed. Results In the sorafenib group, OS of responders (n = 18) was significantly better than that of non-responders (n = 78) (p < 0.0001), where median OS was 27.2 (95% CI, 16.0–not reached) months for responders and 8.9 (95% CI, 6.5–12.6) months for non-responders. HRs from landmark analyses at 4, 6, and 8 months were 0.45 (p=0.0330), 0.37 (p=0.0053), and 0.36 (p=0.0083), respectively. Objective response was an independent predictor of OS based on unstratified Cox regression analyses. In the all patients and the combination group, similar results were obtained. Conclusion In the SILIUS trial, objective response was an independent prognostic factor for OS in patients with HCC.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

In recent years, electroencephalogram (EEG) emotion recognition has emerged as a research hotspot in the field of artificial intelligence (AI). Despite advancements in EEG-based emotion recognition, room for enhancing performance persists due to EEG signal redundancy and limitations in feature extraction, leading to inefficient models and emotional information loss. To fully utilize EEG's emotional information and improve recognition accuracy while reducing computational costs, this paper proposes a Convolutional-Recurrent Hybrid Network with a dual-stream adaptive approach and an attention mechanism (CSA-SA-CRTNN). Firstly, the model utilizes a CSAM module to assign corresponding weights to EEG channels. Then, an adaptive dual-stream convolutional-recurrent network (SA-CRNN and MHSA-CRNN) is applied to extract local spatial-temporal features. After that, the extracted local features are concatenated and fed into a temporal convolutional network with a multi-head self-attention mechanism (MHSA-TCN) to capture global information. Finally, the extracted EEG information is used for emotion classification. We conducted binary and ternary classification experiments on the DEAP dataset, achieving 99.26% and 99.15% accuracy for arousal and valence in binary classification, and 97.69% and 98.05% in ternary classification, surpassing relevant algorithms. Additionally, the model's efficiency is significantly higher than other models, achieving better accuracy with lower resource consumption.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

The aim of this retrospective study was to compare the clinical outcomes of treating isolated surgical neck fractures of the humerus using either the intramedullary nail or the MIROS (Minimally Invasive Reduction and Osteosynthesis System®) system. The study included 42 patients who underwent surgical treatment at the Polyclinic from January 2014 to June 2020. The results indicated that both treatments were effective; however, the MIROS system exhibited a higher complication rate. Intramedullary nailing was more reliable, thus recommended as the primary treatment method. This study underscores the importance of selecting the appropriate fixation technique to minimize complications and enhance patient outcomes.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

Excess nitrogen in agricultural drainage poses a serious threat to the water quality safety of the Yellow River basin. Utilizing aquatic plants to modify the rhizosphere microbial community structure and facilitate nitrogen transformation is a crucial strategy for mitigating regional water eutrophication. Our results revealed that the denitrification rate (DR), dissimilatory nitrate reduction to ammonium rate (DNRAR) and nitrogen fixation rate (NFR) of rhizosphere sediments exhibited a significant increase in artificially cultivated ditch. Compared with those in natural ditches, the richness of the bacterial community and the relative abundances of Bacteroidota, Verrucomicrobiota, Firmicutes, Anaeromyxobacter and Geobacter, which are involved mainly in the nitrogen cycle, in the rhizosphere sediments of artificially cultivated ditch were significantly greater due to improvements in environmental conditions. In artificially cultivated ditch, the dominant functional genes affecting DRNARs in the rhizosphere sediments of P. australis were nrfC and nrfA, while DRs were driven mainly by norB and napA, which were influenced by the nitrogen and carbon levels; and the dominant functional genes affecting NFRs in the rhizosphere sediments of T. orientalis were nifD, nifK and nifH. Our results provide a scientific basis for the use of aquatic plants for mitigating excess nitrogen levels in agricultural drainage.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.