For engines operating with heavy fuel oil (HFO), the nozzle rings of the turbocharger turbines are prone to severe degradation in terms of contamination with unburned fuel deposits. This contamination may lead to increased excitation of blade resonances. A previous study provides technical guidelines on how to extract the relevant information from the pulsation spectra by means of a single probe installed away from the turbine trailing edge and some sound experimental proofs of integral mode turbine vibration detection. These theoretical discussions only allude to the effects of mistuning and interferences due to classical blade passing frequencies on sound radiation patterns emitted by integral blade vibration modes. In this paper, both effects are thoroughly discussed. Combining the knowledge of theoretical study and further experimental results, the application range of this blade vibration detection method can be remarkably extended.

We solve the And\^{o} dilation problem for linear maps on vector space asked by Krishna and Johnson in \textit{[Oper. Matrices, 2022]}. More precisely, we show that any commuting linear maps on vector space can be dilated to commuting injective linear maps.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Sustained hepatic inflammation is a key driver of the transition from simple fatty liver to nonalcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. Hepatic inflammation is orchestrated by chemokines, a family of chemoattractant cytokines, which are produced by hepatocytes, Kupffer cells (liver resident macrophages), hepatic stellate cells, endothelial cells, and vascular smooth muscle cells. Over the last three decades, accumulating evidence from both clinical and experimental investigations demonstrated that chemokines and their receptors are increased in the livers of NAFLD patients and that CC chemokine ligand (CCL) 2 and CCL5, in particular, play a pivotal role in inducing insulin resistance, steatosis, inflammation, and fibrosis in the liver disease. Cenicriviroc (CVC), a dual antagonist of these chemokine’s receptor, CCR2 and CCR5, has been tested in clinical trials in patients with NASH-associated liver fibrosis. Additionally, recent studies revealed that other chemokines, such as CCL3, CCL25, CX3C chemokine ligand 1 (CX3CL1), CXC chemokine ligand 1 (CXCL1), and CXCL16 can also contribute to the pathogenesis of NAFLD. Here, we review recent updates on the roles of chemokines in the development of NAFLD and their blockade as potential therapeutic approaches.

As a photo-catalytic titanium oxide film deposition process, thermal spray is hoped to be utilized practically on the condition that it is relatively easy to deposit anatase rich films. However, because of its high equipment and feedstock powder costs, it is very difficult to introduce thermal spray equipment into small companies. In this study, to develop a low cost thermal spray system, low power atmospheric suspension plasma spray equipment with titanium hydroxide suspension created by hydrolysis of titanium tetra iso butoxide using Ar, N2 as working gases. For avoiding sedimentation of the hydroxide particles in the suspension, mechanical milling of the suspension was conducted to create colloidal suspension before using it as feedstock. Moreover, an Ultrasonic wave container was used to keep the suspension particles moving while the spray process was conducted. After the film deposition, with As for the coating, anatase rich TiO2 film could be obtained. For characterization of the film, microstructure observation by optical microscope and X-ray diffraction was carried out. Consequently, by creation of colloidal suspension, deposition could be conducted without sedimentation of the hydroxide particle in the suspension during operation. Besides, it was proved the film had enough photo-catalytic property to decolor methylene-blue droplet

The bipolar mitotic spindle drives accurate chromosome segregation by capturing the kinetochore and pulling each set of sister chromatids to the opposite poles. In this review, we describe recent findings on the multiple pathways leading to bipolar spindle formation in fission yeast and discuss these results from a broader perspective. Roles of four mitotic kinesins (Kinesin-5, Kinesin-6, Kinesin-12 and Kinesin-14) in spindle assembly are depicted, and how a group of microtubule-associated proteins, sister chromatid cohesion and the kinetochore collaborates with these motors is shown. We have paid special attention to the molecular pathways that render otherwise essential Kinesin-5 to become non-essential: how cells build bipolar mitotic spindles without the need for Kinesin-5 and where the alternate forces come from are considered. We highlight the force balance for bipolar spindle assembly and explain how outward and inward forces are generated by various ways, in which the proper fine-tuning of microtubule dynamics plays a crucial role. Overall, these new pathways have illuminated remarkable plasticity and adaptability of spindle mechanics. Kinesin molecules are regarded as prospective targets for cancer chemotherapy and many specific inhibitors have been developed. However, several hurdles have arisen against their clinical implementation. This review provides insight into possible strategies to overcome these challenges.

This paper presents new perspectives of photonic technologies for capsule endoscopy. It is firstly presented a review about conventional endoscopy (upper endoscopy and colonoscopy), followed by capsule endoscopy (CE), as well as their techniques, advantages, and drawbacks. The technologies for CEs presented in this paper have the potential of integration on the existing endoscopic systems commercially available. Such technologies include narrow band imaging (NBI), photodynamic therapy (PDT), confocal laser endomicroscopy (CLE), Optical coherence tomography (OCT) and Spectroscopy in order to improve the performance of the gastrointestinal (GI) tract examination. In the context of NBI, two optical filters were designed and fabricated for integration into endoscopic capsules, allowing the visualization of light centered at the 415 nm and 540 nm. These optical filters are based on the principle of Fabry-Perot and were made of thin-films of titanium dioxide (TiO2) and silicon dioxide (SiO2). Moreover, strategies and aid solutions for the adaptation of ECs for PDT are also discussed.

We investigated the properties of architected materials made from UV-cured urethane elastomers and the use of such materials for insoles. The durability and reliability of various materials currently used in medical insoles were compared with those of architected materials with microlattice. The results show that architected materials made from UV-cured urethane elastomers have high impact resilience and grip, and the hardness can easily be changed by adjusting the column diameter of the unit cell. Compared with the foam materials used for medical insoles today, these architected materials also demonstrate superior UV resistance, suggesting that, after being washed in water, they can be air-dried outdoors.

Proper bipolar spindle assembly underlies accurate chromosome segregation. A cohort of microtubule-associated proteins orchestrates spindle microtubule formation in a spatiotemporally coordinated manner. Among them, the conserved XMAP215/TOG family of microtubule polymerase plays a central role in spindle assembly. In fission yeast, two XMAP215/TOG members, Alp14 and Dis1, share essential roles in cell viability; however how these two proteins functionally collaborate remains undetermined. Here we show the functional interplay and specification of Alp14 and Dis1. Creation of new mutant alleles of alp14, which display temperature sensitivity in the absence of Dis1, enabled us to conduct detailed analyses of a double mutant. We have found that simultaneous inactivation of Alp14 and Dis1 results in early mitotic arrest with very short, fragile spindles. Intriguingly, these cells often undergo spindle collapse, leading to a lethal “cut” phenotype. By implementing an artificial targetting system, we have shown that Alp14 and Dis1 are not functionally exchangeable and as such are not merely redundant paralogues. Intriguingly, while Alp14 promotes microtubule nucleation, Dis1 does not. Our results uncover that the intrinsic specification, not the spatial regulation, between Alp14 and Dis1 underlies the collaborative actions of these two XMAP215/TOG members in mitotic progression, spindle integrity and genome stability.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. However, these deficiencies can be rescued by simultaneous inactivation of kinesin-14 motors, as they counteract kinesin-5. We conducted detailed genetic analyses in fission yeast to understand the mechanisms driving spindle assembly in the absence of kinesin-5. Here we show that deletion of the nrp1 gene, which encodes a putative RNA-binding protein with unknown function, can rescue temperature sensitivity caused by cut7-22, a fission yeast kinesin-5 mutant. Interestingly, kinesin-14/Klp2 levels on the spindles in the cut7 mutants were significantly reduced by the nrp1 deletion, although the total levels of Klp2 and the stability of spindle microtubules remained unaffected. Moreover, RNA-binding motifs of Nrp1 are essential for its cytoplasmic localization and function. We have also found that a portion of Nrp1 is spatially and functionally sequestered by chaperone-based protein aggregates upon mild heat stress and limits cell division at high temperatures. We propose that Nrp1 might be involved in post-transcriptional regulation through its RNA-binding ability to promote the loading of Klp2 on the spindle microtubules.

This study was aimed at investigating the protective effects of glass ionomer cement (GIC) and surface pre-reacted glass ionomer (S-PRG) fillers used as dental restorative materials on demineralization of bovine enamel. GlasIonomer FX ULTRA (FXU), Fuji IX GP Extra (FIXE), CAREDYNE RESTORE (CDR) were used as GICs. PRG Barrier Coat (BC) was used as the S-PRG filler. They were incubated in a lactic acid solution (pH = 4.0) for 6 d at a temperature of 37 °C. The mineral was etched from the enamel surface, and a large number of Ca and P ions were detected in solution. The Al, F, Na, Sr, and Sr ions were released in GICs and S-RPG fillers. The Zn ion was released only in CDR and the B ion was released only in BC. The presence of apparent enamel prism peripheries was observed after 6 d of treatment for the group containing only enamel blocks. pH values for the FXU, FIXE, CDR, BC, and enamel block groups after 6 d were 6.5, 6.6, 6.7, 5.9, and 5.1, respectively. Therefore, the observed pH neutralization effect suppressed progression of caries due to the release of several ions from the restoratives.

A method of geoengineering/solar radiation management is proposed as global warming countermeasure. The idea is to decrease surface temperature by increasing stratospheric ozone. One-dimensional (vertical) radiative-convective equilibrium temperature calculations show that surface temperature can be lowered by increasing the amount of ozone in the stratosphere. It was the increase in altitude above about 25 km that reduced surface temperatures. The method of increasing the amount of ozone (O3 injection), the rate of decrease of surface temperature after the ozone increase, and the rate of decrease of ozone concentration by photochemical reaction and diffusion/transport after the ozone increase are discussed.

Background: Although cerebral aneurysm (CA) is a defining complication of COL4A1/2-related vasculopathy, the specific factors influencing its onset remain uncertain. This study aimed to identify and analyze these factors. Methods: We described a family presenting with a novel variant in the COL4A1 gene complicated with CA. Concurrently, an exhaustive review of previously documented patients with COL4A1/2-related vasculopathy was conducted by sourcing data from PubMed, Web of Science, Google Scholar, and Ichushi databases. We compared the variant types and locations between patients with CA (positive group) and those without CA (negative group). Results: This investigation encompassed 53 COL4A1/2 variants in 76 patients. Except for one start codon variant, all the identified variants in CA were missense variants. Otherwise, CA was not associated with other clinical manifestations, such as small-vessel disease or other large-vessel abnormalities. A higher frequency of missense variants (95.5% vs 58.1%, p = 0.0035) was identified in the CA positive group. Conclusions: CA development appears to necessitate qualitative alterations in COL4A1/2, and the underlying mechanism seems independent of small vessel disease or other large vessel anomalies. Our findings suggest that a meticulous evaluation of CA is necessary when missense variants in COL4A1/2 are identified.

This study contextualises the background of Japan’s “carbon neutrality and net-zero” (CNN) policy announced in October 2020, thereby identifying important changes in the country’s climate policy between 1990 and 2020. Using four research questions, four main findings were extracted from a narrative technique-based analysis of Japan’s policy documents related to CNN. The following are the findings: [i] the framing of climate change as a “climate crisis” by influential Japanese climate stakeholders was a key motivation for Japan to formally announce its CNN policy in October 2020, [ii] pressure from the international community and the political leadership of the Yoshihide Suga administration are essential factors that led the Japanese government to change its stance and announced this policy, [iii] Japan unintentionally delayed announcement of the policy until 2020 due to the concern among Japanese climate stakeholders about the problem of fairness in Kyoto Protocol’s emission reduction targets, and [iv] this delay was also due to Keidanren’s (or business sector) consistent opposition to the introduction of regulatory schemes. These results emerge for the first time in a study of Japan’s CNN politics, particularly in terms of the broader context of climate politics. Finally, we offer a possible explanation for Suga’s deliberate announcement of the CNN policy. This opens up space for future research to complement our study by providing important indicators on the trajectory of this important policy.

Viroids are known the smallest plant pathogens, and although their genome sequences do not encode proteins, they can cause disease in economically important crops. In order to control viroid diseases and mitigate their damage, genetic resources used for breeding of the viroid-resistant crop have been searched, but the practical resistant trait has not been found in almost all viroid-crop combinations, as well as the tolerant trait. Due to the difficulty in exploiting naturally occurring resistance or tolerance, various effective strategies have been devised to control viroid diseases using non-transforming or transforming techniques. Meanwhile, extensive findings related to viroid resistance and tolerance may lead to confer resistance or tolerance to viroid infection by combining with the recently emerged new technologies (e.g., spray-induced gene silencing and genome-editing technologies), which are believed to be more environmentally viable and acceptable to the general public than previously reported approaches. In particular, some genome-modified crops produced by the latter technology are already on the market. In this review, we comprehensively summarize the current status about investigation of naturally occurring genetic traits for viroid resistance and tolerance, accumulating knowledge about host factors involved in viroid pathogenicity, and various basic technologies developed to try to possible viroid disease control strategies. Furthermore, we discuss prospects and challenges for the achievement of more effective, practical, and sustainable disease control of viroid.

Tracheal agenesis (TA) is a rare congenital anomaly with the incidence of 1 per 50,000 newborns. It appears at birth with severe respiratory distress, cyanosis, and inaudible crying. Prompt esophageal intubation and long-term management of the esophageal airway is essential to overcome the catastrophic condition. In the long-term management, external stenting of the esophageal airway has been reported promising to support the fragile esophageal wall and “trachealize,” which technique was implanted from the surgery for tracheomalacia. We experienced a case of an infant with tracheal agenesis whose respiratory status was stabilized after trachealization of the esophagus using external stenting technique. The stenting was performed based on a lesson learned in the extensive experience in the surgical treatment for tracheomalacia and the surgical techniques for successful stenting in are herein described.

The human mind is multimodal. Yet most behavioral studies rely on century-old measures of behavior—task accuracy and latency (response time). Multimodal and multisensory analysis of human behavior creates a better understanding of how the mind works. The problem is that designing and implementing these experiments is technically complex and costly. This paper introduces versatile and economical means of developing multimodal-multisensory human experiments. We provide an experimental design framework that automatically integrates and synchronizes measures including electroencephalogram (EEG), galvanic skin response (GSR), eye-tracking, virtual reality (VR), body movement, mouse/cursor motion and response time. Unlike proprietary systems (e.g., iMotions), our system is free and open-source; it integrates PsychoPy, Unity and Lab Streaming Layer (LSL). The system embeds LSL inside PsychoPy/Unity for the synchronization of multiple sensory signals—gaze motion, electroencephalogram (EEG), galvanic skin response (GSR), mouse/cursor movement, and body motion—with low-cost consumer-grade devices in a simple behavioral task designed by PsychoPy and a virtual reality environment designed by Unity. This tutorial shows a step-by-step process by which a complex multimodal-multisensory experiment can be designed and implemented in a few hours. When conducting the experiment, all of the data synchronization and recoding of the data to disk will be done automatically.

We evaluated the usefulness of the novel cholesterol-triglyceride subgroup (CTS) indices that potentially reflect the metabolic status regarding risk of coronary heart disease (CHD) using a retrospective longitudinal study of the Japanese general population. We recruited 12,373 individuals from the annual users of our healthcare center. Among them, the first onset of CHD was recorded in 131 individuals between April, 2014 and March, 2020. The multivariate Cox proportional hazards regression analyses for all normalized lipid indices revealed that the CTSqnt index showed a comparable hazard ratio for the CHD outcome to non-high-density lipoprotein cholesterol (nonHDL-c) and triglycerides. The HR of the CTSqlt index was significantly lower than for CTSqnt, but still comparable to that for low-density lipoprotein cholesterol (LDL-c). In comparison with the other indices, CTSqlt is more sensitive to risk increment while the index value increases. Linear regression analyses for the CTS indices and previously known lipid indices suggest that the CTSqnt and CTSqlt indices reflect the quantity of atherogenic lipoproteins and size of smaller and denser LDLs, respectively. Furthermore, the CTSqnt/HDL-c index can be used as a comprehensive risk indicator that may represent the status of lipid metabolism determined by the CTSqlt and CTSqnt indices and thus may be useful for screening. The CTS indices can be used to evaluate the metabolic status of individuals, which may increase the risk of future CHD.

Background: The human mind is multimodal. Yet most behavioral studies rely on century-old measures such as task accuracy and latency. To create a better understanding of human behavior and brain functionality, we should introduce other measures and analyze behavior from various aspects. However, it is technically complex and costly to design and implement the experiments that record multiple measures. To address this issue, a platform that allows synchronizing multiple measures from human behavior is needed. Method: This paper introduces an opensource platform named OpenSync, which can be used to synchronize multiple measures in neuroscience experiments. This platform helps to automatically integrate, synchronize and record physiological measures (e.g., electroencephalogram (EEG), galvanic skin response (GSR), eye-tracking, body motion, etc.), user input response (e.g., from mouse, keyboard, joystick, etc.), and task-related information (stimulus markers). In this paper, we explain the structure and details of OpenSync, provide two case studies in PsychoPy and Unity. Comparison with existing tools: Unlike proprietary systems (e.g., iMotions), OpenSync is free and it can be used inside any opensource experiment design software (e.g., PsychoPy, OpenSesame, Unity, etc., https://pypi.org/project/OpenSync/ and https://github.com/moeinrazavi/OpenSync_Unity). Results: Our experimental results show that the OpenSync platform is able to synchronize multiple measures with microsecond resolution.

Apoptosis under severe hypoxia is induced through p53 phosphorylation and HIF-1α-dependent p53 accumulation via ATR activation by DNA damage response (DDR) activation through replication stress. We previously demonstrated that the topoisomerase I catalytic inhibitor, 3EZ, 20Ac-ingenol, specifically induced apoptosis in Jeko-1 and Panc-1 cells, both of which are cell lines that show cyclin D1 overexpression. After progression to the S phase facilitated by nuclear cyclin D1, in the presence of 3EZ, 20Ac-ingenol, an intra S phase checkpoint was induced in ATR activation as part of replication stress-induced DDR. In this study, we examined whether 3EE, 20Ac-ingenol induces a higher degree of p53 phosphorylation and additional HIF-1α and p53 accumulation in response to replication stress-induced DDR activation under the hypoxic condition than under the normoxic condition by controlling ATR activation. 3EE, 20Ac-ingenol induced p53 activation and HIF-1α-dependent p53 accumulation through cooperative ATR activation via induced DDR with the hypoxia in Panc-1 cells. The Jeko-1 cells showed slight HIF-1α accumulation under hypoxia, but this was not decreased by 3EE, 20Ac-ingenol, so that the cells remained resistant to hypoxia. 3EE, 20Ac-ingenol induces an intricate interplay between p53 and HIF-1α accumulation via ATR activations that results in high p53 accumulation, which advanced transient expression and early disappearance of HIF-1?. The strong p53 accumulation and consequent PTEN activation also decreased HIF-1α accumulation and PD-L1 expression, which resulted in intense apoptosis.

Background and Objectives: Non-cognitive skills (NCS) are vital components of a socially and financially successful life. They are developed through childhood education, family and school environments, and social settings. The aim of this study was to examine the associations between NCS and the parent–child relationship, mental health, and lifestyle at school and at home for adolescents. Materials and Methods: An internet-based survey was conducted with 1,566 mothers and their children (aged 14) in Japan. Survey items for the children included background (i.e., sociodemographic items, school achievements, and lifestyle), NCS (i.e., grit and self-control scales), and mental health, while their mothers provided social, financial, and educational information, and information on parent–child relationships, including descriptions of the fathers and the father–child relationship. Results: Parent–child relationships were mostly good (i.e., 90.9% for mothers and 75.6% for fathers), with bad relationships being less common (1.6% for mothers and 6.7% for fathers). Adolescent lifestyle parameters and mental health were significantly associated with grit and self-control. Adolescents with good parent–child relationships had significantly higher NCS scores regardless of the gender of the parent. Higher NCS scores were significantly associated with better parent–child relationships, more favorable lifestyles, and better mental health among adolescents. Conclusions: These findings imply that good parent–child relationships may aid in the development of adolescents’ NCS, thereby facilitating positive lifestyles at school and home.

An understanding of the cultural conditions that determine the factors affecting nurses’ intention to leave is important for countries suffering from nurse shortage. Aim: to examine factors influencing intention to leave among female hospital nurses in a large Japanese sample, classified into four generations by age considering economic conditions. Methods: a cross-sectional survey with convenience sampling was conducted. Anonymous self-administered questionnaires were distributed to all nurses in 30 hospitals. To assess intention to leave, basic attributes, life conditions, work characteristics, and factors of psychosocial work environment were addressed. After classifying data into four generations based on age cohorts, we conducted multivariate logistic regression analysis using the completed data (N = 5,074, mean age = 36.24). Results: regardless of generational characteristics influenced by economic conditions, effort and monetary reward were generation-common factors. Over-commitment, social support, and the presence of a role model were generation-common factors in three generations. While having children increased intention to leave in the generation born 1965–1979, having family members in need of caregiving other than children decreased the risk in the generation born in the 1980s. Conclusion: generational countermeasures considering factors of psychosocial work environment and life conditions are needed to avert female nurse turnover.

In this study, machine learning was used to predict and analyze the behavior of occupants in Gifu City residences during winter. Global warming is currently progressing worldwide, and it is important to control greenhouse gas emissions from the perspective of adaptation and mitigation. Occupant behavior is highly individualized and must be analyzed to accurately determine a building's energy consumption. The accuracy of heating behavior prediction has been studied using three different methods: logistic regression, support vector machine (SVM), and deep neural network (DNN). The generalization ability of the support vector machine and the deep neural network was improved by parameter tuning. Parameter tuning of the SVM showed that the values of C and gamma affected the prediction accuracy. The prediction accuracy improved by approximately 11.9 %, confirming the effectiveness of parameter tuning on SVM. Parameter tuning of the DNN showed that the values of layer and neuron affected the prediction accuracy. Although parameter tuning also improved the prediction accuracy of DNN, and the rate of increase was lower than that of SVM.

In eutrophic waters, such as Mikawa Bay, Japan, anoxic bottom water develops in summer. This causes sulfide release into seawater by sulfate reduction in the sediment, leading to environmental problems. The addition of iron to sediments is a method used to improve the sediment environment, which was devised from a natural phenomenon. However, this method has not yet been quantitatively evaluated. In this study, we aim to quantitatively evaluate the suppressive effect of iron on sulfide release. First, we develop a sediment model that focuses on S and Fe. We then attempted to reproduce the observations and experiments on sulfide dynamics using the model. Consequently, the proposed model was able to reproduce field sulfur and Fe dynamics in sediments. Additionally, the model described the characteristics of sulfide release considering the effects of additive iron materials. Finally, we conducted predictive calculations and quantitatively evaluated the effects of adding iron materials to the sediments in terms of sulfur and iron cycles.

We provide an extensive and systematic investigation of exciton dynamics in droplet epitaxial quantum dots comparing the cases of (311)A, (001) and (111)A surfaces. In spite of a similar s-shell exciton structure common to the three cases, the absence of a wetting layer for (311)A and (111)A samples leads to a larger carrier confinement with respect to (001), where a wetting layer is present. Moreover, this leads to a more pronounced dependence of the binding energies of s-shell excitons on the quantum dot size and to a strong anti-binding character of the positive charged exciton for smaller quantum dots. In-plane geometrical anisotropies of (311)A and (001) quantum dots lead to a large electron-hole fine interaction (fine structure splitting, FSS ~ 100 ueV) whereas for the three-fold symmetric (111)A counterpart this figure of merit is reduced of about one order of magnitude. In all these cases we do not observe any size dependence of the fine interactions. Heavy-hole/light-hole mixing is present in all the studied cases leading to a broad spread of linear polarization anisotropy (from 0 up to about 50%) irrespective of surface orientation (symmetry of the confinement), fine interactions and nanostructure size. These results are important for the further development of ideal single and entangled photon sources based on semiconductor quantum dots.

We conducted a retrospective analysis of the immunohistochemical (IHC) staining GRP94, an ER stress protein on large B-cell lymphoma (LBCL) cells, intracellular p53, and 15 factors involved in the metabolism of CHOP regimen :AKR1C3 (HO-metabolism), CYP3A4 (CHOP-metabolism) and HO efflux pumps (MDR1, MRP1). The study subjects were 42 patients with LBCL at our hospital. IHC staining using antibodies against the 17 factors. The odds ratios by logistic regression analysis using a dichotomous variable of CR, non-CR/relapse were statistically significant: for MDR1, MRP1, and AKR1C3. The overall survival (OS) after R-CHOP was compared by the log-rank test. The four groups showed that Very good (5-year OS, 100%) consisted of 4 patients showed negative IHC staining for both GRP94 and CYP3A4. Very poor (1-year OS, 0%), consisted of 3 patients who showed positive results of IHC for both GRP94 and CYP3A4. The remaining 35 patients comprised two subgroups: Good (5-year OS 60-80%.): 15 patients who showed negative staining for both MDR1 and AKR1C3, Poor: 5-year OS, 10-20%) :20 patients who showed positive staining for either MDR, AKR1C3,,MRP1 or p53. The Histological Prognostic Index (HPI) (The four groups: Very poor, Poor, Good, and Very pood) is a breakthrough method for stratifying patients based on factors involved in the development of treatment resistance.

Japan is experiencing a super-aging society faster than is anywhere else worldwide. Consequently, extending healthy life expectancy is an urgent social issue. To understand diet that supports the extension of healthy life expectancy, we studied the relationships among quality of life (QOL: SF-36 questionnaire), physical activity (number of steps and activity calculated using an accelerometer), physical function (muscle strength, movement function, agility, static balance, dynamic balance, and walking function) and dietary intake among 469 older adults living in the Tokyo metropolitan area (65–75 years old, men/women = 166/303) from February 23, 2017, to March 31, 2018. There was a significant positive association between physical QOL and steps, moderate-intensity activity, and high-intensity activity (p < 0.05), and a significant positive association (p < 0.05) between physical activity and movement, static balance, and walking functions, but no association with muscle strength. These three body functions were significantly positively correlated with intake of vegetables, seeds, fruits, and milk, and with magnesium, potassium, vitamin B6, and the dietary fibre/carbohydrate ratio and composition ratios (p < 0.05). Balancing food and nutrition may improve QOL in older adults through increased physical function and physical activity. Future verification of interventions is needed.

Previous studies have indicated that facial expressions can serve as an objective evaluation method for hedonics (overall pleasure) of food and beverages. In this study, we aimed to validate the findings of our previous research, which demonstrated that facial expressions induced by tastants can predict the perceived hedonic ratings of these tastants. Facial expressions of 29 female participants (aged 18-55 years) were recorded using a digital camera while they consumed 12 different concentrations of solutions representing five basic tastes. The facial expressions were then analyzed using the widely-used facial expression analysis application, FaceReader, to identify seven emotions (surprise, happiness, scare, neutral, disgust, sadness, and anger) with scores ranging from 0 to 1. Participants also rated the hedonics of each solution on a scale from -5 (extremely unpleasant) to +5 (extremely pleasant). A multiple linear regression analysis was conducted to develop a formula to predict perceived hedonic ratings. The formula's applicability was tested by analyzing emotion scores for 11 additional taste solutions consumed by 20 other participants. The predicted hedonic ratings demonstrated good correlation and concordance with the perceived ratings, supporting the validity of our previous findings using different software and taste stimuli among diverse participants.

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation-contraction coupling. The activity of the RyR is regulated by many intracellular factors such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for change in the cellular environment of muscles.

The advantage of FPGAs lies in the ability to implement a fully hardware solution for interfacing with various input/output (I/O) devices. Each block can work in parallel with all the others, simplifying the satisfaction of timing constraints. However, this hardware utilization consumes FPGA resources that could otherwise be allocated to the primary project. An alternative involves employing a small "soft-core" processor implementing I/O in software. With the goal to design and evaluate a new tiny soft-core processor optimized for FPGA resources in I/O , a novel processor named Baby8 is developed. It is an 8-bit CISC soft-core processor optimized for reduced FPGA resources including program size for 8-bit applications. The number of instructions is not large but any instruction can access arbitrary memory locations. The performance and resource utilization of the newly designed processor are evaluated and compared with a variety of other soft-core processors. The results demonstrate its competitive performance, achieving an average maximum clock frequency of approximately 57 MHz and a power consumption of around 2mW. Furthermore, it conserves nearly half of the FPGA resources in implementation.

This article provides a detailed analysis of non-invasive techniques for prediction and diagnosis of faults in internal combustion engines, focusing on the application of the Proknow-C and Methodi Ordinatio systematic review methods. Initially, the relevance of these techniques in promoting energy sustainability and mitigating greenhouse gas emissions is discussed, aligning with the Sustainable Development Goals (SDGs) of Agenda 2030 and the Paris Agreement. The systematic review conducted in the subsequent sections offers a comprehensive mapping of the state-of-the-art, highlighting the effectiveness of combining these methods in categorizing and systematizing relevant scientific literature. The results reveal significant advancements in the use of artificial intelligence (AI) and digital signal processors (DSP) to enhance fault diagnosis, as well as underscore the crucial role of non-invasive techniques in minimizing interference in monitored systems. Finally, concluding remarks point towards future research directions, emphasizing the need to develop digital twins for internal combustion engines and identify gaps for further improvements in fault diagnosis and prediction techniques.

Quantitative phase imaging by digital holographic microscopy (DHM) is a nondestructive and label-free technique, that has been playing an indispensable role in the field of science, technology, and biomedical imaging. The technique is competent for the imaging and analysis of label-free living cells and the investigation of reflective surfaces. Herein, we introduce a new configuration of a wide field-of-view single-shot common-path off-axis reflective DHM for the quantitative phase imaging of biological cells that leverages with several advantages including less-vibration sensitive to external perturbations due to common-path configuration, compact in size, simple in optical design, highly stable, and cost-effective. A detailed description of the proposed DHM system, including its optical design, working principle, and capability of phase imaging, is presented. The applications of the proposed system are demonstrated by quantitative phase imaging results obtained from the reflective surface (USAF resolution test target) as well as transparent samples (microlens array and living plant cells). The proposed system could find its applications in the investigations of several biological specimens and optical metrology of micro-surfaces.

This paper provides a comparative analysis of AES (Advanced Encryption Standard) and Salsa20 algorithm implementations, focusing on power consumption efficiency in passive RFID (Radio Frequency Identification) tags and ultra-low-power devices. The main objective of this work is to determine which of these algorithms is more suitable to operate in these types of devices. For this purpose, ASIC (Application-Specific Integrated Circuit) implementations of AES and Salsa20 based on low-power approaches were developed and their power consumption was evaluated. Results demonstrate that Salsa20 power consumption is lower than AES (2.82μW and 4.01μW, respectively - both in 0.18μm), indicating that Salsa20 is a better choice than AES for passive RFID tags.

Background: The effect of velamentous cord insertion (VCI) on perinatal outcomes in twin pregnancies is unclear due to conflicting findings. This retrospective study aimed to examine VCI prevalence and related risk factors in twin pregnancies and its association with adverse perinatal outcomes. Methods: Women with twin pregnancies who delivered between January 2012 and December 2021 in a single tertiary hospital were included. The participants were divided into dichorionic (DC) and monochorionic diamniotic (MCDA) groups, and their maternal and fetal characteristics and VCI rates were compared. Logistic regression models were used to identify risk factors for VCI and VCI-related perinatal outcomes. Results: Among the 694 twin pregnancies included in this study, the VCI rate was significantly higher in MCDA than in DC twins. Body mass index and MCDA twins were significant risk factors for VCI, whereas assisted reproductive technology pregnancy was a significant protective factor against VCI. In DC twins, VCI did not affect perinatal outcomes. Conclusion: In MCDA twins, VCI was a significant risk factor for fetal growth restriction, twin-to-twin transfusion syndrome, and preterm birth at

A novel nor-phragmalin-type limonoid, named carapanosin D (1), and two novel mexicanolide-type limonoids, carapanosins E (2) and F (3), were isolated from the seeds oil of Carapa guianensis AUBLET (andiroba), a traditional medicine in Brazil and Latin American countries. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques and HRFABMS. Compounds 1—3 were evaluated for their effects on the production of NO in LPS-activated mouse peritoneal macrophages. The NO inhibitory assay suggested that compound 2 may be valuable as potential inhibitors of macrophage activation.

Conjugated polymers (CPs) offer potentials for sustainable semiconductor devices due to their low cost, and inherent molecular self-assembly. Enhanced crystallinity and molecular orientation in thin films of solution-processable CPs have significantly improved organic electronic device per-formance. In this work, three methods namely spin-coating, dip-coating, and unidirectional float-ing-film transfer method (UFTM) were utilized with their parametric optimization for fabricating RR-P3HT films. These films were then utilized for their characterization via optical and micro-structural analysis to elucidate dominant roles of molecular orientation, and crystallinity in con-trolling charge transport in organic field-effect transistors (OFETs). OFETs fabricated by RR-P3HT thin films using spin-coating and dip-coating displayed field-effect mobility (μ) of 8.0 × 10-4 cm2V-1s-1 and 1.3 × 10-3 cm2V-1s-1, respectively. This two-time enhancement in (µ for dip-coated films was attributed to its enhanced crystallinity. Interestingly, UFTM films based OFETs demon-strated μ of 7.0 × 10-2 cm2V-1s-1, >100 times increment as compared to its spin-coated counterpart This superior device performance is attributed to synergistic influence of higher crystallinity and molecular orientation. Since the crystallinity of dip-coated and UFTM-thin films are similar ~50 times improved µ of UFTM thin films suggest a dominant role of molecular orientation as com-pared to crystallinity in controlling the charge transport.

The automotive industry needs to improve energy efficiency rapidly to achieve carbon neutrality while creating a safe, secure, comfortable driving environment for customers. Porous sound-absorbing materials and porous thermal insulators are typically used to satisfy these requirements despite limitations in mass and space. While these porous materials are similar, the microstructures they offer for high performance differ in the size and connectivity of their fluid phases, which enhances the difficulty of achieving excellent sound absorption and thermal insulation in the same material. In this study, a hydrophobic cellulose nanofiber–poly(methylsiloxane) xerogel composite was developed using computational microstructure modeling. This porous material has high porosity and excellent thermal insulation and sound absorption properties.

ABSTRACT: Objectives: Oncostatin M (OSM), a member of the interleukin (IL)-6 family of cytokines, is known to elicit pathogenic effects involving disruption of the epithelial barrier function as a part of immunological response networks. It is not yet known how these integrated cytokine signals influence inflammation and other physiological processes in the pathology of chronic rhinosinusitis (CRS). We investigated the expression and distribution of OSM and OSM receptor (OSMR) in sinonasal specimens of CRS patients, and we compared the results with a panel of inflammatory cytokine levels and clinical features. Materials and Methods: We classified CRS patients as eosinophilic (ECRS, n=36) or non-eosinophilic (non-ECRS, n=35) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) phenotypic criteria, and we compared their cases with those of 68 non-CRS subjects. We also examined stimulatory effects of OSM on the expression levels of cytokine receptors by using the human bronchial epithelium cell line BEAS-2B. Results: An RT-PCR showed that the OSM mRNA levels were significantly increased in the ethmoid sinus mucosa of the CRS patients. The OSM mRNA levels were positively correlated with those of TNF-α, IL-1β, IL-13, and OSMR-β. In BEAS-2B cells, OSM treatment induced significant increases in the OSMR-β, IL-1R1, and IL-13Ra mRNA levels. Conclusions: Our findings indicate that OSM is involved in the pathogenesis of CRS in both type 1 and type 2 inflammation, suggesting the OSM signaling pathway as a potential therapeutic target for modulating epithelial stromal interactions.

Droplet epitaxy allows the efficient fabrication of a plethora of 3D, III-V-based nanostructures on different crystalline orientations. Quantum dots grown on (311)A-oriented surface are obtained with record surface density, with or without a wetting layer. These are appealing features for quantum-dot lasing, thanks to the large density of quantum emitters and a truly 3D lateral confinement. However, the intimate photophysics of this class of nanostructures has not yet been investigated. Here we address the main optical and electronic properties of s-shell excitons in individual quantum dots grown on (311)A substrates with photoluminescence spectroscopy experiments. We show the presence of neutral exciton and biexciton as well as positive and negative charged excitons. We investigate the origins of spectral broadening, identifying them in spectral diffusion at low temperature and phonon-interaction at higher temperature, the presence of fine interactions between electron and hole spin, and a relevant heavy-hole/light-hole mixing. We interpret the level filling with a simple Poissonian model reproducing the power excitation dependence of the s-shell excitons. These results are relevant for the further improvement of this class of quantum emitters and their exploitation as single photon sources for low density samples as well as for efficient lasers for high density samples.

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator, triggering various inflammatory conditions, including eosinophil activation and recruitment. Despite the unclear mechanism underlying the formation and maintenance of nasal polyp in chronic rhinosinusitis with nasal polyps (CRSwNP), there is strongly indication of its association with type 2 inflammation. This study aimed to quantify PAF-associated gene expression, examining enzymes involved in PAF synthesis (lysophosphatidylcholine acyltransferase 1 (LPCAT1), LPCAT2, LPCAT3, and LPCAT4), and PAF degradation (PAF acetylhydrolases 1 B2 (PAFAH1B2), PAFAH1B3, and PAF acetylhydrolases 2 (PAFAH2)), and PAF receptor (PTAFR). Transcriptomic analysis encompassed CRSwNP, including eosinophilic CRS (ECRS) (n=9), nonECRS (n=8), and a subgroup of ECRS with aspirin exacerbated respiratory disease (Asp) (n=3) based on the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria. Gene expression profiles from nasal polyps in CRSwNP patients and the uncinate process in normal subjects (controls) (n=6) were analyzed using bulk RNA barcoding and sequencing (BRB-seq). Hierarchal analysis, utilizing the average linkage method with iDEP1.1, clarified the relationship between Differentially Expressed Genes (DEG) expressions and cluster formation. Two clusters (cluster 1 (n=11) and cluster 2 (n=9)) of CRSwNP divided by hierarchal analysis showed distinct gene expression profiles in the specific pathway of “cytokine-cytokine receptor interaction” in KEGG pathway and upregulated type 2 inflammatory gene expression in cluster 2. In CRSwNP subclassification of ECRS, nonECRS, and Ctrl, PTAFR was only upregulated in ECRS and nonECRS. In cluster analysis, cluster 1 showed significant downregulation of LPCAT2 and upregulation of PTAFR expression, while cluster 2 showed significant upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. These findings suggest that cluster 2, characterized by severe type 2 inflammatory gene expression, manifest a prominent PAF-associated pathophysiology. Understanding this high PAF-associated pathophysiology in cluster 2 could provide valuable insights into the treatment and management of CRSwNP.

We have previously clarified that the strongly electron-withdrawing CF3 group nicely affected the base-mediated proton migration reactions of CF3-containinig propargylic or allylic alcohols to afford the corresponding a,b-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols, followed by isomerization to the corresponding allyl vinyl ethers, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner where a palladium catalyst attained an excellent diastereoselectivity.

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.

Prediction of tumor consistency is valuable for planning transsphenoidal surgery for pituitary adenoma. A prospective study was conducted involving 49 participants with pituitary adenoma to determine whether quantitative pharmacokinetic analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is useful for predicting consistency of adenoma. Pharmacokinetic parameters in the adenomas including volume of extravascular extracellular space (EES) per unit volume of tissue (ve), blood plasma volume per unit volume of tissue (vp), volume transfer constant between blood plasma and EES (Ktrans), and rate constant between EES and blood plasma (kep) were obtained. The pharmacokinetic parameters and the histologic percentage of collagen content (PCC) were compared between soft and hard adenomas using Mann–Whitney U test. Pearson’s correla-tion coefficient was used to correlate pharmacokinetic parameters with PCC. Hard adenomas showed significantly higher PCC (44.08 ± 15.14% vs. 6.62 ± 3.47%, p < 0.01), ve (0.332 ± 0.124% vs. 0.221 ± 0.104%, p = 0.02), and Ktrans (0.775 ± 0.401/min vs. 0.601 ± 0.612/min, p = 0.02) than soft adenomas. Moreover, a significant positive correlation was found between ve and PCC (r = 0.601, p < 0.01). The ve derived using DCE-MRI may have predictive value for consistency of pituitary adenoma.

When designing rule-based dialogue systems, the need for elaborate design by the designer is a challenge for dialogue systems. One way to reduce the cost of creating content is to generate utterances from data collected in an objective and reproducible manner. This study focuses on rule-based dialogue systems using survey data, and more specifically on opinion dialogue where the system models the user. In opinion dialogue, there has not been much study of topic transition methods for modeling users while maintaining their motivation for dialogue. To model them, we adopted information content. Our contribution includes the design of a rule-based dialogue system that does not require elaborate design. We also reported an appropriate topic transition method based on information content. This is confirmed by the influence of the user's personality characteristics. The content of questions can give the user a sense of the system's intention to understand them. We also reported the possibility that the system's rational intention contributes to the user's motivation for dialogue with the system.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Hundreds of thousands of people living along the Yatsushiro Sea coast have been exposed to methylmercury from the contaminated water of the Chisso factory in Minamata. Methylmercury causes neurological deficits in the cerebrum and cerebellum, with symptoms of ataxia, dysarthria, and visual field constriction in severe cases, but the most common symptom of a milder disorder is somatosensory disturbance due to parietal lobe damage. We investigated the characteristics of the somatosensory disturbances in detail by studying subjective complaints, neurological findings, and quantitative sensory tests in 197 residents (63.2 ± 10.7 years old) from contaminated areas exposed to methylmercury from seafood and 130 residents (63.7 ± 9.3 years old) from control areas. The most commonly affected sensory modalities were superficial peripheral touch and pain in the extremities, followed by two-point discrimination and deep senses, and in the most severe cases, full-body sensory dysfunction and impairment of all sensory submodalities. Although the severity of the sensory submodalities correlated with each other, there was almost no correlation between the severity of these submodalities and indices of peripheral nerve conduction studies, suggesting that the primary cause of the sensory deficits was damage to the central nervous system. The health effects of chronic methylmercury toxicosis can be elucidated by a detailed examination of sensory deficits.

Pistol shrimps generate cavitation bubbles. Cavitation impacts due to bubble collapses are harmful phenomena, as they cause severe damage to hydraulic machineries, such as pumps and valves. However, cavitation impacts can be utilized for mechanical surface treatment to improve the fatigue strength of metallic materials, which is called “cavitation peening”. Through conventional cavitation peening, a cavitation is generated by a submerged water jet, i.e., a cavitating jet or a pulsed laser. The fatigue strength of magnesium alloy when treated by the pulsed laser is larger than that of the jet. In order to drastically increase the processing efficiency of cavitation peening, the mechanism of pistol shrimp (specifically when used to create a cavitation bubble), i.e., alpheus randalli, was quantitatively investigated. It was found that a pulsed water jet generates a cavitation bubble when a shrimp snaps its claws. Furthermore, two types of cavitation generators were developed, namely, one that uses a pulsed laser and one that uses a piezo actuator, and this was achieved by mimicing a pistol shrimp.

The Japanese city presents a certain number of peculiarities in the organization of its physical space (weak zoning regulations, fast piecemeal destruction/reconstruction of buildings and blocks, high compacity, incremental reorganization). Compared to countries where urban fabrics are more perennial and easily distinguishable (old centers, modern planned projects, residential areas, etc.), in Japanese metropolitan areas we often observe higher heterogeneity and more complex spatial patterns. Even within such a model, it should be possible to recognize the internal organization of the physical city. The aim of this paper is thus to study the spatial structure of the contemporary Japanese city, generalizing on the case study of Osaka and Kobe. In order to achieve this goal, we will need to identify urban forms at different local scales (building types, urban fabrics) and to analyze them at a wider scale to delineate morphological regions and their structuring of the overall layout of the contemporary Japanese city. Several analytical protocols are used together with field observations and literature. The results, and more particularly the building and urban fabrics types and their location within the Osaka-Kobe metropolitan area, are interpreted in the light of Japanese history and model of urbanization. A synoptic graphical model of an urban morphological structure based upon Osaka is produced and proposed as an interpretative pattern for the Japanese metropolitan city in general.

Holographic projection is a simple projection because it enlarges or reduces reconstructed images without using a zoom lens. However, one major problem associated with this projection is the deterioration of image quality as the reconstructed image enlarges. In this paper, we propose a time-division holographic projection, in which the original image is divided into blocks and the holograms of each block are calculated. Using a digital micromirror device (DMD), the holograms were projected at high speed to obtain the entire reconstructed image. However, the holograms on the DMD need to be binarized, thereby causing uneven brightness between the divided blocks. We correct this by controlling the displaying time of each hologram. Additionally, combining both the proposed and noise reduction methods, the image quality of the reconstructed image was improved. Results from the simulation and optical reconstructions show we obtained a full-color reconstruction image with reduced noise and uneven brightness.

This observational pilot study aimed to investigate continuous glucose monitoring (CGM) metrics in older Japanese patients with type 2 diabetes mellitus (T2DM) using a continuous glucose monitoring system (FreeStyle Libre Pro) for CGM during the first tirzepatide administration and compared the glycemic control measures before and after the treatment. The four patients re-ported a mean age of 79.5 years (standard deviation [SD]: 5.8), mean body mass index of 24.63 kg/m2 (SD: 4.7), and mean glycated hemoglobin level of 9.1% (SD: 2.1). After tirzepatide treatment, the mean of time in range, time above range, and time below range changed from 53.2% to 78.9% (p = 0.041), 45.8% to 19.7% (p = 0.038), and 1.0% to 1.5% (p = 0.206), respectively. Improved hy-perglycemia reduced the oral glucose medication in two cases and decreased the frequency of insulin injections in two cases. All cases demonstrated the CGM index improvement during short-term observation despite some differences. Future studies need to investigate the long-term impact on functional prognosis, safety, and tolerability, especially in nonobese older Asian pa-tients, to elucidate the potential benefits of tirzepatide. However, tirzepatide-associated robust glycemic improvement may simplify and reduce diabetes treatment-associated complication in older patients with T2DM.

Sterepinic acids A–C (1–3), new carboxylic acids with two primary alcohols, have been isolated from a fungal strain of Stereum sp. OUPS-124D-1 attached to the marine alga Undaria pinnatifida. Dihydro-1,5-secovibralactone (4), a new vibralactone derivative, was isolated from the same fungal metabolites together with known vibralactone A (5), and 1,5-secovibralactone (6). The planar structures of these compounds have been elucidated by spectroscopic analyses using IR, HRFABMS, and NMR spectra. To determine the absolute configuration of the compounds, we used the phenylglycine methyl ester (PGME) method. These compounds exhibited less activity in the cytotoxicity assay against cancer cell lines.

Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, and most of them recur within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment and prognosis in patients with HNSCC are associated, investigations are insufficient. In this study, patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n = 500). A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing early recurrence (ER) (recurrence within 2–6 months) and late recurrence (LR) (recurrence after 7 months), respectively. There were two independent risk factors for poor prognosis in the multivariate analyses: ER (hazard ratio [HR] = 3.200, 95% confidence interval [CI] = 1.570–6.521, p = 0.001) and no radiotherapy (HR = 0.374, 95% CI = 0.191–0.733, p = 0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in patients. During the selection of treatment for patients with recurrence, the recurrent area, initial treatment content, and strategy of changing salvage therapy depending on the recurrence status should be considered.

Gender recognition is trivial for physiotherapist, but it is considered a challenge for computers. The electromyography (EMG) and heart rate variability (HRV) were utilized in this work for gender recognition during the stepping exercise using a stepper. The relevant features were extracted and selected. The selected features were then fused to automatically predict gender recognition. However, the feature selection for gender classification became a challenge to ensure better accuracy. Thus, in this paper, a feature selection approach based on both the performance and the diversity between the two features from the rank-score characteristic (RSC) function in a combinatorial fusion approach (CFA) was employed. Then, the features from the selected feature sets were fused using a CFA. The results were then compared with other fusion techniques such as naive bayes (NB), decision tree (J48), k-nearest neighbor (KNN) and support vector machine (SMO). Besides, the results were also compared with previous researches in gender recognition. The experimental results showed that the CFA was efficient for feature selection. The fusion method was also able to improve the accuracy of the gender recognition rate. The CFA provides much better gender classification results which is 94.51% compared to Nazarloo's work (90.34%) and other classifiers.

The clinical significance of carbon-ion radiotherapy (CIRT) for adenocarcinoma (AC) of the uterine cervix has been assessed in several single-institutional studies. To validate the significance, we conducted a multi-institutional survey of CIRT for locally advanced AC (LAAC) of the uterine cervix. We retrospectively analyzed the clinical outcomes of patients with stage IIB–IVA LAAC of the uterine cervix who underwent chemo-CIRT or CIRT alone between April 2010 and April 2016. Patients received 74.4 Gy (relative biological effectiveness [RBE]) in 20 fractions of CIRT or 55.2 Gy (RBE) in 16 fractions of CIRT plus 3 sessions of brachytherapy. Patients aged ≤70 years with adequate bone marrow and organ function were administered cisplatin weekly (40 mg/m2 per week for up to 5 weeks). Fifty-five patients were enrolled in this study. The median follow-up period was 67.5 months. The 5-year overall survival (OS) and local control (LC) rates were 68.6% and 65.2%, respectively. Multivariate analysis showed that the initial tumor response within 6 months was significantly associated with LC and OS. The present study represents promising outcomes of CIRT or chemo-CIRT for LAAC of the uterine cervix, especially in the cases showing initial rapid regression of the tumor.

To cope the high glycemic variability (GV) is crucial in the management of multiple daily insulin (MDI) in diabetes. We compared the effect of low dose metformin 750mg/d adding vildagliptin 100mg/d (DPP4+LMET) or the high dose metformin 1500mg/d (HMET), in type 2 diabetes (T2D) with MDI, evaluating GV by continuous glucose monitoring (CGM). Single center, open-label, 12 weeks - 2 period crossover design. Twenty T2D with inadequately controlled (7.0% <HbA1c ≦9.0%) with MDI + LMET were enrolled. Primary endpoints were GV and hypoglycemia derived from CGM performed after each 12 weeks treatment periods. There was no significant difference in HbA1c, body weight changes, total daily dose of insulin. DPP4+LMET compared to the HMET, significantly reduced the calculated GV value, mean (7.15±1.3 vs 7.82±1.6, p<0.05), standard deviation (1.78±0.55 vs 2.27±1.11, p=0.03), continuous overlapping net glycemic action (6.44±1.28 vs 7.12±1.69, p<0.05), J-Index (26.7±11.0 vs 34.9±19.8, p<0.05), high blood glucose index (3.01±1.96 vs. 6.73±4.85, p=0.02), and mean amplitude of glycemic excursions (4.53±1.35 vs 5.50±2.34, p=0.03). The GV metrics with hypoglycemia and nocturnal hypoglycemia were not significantly different. DPP4+LMET decreased GV associated with hyperglycemia. Adding DPP4 inhibitor to the lower dose of metformin is an alternative approach to the stable GV in MDI.

The blood–brain barrier (BBB) plays pivotal roles in synaptic and neuronal functioning by sealing the space between adjacent microvascular endothelial cells. BBB breakdown is present in patients with mild cognitive impairment (MCI) or Alzheimer disease (AD). Claudin-5 (CLDN-5) is a tetra-spanning protein essential for sealing the intercellular space between adjacent endothelial cells in the BBB. In this study, we developed a blood-based assay for CLDN-5 and investigated its diagnostic utility by using 100 cognitively normal (control) subjects, 100 patients with MCI, and 100 patients with AD. Plasma CLDN-5 levels were increased in patients with AD (3.08 ng/mL) compared with controls (2.77 ng/mL). Plasma levels of phosphorylated tau (pTau181), a biomarker of pathological tau, were elevated in patients with MCI or AD (2.86 and 4.20 pg/mL, respectively) compared with control subjects (1.81 pg/mL). In patients with MCI or AD, plasma levels of CLDN-5—but not pTau181—decreased with age, suggesting some age-dependent BBB changes in MCI and AD. These findings suggest that plasma CLDN-5 may a potential biochemical marker for the diagnosis of MCI and AD.

Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. The mechanism, at the functional protein level, of the resistance to therapy of TCL has not yet been well clarified. To comprehensively clarify the mechanism, we first reviewed the literature, as mentioned in the Introduction section, on 22 types of representative functional proteins reported as being potentially associated with treatment resistance, mainly in hematologic tumors. Next, we retrospectively analyzed the tumor cell expressions of these 22 functional proteins in 16 randomly selected patients with TCL who had received CHOP (cyclophosphamide, hydroxyl doxorubicin, oncovin, and prednisolone) therapy as first-line treatment. As a result, we propose a new three-group prognostic classification of TCL (the TCL Urayasu Classification) based on the mechanism of resistance to treatment of these tumors. The study subjects included 7 patients (44%) with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 6 patients (38%) with angioimmunoblastic T-cell lymphoma (AITL), and 3 patients (19%) with anaplastic large T-cell lymphoma (ALCL). Immunohistochemistry was performed in paraffin-embedded tumor tissue sections prepared from these patients as antigens using antibodies against the 22 previously reported treatment-resistance-related proteins to determine the tumor cell expression statuses of these proteins. Log-rank test was performed to compare the overall survival (OS) after CHOP therapy of the patients showing positive and negative immunostaining for these proteins, as well as among patients grouped based on other factors. Overall, the median OS of the TCL patients was about 33.5 months. When compared by the disease type, the prognosis was found to be worse in the order of ALCL, AITL, and PTCL. A multivariate analysis showed that expression of glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with shortened survival. No significant difference was observed for the conventional poor prognostic factors: high-risk International Prognostic Index (IPI) and high-risk Prognostic Index for peripheral T-cell lymphoma, unspecified (PTCL-U) (PIT). However, when GRP94 was combined with six other factors, listed below, as survival-shortening factors, significant differences were observed. The 6 factors were 1) programmed cell death-ligand 1 (PD-L1) and 2) programmed cell death 1 (PD-1), which are involved in immune surveillance; 3) aldo-keto reductase family 1 member C3 (AKR1C3), which is an enzyme that inactivates HO (hydroxyl doxorubicin [H] and oncovin [O]) of CHOP; 4) P53, a tumor suppressor; 5) Glucose-regulated protein 78 (GRP78), an ER stress protein; 6) thymidine phosphorylase (TP), which is an enzyme involved in thymidine catabolism. Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (group with a relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (group with a poor prognosis): GRP94-positive, plus expression of 2 of the 6 aforementioned factors (n = 5; median OS, 25 months; p > 0.05); and Group 3 (group with a very poor prognosis): GRP94-positive, plus expression of at least 3 of the 6 aforementioned factors (n = 5; median OS, 10 months; p < 0.01). Thus, the TCL Urayasu prognostic classification is a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. Accumulation of more cases and further analyses are expected in the future to enable clinical application, such as use of a stratified treatment approach and treatment using inhibitors.

Platelet polyphosphate (polyP) can be conveniently quantified by a recent methodological breakthrough using 4′,6-diamidino-2-phenylindole (DAPI). However, the preservation of these biological samples has not yet been standardized. In a preliminary study, possible protocols were screened, and passed protocols were further tested in this study. Pure-platelet-rich plasma (P-PRP) samples and washed platelet suspensions were prepared using blood obtained from non-smoking, healthy male donors and fixed with ThromboFix for 24 h at 4 °C. Mass polyP levels were determined using a fluorometer at wavelengths of 425 and 525 nm. Platelet polyP levels were normalized to platelet counts. Statistical analyses were performed using non-parametric tests. In platelet suspension maintained in fixed conditions at 4 °C (control), platelet polyP levels significantly decreased by 20% at and after 7 days. In contrast, platelet polyP levels in both P-PRP and washed platelet suspensions were maintained without significant reduction for up to 6 weeks by removing ThromboFix after fixation and subsequent freezing in pure water at −80 °C. Owing to the low specificity of DAPI binding and the wavelengths used, fluorometric polyP quantification is often interfered with. Our validated protocols will enable long-term preservation and high-throughput polyP quantification and could be applied to relatively large cohort studies.

Contrast-enhanced ultrasonography (CEUS) is useful for evaluation of the hemodynamics of hepatic tumors and surrounding he-patic parenchyma in real time. CEUS with intravenous contrast administration is well established for evaluation of hepatocellular carcinoma (HCC). On the other hand, intra-arterial (transcatheter) CEUS (IAUS) is an emerging technique that allows more selective evaluation of the arterial supply to the tumor. IAUS was performed by administration of Sonazoid® through the microcatheter and imaging of the area of the target lesion with a dedicated, contrast-specific technique. Sonazoid® (0.5 ml diluted with 49.5 ml of distilled water) was used as the contrast medium in IAUS. The diluted Sonazoid® was introduced into the feeding artery by in-termittent injection of 0.3-1.0 ml through a microcatheter placed in the artery and flushing with saline at the same flow rate. We report the three cases in which IAUS was useful in transarterial chemoembolization (TACE) for HCC. Two cases were performed TACE for hepatic metastasis. In any cases, plain computed tomography (CT) after TACE showed accumulation of Lipiodol® only in the metastases. One case was suspected having HCC rupture and urgent abdominal angiography was performed. IAUS was performed frequently to reduce the amount of iodinated contrast agent as much as possible because of renal failure. Concomitant use of IAUS enabled reduction of the amount of contrast agent.

Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Recently, others have found that diverse cell types, including EVTs, produce exosomes filled with molecular cargo (mainly proteins and RNAs) that can be transported to other cells and organs both locally and long-range. The cargo delivered by exosomes can signal to and modify the receiving cells and their environment, and EVT-derived exosomes may influence the pathogenesis of PE. Because the risk of PE is actually decreased by cigarette smoking, we considered the possibility that nicotine, a critical component of tobacco smoke, might protect against PE by modifying the content of exosomes from EVTs. In this study, we applied nicotine stimulation to cultured EVTs and subjected their secreted exosomes to proteomic analysis. We identified many proteins whose abundance in exosomes was modified by nicotine treatment of the donor EVTs, and we used bioinformatic annotation and network analysis to select five key hub proteins with potential roles in the pathogenesis or prevention of PE.

This paper describes the proposal and development of a proof of concept (PoC) for a data logger system designed for operation and fault detection in bench testing of combustion engines. The main objective was to develop a data logger system that collects data on vibration, sound, temperature, and CO2 levels to identify ignition and combustion faults, thereby contributing to reducing greenhouse gas emissions (GHG). The paper presents (i) the proposal and development and (ii) the open-source code: proof of concept for a data logger system focused on detecting faults and monitoring the operational condition of benchtop combustion engines. The results indicate the feasibility of the PoC for data acquisition and dataset creation for Research and Development purposes.

Abstract: Targeted ubiquitination and proteasomal degradation regulates various cellular pathways, and the discovery that CPT induced rapid proteasomal degradation of topoI is the primary mechanism of CPT resistance was novel and compelling. CPTs are used extensively to treat various solid tumors like colorectal, gastric, pancreatic, ovarian and small cell lung cancer. The response rate is low and the classical mechanisms of drug resistance are yet to be validated. Remarkably, CPT resistant cells degrade topoI rapidly by UPP and recently we’ve published the molecular determinants of this pathway. To further understand the UPP mediated CPT resistance mechanism we used targeted proteasome prohibition by ixazomib (MLN9708) to stabilize topoI and determine its impact on CPT resistance. CPT resistant and sensitive cancer lines were both treated with ixazomib in combination with CPT. The CPT induced rate of topoI degradation, and its stabilization by ixazomib, was visualized and estimated by immunohistochemistry, immunofluorescence and immunoblotting assays, MTT and subG1 assays provided the drug sensitivity. Our results demonstrate that cells that degrade topoI rapidly are very resistant to CPT, and ixazomib significantly inhibits CPT induced topoI degradation. Notably, inhibition of proteasomal degradation by ixazomib overcomes the drug resistance and sensitizes the cells for CPTs.

Abstract Background Context Pelvic ring fractures are becoming more common in the aging population and can prove to be fatal, having mortality rates between 10% and 16%. Stabilization of these fractures is challenging and often require immediate internal fixation. Therefore, it is necessary to have a biomechanical understanding of the different fixation techniques for pelvic ring fractures. Methods A previously validated three-dimensional finite element model of the lumbar spine, pelvis, and femur was used for this study. A unilateral pelvic ring fracture was simulated by resecting the left side of the sacrum and pelvis. Five different fixation techniques were used to stabilize the fracture. A compressive follower load and pure moment was applied to compare different biomechanical parameters including range of motion (contralateral sacroiliac joint, L1-S1 segment, L5-S1 segment), and stresses (L5-S1 nucleus stresses, instrument stresses) between different fixation techniques. Results Transiliac -trans sacral screw fixation at S1 and S2 showed the highest stabilization for horizontal and vertical displacement at the sacral fracture site and reduction of contralateral sacroiliac joint for bending and flexion range of motion by 165% and 121%, respectively. DTSF (Double transiliac rod and screw fixation) model showed highest stabilization in horizontal displacement at the pubic rami fracture site, while the L5_PF_W_CC (L5-Ilium posterior screw fixation with cross connectors) and L5_PF_WO_CC ( L5-Ilium posterior screw fixation without cross connectors) showed higher rod stresses, reduced L1-S1 (approximately 28%), and L5-S1 (approximately 90%) range of motion. Conclusions Longer sacral screw fixations were superior in stabilizing sacral and contralateral sacroiliac joint range of motion. Lumbopelvic fixations displayed a higher degree of stabilization in the horizontal displacement compared to vertical displacement of pubic rami fracture, while also indicating the highest rod stresses. When determining the surgical approach for pelvic ring fractures, patient-specific factors should be accounted for to weigh the advantages and disadvantages for each technique.

Background: The number of young Japanese Brazilians, who are return migrants with Japanese ancestral roots, is increasing rapidly in Japan. However, the characteristics of their mental health and the relation between mental health and a complex ethnic identity remains unclear. Methods: This cross-sectional study compared 25 Japanese-Brazilian high school students with 62 Japanese high school students living in the same area. Research using self-report questionnaires on mental health, help-seeking behavior tendencies, and ethnic identity was conducted. The Japanese-Brazilian group was also divided into high and low ethnic identity groups, and their mental health conditions were compared. Results: The Japanese-Brazilian group had significantly poorer mental health conditions and lower ethnic identities than the Japanese group and were less likely to seek help from family members and close relatives. Among the Japanese Brazilians, those with low ethnic identity had significantly poorer mental health than those with high ethnic identity. Conclusions: Young Japanese Brazilians may face conflicts of ethnic identity that can disturb their mental health. To build an inclusive society, the establishment of community services to support mental health and to help return migrants develop their ethnic identity is essential.

Background: In schizophrenia (SZ), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. Methods: Using data obtained through an internet survey, 210 patients with SZ or MDD were selected using propensity score matching based on their demographic information and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each disease group. Invariances of the mediation model across the two groups were then analyzed. Results: The SZ and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. Conclusion: The role of social cognition in patients with chronic depression was similar to that in schizophrenia. Social cognition could be a common endophenotype for various psychiatric disorders.

To investigate proposed ferromagnetic fluctuations in the single-layer Bi-2201 and La-214 high-Tc cuprates, we performed magnetization and electrical-resistivity measurements using single-layer Tl-2201 cuprates Tl2Ba2CuO6+d as well as La-214 La2-xSrxCuO4 in the heavily overdoped regime. Magnetization of Tl-2201 exhibited the tendency to be saturated in high magnetic fields at low temperatures, suggesting the precursor behavior toward the formation of a ferromagnetic order. It was found that the power of temperature n obtained from the temperature dependence of the electrical resistivity is ~ 4/3 and ~5/3 for Bi-2201 and La-214, respectively, and is ~ 4/3 at high temperatures and ~5/3 at low temperatures in Tl-2201. These results suggest that two-dimensional ferromagnetic fluctuations exist in Tl-2201 at high temperatures and Bi-2201 and that three-dimensional ferromagnetic fluctuations exist in Tl-2201 at low temperatures and La-214. The dimensionality of ferromagnetic fluctuations is understood in terms of the dimensionality of the crystal structure and the bonding of atoms in the blocking layer.

USP21, a member of the ubiquitin protease family, plays a vital role in various biological functions. However, the effects of USP21 dysfunction have yet to be fully understood. Here, we generated Usp21 knockout (KO) mice and conducted microarray to identify genes that Usp21 regulates. Its results raised several genes based on their biological characteristics, and RT-qPCR confirmed their expression. KO mice exhibited significant elevations in the expression of the genes Fabp7 and Nlrc5, which play a role in lipid metabolisms, compared to wild-type mice. Blood tests showed no impairment of liver function but did reveal elevated levels of total cholesterol and free fatty acids in KO mice compared to wild-type mice. These data suggest that Usp21 may play roles in lipid metabolism associated with Fabp7 and Nlrc5. To clarify the involvement of USP21 in human hypercholesterolemia, we examined single nucleotide polymorphisms (SNPs) around USP21 in non-hypercholesterolemic and hypercholesterolemic outpatients. We found that the rs11421 SNP downstream of USP21 was associated with hypercholesterolemia. These data suggest that USP21 plays a role in mice and human lipid metabolism and that its polymorphism may be a diagnostic marker for human hypercholesterolemia.

This study attempts to investigate a method for creating an index from mobility data that not only correlates with the number of people who relocate to a place but also has causal influence on the number of such individuals. By creating an index based on human mobility data, it becomes possible to predict the influence of urban development on future residential movements. In this paper, we propose a method called the travel cost method for multiple places (TCM4MP) by extending the conventional travel cost method (TCM). We assume that the opportunity cost of travel time on non-working days reflects the convenience and amenities of a neighborhood. However, conventional TCM does not assume that the opportunity cost of travel time varies according to the departure place. In this paper, TCM4MP is proposed to estimate the opportunity cost of travel time with respect to the departure place. We consider such estimation to be possible due to the use of massive mobility data. We assume that the opportunity cost of travel time on non-working days reflects the convenience and amenities of the neighborhood. Therefore, we consider that the opportunity cost of travel time has a causal influence on future residential mobility. In this paper, the validity of the proposed method is tested using the smart card data of public transportation in Western Japan. Our proposed method is beneficial for urban planners in estimating the effects of urban development and detecting the shrinkage and growth of a population.

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.

Ethyl loflazepate (EL) is a benzodiazepine derivative that has been reported to activate the gustatory cortex. Our department routinely uses EL as a first-line treatment for idiopathic and psychogenic taste disorders, although little has been reported in the literature with respect to patient outcomes, so we conducted a retrospective study examining its safety and efficacy. Between 2008 and 2020, 49 patients (14 males and 35 females; mean age, 62.1 years) were diagnosed with taste disorders and received EL as their only treatment for &gt;14 days. Severity of taste disorder was evaluated using the paper disc method by Sakai et al [7], and treatment efficacy was evaluated using the Visual Analogue Scale, wherein patients gave subjective ratings for their symptoms (reductions by &gt;50% after administration of EL for 4 weeks were defined as mprovements). Results showed that the improvement rates for patients with idiopathic and psychogenic taste disorders were 55% and 70%, respectively. Additionally, the majority (78%) improved within 2 weeks, and side effects were mild (seven cases of sleepiness and one case of dizziness). We conclude that EL is an appropriate first-line medication for patients with idiopathic and psychogenic taste disorders.

A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium β-hydroxy-β-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight was significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p &lt; 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

This study investigates the transition from surface to underground mining at the Sepon Gold mine. The stability of surface slopes is assessed prior to commencing underground operations. Stope mining is adopted based on ore body characteristics and geological features. Finite element numerical analysis, employing the Generalized Hoek-Brown criterion, evaluates slope stability for surface slopes and opening stopes. The pit design comprises a 70° slope angle, 20 m height, and 10-15 m safety berm, meeting stability requirements with a factor of safety of 2.46. Underground mining design includes a 62° ore body dip, 50 m thick crown pillar to prevent surface subsidence, and 5 m wide, 5 m high stopes. Sill pillars are left for support after each level excavation. Rock bolts are employed in specific stope areas where is necessary, with continuous monitoring for surface deformation. The study analyzes the influence of stope sizes on pit wall and pit bottom stability, identifying slope failures near the hanging wall close to the pit bottom during underground mining. A slight increase in the displacement zone is observed on the upper crest of the top footwall. Overall, the findings demonstrate successful stability in the transition from surface to underground mining at Sepon Gold mine.

Quartz Crystal Microbalance (QCM) is a well-known method to measure the mass of ligands bound to receptor-covered surfaces in various fields, ranging from materials science to biology. Actin molecule is essential in various cellular processes through its function of monomer-to-filament polymerization, forming a double-stranded filament with a 75 nm pitch. In this study, QCM was applied to measure the physical properties of actin, finding that the frequency shifted negatively when monomeric actin bound to the QCM surface, whereas the frequency shifted positively when filaments bound. Using fluorescence light microscopic observations, we have examined whether negative and positive frequency shifts originated from their length. In order to control this process, a severing protein, fragmin was used to change the length of actin filament. When the average length of filaments shortened, the magnitude of positive shift decreased in a concentration-dependent manner. However, shorter filaments showed a negative frequency shift depending on their concentration, showing that the weight derived from the loaded concentration and the function derived from actin polymerization dynamics are detectable. Interestingly, the transition from positive to negative occurred when the average length of actin was ~33 nm, or approximately equal to the half-pitch of filaments. Thus, actin filaments can serve as an excellent standard to measure the mechanical properties of biopolymers. Our results show that the QCM sensor could be both a "weight" and a "function" sensor of biomolecules in vitro.

This study aimed to develop a Laotian adolescent version of the Center for Epidemiologic Studies Depression Scale (CES-D), determine its reliability and validity, and examine its factorial properties. The study targeted at 7,554 students in lower secondary schools and teacher training colleges in Lao PDR. Self-administered questionnaires were collected from 2012 to 2014. Exploratory factor analysis performed in three age groups using the weighted least square mean and variance adjusted estimation with robust maximum likelihood methods. The factor structure for each age group was the same; therefore, data from the full sample were analyzed further. The model was then tested by confirmatory factor analysis. A 2-factor model was determined as a common model among the age groups by using paralleled analysis. We determined a best-fitting structure comprising two factors: “Negative affect” and “Positive affect.” The Cronbach’s alpha was .81. “Effort” items loaded on the “Somatic and retarded activity” factor in the original model but loaded on the “Positive affect” factor in the adolescent model. “Depressed affect,” “Somatic and retarded activity,” and “Interpersonal” items were combined into the “Negative affect” factor in the adolescent model.

A warning sign for impending cardio-vascular events is not fully established. In the process to plaque rupture, formation of vulnerable plaque is important, and oxidized cholesterols play important role in its progression. Furthermore, the significance of vasa vasorum penetrating medial smooth muscle layer and rich in atheromatous lesion should be paid attention. Cardio-ankle vascular index (CAVI) is new arterial stiffness index of the arterial tree from the origin of the aorta to the ankle. CAVI reflects functional stiffness in addition to structural stiffness. Rapid rise of CAVI means medial smooth muscle cell contraction, and strangling vasa vasorum. We reported rapid rise of CAVI in peoples after big earthquake, following high frequency of cardiovascular events. And we met several cases who showed rapid rise of CAVI a few weeks or months before suffering cardiovascular events. To explain these sequences of events, we proposed a hypothesis; A rapid rise of CAVI means medial smooth muscle contraction, strangling vasa vasorum, leading ischemia, necrosis of vulnerable plaque, then, the plaque ruptures. In individuals having high CAVI, further rapid rise of CAVI might be a warning sign for impending cardiovascular events. In such case, treatments to decrease CAVI had better to be taken soon.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.

Background: Carnitine deficiency is common in patients on dialysis. Serum free carnitine concentration is significantly lower in patients on hemodialysis (HD) than in healthy individuals. However, there are few reports on serum free carnitine concentration in patients on peritoneal dialysis (PD). Methods: We examined serum concentrations of total, free, and acylcarnitine and the acylcarnitine/free carnitine ratio in 34 PD and 34 age-, sex-, and dialysis duration-matched HD patients. We investigated the prevalence of carnitine deficiency and clinical factors associated with carnitine deficiency in the PD group. Results: Prevalence of carnitine deficiency was 8.8% in the PD group and 14.7% in the HD group (P = 0.45). High risk of carnitine deficiency was found in 79.4% of the PD group and 85.3% of the HD group (P = 0.52). Carnitine insufficiency was found in 82.3% of the PD group and 88.2% of HD group (P = 0.49). Multivariate analysis revealed that duration of dialysis and age were independent predictors of serum free carnitine level in the PD group. Conclusions: The prevalence of carnitine deficiency, high risk of carnitine deficiency, and carnitine insufficiency in PD patients was 8.8%, 79.4%, and 82.3%, respectively. These rates were comparable to those in patients on HD.

Background and Objectives: A novel synthetic self-assembling peptide, PuraStat, has been introduced as a hemostatic agent. This case series aimed to evaluate the clinical efficacy of PuraStat for gastrointestinal bleeding during emergency endoscopy. Cases: Twenty-five patients with gastrointestinal bleeding who had undergone emergency endoscopy with PuraStat between August 2021 and December 2022 were retrospectively examined. Six patients were receiving antithrombotic agent, and ten patients with refractory gastrointestinal bleeding had undergone at least one endoscopic hemostatic procedure. The breakdown of bleeding was gastroduodenal ulcer/erosion in 12 cases, bleeding after gastroduodenal or colorectal endoscopic resection in 4 cases, rectal ulcer in 2 cases, postoperative anastomotic ulcer in 2 cases, and gastric cancer, diffuse antral vascular ectasia, small intestinal ulcer, colonic diverticular bleeding, and radiation proctitis in each case. The method of hemostasis was only PuraStat application in six cases, and hemostasis in combination with high-frequency hemostatic forceps, hemostatic clip, argon plasma coagulation, and hemostatic agents (i.e. thrombin) in the remaining cases. Rebleeding was observed in three cases. Hemostatic efficiency was observed in 23 cases (92%). Conclusions: PuraStat has the expected hemostatic effect on gastrointestinal bleeding during emergency endoscopy. The use of PuraStat should be considered in emergency endoscopic hemostasis of gastrointestinal bleeding.

Seirogan, a wood creosote, is a nonprescription drug used to treat diarrhea. However, reports of its clinical use are rare. Here, we report on the efficacy of wood creosote (3 capsules daily) for the alleviation of diarrheal symptoms in 148 patients from 10 clinics in Japan. The wood creosote capsules were classified as remarkably effective (44 patients), effective (71 patients), and partially effective (13 patients) based on the degree of alleviation of diarrheal symptoms that were induced by a variety of causes. The antidiarrheal efficacy of the capsules did not differ between males and females, and young patients (21–30 years) showed greater improvement in diarrheal symptoms than did old patients (> 61 years). Although this report is based on the re-evaluation of old data that had been preserved by our company, the effectiveness and range of symptoms that were treatable with wood creosote has likely remained unchanged. To the best of our knowledge, this is the first public report on the clinical effectiveness of wood creosote capsules for the treatment of a wide range of diarrheal symptoms.

An application of CO2/HCO3--free solution (Zero-CO2) did not increase intracellular pH (pHi) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in the beating frequency (CBF) or bend distance (CBD, an index of amplitude). This study demonstrated that the pHi of the c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while that of the ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). Upon applying Zero-CO2, an extremely high level of pHi caused the pHi, CBF and CBD to decrease, while a low level of pHi caused them to increase. The high pHi was generated by a high rate of HCO3- influx via interac-tions between CAIV and Na+/HCO3- cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased the pHi and CBF, and Zero-CO2 application increased the CBF in S0859-treated c-hNECs. In conclusion, the interactions of CAIV and NBC maximize the HCO3- influx to increase the pHi in c-hNECs. This novel mechanism causes the pHi to decrease, leading to no increase in CBF and CBD in c-hNECs upon Zero-CO2 application, and appears to play a crucial role in maintaining pHi, CBF and CBD in c-hNECs periodically exposed to air (0.04% CO2) with respiration.

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-hour delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Most pivotal clinical trials in advanced non-small cell lung cancer (NSCLC) have excluded patients with poor performance status (PS), and data on the efficacy and safety of pharmacotherapy have not been fully accumulated. For NSCLC patients with PS 2 and without druggable genetic alterations, monotherapy with cytotoxic agents or carboplatin-based combination therapy is usually administered based on the results of several randomized trials. However, the evidence of cytotoxic chemotherapy for patients with PS 2 is insufficient, with limited efficacy and toxicity concerns. Immune checkpoint inhibitors (ICIs) are a promising treatment for patients with PS 2 because of lower incidence of severe toxicity compared to cytotoxic chemotherapy. Meanwhile, several reports suggest that anti-PD-1 antibodies monotherapy is less effective for patients with PS 2, especially for those with PS 2 caused by disease burden. Although the combination therapy of nivolumab and ipilimumab is a promising treatment option, there is a divergence in efficacy data between clinical trials. The standard of care for advanced NSCLC with PS 2 has not been established, and future therapeutic strategies should take into account the heterogeneity of the PS 2 population.

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.

Pyrrole-imidazole (PI) polyamides are novel gene silencers that strongly bind the promoter region of target genes in a sequence-specific manner to inhibit gene transcription. We developed a PI polyamide targeting human TGF-b1 (hTGF-b1). To develop PI polyamide targeting hTGF-b1 (Polyamide) as a practical medicine for progressive renal diseases, we examined the effects of Polyamide in two common marmoset models of nephropathy.We performed lead optimization of PI polyamides targeting hTGF-b1 by the dose-dependent inhibition of the PMA-stimulated expression of TGF-b1 mRNA in marmoset fibroblasts. Marmosets were housed with a 0.05% NaCl and magnesium diet and treated with cyclosporine A (CsA; 37.5 mg/kg/day, 8 weeks) to establish chronic nephropathy. Marmosets with nephropathy were treated with Polyamide (1 mg/kg/week, 4 weeks). We also established a unilateral urethral obstruction(UUO) model and examined the effects of Polyamide (1 mg/kg/week, 4 times) in marmosets.Histologically, the renal medulla from CsA-treated marmosets showed cast formation and interstitial fibrosis in the renal medulla. Immunohistochemistry showed strong staining of Polyamide in the renal medulla from CsA-treated marmosets.Polyamidetreatment (1 mg/kg/week, 4 times) reduced hTGF-b1 staining and urinary protein excretion in CsA-treated marmosets. Polyamide reduced the glomerular injury score (GIS) and tubulointerstitial injury score (TIS) in UUO kidneys from marmosets. Polyamide significantly suppressed the hTGF-b1 and Snail mRNA expressionin UUO kidneys from marmosets.PI polyamide effectively improved CsA- and UUO-associated nephropathy, indicating its potential application in the prevention of renal fibrosis in progressive renal diseases.

Chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer; however, CRT may cause post-treatment dysphagia. Transcutaneous electrical sensory stimulation (TESS), developed in recent years for swallowing rehabilitation, has been used at many medical facilities. Although TESS has been used for dysphagia in several fields, its safety and efficacy in patients with head and neck cancer remain to be clarified. Therefore, this study evaluated the safety of TESS in ten patients with head and neck cancers undergoing CRT. Swallowing rehabilitation intervention and TESS implementation were performed for all patients during CRT. Non-blood toxicity adverse events (AEs), such as dermatitis and mucositis, occurred during CRT; however, the severity was less than Grade 3. No patient experienced pain due to TESS. As survival time analysis using the Kaplan–Meier method for interferential current device implementation rates revealed a feasibility of 100% for up to 60 Gy and a feasibility of 78% for up to 70 Gy, it concludes that TESS was feasible until 70 Gy. This study confirmed the feasibility and safety of TESS in the head and neck region, even during CRT. Although the precise mechanism of TESS on dysphagia is not yet clear, its continued use has great potential for improving sensory disturbance.

To increase the prediction accuracy of positive oral food challenge (OFC) outcome during stepwise slow oral immunotherapy (SS-OIT) in children with hen’s egg (HE) allergy, we evaluated the predictive value of the combination of antigen-specific IgE (sIgE) with antigen binding-avidity and sIgG4 values. Sixty-three children with HE allergy undergoing SS-OIT were subjected to repeated OFC with HE. We measured the ovomucoid (OVM)-sIgE by ImmunoCAP or densely carboxylated protein (DCP) microarray, sIgG4 by DCP microarray, and the binding-avidity of OVM-sIgE defined as the level of 1/ IC50 (nM) measured by competitive binding inhibition assays. The OFC was positive in 37 (59%) patients undergoing SS-OIT. Significant differences in DCP-OVM-sIgE, CAP-OVM-sIgE, I/ IC50, DCP-OVM-sIgG4, the multiplication products of DCP-OVM-sIgE and binding-avidity of DCP-OVM-sIgE (DCP-OVM-sIgE/IC50) and DCP-OVM-sIgE/sIgG4 were compared between the negative and positive groups (p<0.01). Among them, the variable with greatest area under the receiver operating characteristic curve was DCP-OVM-sIgE/IC50 (0.84), followed by DCP-OVM-sIgE/sIgG4 (0.81). DCP-OVM-sIgE/IC50 and DCP-OVM-sIgE/sIgG4 are potentially useful markers for the prediction of positive OFC during HE-SS-OIT and may allow proper evaluation of the current allergic status in the healing process during HE-SS-OIT

To analyze the viral titers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) at the anterior nasal site (ANS) and nasopharyngeal site (NS), evaluate their virological dynamics, and validate the usefulness of a newly developed two antigen-detecting rapid antigen diagnostic test (Ag-RDT) that simultaneously detects SARS-CoV-2 and RSV using clinical specimens. This study included 195 asymptomatic to severely ill patients. Overall, 668 specimens were collected simultaneously from the ANS and NS. The cycle threshold (Ct) values calculated from real-time polymerase chain reaction were used to analyze temporal changes in viral load and evaluate the sensitivity and specificity of the Ag-RDT. The mean Ct values for SARS-CoV-2-positive, ANS, and NS specimens were 28.8, 28.9, and 28.7, respectively. The mean Ct values for RSV-positive, ANS, and NS specimens were 28.7, 28.8, and 28.6, respectively. SARS-CoV-2 and RSV showed the same trend in viral load, although the viral load of NS was higher than that of ANS. The sensitivity and specificity of the newly developed Ag-RDT were excellent in specimens collected up to 10 days after the onset of SARS-CoV-2 infection and up to 6 days after the onset of RSV infection.

Long-term care (LTC) settings are increasingly used for palliative care in Japan. This study aimed to assess the proportion of LTC settings that provide palliative care services for older clients with advanced dementia in Japan and the trends across the types of settings. A nationwide questionnaire survey was conducted between November 2022 and January 2023, targeting 1,000 geriatric hospitals (GHs), 1,000 geriatric health services facilities (GHSFs), and 1,000 home nursing care stations (HNCSs). The palliative care practices for older patients with advanced dementia and their families in the agencies were assessed. Less than half of the GHs supported family participation or the spiritual needs of their older clients with dementia, while many had access to pain and symptom assessments and analgesic prescriptions by physicians. Less than half the GHSFs used pain assessment tools, assessed and supported family caregivers' pain and distress, and supported family participation in palliative care. More than 80% of the HNCSs practiced most of the listed palliative care. Current palliative care practices for older adults with dementia vary among GHs, GHSFs, and HNCSs. This emphasizes the need for targeted approaches to improve the provision of palliative care for patients with dementia across LTC settings in Japan.

As a high-frequency carrier, the Terahertz (THz) wave is essential for achieving high-data-rate wireless transmission due to its ultra-wide bandwidth. Phase stabilization becomes crucial to enable phase-shift-based multilevel modulation for high-speed data transmission. We developed a Mach-Zehnder interferometric phase stabilization technique for photomixing, which has proved a promising method for phase-stable continuous THz-wave generation. However, this method faces inefficiencies in generating phase-modulated THz waves due to the impact of the phase modulator on the phase stabilization system. By photomixing, which is one of the promising methods for generating THz waves, the phase of the generated THz waves can be controlled in the optical domain so that the stability of the generated THz wave can be controlled by photonics technologies. Thus, we have devised a new phase stabilization approach using backward-directional lightwave, which is overlapped with the THz wave generation system. This study presents a conceptual and experimental framework for stabilizing the phase differences of optical carrier signals. We compare the optical domain and transmission performances between forward-directional and backward-directional phase stabilization methods. Remarkably, our results demonstrate error-free transmission at a modulation frequency of 3 Gbit/s and higher.

Community co-creation is increasingly crucial to the building of sustainable societies. Communities must proactively and independently create value chains in the face of many wicked problems. However, practical frameworks and tools for facilitating community co-creation require further development. As such, for this paper, we propose a theoretical framework for analyzing community co-creation value chain mechanisms based on a narrative review of literature on Collective Impact, social impact assessment, and Community Capital from the perspective of collective impact, a framework with a fair amount of previous research. We argue for the importance of applying knowledge of social impact assessment, particularly for the collective impact conditions of common agenda and shared measurement system. We discuss its relationship with the Theory of Change and the use of systems thinking to mitigate the subjectivity and arbitrariness of design thinking. Furthermore, we emphasize the value of employing the community capital concept as a framework for analyzing interrelationships among elements. By integrating multiple concepts, we enhance the collective impact framework and outline potential avenues for future research on analyzing and effectively implementing co-creation value chain mechanism in a community-based approach.

Purpose: The aim of present study was to compare the treatment results of daily cisplatin (CDDP), weekly docetaxel (DOC) intra-arterial infusion chemotherapy combined with radiotherapy (DIACRT) regimen and weekly CDDP intra-arterial infusion chemotherapy combined with radiotherapy (WIACRT) for patients with tongue cancer. Materials and Methods: Between January 2007 and December 2016, a total of 11 patients treated with WIACRT and 45 patients treated with DIACRT were enrolled in present study. In DIACRT group, 25 patients had T2, 20 patients had T3. A total of 9 patients had T2 and 2 had T3 in WIACRT (p = NS). In DIACRT, the treatment schedule consisted of intra-arterial chemotherapy (DOC, total 60 mg/m²; CDDP, total 150 mg/m²) and daily concurrent radiotherapy (RT) (total, 60 Gy). In WIACRT, the treatment schedule consisted of intra-arterial chemotherapy (CDDP, total 360 mg/m²) and daily concurrent RT (total, 60 Gy). Results: The median follow-up periods for DIACRT and WIACRT were 61 and 66 months respectively. The 5-year local control (LC) and overall survival (OS) rate were 94.5% and 89.6% for DIACRT group, 60.6% and 63.6% for WIACRT group respectively. The LC rate and OS of DIACRT group were significantly higher than that of WIACRT group. As regards toxicities, no treatment-related deaths were observed during the follow-up periods both in two groups. Conclusions: DIACRT was found to be feasible and effective for patients with tongue cancer and could become a new treatment modality.

Background and Aim: Zinc plays a pivotal role in various zinc enzymes, resulting in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. It remains unknown whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development. Patients and Methods: Two hundred sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients) were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Results: Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p<0.001). According to the serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dl (p<0.001). Conclusion: Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dl.

We present a first formal analysis of specific and complete local integration. Complete local integration was previously proposed as a criterion for detecting entities or wholes in distributed dynamical systems. Such entities in turn were conceived to form the basis of a theory of emergence of agents within dynamical systems. Here, we give a more thorough account of the underlying formal measures. The main contribution is the disintegration theorem which reveals a special role of completely locally integrated patterns (what we call ι-entities) within the trajectories they occur in. Apart from proving this theorem we introduce the disintegration hierarchy and its refinement-free version as a way to structure the patterns in a trajectory. Furthermore we construct the least upper bound and provide a candidate for the greatest lower bound of specific local integration. Finally, we calculate the i-entities in small example systems as a first sanity check and find that ι-entities largely fulfil simple expectations.

Background The incidence of congenital cholesteatoma (CC) has rarely been discussed, particularly from the demographic viewpoint. Therefore, we conducted an epidemiological study of CC using local medical characteristics. Materials and methods The participants were 100 patients (101 ears) who underwent initial surgical treatment at university hospitals in two rural prefectures between 2006 and 2022. Sixty-eight percent of the patients were males and 32% were females, with a median age of 5 years. We reviewed the medical records for the date of birth, date of surgery, stage of disease, and first symptom of the disease. Result The total incidence of CC was calculated to be 26.44 per 100,000 births and tended to increase. No significant difference was found between the incidences in the two prefectures. The number of surgeries performed was higher in the second half of the study period. No difference in the stage of progress was observed based on age. Conclusion The incidence of CC was estimated to be 26.44 per 100,000 new-born births. The number of patients with CC has tended to increase; however, this can be attributed to an increase in the detection rate rather than the incidence.

Plasma osteopontin (OPN) levels are elevated in mycobacterium tuberculosis patients and may involve granuloma formation. New inhibitors using brefelamide, an aromatic amide isolated from Dictyostelium cellular slim molds which may inhibit OPN transcription at concentration of 1M, were synthesized as compounds C, D and E. Their inhibitory activity against OPN synthesis in phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells was confirmed using enzyme-linked immunosorbent assay (ELISA), a multicolor immune-fluorescent microscope and western blot analysis. For the ELISA performed using the full-length OPN, each compound showed significant inhibition. Detailed analysis were done using C and D. They also showed inhibitory activity when used on another ELISA system to detect the immune-related form of OPN and their IC50 were 0.6 and 1.2 M for compounds C and D, respectively. Fluorescent particle count of stained cell numbers by O-17 showed the inhibition. Antibodies for O-17 and 34E3, which recognize OPN N-terminus and thrombin-cleaved site, respectively, detected distinct bands on the western blots following PMA stimulation. The decrease in full-length OPN detected by O-17 in the compound-treated cells was identified via western blot analysis. These newly-developed compounds may therefore be used in clinical trials for cancer and infectious diseases.

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.

In vivo, articular cartilage tissue is surrounded by a cartilage membrane, and HP (HP) and compressive strain increases simultaneously with the compressive stress. However, it has been impossible to investigate the effects of simultaneous loading in vitro. In this study, a bioreactor capable of applying compressive stress under HP was developed to reproduce ex vivo the same physical loading environment found in cartilage in vivo. First, a HP stimulation unit was constructed to apply cyclic HP pressure-resistant chamber by controlling a pump and valve. A compression-loading mechanism that can apply compressive stress using an electromagnetic force was implemented in the chamber. The synchronization between the compression and HP units were evaluated and the stimulation parameters were quantitatively evaluated. Physiological HP and compressive strain were applied to the chondrocytes encapsulated in alginate and gelatin gels after applying high HP at 25 MPa, which induced damage to chondrocytes. It was found that compressive stimulation increased the expression of genes related to osteoarthritis. Furthermore, the simultaneous application of compressive strain and HP, which is similar to the physiological environment in cartilage, had an inhibitory effect on the expression of genes related to osteoarthritis. HP alone also suppressed the expression of osteoarthritis-related genes. Therefore, the simultaneous hydrostatic and compressive stress-loading device developed to simulate the mechanical environment in vivo may be an important tool for elucidating the mechanisms of disease onset and homeostasis in the cartilage.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

Quality-of-life (QOL) is important for cancer patients with poor prognosis. However, QOL survey is difficult using patients. We created cancer scenarios and investigated QOL utility values among the general public using vignette-based methods. On the other hand, some scenarios may have been difficult for the general public to image and understand. Therefore, we conducted a QOL survey among physicians. This survey was conducted by interviewing physicians adminis-tering chemotherapy to patients for recurrent/metastatic pancreatic cancer. Responses were eval-uated using Composite Time Trade-Off (cTTO) and Visual Analog Scale (VAS) for 11 pancreatic cancer status scenarios to be evaluated (survey scenarios). Survey scenarios consisted of health state, type and Grade of adverse events. Health status was classified into two categories: Stable disease (SD) and Progressive disease (PD). Twenty responders answered in this survey, however two responses were excluded because of inconsistent responses. The stable disease had the highest QOL value for both assessment method. Whereas progression disease (PD) had the lowest QOL value. The physicians scored higher QOL values on VAS and cTTO than the general public in all survey scenarios. The QOL values obtained by physicians were consistent with the degree of sta-tus in any assessment scenarios.

Objective: Local ablation therapies (radiofrequency ablation (RFA), and microwave ablation (MWA)) are important as curative treatment option in patient with early-stage hepatocellular carcinoma (HCC) and option for intrahepatic tumor volume reduction in those with unresectable HCC. Various techniques; contrast-enhanced ultrasound (CEUS), real-time virtual sonography (RVS), artificial pleural and ascites fluid infusion, and body position change (BPC) have been used to accurately and safely perform local ablation therapies. However, there have been few reports on the usefulness of BPC. Therefore, this study focused on the usefulness of BPC during local ablation therapies in patients with HCC. Methods: We evaluated the technical success rates, treatment time, and prognosis of 283 nodules treated with local ablation therapies. Furthermore, we defined nodules adjacent to large vessels or extrahepatic organs, or poorly visible nodules using US as HCC in high-risk locations. High-risk locations HCC were classified into phase 1 (before active use of BPC, January 2018 to December 2019) and phase 2 (after active use of BPC, January 2020 to January 2022). Results: One hundred seventy-six nodules (62%) were classified as high-risk location group. Compared to non-high risk HCC, treatment-assist techniques, such as BPC (61 vs. 24 %, p<0.001), artificial pleural fluid infusion (24 vs. 5.6%, p<0.001), artificial ascites infusion (50 vs. 11%, p<0.001), fusion imaging (28 vs. 8.4%, p<0.001) and CEUS (26 vs. 4.7%, p<0.001) were performed more frequently for high-risk HCC. The technical success rates were 96% (271/283 nodules), 96% (167/173 nodules) and 95% (102/107 nodules), for all nodules, the high-risk location group and the non-high risk location group, respectively. In the high-risk location group, the technical success rates of the group without BPC were lower than that with BPC (91 vs. 99%, p=0.015). Only BPC was a related factor for the technical success rate for high-risk locations HCC (OR 10 (1.2-86), p=0.034). In contrast, no differences were found in the treatment time, the local tumor progression rates, intrahepatic distant recurrence rates, and overall survival between the group with BPC and that without BPC in the high-risk location HCC. Conclusion: BPC during local ablation therapies in patients with HCC in high-risk locations was safe and efficient. Body position should be adjusted for HCC in high-risk locations to maintain good US visibility and ensure safe puncture route in patients undergoing local ablation therapies.