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Background: We aimed to gain insight into psychological barriers toward initiation of strong opioid analgesic use in patients with advanced recurrent cancer. Methods: This study included 46 patients who were prescribed with opioid analgesics for advanced recurrent cancer. The primary outcome was psychological barriers assessed using the Japanese version of the Barriers Questionnaire-II (JBQ-II). The secondary outcomes were psychological changes and pain relief one week after the induction of strong opioid analgesics. Results: The mean age of participants was 63.6 years. Furthermore, 26.1% had an Eastern Cooperative Oncology Group (ECOG) performance status of ?3. The mean JBQ-II total score was 1.97 (95% confidence interval: 1.75?2.19). At the initiation of opioid therapy, there was no difference in the total scores between the baseline and one week later. Nevertheless, there was a significant difference in the subscale ?disease progression? score (mean 2.97 vs. 2.59, difference in means 0.38, standard error 0.16, p?=?0.026). Personalized Pain Goal (PPG) was achieved in about half of the participants, and a trend toward a higher score in the subscale ?harmful effects? (concern about adverse events) was observed in those who did not achieve PPG. Conclusion: This study showed that patients with advanced recurrent cancer have psychological barriers to opioid induction. The relationship between the presence of psychological barriers before and after induction of opioid analgesics and the speed of pain improvement was determined. The results may provide fundamental information for prospective intervention studies to develop individualized education programs for patients with psychological barriers to opioids. Clinical Trial Registration Number UMIN000042443.

In this paper, we address the design of personalized control systems, which pursue individual objectives defined for each user. To this end, a problem of reinforcement learning is formulated where an individual objective function is estimated based on the user rating on his/her current control system and its corresponding optimal controller is updated. The novelty of the problem setting is in the modelling of the user rating. The rating is modelled by a quantization of the user utility gained from his/her control system, defined by the value of the objective function at his/her control experience. We propose an algorithm of the estimation to update the control law. Through a numerical experiment, we find out that the proposed algorithm realizes the personalized control system.

This paper addresses the modelling and management problems for human behavioural change, in particular, aiming reduced congestion. First, the behavioural change driven by incentivizing and informational nudging is modelled reflecting the tendency of a human group. Next, an incentive- and nudge-based optimal management problem is formulated, where the model of behavioural change is taken into account. Finally, the effectiveness of the incentive and nudge design is verified in a numerical experiment.

Abstract Recently, TNF receptor type 2 (TNFR2) signaling was found to be involved in the proliferation and activation of regulatory T cells (Tregs), a subpopulation of lymphocytes that suppress immune responses. Tregs mediate peripheral immune tolerance, and the disruption of their functions causes autoimmune diseases or allergy. Therefore, cell expanders or regulators of Tregs that control immunosuppressive activity can be used to treat these diseases. We focused on TNFR2, which is preferentially expressed on Tregs, and created tumor necrosis factor-α (TNF-α) muteins that selectively activate TNFR2 signaling in mice and humans, termed R2agoTNF and R2-7, respectively. In this study, we attempted to optimize the structure of muteins to enhance their TNFR2 agonistic activity and stability in vivo by IgG-Fc fusion following single-chain homo-trimerization. The fusion protein, scR2agoTNF-Fc, enhanced the expansion of CD4+CD25+ Tregs and CD4+Foxp3+ Tregs and contributed to their immunosuppressive activity ex vivo and in vivo in mice. The prophylactic administration of scR2agoTNF-Fc suppressed inflammation in contact hypersensitivity and arthritis mouse models. Furthermore, scR2-7-Fc preferentially expanded Tregs in human peripheral blood mononuclear cells via TNFR2. These TNFR2 agonist-Fc fusion proteins, which have bivalent structures, are novel Treg expanders.

Abstract Background and Aim Metachronous gastric cancer (GC) frequently occurs in patients who have undergone endoscopic resection (ER) for GC. We evaluated the risk for development of metachronous GC following ER for GC based on genetic polymorphisms for alcohol dehydrogenase‐1B (ADH1B) and aldehyde dehydrogenase‐2 (ALDH2), as well as alcohol consumption and smoking habits. Methods We studied 77 patients who underwent ER for GC (median follow‐up of 84 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. Histories of alcohol consumption and smoking before and after ER and Helicobacter pylori eradication were documented. Results Multivariate analyses revealed that homozygous slow‐metabolizing ADH1B (hazard ratio [HR] = 2.38, P

Abstract Background Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. Methods This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. Results ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7–99.7%), specificity (95% CI) was 100% (92.7–100%), diagnostic accuracy (95% CI) was 98.9% (94.0–99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4–100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5–99.7%). Conclusions ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.

Key Clinical Message Trichuris trichiura parasitizes only humans through fecal‐oral transmission. In non‐endemic areas, the frequency of endoscopic identification has been increasing due to the increasing number of immigrants from endemic countries. To prevent infection, it is important to pay attention to sanitary conditions such as soil and water sources.

El control predictivo engloba a una familia de controladores que replanifican continuamente las entradas del sistema durante un cierto horizonte temporal con el fin de optimizar su evolución esperada conforme a un criterio dado. Esta metodología tiene entre sus retos actuales la adaptación al paradigma de los llamados sistemas ciberfísicos, que están compuestos por computadoras, sensores, actuadores y entidades físicas de diversa índole entre las que se incluyen robots e incluso seres humanos que intercambian información con el objetivo de controlar procesos físicos. Este tutorial presenta los conceptos centrales de la integración del control predictivo en este tipo de sistemas mediante el repaso a una serie de ejemplos que explotan la versatilidad de este marco de diseño de controladores para resolver los desafíos que presentan las aplicaciones del siglo XXI.

Abstract Background Therapy for eradication of Helicobacter pylori (H. pylori) improves symptoms of H. pylori-associated dyspepsia (HPD), but the effects of eradication in elderly patients are unclear. The aim of our study was to investigate dyspepsia symptoms and long-term effects of eradication in elderly patients. Methods This retrospective study included 496 patients who received H. pylori eradication therapy. The patients were divided into a group of elderly patients (group E: ≧ 65 years old) and a group of non-elderly patients (group N:

In real-world social infrastructures such as power systems, proven controllers are already implemented and operated stably. To further improve the control performance reliably, bi-layered control with inheriting the existing controller is proposed: the existing controller generates the baseline control signal in the upper layer, while multiple sub-controllers individually coordinate the signal to actuate the infrastructure system in the lower layer. The sub-controllers are characterized by few parameters that represent the degree of coordination. Then, the update strategy of the parameter with guaranteeing the safety of the overall system is proposed. The effectiveness of the bi-layered control is shown via a numerical experiment with a power system model.

A man in his 50s presented with pitting edema of both lower legs and abdominal distension as his chief complaint. His personal medical history and family history were unremarkable, except that he was a heavy drinker consuming 66 g of alcohol per day and a heavy smoker. Blood tests upon admission showed slight hepatic dysfunction, thrombocytopenia, jaundice, hypoalbuminemia, and decreased coagulability. Tumor marker tests showed elevated levels of CA19-9 and PIVKA-II. Contrast-enhanced computed tomography revealed enhancement of multiple masses predominantly in the right lobe of the liver in the early phase, followed by diffuse enhancement of the entire liver in the delayed phase. Hepatic arteriography demonstrated large hemangioma-like lesions corresponding to the masses revealed by computed tomography. That findings seemed to be cotton wool appearance. On magnetic resonance images, there were multiple mass-like lesions that showed homogeneous or heterogeneous low signal intensity on T1-weighted images, and clearly high signal intensity on T2-weighted images. The findings were atypical and no definite diagnosis could be made. Hepatic failure then rapidly worsened, and the patient died on hospital day 20. Autopsy led to the diagnosis of hepatic angiosarcoma.

We investigate the magnetic properties and spin-orbit-torque-induced (SOT-induced) magnetization switching in Ta/MnGa/Cr and Ta/MnGa/NiAl structures. Out-of-plane hysteresis loops for the Ta/MnGa/Cr (NiAl) structures are skewed (square). In-plane currents I are applied to Hall devices made of structures exposed to in-plane magnetic fields Hin along the channel direction. Clear asymmetric magnetization switching with respect to the polarity of I and Hin is detected for the Ta/MnGa/NiAl device. Similar asymmetric magnetization switching is observed for the Ta/MnGa/Cr device, although the magnetization is partially switched regardless of the polarity of I and Hin. These results suggest that an in-plane magnetization component opposite to Hin is present in the Cr-buffer structure and that the formation of such a component is suppressed in the NiAl-buffer structure.

In this paper, we address a design method of binaural sound reproduction over loudspeakers, which is a virtual realization of three-dimensional audio. The reproduction is achieved by a model matching control to reproduce a desired sound field in a reproduced sound field. It is known that any sound field includes unstable zeros that are originated from the inherent propagation delay. Therefore, the model matching controller including the direct inversion of the reproduced sound field is inevitably unstable and cannot be implemented to actual systems. To avoid this instability, we propose a design method of a stable feedforward controller based on an H8 model matching problem. Additional low gain specification is imposed on the controller to enhance the robustness against modeling errors of the sound field. We apply the design method to actual experimental data of a sound field and also demonstrate through a numerical experiment that the designed controller realizes binaural reproduction accurately.

In a standard setup of conventional state estimation problems, the output signal of a dynamical system is sampled at every regular time interval. This paper addresses an estimation problem under event-triggered sampling: an irregular sampling rule in which the output signal is sampled only when a specified event occurs. In particular, this paper focuses on the Lebesgue sampling, which is a type of event-triggered sampling such that the output signal is sampled only when it crosses specific thresholds. In the proposed estimation method, not only information in the sampled points but also that in the inter-sample intervals are utilized to improve the estimation accuracy efficiently. The particle filter is applied to the estimation since the inter-sample information makes the distribution of the estimates non-Gaussian. Furthermore, the proposed estimator is combined with a linear-quadratic-regulator (LQR) type state-feedback controller. The derived control law can be an effective approach to an event-triggered control problem in which the Lebesgue-sampled output is utilized. The effectiveness of both of estimation and control methods is examined through numerical examples.

In this paper, we address the data-driven modeling of a nonlinear dynamical system while incorporating a priori information. The nonlinear system is described using the Koopman operator, which is a linear operator defined on a lifted infinite-dimensional state-space. Assuming that the L2 gain of the system is known, the data-driven finite-dimensional approximation of the operator while preserving information about the gain, namely L2 gain-preserving data-driven modeling, is formulated. Then, its computationally efficient solution method is presented. An application of the modeling method to feedback controller design is also presented. Aiming for robust stabilization using data-driven control under a poor training dataset, we address the following two modeling problems: (1) Forward modeling: the data-driven modeling is applied to the operating data of a plant system to derive the plant model; (2) Backward modeling: L2 gain-preserving data-driven modeling is applied to the same data to derive an inverse model of the plant system. Then, a feedback controller composed of the plant and inverse models is created based on internal model control, and it robustly stabilizes the plant system. A design demonstration of the data-driven controller is provided using a numerical experiment.

Tumor necrosis factor-α (TNF), which is an immuno-modulatory cytokine, has been suggested to cause inflammatory responses as well as protection against tissue dysfunction by binding two types of TNF receptor (TNFR1/TNFR2). However, the physiological effects of TNFR2-specific activation remain unclear. We therefore aimed to generate a TNF mutant with full TNFR2-selective agonist activity as a functional analytical tool. In this study, we utilized a phage display technique to create mouse TNFR2 (mTNFR2)-selective TNF mutants that bind specifically to mTNFR2 and show full bioactivity compared with wild-type TNF. A new phage library displaying TNF mutants was created, in which nine amino acid residues at the predicted receptor-binding site were randomized. From this library, an agonistic TNF mutant exhibiting high binding selectivity and bioactivity to mTNFR2 was isolated. We propose that this TNF mutant would be a powerful tool with which to elucidate the functional roles of mTNFR2.•We generated a TNF mutant with full TNFR2-selective agonist activity.•This mutant was identified using a phage display technique.•This agonist exhibited high binding selectivity and bioactivity to mouse TNFR2.•This would be a powerful tool to elucidate the functional roles of mouse TNFR2.

This paper focuses on an evaluation of core losses in laminated magnetic block cores assembled with a high Bs nanocrystalline alloy in high magnetic flux density region. To discuss the soft magnetic properties of the high Bs block cores, the comparison with amorphous (SA1) block cores is also performed. In the high Bs block core, both low core losses and high saturation flux densities Bs are satisfied in the low frequency region. Furthermore, in the laminated block core made of the high Bs alloy, the rate of increase of iron losses as a function of the magnetic flux density remains small up to around 1.6 T, which cannot be realized in conventional laminated block cores based on amorphous alloy. The block core made of the high Bs alloy exhibits comparable core loss with that of amorphous alloy core in the high-frequency region. Thus, it is expected that this laminated high Bs block core can achieve low core losses and high saturation flux densities in the high-frequency region.

We have recently found that combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and mice and that estrogen replacement and chronic treatment with Ginkgo biloba extract EGb 761 suppress the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of placental extract on the memory impairment and neuromorphological change in OVX/stress-subjected mice. Female Slc:ICR strain mice were randomly divided into four groups: vehicle-treated OVX, porcine placental extract (120 and 2160 mg/kg)-treated OVX, and sham-operated control groups. Two weeks after surgical operation, OVX mice underwent restraint stress for 21 days (6 h/day), and all animals were then subjected to a contextual fear conditioning test followed by morphological examination by Nissl staining. Placental extract was orally administered once daily until the behavioral analysis was carried out. Chronic treatment with both doses of placental extract improved the OVX/stress-induced fear memory impairment and Nissl-positive cell loss of the hippocampal CA3 region, although it did not affect the loss of bone mineral density and increase in body weight after OVX. These results have important implications for the neuroprotective and cognition-enhancing effects of placental extract in postmenopausal women. Keywords:: postmenopausal animal model, chronic stress, ovariectomy, cognition, hippocampus

Ephrin receptor A10 (EphA10), a transmembrane receptor that binds to ephrin, is a newly identified breast cancer marker protein that has also been detected in HER2-negative tissue. In this study, we report creation of a novel bispecific antibody (BsAb) binding both EphA10 and CD3, thereby forming a bridge between antigens expressed on both tumor and immune cells and promoting recognition of tumor cells by immune cells and redirection of cytotoxic T cells (CTL). This BsAb (EphA10/CD3) was expressed in supernatants of BsAb gene-transfected cells as monomeric and dimeric molecules. Redirected T-cell lysis was observed when monomeric and dimeric BsAb were added to EphA10-overexpressing tumor cells in vitro. Furthermore, dimeric BsAb (EphA10/CD3) was more cytotoxic than monomeric BsAb, with efficient tumor cell lysis elicited by lower concentrations (≤10(-1) μg/mL) and a lower effector to target (E/T) cell ratio (E/T = 2.5). Dimeric BsAb (EphA10/CD3) also showed significant anti-tumor effects in human xenograft mouse models. Together, these results revealed opportunities to redirect the activity of CTL towards tumor cells that express EphA10 using the BsAb (EphA10/CD3), which could be tested in future clinical trials as a novel and potent therapeutic for breast cancer tumors.