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BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI. METHODS: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted. In this international, multicenter clinical trial, eligible participants had moderate-to-severe TBI, were ≥12 months postinjury, and had chronic motor deficits. Participants were randomized in a 1:1:1:1 ratio to stereotactic surgical intracranial implantation of SB623 cells (2.5 × 106, 5.0 × 106, 10 × 106) or surgical sham-controlled procedure. The prespecified primary efficacy end point was significantly greater change from baseline of the Fugl-Meyer Motor Scale (FMMS) score, a measure of motor status, for the SB623 pooled vs control arm at 24 weeks. RESULTS: A total of 211 participants were screened, 148 were excluded, and 63 underwent randomization, of which 61 (97%; mean age, 34 [SD, 12] years; 43 men [70.5%]) completed the trial. Single participants in the SB623 2.5 × 106 and 5.0 × 106 cell dose groups discontinued before surgery. Safety and efficacy (modified intent-to-treat) were assessed in participants who underwent surgery (N = 61; SB623 = 46, controls = 15). The primary efficacy end point (FMMS) was achieved (least squares mean [SE] SB623: +8.3 [1.4]; 95% CI 5.5-11.2 vs control: +2.3 [2.5]; 95% CI -2.7 to 7.3; p = 0.04), with faster improvement of the FMMS score in SB623-treated groups than in controls at 24 weeks and sustained improvement at 48 weeks. At 48 weeks, improvement of function and activities of daily living (ADL) was greater, but not significantly different in SB623-treated groups vs controls. The incidence of adverse events was equivalent in SB623-treated groups and controls. There were no deaths or withdrawals due to adverse events. DISCUSSION: Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02416492. Submitted to registry: April 15, 2015. First participant enrolled: July 6, 2016. Available at: classic.clinicaltrials.gov/ct2/show/NCT02416492. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that intracranial implantation of allogeneic stem (SB623) cells in adults with motor deficits from chronic TBI improves motor function at 24 weeks.

Wisdom is the hallmark of social judgment, but how people across cultures recognize wisdom remains unclear-distinct philosophical traditions suggest different views of wisdoms cardinal features. We explore perception of wise minds across 16 socio-economically and culturally diverse convenience samples from 12 countries. Participants assessed wisdom exemplars, non-exemplars, and themselves on 19 socio-cognitive characteristics, subsequently rating targets wisdom, knowledge, and understanding. Analyses reveal two positively related dimensions-Reflective Orientation and Socio-Emotional Awareness. These dimensions are consistent across the studied cultural regions and interact when informing wisdom ratings: wisest targets-as perceived by participants-score high on both dimensions, whereas the least wise are not reflective but moderately socio-emotional. Additionally, individuals view themselves as less reflective but more socio-emotionally aware than most wisdom exemplars. Our findings expand folk psychology and social judgment research beyond the Global North, showing how individuals perceive desirable cognitive and socio-emotional qualities, and contribute to an understanding of mind perception.

We propose that food choice may serve as a categorical basis for an individual’s self-identity, meaning “what you eat reveals who you are.” This type of social identity, namely, food identity (FI), can be a significant determinant of consumers’ attitudes and behavior. Whereas previous studies on FI have focused mainly on the choice of eating meat, we maintain that concerns about health and the moral implications of eating meat may entail FI involving a broader range of food choices. A food identity scale was constructed to measure the strength of FI among Japanese individuals. A factor analysis revealed two components of FI: health-oriented identity and amusement-oriented identity. The former component of FI was found to connote liberal-leaning values, whereas the latter component was interpreted as a reactionary tendency against the “do-gooder” character of the former. The results, including the value-laden implications, were consistent with evidence from a preceding study analyzing social media data. The roles played by social identity and ethical values with ideological connotations in consumer behavior are discussed.

Focusing on the COVID-19 period in Japan, this study identifies the effectiveness of a municipal unit-based pricing (UBP) system on household waste reduction through a panel data analysis targeting 770 cities for 2013–2022. It focuses on simple unit pricing (SUP) and two-tiered pricing (TTP) systems as the UBP components. As previous studies have not considered the COVID-19 period when assessing UBP, this study significantly contributes to the literature by providing new evidence. The main findings are as follows: First, SUP effectively reduced household waste even during the COVID-19 period; however, its effectiveness was slightly neutralized owing to the pandemic environment. Second, TTP also restrained household waste efficiently; however, its effect was smaller than that of SUP, and its reduction effect accelerated during the COVID-19 period (in 2020) because people became cautious about excessive waste volumes beyond the TTP criteria. The study implicates the need to expand the municipal adoption of the UBP system for household waste reduction.

Introduction BRAF mutations in bladder cancer are rare. MEK inhibitors have excellent clinical benefits in the treatment of melanoma. Case presentation A 60‐year‐old male was diagnosed with muscle‐invasive bladder cancer and underwent total cystectomy and ileal conduit diversion. Despite 4 cycles of gemcitabine and cisplatin chemotherapy and 3 courses of pembrolizumab, the left obturator lymph node enlarged. Cancer multi‐gene panel testing confirmed the BRAF G469A mutation and trametinib was recommended. Three months after the initiation of trametinib (2 mg, qd), the left obturator lymph node shrank by more than 50%. The disease has remained stable for more than 18 months. Conclusion The present case indicates the potential of trametinib to treat mBUC patients with the BRAF G469A mutation in this setting.

Do negative attitudes toward older adults vary according to the occupation of the older adult? Addressing this question is crucial to foster continued employment opportunities for older individuals. To explore this, we conducted an online experiment with Japanese participants, examining how negative attitudes fluctuate when comparing non-older and older adults within specific occupations. This study applied the stereotype content model across 16 occupations and unveiled a three-cluster solution, indicating variations in stereotype mappings between non-older and older workers. Moreover, it was observed that the propensity for these differences varied across clusters. Notably, in occupations where the workers were perceived as more competent and warmer than the general older adults, stereotypes shifted more positively when participants were informed that the workers were older. Conversely, in occupations where workers were perceived as more competent and less warm, both competence and warmth shifted in a negative direction with the introduction of age information. In addition, respect—the degree to which the target person is esteemed and/or admired by others—was strongly associated with both competence and warmth. It is anticipated that the insights gleaned from this study can inform practical interventions aimed at mitigating negative attitudes toward older adults concerning employment.

Existing research has examined people’s judgments concerning moral dilemmas involving non-human driving agents (i.e. an autonomous vehicle, abbr. AV). However, more evidence is needed to clarify the underlying cognitive mechanism accounting for the differential attribution of blame between non-human (e.g., robot) drivers and human drivers when facing a dilemma where obeying the traffic rule conflicts with humanitarian goals. Drawing on literature from moral psychology and human-robot interaction, we argued that the perception of mental state might account for this difference. In three studies, we investigated the mediating role of intentionality perceived in the drivers using a constructed scenario that mirrored real-life moral dilemmas. Studies 1 and 2 revealed that participants assigned greater blame and perceived higher levels of intentionality to human drivers than to robot drivers. Mediation analyses demonstrated that robot drivers received less of blame to the extent that they were perceived as less intentionally violating the traffic rule. In Study 3, we excluded a mitigating factor of blaming the robot, i.e. holding a third party (e.g., the manufacturers) accountable. We found that the mediation effect of perceived intentionality remained regardless. This research provides insights into the attribution of blame directed toward non-human drivers such as AVs and their assumed intentionality.

Abstract Background Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence. Methods Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n = 114) and control (UA ≤7.0 mg/dL; n = 609) groups and were followed for a median of 24 (12–48) months after ablation. Results The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p = .017) and a lower incidence of AF‐free survival (p = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF‐free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12–2.40), female gender (1.91, 1.36–2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14–2.22), and alcohol consumption ≥20 g/day (1.49, 1.03–2.15) (all p

The 6th Asia Partnership Conference of Regenerative Medicine (APACRM) was held in person with online on April 20, 2023, to promote the regulatory harmonization of regenerative medicine products throughout Asia. Recognizing domestic regulatory guidelines within each country and region and the underlying rationales are important initial steps toward harmonizing regulations. The 6th APACRM featured an open dialog regarding non-clinical evaluation for advanced CAR-T products, regulation of clinical trials for AAV-based gene therapies, and cell and gene therapies provided to patients as medical care/medical practices without market authorization through presentations from the industry and panel discussions with regulatory agencies. The latest updates on regenerative medicine in each country and region are introduced. This paper summarizes the proceedings of the 6th APACRM for public dissemination to foster future discussions.

Faunal studies of oceanic islands provide unique opportunities to study ecology and evolution. Four Armadillidae taxa were recorded from the Izu Islands, a group of oceanic islands off the coast of Japan. The distributions of these taxa and a phylogenetic tree are based on molecular data for 249 specimens from 88 sites. The Spherillo russoi (Arcangeli, 1927) species complex is distributed widely throughout these islands, and dispersal may have occurred via oceanic currents. On the nearby Izuoshima and Toshima Islands, Spherillo dorsalis (Iwamoto, 1943) may have recently migrated from the Izu Peninsula either via currents or been transported by human activity. In the middle islands, Shikinejima, Kozushima, Miyakejima, and Mikurajima, Venezillo hasegawai (Nunomura, 1991) was found, which may be derived from Spherillo obscurus (Budde-Lund, 1885) distributed in the Kanto region on the mainland. On the most southern and distant Hachijojima Island, Spherillo punctatus Nunomura, 2007 was found, and it does not differ genetically from specimens from Izenajima and Tokunoshima Islands in the Nansei Island Group, despite an approximate 1,000-km distance between them; this species may have been transferred by human activity. Our study showed that the Armadillidae assemblages in the Izu Islands were formed by several migration routes.

Objectives To investigate the prevalence, associated factors, treatment status and burden of constipation in workers with depression or anxiety.Study design This was a retrospective observational study using a pre-existing database.Setting Claims data from October to November 2022 and data from the survey conducted in November 2022 were extracted from the database.Participants This study included self-reported workers who completed the survey, after excluding those with major mental disorders diagnosed as distinct from depression or anxiety and constipation due to organic diseases identified by International Classification of Diseases (ICD-10) codes.Outcome measures The subjects were divided into three groups: treated depression/anxiety, untreated depression/anxiety and no depression/anxiety. The prevalence of constipation, factors associated with constipation and medications prescribed for constipation were analysed. Work productivity and quality of life (QOL) were compared between three subgroups based on constipation status: treated constipation, untreated constipation and no constipation subgroup.Results Of the 18 585 respondents in the analysis population, 950 respondents (5.1%) were classified into the treated depression/anxiety group, 6035 respondents (32.5%) into the untreated depression/anxiety group and the remaining respondents into the no depression/anxiety group (11 600 (62.4%)). The prevalence of constipation was 22.5% in the treated group, 22.3% in the untreated group and 10.4% in the no depression/anxiety group, respectively. Depression and anxiety severity were independently associated with an increased risk of constipation. In all groups, the most commonly prescribed drug class was osmotic laxatives. Work productivity and QOL tended to indicate a greater burden in the untreated constipation subgroup than in the treated or no constipation subgroups.Conclusions The prevalence of constipation was twice as high if workers had depression/anxiety. Considering that the comorbidity of constipation with mental disorders may increase multiple burdens, appropriate medical interventions are required to treat both mental (depression/anxiety) and physical (constipation) conditions. This should be widely recognised by physicians and employers.

IntroductionHuman alveolar echinococcosis caused by Echinococcus multilocularis is an important zoonotic disease in the northern hemisphere. The life cycle of E. multilocularis is maintained primarily in wild animals and requires an intermediate host (mainly small mammals). Human can become an intermediate host through accidental ingestion of E. multilocularis eggs. Hokkaido Prefecture is the only area of Japan in which human alveolar echinococcosis is endemic. The purposes of this study were to elucidate the land use ecological factors associated with the density of red fox feces along paved roads and the relationship between the distributions of red fox (Vulpes vulpes) populations and fox feces, which determine the level of hazard from eggs.MethodsA series of surveys was conducted in the central part of the Nemuro Peninsula of Hokkaido, excluding urban areas, over a total of 4 years in May–June in 2014 and 2016–2018 when red foxes remain with their cubs around the dens. Transects of 500 m were set up on paved roads, and feces within the transects were counted. Univariable and multivariable analyses were performed to examine ecological factors including the principal components (PCs) of five land use–type occupancy proportions within 500 m and 1 km, respectively, as explanatory fixed-effect variables. The number of feces in each transect was examined as the response variable using integrated nested Laplace approximation with negative binomial errors with a spatio-temporal autocorrelations structure to separate the effects of similarities of neighboring locations and annual variation. The multivariable models with the lowest widely applicable information criterion values were selected.ResultsThe feces density was explained by the PC of the 500- m buffer (−0.27, 2.5th and 97.5th percentiles: −0.44, −0.10) characterized by mixed forests (−0.82) and scarcity of residential areas (0.29) and the proximity to the nearest livestock farm house (−0.35, 2.5th and 97.5th percentiles: −0.53, −0.17). This suggested that foxes defecate in the areas where prey is abundant, avoiding humans.DiscussionPolicy discussions regarding bait distribution design targeting these conditions should be initiated.

Identifying and improving existing morality perceptions regarding older adults is crucial for fostering intergenerational cooperation and constructing an inclusive society. In this study, we conducted two online experiments with Japanese participants to investigate the degrees to which older adults are perceived as moral. We predicted that older adults are more likely to be perceived as morally good compared to middle-aged individuals (Hypothesis 1), and that regardless of the target person's age, individuals perceived as warm (Hypothesis 2) and competent (Hypothesis 3) are more likely to be regarded as morally good. In Study 1, participants were instructed to freely describe a typical older (aged 80 years) or middle-aged (aged 50 years) target individual. Contrary to expectations, the middle-aged target individual was perceived as morally better than the older counterpart. Meanwhile, regardless of the target individual's age, the target individuals perceived as warm and competent were more likely to be viewed as morally good. In Study 2, participants were presented with a simple vignette describing an older (aged 80 years) or middle-aged (aged 50 years) target individual, manipulating their warmth (warm/cold) and competence (competent/incompetent). The results indicated no effect of target age on moral perceptions, but warmer and/or more competent target individuals elicited higher moral perceptions. Thus, Hypothesis 1 was not supported in either study, whereas Hypotheses 2 and 3 were supported across both studies. These findings underscore the importance of enhancing moral perceptions, warmth, and competence regarding older adults to facilitate appropriate assistance from other generations.

Yukihiro Matsumoto,1– 3 Yuichi Azuma,3 Yasue Karasawa,2 Noriyuki Suzuki3 1Eye Care Clinic, Saitama, Japan; 2Eye Care Clinic Tokyo, Tokyo, Japan; 3Eye Care Clinic Fukushima, Fukushima, JapanCorrespondence: Yukihiro Matsumoto, Eye Care Clinic, 829 Hikawa-cho, Souka, Saitama, 340-0034, Japan, Tel +81 30 6262 6100, Email ginzaeyecare@gmail.comPurpose: To evaluate postoperative outcomes after implantation of toric intraocular lenses (IOLs) made of high-water-content hydrophobic acrylic material in Japanese patients using a swept-source optical coherence tomography (SS-OCT) biometer integrated with a surgical guiding system.Patients and Methods: In this prospective observational study, toric IOL models CNW0T3 to CNW0T9 (Alcon) were implanted in 33 eyes of 33 patients and followed-up for one month. Powers and toric models were determined using an SS-OCT biometer ARGOS® Ver 1.5 (Alcon), and the IOLs were aligned using surgical guidance. Differences between planned and actual axis positions at the end of the surgery (misalignment) and rotations from the end of surgery to one month postoperatively were measured. Additionally, postoperative uncorrected visual acuity, refraction, and residual astigmatism were evaluated.Results: Mean and median misalignments were 2.3° (standard deviation [SD]: 1.6, 95% confidence interval [CI]: 1.7– 2.9) and 2°, and those of postoperative rotation were 2.4° (SD: 2.6, 95% CI: 1.5– 3.4) and 2°, respectively. Mean postoperative refraction was 0.06 D (SD: 0.62). Prediction errors within ± 0.5 and ± 1.0 D were 69.7% and 93.9%, respectively. Mean residual astigmatisms were 0.19 D (SD: 0.41), and mean uncorrected visual acuity was 0.00 logMAR (SD: 0.11), and 64% of the eyes scored 20/20 or better.Conclusion: Implantation of high-water-content hydrophobic acrylic toric IOLs using SS-OCT biometry integrated with a surgical guiding system effectively corrected corneal astigmatism with accurate IOL alignment in Japanese patients.Keywords: toric intraocular lens, swept-source optical coherence tomography, biometry, surgical guiding system

Book review of Irvine, Susan, ed. 2023. Alfredian Prologues and Epilogues. Oxford: Oxford University Press. Pp. xi + 296. ISBN 9780199692101.

Summary: Insulin plays a crucial role in regulating the metabolism of blood glucose, amino acids (aa), and lipids in humans. However, the mechanisms by which insulin selectively regulates these metabolites are not fully understood. To address this question, we used mathematical modeling to identify the selective regulatory mechanisms of insulin on blood aa and lipids. Our study revealed that insulin negatively regulates the influx and positively regulates the efflux of lipids, consistent with previous findings. By contrast, we did not observe the previously reported insulin’s negative regulation of branched-chain aa (BCAA) influx; instead, we found that insulin positively regulates BCAA efflux. We observed that the earlier peak time of lipids compared to BCAA is dependent on insulin’s negative regulation of their influx. Overall, our findings shed new light on how insulin selectively regulates the levels of different metabolites in human blood, providing insights into the metabolic disorder pathogenesis and potential therapies.

Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults. Blood samples were collected from 463 participants, 31–84 years of age, who lived in Tokyo. A second blood sample was collected 5 years later from 241 of the participants, allowing us to evaluate the temporal stability of the inverse correlation between HDL-C level and HDL-C peroxide content. Glucoregulation and inflammatory activity were assessed because both can be associated with dyslipidemia and HDL-C dysfunction. Obesity and central adiposity were also considered. Overall, women had healthier HDL-C profiles than men. Elevated HDL-C (>90 mg/dL) was common (16.6%) and found more often in women. Higher HDL-C peroxide content was associated with older age and central adiposity and incremented further when HA1c and CRP were higher. When assessed 5 years later, lower HDL-C peroxide content continued to be evident in adults with higher HDL-C. While similar associations have been described for other populations, most Japanese adults typically had healthier levels of HDL-C with lower HDL-C peroxide content than previously reported for American adults.

The theory of polymer dynamics describes the intermediate scattering function for a polymer molecule in terms of relaxation modes defined by normal coordinates for the corresponding coarse-grained model. However, due to the difficulty of defining the normal coordinates for arbitrary polymer molecules, it is generally challenging to express the intermediate scattering function for a polymer molecule in terms of relaxation modes. To overcome this challenge, we propose a general method to calculate the intermediate scattering function for a polymer molecule on the basis of a relaxation mode analysis approach [Takano and Miyashita, J. Phys. Soc. Jpn. 64, 3688 (1995)]. In the proposed method, relaxation modes defined by eigenfunctions in a Markov process are evaluated on the basis of the simulation results for a polymer molecule and used to calculate the intermediate scattering function for that molecule. To demonstrate the effectiveness of the present method, we simulate the dynamics of a linear polymer molecule in a dilute solution and apply it to the calculation of the intermediate scattering function for the polymer molecule. The evaluation results regarding the relaxation modes reasonably describe the intermediate scattering function on the length scale of the radius of gyration of the polymer molecule. Accordingly, we examine the contributions of the pure relaxation and oscillatory relaxation processes to the entire intermediate scattering function. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim Stimulant laxatives may cause electrolyte abnormalities, dehydration, and abdominal pain; their long‐term use can lead to tolerance and subsequent refractory constipation. We investigated the effectiveness, safety, and quality of life after switching from stimulant laxatives to lubiprostone in elderly patients with chronic constipation (CC). Methods This multicenter, interventional, open‐label, single‐arm, before‐and‐after comparison study enrolled 99 Japanese patients aged 65–90 years with CC who took stimulant laxatives for ≥2 weeks prior to switching to lubiprostone monotherapy. Results The mean ± SD spontaneous defecations at Week 1 of 7.8 ± 6.2 times/week was not significantly different from that at baseline (8.3 ± 4.7). Spontaneous defecations were significantly reduced at Weeks 2 (−1.5 ± 4.0, P