Shujitsu University

A concise and metal‐free procedure has been developed for the synthesis of 2‐vinylanilines. Reactions of indolines with tert‐BuOK in DMSO afford the decorated 2‐vinylanilines in yields up to 92%. In addition, the 2, or 3‐substituted indolines could be converted to trisubstituted alkenes. Also, the protocol can be scaled to afford gram quantities of the decorated 2‐vinylanilines.

In many medical institutions, standardized eGFR, which is based on generalized body surface area, is used for drug dosing evaluations. This can lead to overdosing. This study aimed to investigate the discrepancy between personalized eGFR and standardized eGFR and to identify indicators necessary for pharmacists to perform appropriate pharmacotherapy. From October 2022 to February 2023, the study targeted patients aged 18 years and older who continuously visited the Saera Pharmacy Kurashiki. Among the 347 participants, a significant discrepancy of 6.3 mL/min was observed between personalized eGFR and standardized eGFR (p < 0.001). Factors predicting an eGFR discrepancy of 10 mL/min or more were identified as follows: for males, a serum Na level below 140 mEq/L (area under the ROC curve: AUC = 0.656), and for females, a BUN level below 13 mg/dL (AUC = 0.647). Recognizing that patients with these factors are at risk of inaccurate renal function assessment, it is considered beneficial for pharmacists to prioritize obtaining height and weight measurements to ensure appropriate dosing of renally excreted drugs.

A series of carbazole‐containing azaborines, furano‐fused 1–2F and 1–3F and thieno‐fused 1–2T and 1–3T, were efficiently synthesized from a common carbazole boronic acid ester in two steps. The structural effects of the fused ring moieties and the patterns of the ring fusion were clarified. According to X‐ray crystal structure analysis, the furano‐ and thieno‐fused carbazole azaborines had planar structures and generally formed 1D columns. UV–vis analysis revealed that their absorption properties were significantly affected by the fused ring moieties. In contrast, the fluorescence properties were affected by the ring fusion patterns. π‐Extended derivatives of 1–2T and 1–3T, benzothieno‐fused 1–2BT and 1–3BT and phenyl‐substituted 1–2T‐Ph2 and 1–3T‐Ph2 were synthesized, and the effects of π‐extension on physical properties were also investigated. All the π‐extended compounds showed red‐shifts in absorption and fluorescence spectra compared with the pristine 1–2T and 1–3T. The color of solid‐state emission of the synthesized azaborines was tuned from purple to green without electron‐rich or ‐deficient substituents. The structural effects on the electronic structures were also discussed based on theoretical calculations.

Background Both mutation induction and clonal expansion of mutated cells cause cancer. The probability of cancer development depends on mutations, clonal growth rates, and carcinogenic mechanisms. A recent study showed cases of occupational cholangiocarcinomas that originate multifocally, with higher mutation burden levels than those in common cholangiocarcinomas. This study aimed to identify the effect of clonal expansion on and estimate the risk of occupational and common intrahepatic cholangiocarcinomas (ICCs) using a multistage model modified to include the effect of cell expansion at any carcinogenic stage. Methods The age-specific incidence of common ICC estimated from the Vital Statistics in Japan and the prognosis of ICC, and mutation frequencies of occupational and common ICC available from the previous report, were applied to a multistage model modified with cell proliferation effects. From the fittest model, the risk after exposure was estimated. Results The required number of stages for carcinogenesis was estimated to be three based on the incidences and mutation frequencies of occupational and common ICCs. Based on this estimation, the predicted incidence curve under the model was similar to that estimated from the ICC mortality rate, except for older adults. The model indicated a minor effect of clonal expansion on the observed occupational ICC risk. It predicted a rapid decrease in ICC risk after the cessation of occupational exposure, although the time of clinical detection of cancer after the exposure was affected by latency. The model predicted an increase in cancer risk in older adults caused by cell expansion and common background mutations. However, the risk in older adults was overestimated in the case of common ICC; this divergence could influence occupational ICC cases. Conclusions Three-stage ICC carcinogenesis has been proposed. The high mutation burden levels caused by occupational exposure led to an immediate incidence of cancer. After a long period of relatively low cancer risk, an increased risk in older adults was also predicted. Supplementary Information The online version contains supplementary material available at 10.1186/s41021-024-00315-7.

This paper explores the evolving landscape of business ethics in Japan, with a particular focus on recent research trends and methodologies. It begins by examining historical influences on Japanese corporate governance and business ethics, but places greater emphasis on findings from a survey of Japanese business ethics scholars. Conducted as part of the Global Survey for Business Ethics (GSBE), the survey targeted researchers affiliated with the Japan Society for Business Ethics (JABES) from 1994 to 2022. This paper discusses how business ethics research has developed in Japan, largely conducted in Japanese, and highlights key areas of focus such as compliance, CSR, and corporate governance. Using text analysis of research paper titles, it identifies trends across different decades, noting a shift toward more empirical studies and topics like AI ethics, human rights, and sustainability in recent years. The survey also reveals the broader roles of Japanese business ethics researchers, ranging from academic teaching to consulting and policy development. Looking ahead, the chapter highlights emerging research themes, including the ethical implications of artificial intelligence, transparency, and supply chain management, while acknowledging that Japan’s unique corporate context adds distinct dimensions to these global issues.

Background: Understanding the roles and competencies of professions outside of one's specialty is essential for providing efficient healthcare. However, it is difficult for medical professionals to understand the roles and competencies of other related professions while performing their duties. This study examined the impact of clinical practice-based interprofessional education (IPE) on pharmacy students, who are future medical professionals. Methods: Sixty-eight pharmaceutical students undergoing clinical practice were divided into non-IPE or IPE groups, with the IPE group attending an educational program with medical students conducted by doctors, pharmacists, and teachers during the clinical practice period. The effect was evaluated through a group survey using self-administered questionnaires focusing on contributing to multidisciplinary team medicine based on the Readiness for Interprofessional Learning Scale. The survey included specific behavioral objectives (SBOs), the Readiness for Interpersonal Learning Scale (RIPLS), and Kikuchi's Scale of Social Skills (KiSS-18). Results: Regardless of group, SBOs [non-IPE: 3.2, 95% CI (2.6-3.8), p < 0.001; IPE: 3.7, 95% CI (2.5-4.9), p < 0.001] and social skills [non-IPE: 4.0, 95% CI (2.5-6.1), p < 0.001; IPE: 6.7 95% CI (3.0-10.4), p < 0.001] showed improvement after the clinical practice. In RIPLS Factor 3, pharmacy students with IPE awareness scored significantly higher by 1.5 points [95% CI (0.2-2.8), p = 0.025] post-practice than those without IPE awareness. Conclusions: This study suggests that IPE for students during clinical practice could enhance their expertise in multidisciplinary medicine and facilitate the development of seamless team care in the future. Trial registration: This study was retrospectively registered and conducted in compliance with the "Ethical Guidelines for Medical Research Involving Human Subjects" and was approved by The Ethics Committee of Tokushima University Hospital (approval number: 3544).

The persistent symptoms of anxiety, depression, and fatigue that follow severe acute respiratory syndrome coronavirus 2 infection and accompany pulmonary inflammation pose significant clinical challenges. However, the correlation between pulmonary inflammation and mental health remains unclear. This study sought to examine the effects of intratracheal injection of lipopolysaccharide (LPS), a bacterial endotoxin, on anxiety-like behaviour in a mouse model suffering with pulmonary inflammation. The reactions of these animal models to new environments were evaluated using light–dark box and hole-board tests as anxiety-inducing stimuli. Microglial responses were evaluated via immunohistochemistry, and serum concentrations of tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. Both intraperitoneal and intratracheal injections of LPS induced anxiety-like behaviours, as indicated by the outcomes of the light–dark box and hole-board tests. Serum levels of TNF-α and IL-6 considerably increased following both injection routes. The protein levels of the 5-HT2A and 5-HT1A receptors, which are crucial for neuropsychological function, in the frontal cortex and hippocampus of mice remained unchanged following LPS injections. Notably, hippocampal levels of brain-derived neurotrophic factor (BDNF) remarkably decreased following LPS injections. In the lungs, the administration of LPS via the intratracheal route led to a significant rise in the number of white blood cells present in the bronchoalveolar lavage fluid compared to the intraperitoneal injection method. These findings suggest that inflammation induced by intratracheal LPS injection may lead to anxiety-like behaviours in mice, potentially involving mechanisms related to hippocampal BDNF expression, which contributes to anxiety after pulmonary inflammation.

Despite advancements in the sensitivity and performance of analytical instruments, sample preparation remains a bottleneck in the analytical process. Currently, solid-phase extraction is more widely used than traditional organic solvent extraction due to its ease of use and lower solvent requirements. Moreover, various microextraction techniques such as micro solid-phase extraction, dispersive micro solid-phase extraction, solid-phase microextraction, stir bar sorptive extraction, liquid-phase microextraction, and magnetic bead extraction have been developed to minimize sample size, reduce solvent usage, and enable automation. Among these, in-tube solid-phase microextraction (IT-SPME) using capillaries as extraction devices has gained attention as an advanced “green extraction technique” that combines miniaturization, on-line automation, and reduced solvent consumption. Capillary tubes in IT-SPME are categorized into configurations: inner-wall-coated, particle-packed, fiber-packed, and rod monolith, operating either in a draw/eject system or a flow-through system. Additionally, the developments of novel adsorbents such as monoliths, ionic liquids, restricted-access materials, molecularly imprinted polymers (MIPs), graphene, carbon nanotubes, inorganic nanoparticles, and organometallic frameworks have improved extraction efficiency and selectivity. MIPs, in particular, are stable, custom-made polymers with molecular recognition capabilities formed during synthesis, making them exceptional “smart adsorbents” for selective sample preparation. The MIP fabrication process involves three main stages: pre-arrangement for recognition capability, polymerization, and template removal. After forming the template-monomer complex, polymerization creates a polymer network where the template molecules are anchored, and the final step involves removing the template to produce an MIP with cavities complementary to the template molecules. This review is the first paper to focus on advanced MIP-based IT-SPME, which integrates the selectivity of MIPs into efficient IT-SPME, and summarizes its recent developments and applications.

Introduction In this study, we aimed to examine the effects of chotosan, a traditional Japanese botanical drug, and its active component, Uncaria hook, on anxiety-like behaviors induced by systemic inflammation in mice. Methods To induce systemic inflammation, the mice were treated with lipopolysaccharide (LPS), a bacterial endotoxin. Prior to LPS treatment, the mice were administered chotosan or Uncaria hook orally each day for 14 days. Anxiety-like behavior of the mice was evaluated using the light–dark test 24 h after LPS treatment. Results Repeated administration of chotosan prevented anxiety-like behavior in both normal and LPS-treated mice. Similarly, administration of Uncaria hook suppressed LPS-induced anxiety-like behavior in mice. Furthermore, treatment with tandospirone, a 5-HT1A receptor agonist, alleviated anxiety-like behavior in mice, whereas treatment with DOI, a 5-HT2A receptor agonist, enhanced anxiety-like behavior in mice. LPS treatment significantly increased serotonin (5-HT)2A receptor mRNA expression in the frontal cortex, whereas 5-HT1A receptor mRNA expression remained unchanged in the hippocampus. Notably, chotosan significantly suppressed the mRNA expression of 5-HT2A receptor. Discussion These findings indicate that chotosan exerts anxiolytic-like effects in the context of inflammation-induced anxiety, potentially mediated by the inhibition of 5-HT2A receptor hyperfunction in LPS-treated mice. Consequently, we postulate that chotosan may be effective in managing inflammation-induced anxiety-like behaviors.

Passive smoking from environmental tobacco smoke not only increases the risk of lung cancer and cardiovascular disease but may also be a stressor triggering neuropsychiatric and other disorders. To prevent these diseases, understanding the relationship between passive smoking and stress is vital. In this study, we developed a simple and sensitive method to simultaneously measure nicotine (Nic) and cotinine (Cot) as tobacco smoke exposure biomarkers, and cortisol (CRT), serotonin (5-HT), melatonin (MEL), dopamine (DA), and oxytocin (OXT) as stress-related biomarkers. These were extracted and concentrated from saliva by in-tube solid-phase microextraction (IT-SPME) using a Supel-Q PLOT capillary as the extraction device, then separated and detected within 6 min by liquid chromatography–tandem mass spectrometry (LC−MS/MS) using a Kinetex Biphenyl column (Phenomenex Inc., Torrance, CA, USA). Limits of detection (S/N = 3) for Nic, Cot, CRT, 5-HT, MEL, DA, and OXT were 0.22, 0.12, 0.78, 0.39, 0.45, 1.4, and 3.7 pg mL−1, respectively, with linearity of calibration curves in the range of 0.01–25 ng mL−1 using stable isotope-labeled internal standards. Intra- and inter-day reproducibilities were under 7.9% and 14.6% (n = 5) relative standard deviations, and compound recoveries in spiked saliva samples ranged from 82.1 to 106.6%. In thirty nonsmokers, Nic contents positively correlated with CRT contents (R2 = 0.5264, n = 30), while no significant correlation was found with other biomarkers. The standard deviation of intervals between normal beats as the standard measure of heart rate variability analysis negatively correlated with CRT contents (R2 = 0.5041, n = 30). After passive smoke exposure, Nic levels transiently increased, Cot and CRT levels rose over time, and 5-HT, DA, and OXT levels decreased. These results indicate tobacco smoke exposure acts as a stressor in nonsmokers.

Herein, we introduce a new synthetic protocol using 2-aminobenzoyl surrogates, allowing concise entry to decorated 2-aminobenzoyl derivatives in the absence of transition metals, acid chlorides, and specific reagents.

Background Drug-drug interactions (DDIs) increase the incidence of adverse drug reactions (ADRs). In a previous report, we revealed that the incidence of potential DDIs due to the same CYP molecular species in one prescription exceeds 90% among patients taking six or more drugs and that CYP3A4 markedly influences the increase in the number of potential DDIs in clinical practice. However, the factors contributing to an increased number of potential DDIs in prescriptions from multiple clinical departments remain poorly clarified. Methods This observational study was performed at five pharmacies in Okayama Prefecture, Japan. Patients who visited these pharmacies from 11 April 2022 to 24 April 2022 were included, except those who had prescriptions only from a single clinical department. A stratified analysis was performed to determine the incidence of CYP3A4-related potential DDIs according to the number of drugs taken. Additionally, factors associated with an increase in the number of drugs involved in CYP3A4-related potential DDIs were identified using multiple linear regression analysis. In this study, potential DDIs for the prescription data subdivided by clinical department, containing two or more drugs, were used as control data. Results Overall, 372 outpatients who received prescriptions from multiple clinical departments were included in the current study. The number of drugs contributing to CYP3A4-related potential DDIs increased with an increase in the number of clinical departments. Notably, in cases taking fewer than six drugs, prescriptions from multiple clinical departments had a higher frequency of CYP3A4-related potential DDIs than those in prescriptions subdivided by clinical department. Multiple regression analysis identified "Cardiovascular agents", "Agents affecting central nervous system", and "Urogenital and anal organ agents" as the top three drug classes that increase CYP3A4-related potential DDIs. Conclusion Collectively, these results highlight the importance of a unified management strategy for prescribed drugs and continuous monitoring of ADRs in outpatients receiving prescriptions from multiple clinical departments even if the number of drugs taken is less than six.

This study investigates the strategic orchestration of New Product Development (NPD) teams, focusing on how age diversity influences their innovation capabilities within the competitive landscape of firms. As firms encounter an evolving demographic landscape, the role of team composition, particularly age diversity, becomes critical in tuning innovation and market alignment. This paper synthesises the disparate findings from the innovation management literature on the impact of age diversity, employing dual theoretical perspectives: information/decision-making and similarity/categorisation. The former suggests that age diversity brings diverse knowledge that boosts innovation, while the latter indicates it might hinder social cohesion and team performance. Addressing the gaps in existing research, this study explores tenure diversity and team familiarity as moderators in the age diversity–performance relationship. It hypothesises that tenure diversity can enhance knowledge exchange and innovation but may complicate social interactions, whereas high team familiarity might restrict new idea generation by homogenising knowledge. Empirical analysis conducted on a dataset of 21,370 observations from Japanese sake breweries reveals that tenure diversity and team familiarity are critical in moderating the effects of age diversity on NPD outcomes. These findings enrich the NPD literature by highlighting the importance of demographic diversity and provide new insights into managing age-related dynamics in team settings. The study underscores the need for managerial strategies that leverage demographic diversity to enhance NPD effectiveness.

Introduction Pharmacists are needed as members of oncology teams. The Japanese Society of Hospital Pharmacists (JSHP) conducts a nationwide survey annually to analyze the actual situation and generate fundamental information about hospital pharmacy practice in Japan. Using data from this large-scale survey, we described pharmacists’ involvement in cancer chemotherapy. We explored the factors related to the acceleration of pharmacists’ tasks or involvement in clinical practice, primarily in oncology. Methods Data were obtained from annual surveys conducted by JSHP from 2015 to 2020. All variables were expressed as categorical variables and tabulated. The Chi-square and Fisher's exact tests were used to compare the categorical variables. The Cochran–Armitage trend test was used to identify significant trends. Results From 2015 to 2020, 22,362 responses were recorded. After applying the exclusion criteria, 20,906 were analyzed. The proportion of hospitals enrolling pharmacists with oncology-related certifications significantly increased in all hospitals providing cancer care. Multivariable logistic regression analysis indicated that a smaller number of beds per pharmacist significantly correlated with additional fees for outpatient pharmacy services ( p = 0.0002 for trend). Conclusion Hospitals charging increased fees for outpatient oncology pharmacy services were associated with a smaller number of beds per pharmacist, regardless of hospital size. A balance between the number of beds and pharmacists, particularly certified oncology pharmacists, is crucial for safe and high-quality cancer treatment.

Interstitial lung disease (ILD) is a serious adverse event caused by the administration of immune checkpoint inhibitors (ICIs). However, only few large-scale studies have explored the association among ICI use, underlying cancer type, and ILD complications. This study aimed to analyze the association between the primary cancer type and ICI-induced ILD in a cross-sectional manner using the Japanese Adverse Drug Event Report (JADER) database. Nivolumab and pembrolizumab (anti-programmed cell death 1 (PD-1) antibodies) and durvalumab, avelumab, and atezolizumab (anti-programmed cell death ligand 1 (PD-L1) antibodies) were included as ICIs in this study. Adverse events were identified based on the preferred terms of Medical Dictionary for Regulatory Activities (MedDRA) version 27.0/J listed in the Standardized MedDRA Queries (SMQ) “interstitial lung disease.” The reporting odds ratio was calculated to detect the association between ICI use and ILD complications, and a signal was detected if the lower limit of the 95% confidence interval exceeded 1. In the analysis of all cancer types, a signal was detected for all ICIs except avelumab. An association between ICI and ILD was detected for all cancer types with nivolumab. However, pembrolizumab exhibited a signal only in colorectal cancer. In contrast, anti-PD-L1 antibodies displayed signals in five cancer types, excluding head and neck cancer, which was not reported in JADER. Among these cancer types, atezolizumab exhibited a signal only in breast cancer. The results of this study will help guide the safe use of ICIs based on the underlying cancer type in terms of ILD complications. Fullsize Image

Background An increased risk of anemia during edoxaban thromboprophylaxis in orthopedic surgery has been reported. However, the risk factors for the exacerbation of anemia requiring transfusion with irradiated red blood cell concentrates during postoperative edoxaban thromboprophylaxis remain unknown. Therefore, this study investigated the factors that increase the possibility of transfusion during edoxaban thromboprophylaxis after orthopedic surgery by reanalyzing clinical data from a previous collection. Methods A total of 221 patients who underwent total hip or knee arthroplasty at a single center between July 2011 and June 2012 were included in this study. Among these, 167 patients who received 30 mg of postoperative edoxaban thromboprophylaxis were retrospectively analyzed to identify critical factors for transfusion during edoxaban thromboprophylaxis after orthopedic surgery. Results Lower preoperative hemoglobin levels and higher intraoperative blood loss per body weight were significantly associated with an increase in the frequency of transfusion during postoperative edoxaban thromboprophylaxis. These factors were also potentially related to increased coagulation parameters during edoxaban thromboprophylaxis. Conclusion Our study shows that lower preoperative hemoglobin levels and higher intraoperative blood loss are associated with increased coagulation parameters with edoxaban thromboprophylaxis after orthopedic surgery and may lead to worsening of anemia, thereby requiring blood transfusion.

Herbal teas have attracted attention as functional beverages containing luteolin and apigenin, which exhibit antioxidant and anti-inflammatory effects. The objective of this study was to develop a sensitive online automated method to determine these flavones’ contents in herbal teas using in-tube solid-phase microextraction (IT-SPME) coupled with liquid chromatography–tandem mass spectrometry (LC–MS/MS). These compounds were extracted and concentrated by IT-SPME using a Supel Q PLOT capillary column and then separated and detected within 6 min using a CAPCELL PAK C18 MG III analytical column and a negative electrospray ionization-mode multiple-reaction monitoring system by LC–MS/MS. The detection limits (S/N = 3) for luteolin and apigenin were 0.4 and 0.8 pg mL−1, respectively, and the calibration curves were linear in the range of 2–2000 pg mL−1 with correlation coefficients above 0.9995, and intra-day and inter-day precisions with relative standard deviations below 2.9 and 3.6% (n = 6), respectively. The luteolin and apigenin in herbal tea were quantified using IT-SPME/LC-MS/MS following the acid hydrolysis of their glycosides. Among the 10 herbal teas tested, luteolin was detected in peppermint and sage at concentrations of 375 and 99 µg mL−1, respectively, while apigenin was detected in German chamomile at 110 µg mL−1, which were higher than in the other herbal teas. The method is expected to be a useful method for evaluating the efficacy of luteolin and apigenin in herbal teas as functional beverages.