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Keiko Ino,1 Sei Ogawa,1 Masaki Kondo,1 Risa Imai,1 Toshitaka Ii,1 Toshi A Furukawa,2 Tatsuo Akechi1 1Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, 2Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan Background: Panic disorder (PD) is a common disease and presents with broad dimensions of psychopathology. Cognitive behavioral therapy (CBT) is known to improve these broad dimensions of psychopathology in addition to PD symptoms. However, little is known about the predictors of treatment response in comorbid psychiatric symptoms after CBT for PD. Recent studies suggest that anxiety sensitivity (AS) may be a key vulnerability for PD. This study aimed to examine AS as a predictor of broad dimensions of psychopathology after CBT for PD. Materials and methods: In total, 118 patients with PD were treated with manualized group CBT. We used multiple regression analysis to examine the associations between 3 Anxiety Sensitivity Index (ASI) factors (physical concerns, mental incapacitation concerns, and social concerns) at baseline and the subscales of the Symptom Checklist-90 Revised (SCL-90-R) at endpoint. Results: Low levels of social concerns at baseline predicted low levels on 5 SCL-90-R subscales after CBT: interpersonal sensitivity, depression, hostility, paranoid ideation, and psychosis. High levels of mental incapacitation concerns significantly predicted low levels on 3 SCL-90-R subscales after treatment: interpersonal sensitivity, hostility, and paranoid ideation. Physical concerns at baseline did not predict broad dimensions of psychopathology. Conclusion: This study suggested that the social concerns and mental incapacitation concerns subscales of the ASI at baseline predicted several dimensions of psychopathology after CBT for PD. To improve comorbid psychopathology, it may be useful to direct more attention to these ASI subscales. Keywords: panic disorder, anxiety sensitivity, comorbid psychopathology, predictor, cognitive behavioral therapy

A new inductive writer design for MR head with a trimmed and planarized top shield and an over-sized trailing pole is presented. The normal P2 pole is located right above the trimmed top shield, Modeling has been conducted on the write field fringing for this new design. [t shows that the field distribution pattern is just a reverse image of the traditional MR write head. With this new design, the straight fringe pattern is located at the trailing side and a better written track is expected due to the elimination of the curved write field fringing in a traditional head. The actual samples were fabricated and their performance was evaluated by MFM image. The result shows the written track is straight with nearly zero erase hand. The track width is independent of the bit density as expected.

Background: Gestational trophoblastic diseases (GTDs) are related to trophoblasts, and human chorionic gonadotropin (hCG) is secreted by GTDs as well as normal placentas. However, the asparagine-linked sugar chains on hCG contain abnormal biantennary structures in invasive mole and choriocarcinoma, but not normal pregnancy or hydatidiform mole. N-acetylglucosaminyltransferase-IV (GnT-IV) catalyses β1,4-N-acetylglucosamine branching on asparagine-linked oligosaccharides, which are consistent with the abnormal sugar chain structures on hCG.Methods: We investigated GnT-IVa expression in GTDs and placentas by immunohistochemistry, western blot, and RT-PCR. We assessed the effects of GnT-IVa knockdown in choriocarcinoma cells in vitro and in vivo.Results: The GnT-IVa was highly expressed in trophoblasts of invasive mole and choriocarcinoma, and moderately in extravillous trophoblasts during the first trimester, but not in hydatidiform mole or other normal trophoblasts. The GnT-IVa knockdown in choriocarcinoma cells significantly reduced migration and invasive capacities, and suppressed cellular adhesion to extracellular matrix proteins. The extent of β1,4-N-acetylglucosamine branching on β1 integrin was greatly reduced by GnT-IVa knockdown, although the expression of β1 integrin was not changed. In vivo studies further demonstrated that GnT-IVa knockdown suppressed tumour engraftment and growth.Conclusion: These findings suggest that GnT-IVa is involved in regulating invasion of choriocarcinoma through modifications of the oligosaccharide chains of β1 integrin. [ABSTRACT FROM AUTHOR]

Objective: To examine the relationship of fear of fear and broad dimensions of psychopathology in panic disorder with agoraphobia over the course of cognitive behavioural therapy in Japan. Methods: A total of 177 Japanese patients with panic disorder with agoraphobia were treated with group cognitive behavioural therapy between 2001 and 2015. We examined associations between the change scores in Agoraphobic Cognitions Questionnaire or Body Sensations Questionnaire and the changes in subscales of Symptom Checklist-90 Revised during cognitive behavioural therapy controlling the change in panic disorder severity using multiple regression analysis. Results: Reduction in Agoraphobic Cognitions Questionnaire score was related to a decrease in all Symptom Checklist-90 Revised (SCL-90-R) subscale scores. Reduction in Body Sensations Questionnaire score was associated with a decrease in anxiety. Reduction in Panic Disorder Severity Scale score was not related to any SCL-90-R subscale changes. Conclusions: Changes in fear of fear, especially maladaptive cognitions, may predict broad dimensions of psychopathology reductions in patients of panic disorder with agoraphobia over the course of cognitive behavioural therapy. For the sake of improving a broader range of psychiatric symptoms in patients of panic disorder with agoraphobia, more attention to maladaptive cognition changes during cognitive behavioural therapy is warranted. [ABSTRACT FROM AUTHOR]

Electrochemiluminescence (ECL) is a chemiluminescence phenomenon triggered by electrochemical reactions and is widely used for (bio)chemical analyses and electrochemical bioimaging. Compared to fluorescence sensing, ECL sensing reduces background noise by eliminating autofluorescence associated with excitation light. In addition, compared with conventional electrochemical imaging with scanning electrochemical microscopes, ECL imaging is faster as it requires no scanning. Furthermore, unlike electrode arrays, ECL devices can function without complex wiring, simplifying their construction. These characteristics render ECL sensing a useful analytical tool. Recently, ECL sensing has been widely used for in vitro cell analysis due to high demand for biochips in regenerative medicine, drug screening, and microphysiological systems. This review focuses on recent advancements in ECL-based cell analysis with applications for the detection of H 2 O 2 , respiration activity, cell adhesion, lipid membranes, and bipolar electrochemistry-based devices., Competing Interests: Declarations. Conflict of interest: All authors declare that they have no conflicts of interest., (© 2025. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Two-layer microfluidic devices with porous membranes have been widely used in bioapplications such as microphysiological systems (MPS). Porous electrodes, instead of membranes, have recently been incorporated into devices for electrochemical cell analysis. Generally, microfluidic channels are prepared using soft lithography and assembled into two-layer microfluidic devices. In addition to soft lithography, three-dimensional (3D) printing has been widely used for the direct fabrication of microfluidic devices because of its high flexibility. However, this technique has not yet been applied to the fabrication of two-layer microfluidic devices with porous electrodes. This paper proposes a novel fabrication process for this type of device. In brief, Pluronic F-127 ink was three-dimensionally printed in the form of sacrificial layers. A porous Au electrode, fabricated by sputtering Au on track-etched polyethylene terephthalate membranes, was placed between the top and bottom sacrificial layers. After covering with polydimethylsiloxane, the sacrificial layers were removed by flushing with a cold solution. To the best of our knowledge, this is the first report on the sacrificial approach-based fabrication of two-layer microfluidic devices with a porous electrode. Furthermore, the device was used for electrochemical assays of serotonin and could successfully measure concentrations up to 5 µM. In the future, this device can be used for MPS applications.

Although prescription review is an important role for pharmacists in anticancer drug therapy, there are no guidelines in Japan that specify what pharmacists should check for in chemotherapy regimens. This prospective multicenter survey aimed to investigate the implementation of chemotherapy regimen checks by pharmacists in general hospitals by focusing on 19 recommended confirmation items designed to enhance chemotherapy safety. This study involved 14 hospitals within the National Hospital Organization in different regions of Japan. The top five cancers in Japan (gastric, colorectal, lung, breast, and gynecological) were targeted and specific chemotherapy regimens were analyzed. This study assessed the amount of time required for regimen checks, the number of confirmation items completed, the number and the content of inquiries raised regarding prescriptions, and the pharmacists' opinions using a questionnaire that had a maximum score of 10 points. Pharmacists checked 345 and 375 chemotherapies of patients in the control group (CG) and recommended items group (RIG), respectively. The mean time periods required for completing a chemotherapy regimen check were 4 min and 14 s (SD ±1 min and 50 s) and 6 min and 18 s (SD, ±1 min and 7 s) in the CG and RIG, respectively. The mean of the recommended items for the CG = 12.4 and for the RIG = 18.6. The items that the pharmacists did not confirm included urine protein (sixty-nine cases, 18.4%), allergy history (four cases, 1%), previous history (two cases, 0.5%), and a previous history of hepatitis B virus (sixty-nine cases, 18.4%). The number of inquiries for a doctor's prescription order was higher in the RIG than in the CG (41 vs. 27 cases). This multicenter survey demonstrated the potential effectiveness of implementing 19 recommended confirmation items in the regimen checks by pharmacists in general hospitals other than cancer treatment collaborative base hospitals.

Tacrolimus interacts with letermovir and azole antifungals, whereas letermovir has nonuniform effects on the pharmacokinetics of azole antifungals. We retrospectively investigated the interaction of tacrolimus (continuous infusion) with letermovir considering co-administered azole antifungals in adult hematopoietic stem cell transplantation patients. The extent of intraindividual variation in the ratio of tacrolimus concentration to dose normalized by body weight (C/D ratio) was investigated. The correlation between the C/D ratio and estimated glomerular filtration rate (eGFR) was analyzed. In 35 patients (795 points), the C/D ratio was higher in the tacrolimus plus letermovir period than in the tacrolimus alone period (1234.7 [566.2-2721.0] ng/mL/mg/kg vs. 564.4 [245.3-1861.3] ng/mL/mg/kg, p < .001). This trend was observed when co-administered with azole antifungals (n = 30, 1285.5 [662.7-2506.7] ng/mL/mg/kg vs. 547.1 [245.3-1861.3] ng/mL/mg/kg, p < .001), but not without azole antifungals (n = 5, 809.9 [566.2-1573.3] ng/mL/mg/kg vs. 616.1 [350.6-979.8] ng/mL/mg/kg, p = .125). For patients co-administered fluconazole, the tacrolimus C/D ratio increased in patients with letermovir than those without letermovir (n = 28, 1215.0 [662.7-2506.7] ng/mL/mg/kg vs. 529.9 [245.3-1654.4] ng/mL/mg/kg, p < .001). Tacrolimus C/D ratio did not correlate with eGFR under letermovir and fluconazole administrations (y = 0.1x + 1307.1, r = .008, p = .968). Close blood concentration monitoring of intravenous tacrolimus is required when patients administered letermovir and azole antifungals., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Background: Posttraumatic stress disorder (PTSD) is a robust risk factor for suicide. Studies have suggested an association between suicide and elevated inflammatory markers, although such evidence in PTSD is scarce. Suicide risk, PTSD, and inflammatory molecules are all shown to be associated with childhood maltreatment and genetic factors., Methods: We examined the association between suicidal ideation/risk and inflammatory markers in 83 civilian women with PTSD, and explored the possible influence of childhood maltreatment and inflammatory genes. Suicidal ideation and risk were assessed using the Beck Depression Inventory-II and the Mini-International Neuropsychiatric Interview. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire (CTQ). Blood levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and high-sensitivity tumor necrosis factor-α were measured. Genetic polymorphisms of CRP rs2794520 and IL6 rs1800796 were genotyped., Results: Suicidal ideation was significantly positively correlated with hsCRP (p = 0.002) and IL-6 (p = 0.015) levels. Suicide risk weighted score was significantly positively correlated with hsCRP (p = 0.016) levels. The risk alleles of CRP rs2794520 and IL6 rs1800796 leading to increased respective protein levels were dose-dependently associated with higher risk of suicide (p = 0.007 and p = 0.029, respectively). The CTQ total score was significantly correlated with suicidal ideation and risk, but not with inflammatory marker levels. Furthermore, a multivariate regression analysis controlling for PTSD severity and potential confounders revealed that rs2794520 and rs1800796, but not hsCRP or IL-6 levels, significantly predicted suicidal ideation (p < 0.001) and risk (p = 0.007), respectively., Conclusion: Genetic variations within inflammatory genes might be useful in detecting PTSD patients at high risk of suicide., Competing Interests: The authors declare that they have no competing interests., (© 2023 The Authors.)

Heterogeneous nature is a pivotal aspect of cancer, rendering treatment problematic and frequently resulting in recurrence. Therefore, advanced techniques for identifying subpopulations of a tumour in an intact state are essential to develop novel screening platforms that can reveal differences in treatment response among subpopulations. Herein, we conducted a non-invasive analysis of oxygen metabolism on multiple subpopulations of patient-derived organoids, examining its potential utility for non-destructive identification of subpopulations. We utilised scanning electrochemical microscopy (SECM) for non-invasive analysis of oxygen metabolism. As models of tumours with heterogeneous subpopulations, we used patient-derived cancer organoids with a distinct growth potential established using the cancer tissue-originated spheroid methodology. Scanning electrochemical microscopy measurements enabled the analysis of the oxygen consumption rate (OCR) for individual organoids as small as 100 µm in diameter and could detect the heterogeneity amongst studied subpopulations, which was not observed in conventional colorectal cancer cell lines. Furthermore, our oxygen metabolism analysis of pre-isolated subpopulations with a slow growth potential revealed that oxygen consumption rate may reflect differences in the growth rate of organoids. Although the proposed technique currently lacks single-cell level sensitivity, the variability of oxygen metabolism across tumour subpopulations is expected to serve as an important indicator for the discrimination of tumour subpopulations and construction of novel drug screening platforms in the future., Competing Interests: KO and MI belong to the Department of Clinical Bio-Resource Research and Development at Kyoto University, which is sponsored by KBBM, Inc. MI is an inventor of the patents related to the CTOS method. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nashimoto, Shishido, Onuma, Ino, Inoue and Shiku.)

The Limulus amebocyte lysate (LAL) reaction-based assay, the most commonly used endotoxin detection method, requires a skilled technician. In this study, to develop an easy-to-use and highly sensitive endotoxin sensor, we created an electrochemical endotoxin sensor by using an interdigitated array electrode (IDAE) device with advantages of amplifiable signals via redox cycling and portability. We added Boc-Leu-Gly-Arg- p -aminophenol (LGR-pAP) as an electrochemical substrate for an LAL reaction and detected p -aminophenol (pAP) released from LGR-pAP as a product of an endotoxin-induced LAL reaction via an IDAE device. The IDAE device showed a great redox cycling efficiency of 79.8%, and a 4.79-fold signal amplification rate. Then, we confirmed that pAP was detectable in the presence of LGR-pAP through chronoamperometry with the potential of the anode stepped from -0.3 to 0.5 V vs. Ag/AgCl while the cathode was biased at -0.3 V vs. Ag/AgCl. Then, we performed an endotoxin assay by using the IDAE device. Our endotoxin sensor detected as low as 0.7 and 1.0 endotoxin unit/L after the LAL reaction for 1 h and 45 min, respectively, and these data were within the cut-off value for ultrapure dialysis fluid. Therefore, our highly sensitive endotoxin sensor is useful for ensuring medical safety.

Accumulated evidence shows that psychological trauma and posttraumatic stress disorder (PTSD) are associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis. Besides the HPA axis hormones, recent evidence suggests that the renin-angiotensin-aldosterone (RAA) system and genetic factors may be involved in trauma/PTSD as well as in HPA axis regulation. This study attempted to better understand the HPA axis function in relation to PTSD and childhood maltreatment by simultaneously examining RAA system and genetic polymorphisms of candidate genes. Here we studied 69 civilian women with PTSD and 107 healthy control women without DSM-IV-based traumatic experience. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire. PTSD severity was assessed with the Posttraumatic Diagnostic Scale. Functional disability was assessed with the Sheehan Disability Scale. HPA axis was examined by measuring blood levels of cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone-sulphate (DHEA-S). RAA system was examined by measuring blood renin and aldosterone levels. The FKBP5 rs1360780 and CACNA1C rs1006737 polymorphisms were genotyped. No significant differences were seen between patients and controls in any of the five hormone levels. DHEA-S levels were significantly negatively correlated with overall PTSD severity ( p = 0.003) and functional disability ( p = 0.008). A two-way analysis of variance with diagnostic groups and genotypes as fixed factors revealed that patients with the rs1006737 A-allele had significantly lower DHEA-S levels than patients with the GG genotype ( p = 0.002) and controls with the A-allele ( p = 0.006). Childhood maltreatment history was not significantly correlated with any of the five hormone levels. These results were generally unchanged after controlling for the potentially confounding effect of age, depression, and anxiety. Our findings suggest that lower DHEA-S levels could indicate more severe subtype of PTSD, the association of which might be partly modified by the CACNA1C polymorphism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kakehi, Hori, Yoshida, Itoh, Lin, Niwa, Narita, Ino, Imai, Sasayama, Kamo, Kunugi and Kim.)

Microphysiological systems (MPSs) with three-dimensional (3D) cultured models have attracted considerable interest because of their potential to mimic human health and disease conditions. Recent MPSs have shown significant advancements in engineering perfusable vascular networks integrated with 3D culture models, realizing a more physiological environment in vitro; however, a sensing system that can monitor their activity under biomimetic vascular flow is lacking. We designed an open-top microfluidic device with sensor capabilities and demonstrated its application in analyzing oxygen metabolism in vascularized 3D tissue models. We first validated the platform by using human lung fibroblast (hLF) spheroids. Then, we applied the platform to a patient-derived cancer organoid and evaluated the changes in oxygen metabolism during drug administration through the vascular network. We found that the platform could integrate a perfusable vascular network with 3D cultured cells, and the electrochemical sensor could detect the change in oxygen metabolism in a quantitative, non-invasive, and real-time manner. This platform would become a monitoring system for 3D cultured cells integrated with a perfusable vascular network., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: This study aims to estimate the population-based incidence of gestational trophoblastic diseases (GTDs) and to identify the characteristics of gestational trophoblastic neoplasia (GTN) in Japan., Methods: The annual number of GTD and live births from 1974 to 2018 were used to estimate the incidence of GTD. The data of 1,574 GTN cases from 1999 to 2018 were analyzed to identify the characteristics of low-risk GTN, high-risk GTN, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)., Results: The incidence of hydatidiform mole was 2.02 per 1,000 live births on average which decreased from 1974 to 2008 and increased from 2009 to 2018. The incidence of low-risk GTN, high-risk GTN, PSTT, and ETT was 15.3, 3.5, 0.3, and 0.07 per 100,000 live births, respectively. The estimated incidence of post-molar GTN was 9.8% of molar patients. High-risk GTN was diagnosed more pathologically, had more various kinds of antecedent pregnancies, and had longer intervals after the antecedent pregnancy compared to low-risk GTN. Furthermore, 8.2% of high-risk GTN occurred after the subsequent non-molar pregnancy of hydatidiform mole. The cumulative percentage of developing high-risk GTN after hydatidiform mole reached 89.3% at the 60th month., Conclusion: The incidence of hydatidiform mole, low-risk GTN, high-risk GTN was 2.02 per 1,000 live births, 15.3 per 100,000 live births, and 3.5 per 100,000 live births, respectively. High-risk GTN was diagnosed more pathologically and later after the antecedent pregnancy than low-risk GTN. Following molar patients for five years is needed to improve the mortality of malignant GTN., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Endothelial cells have been widely used for vascular biology studies; recent progress in tissue engineering have offered three-dimensional (3D) culture systems for vascular endothelial cells which can be considered as physiologically relevant models. To facilitate the studies, we developed an electrochemical device to detect nitric oxide (NO), a key molecule in the vasculature, for the evaluation of 3D cultured endothelial cells. Using an NO-sensitive catalyst composed of Fe-N co-doped reduced graphene oxide, the real-time monitoring of NO release from the endothelial cell spheroids was demonstrated., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Calnexin (CNX), a membrane-bound molecular chaperone, is involved in protein folding and quality control of nascent glycoproteins in the endoplasmic reticulum. We previously suggested critical roles of calreticulin, a functional paralogue of CNX, in placentation, including invasion of extravillous trophoblasts and syncytialization of cytotrophoblasts. However, the roles of CNX in placentation are unclear. In human choriocarcinoma BeWo cells, which serve as an experimental model of syncytialization, CNX knockdown suppressed forskolin-induced cell fusion and β-human chorionic gonadotropin (β-hCG) induction. Cell-surface luteinizing hormone/chorionic gonadotropin receptor, a β-hCG receptor, was significantly down-regulated in CNX-knockdown cells, which suggested the presence of a dysfunctional autocrine loop of β-hCG up-regulation. In this study, we also found abundant CNX expression in normal human placentas. Collectively, our results revealed the critical role of CNX in the syncytialization-related signaling in a villous trophoblast model and suggest a link between CNX expression and placenta development.

The association between endometrial cancer and the BRCA1 and BRCA2 genes is not fully understood, and the risk elevation of endometrial cancer in patients with hereditary breast and ovarian cancer (HBOC) is not understood. The present report examines a rare case of HBOC syndrome and an uncharacterized variant of the BRCA1 gene in a patient diagnosed with endometrial cancer. A 46-year-old woman, gravida 1 para 1, was referred to Wakayama Medical University Hospital (Wakayama, Japan) because positron emission tomography/computed tomography (PET/CT) showed a high FDG uptake in the corpus uteri and the left ovary. PET/CT was performed just after mastectomy for left-sided breast cancer (triple negative). The patient had previously undergone partial mastectomy for right-sided breast cancer (triple negative) and was treated with radiation therapy to the right residual breast when she was 39 years old. Laparoscopic hysterectomy and bilateral adnexectomy were performed, and the histological diagnosis was endometrioid carcinoma, grade 1. Her germline BRCA status was tested by blood examination and the result was 'NM&#95;007294.4(BRCA1):c.49G>C (p.Ala17Pro)'. The variant was evaluated as 'likely pathogenic'. The patient was diagnosed with HBOC syndrome and endometrial cancer, pT1ANxM0. The patient had no recurrence of breast or endometrial cancer 16 months after gynecologic surgery., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Mabuchi et al.)