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Objective: This study was undertaken by the Epilepsy Subcommittee of the Japanese Society of General Hospital Psychiatry (JSGHP) to explore the challenges faced by psychiatrists in treating epilepsy and the difficulties encountered during the transition of patients with epilepsy (PWE) from pediatric to adult care., Methods: An online survey targeting 1,980 JSGHP-affiliated psychiatrists was conducted from May to July 2022. The participants were asked to complete a questionnaire on epilepsy care. We analyzed the factors associated with participant hesitancy to treat epilepsy and their professional characteristics., Results: Responses were obtained from 545 of the 1,980 solicited psychiatrists (response rate: 27.5 %). The mean number of years of clinical experience in psychiatry was 20.9 ± 10.3 years. A majority of the psychiatrists were hesitant toward treating epilepsy (89.2 %) and managing the transition of PWE from pediatric services to adult care (83.3 %). Logistic regression analysis showed that the absence of hesitation toward epilepsy treatment was significantly associated with years of clinical experience in psychiatry (OR: 1.05, p = 0.002), being a board-certified epileptologist (OR: 4.36, p = 0.037), having colleagues who are specialists in epilepsy care that may be consulted in the workplace (OR: 2.12, p = 0.027), and general confidence in managing PWE transition from pediatric to adult care (OR 3.54, p < 0.001). Confidence in managing the transition was positively correlated with being a board-certified psychiatrist of the Japanese Society of Psychiatry and Neurology (OR: 4.55, p = 0.048), being a board-certified psychiatrist of the JSGHP (OR: 1.75, p = 0.034), treating six or more PWE per month (OR: 3.54; 95 % CI, p < 0.001), and overall confidence in treating epilepsy (OR: 3.38, p < 0.001)., Conclusions: Alleviation of reluctance to providing epilepsy care and managing the process of transition are correlated; however, the factors influencing each are distinct. To reduce resistance to epilepsy treatment, enhancing the knowledge of epilepsy and creating an environment conducive to consultations are essential. Improving transition-related outcomes, having substantial psychiatric expertise, and increasing opportunities to treat PWE are of great significance. The integration of these approaches may enable psychiatrists to alleviate hesitancy towards epilepsy care and enhance both treatment and transitional care modalities., 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 © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study was designed to investigate the prognostic significance of artificial intelligence (AI)-based quantification of myxoid stroma in patients undergoing esophageal squamous cell carcinoma (ESCC) surgery after neoadjuvant chemotherapy (NAC) and to verify its significance in an independent validation cohort from another hospital., Methods: We evaluated two datasets of patients with pathological stage II or III ESCC who underwent surgery after NAC. Cohort 1 consisted of 85 patients who underwent R0 surgery for the primary tumor after NAC. Cohort 2, the validation cohort, consisted of 80 patients who received same treatments in another hospital. AI-based myxoid stroma was evaluated in resected specimens, and its area was categorized by using the receiver operating characteristic curve for overall survival (OS) of cohort 1., Results: The F1 scores, which are the degree of agreement between the automatically detected myxoid stroma and manual annotations, were 0.83 and 0.79 for cohorts 1 and 2. The myxoid stroma-high group had a significantly poorer prognosis than the myxoid stroma-low group in terms of OS, disease-specific survival (DSS), and recurrence-free survival (RFS) in cohort 1. Comparable results were observed in cohort 2, where OS, DSS, and RFS were significantly affected by myxoid stroma. Multivariate analysis for RFS revealed that AI-determined myxoid stroma-high was one of the independent prognostic factors in cohort 1 (hazard ratio [HR] 1.97, p = 0.037) and cohort 2 (HR 4.45, p < 0.001)., Conclusions: AI-determined myxoid stroma may be a novel and useful prognostic factor for patients with pathological stage II or III ESCC after NAC., (© 2024. Society of Surgical Oncology.)

A practical and improved synthetic route for the scalable synthesis of homohalichondrin B has been developed. Formation of the highly stereoselective [6,6]-spiroskeleton system through a convergent Ni/Zr-mediated ketone coupling, followed by acid-promoted spiroketalization, simplified the route considerably. Higher coupling efficiency was achieved by fine-tuning the Ni I /Ni II (1:50) catalyst loadings with an equimolar (1:1) mixture of coupling partners.

Superior mesenteric artery (SMA) invasion by a malignant tumour is a serious condition leading to intestinal ischaemia. Although SMA stenting has been reported to be useful for SMA dissection and stenosis caused by atherosclerotic plaque, SMA stenting for stenosis caused by malignant tumour invasion is rarely reported and uncertain. A 75-year-old woman presented intestinal ulcer and melena caused by SMA invasion of unresectable pancreatic cancer. The bare metal stent was implanted for the vessel stenosis, and a small intestinal ulcer was markedly improved after stenting. However, one and a half months after stenting the stent was occluded and a thrombectomy was performed. After thrombectomy, residual stenosis caused by tumour invasion was observed in the stent. The patient suddenly died 2 days after thrombectomy before additional covered stenting for residual stenosis. Stent implantation may be a treatment option for intestinal ischaemia caused by vessel invasion of malignant tumours. On the other hand, re-stenosis of the stent due to tumour ingrowth is a problem, and covered stenting is considered for long-term stent patency., Competing Interests: The authors declare that they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Tumor markers such as carbohydrate antigen 19-9 (CA19-9) are generally useful in ruling out malignancy of hepatic cysts. The patient was a 72-year-old man who had a ruptured liver cyst in the right liver, which had been noted since he was 67 years old at another hospital. The initial laboratory tests demonstrated elevated CA19-9 (193 784.3 U/mL). We made the diagnosis with a simple ruptured liver cyst from magnetic resonance imaging and cytological examination of ascites, and laparoscopic fenestration with drainage of the abdominal fluid was performed. Pathological diagnosis of the resected wall cyst was non-parasitic simple hepatic cyst with acute inflammation and hemorrhage. The patient's serum levels of CA19-9 were 164.0 U/mL on postoperative day 23. The follow-up abdominal computed tomography scan performed 2 months later did not any finding of tumor., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background and study aims Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) has the potential to reduce the occurrence of delayed adverse events (AEs) such as bleeding and perforation. This study aimed to assess the feasibility and effectiveness of the Loop9 method for closing mucosal defects following colorectal ESD. Patients and methods A retrospective single-center study was conducted using prospectively collected data from May 2020 to March 2023. Loop9 was deployed through a single instrument channel and anchored with clips at the defect site. Closure was accomplished by tightening the loop and deploying additional conventional clips as needed for complete closure. The primary outcome was complete closure rate, with secondary outcomes including the sustained closure rate at 4 to 5 days post-ESD, closed defect size, closure time, number of additional clips, and incidence of delayed AEs. Results This study included 118 cases. Complete closure was achieved in 96.6% of cases (114/118) with a sustained closure rate of 93.9% (107/114). The median size of the closed mucosal defects was 30 mm (interquartile range [IQR]: 25-38, range: 15-74). The median closure time was 14 minutes (IQR: 11.25-17), and the median number of additional clips deployed was six (IQR: 4-7). Stenosis requiring balloon dilatation was observed in one patient; however, there were no instances of post-ESD bleeding or delayed perforation. Conclusions The Loop9 method proved feasible and effective for closing mucosal defects following colorectal ESD, achieving high rates of complete and sustained closure., Competing Interests: Conflict of Interest Author H.I. serves as an advisor for Olympus Corporation and Top Corporation. In addition, he has received educational grants from Olympus Corporation and Takeda Pharmaceutical Company. The remaining authors have no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Rationale: Clozapine, the standard treatment for treatment-resistant schizophrenia (TRS), is generally recommended in a multiple-daily dosing regimen. However, it is commonly administered once daily in clinical practice. Few studies have compared the longitudinal clinical outcomes of these two dosing regimens., Objective: To investigate the effect of once-daily versus multiple-daily dosing regimens of clozapine on relapse in patients with TRS., Methods: This retrospective cohort study included patients with TRS who commenced treatment with clozapine during hospitalization and were discharged between April 2012 and January 2022 from a tertiary psychiatric hospital in Japan. Relapse, defined as a psychiatric exacerbation requiring re-hospitalization within the first-year post-discharge, was analyzed. Multivariable Cox proportional hazards regression analysis compared the relapse risk between once-daily and multiple-daily dosing regimens. A subgroup analysis was conducted to examine the potential interactions between dosing regimen and dose category (low versus high dose)., Results: Among 179 patients, 107 (59.8%) received clozapine once daily. No significant difference in the relapse risk was observed between once-daily and multiple-daily dosing regimens (adjusted hazard ratio [aHR]: 1.16; 95% confidence interval [CI]: 0.68-1.99; p = 0.58). However, in patients receiving high doses of clozapine (> 300 mg/day), multiple-daily dosing increased the relapse risk compared to once-daily dosing (aHR: 2.23; 95% CI: 1.00-4.97; p = 0.049)., Conclusions: Once-daily clozapine dosing may not be associated with an increased relapse risk. The increased relapse risk in high-dose multiple-daily dosing may be confounded by unmeasured non-adherence. Further randomized controlled trials are required to validate these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study examined whether patient-reported measures (PRMs) addressing quality of life, personal agency, functional impairment, and treatment satisfaction at hospital discharge were associated with future readmission during a 12-month follow-up period. The study also examined whether readmission influenced changes in the same measures., Methods: A multicenter prospective cohort study was conducted at 21 psychiatric hospitals in Japan. Participants completed the EuroQol-five-dimensions-five-level (EQ-5D), the Five-item Subjective Personal Agency Scale, and the Sheehan Disability Scale (SDS) at the time of index admission (T1), discharge from index admission (T2), and 6 months (T3) and 12 months (T4) after discharge. Inpatient treatment satisfaction was assessed at T2. Readmission and variables potentially associated with hospitalization and PRMs were evaluated using mixed-effects logistic regression models and mixed models for repeated measures., Results: A total of 491 participants were followed for 12 months (attrition rate: 19.4%), and 480 were included in the EQ-5D analysis. The most common diagnoses were schizophrenia (59%), depression (14%), and bipolar disorder (13%). No patient-reported measures were significantly associated with readmission over the follow-up period. Interaction of readmission and time did not significantly affect changes in EQ-5D. Readmission did significantly influence SDS score changes between T2 and T3 (B = 1.78, 95% CI = 0.30-3.25, p = 0.018) and between T3 and T4 (B = 1.43, 95% CI = 0.14-2.72, p = 0.029). The same influence of readmission on SDS score changes was not observed in the model which adjusted for all potential covariates., Conclusion: Readmission was potentially associated with changes in self-reported functional impairment. Findings highlight the potential role of intensive post-discharge services in preventing readmission, rather than relying on time-of-discharge PRMs in order to predict readmission risk., Trial Registration: This study was registered in UMIN Clinical Trials Registry (UMIN000034220)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Importance: Delirium is common among older hospitalized adults. In addition to presenting immediate management issues, delirium can increase the long-term risk of dementia, institutionalization, and mortality. Delirium is associated with disrupted sleep, and prior studies suggest that some specific sleep-promoting agents may reduce delirium., Objective: To evaluate the orexin receptor antagonist suvorexant for reducing delirium in older adults at high risk for delirium after hospitalization., Design, Setting, and Participants: This double-blind, placebo-controlled, phase 3 randomized clinical trial was conducted at 50 hospitals in Japan between October 22, 2020, and December 23, 2022. The study population included Japanese adults aged 65 to 90 years who were at high risk for delirium (mild cognitive impairment or mild dementia, history of delirium at prior hospitalization, or both) and had been hospitalized for acute disease or elective surgery. Data analysis was performed between January 23 and March 13, 2023., Intervention: Participants were randomized 1:1 to suvorexant (15 mg) or placebo taken at bedtime for up to 7 days while in the hospital., Main Outcomes and Measures: Delirium, the primary end point, was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria while participants were hospitalized. The treatment difference in the proportion of participants with delirium was analyzed., Results: This study included 203 participants: 101 were treated with suvorexant (mean [SD] age, 81.5 [4.5]; years; 52 men [51.5%] and 49 women [48.5%]) and 102 received placebo (mean [SD] age, 82.0 [4.9] years; 45 men [44.1%] and 57 women [55.9%]). There were 17 participants with delirium (16.8%) in the suvorexant group compared with 27 (26.5%) in the placebo group (difference, -8.7% [95% CI, -20.1% to 2.6%]; P = .13). Adverse events were similar between the 2 groups., Conclusions and Relevance: In this randomized clinical trial of suvorexant in older adults at high risk for delirium after hospitalization, fewer participants taking suvorexant had delirium compared with placebo, but the difference was not statistically significant. Further studies are needed to determine whether suvorexant may be useful for reducing delirium, particularly delirium with a hyperactive component, in this population., Trial Registration: ClinicalTrials.gov Identifier: NCT04571944.

The lack of a widely accessible method for expressing genes of interest in wild-type embryos is a fundamental obstacle to understanding genetic regulation during embryonic development. In particular, only a few methods are available for introducing gene expression vectors into cells prior to neural tube closure, which is a period of drastic development for many tissues. In this study, we present a simple technique for injecting vectors into the amniotic cavity and allowing them to reach the ectodermal cells and the epithelia of endodermal organs of mouse embryos at E8.0 via in utero injection, using only a widely used optical fiber with an illuminator. Using this technique, retroviruses can be introduced to facilitate the labeling of cells in various tissues, including the brain, spinal cord, epidermis, and digestive and respiratory organs. We also demonstrated in utero electroporation of plasmid DNA into E7.0 and E8.0 embryos. Taking advantage of this method, we reveal the association between Ldb1 and the activity of the Neurog2 transcription factor in the mouse neocortex. This technique can aid in analyzing the roles of genes of interest during endo- and ectodermal development prior to neural tube closure., 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 © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We investigated whether the preoperative treatment of patients with pancreatic cancer is a risk factor for hepatic steatosis (HS), and whether preoperative HS affects the short-term postoperative outcomes., Methods: Patients who underwent radical surgery for pancreatic cancer between 2010 and 2023 were enrolled. The patients' medical records were reviewed. Albumin and carbohydrate antigen 19-9 were measured before and after chemotherapy in the patients who received preoperative chemotherapy. A logistic regression univariate analysis was performed to analyze the factors associated with new-onset HS., Results: A total of 230 patients who underwent surgery were included. HS was observed on the date of surgery in 11 (10%) and two (2%) patients with and without preoperative chemotherapy, respectively. Female sex, initially borderline resectable or unresectable disease, history of cholangitis, presence of PEI, long-term (≥ 3 months) biliary drainage, preoperative chemotherapy, and serum albumin ≥ 3.9 mg/dl before chemotherapy were identified as risk factors for HS. The incidence of postoperative morbidity did not differ between the patients with and without preoperative steatosis., Conclusions: Preoperative chemotherapy, a history of cholangitis, the presence of PEI, and ≥ 3 months' duration of biliary drainage were risk factors for the development of HS before surgery for pancreatic cancer. However, preoperative HS did not affect the short-term postoperative outcomes., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Schizophrenia develops during adolescence. Maternal infections during the fetal period increase the incidence of schizophrenia in children, which suggests that the pathogenesis involves neuroinflammation. Here, we report a case of new-onset schizophrenia in a 16-year-old boy after COVID-19. After developing COVID-19, he entered a catatonic state 4 days later and was hospitalized. Benzodiazepines alleviated his catatonia, but hallucinations and delusions persisted. Encephalitis and epilepsy were excluded by magnetic resonance imaging (MRI), encephalography, and cerebrospinal fluid examination. Psychosis persisted after the virus titer declined and the inflammatory response subsided. Moreover, the patient exhibited delusions of control-a Schneider's first-rank symptom. Schizophrenia was diagnosed, and olanzapine improved his symptoms. He had a brief history of insomnia before COVID-19 but his symptoms did not satisfy the ultra-high-risk criteria. However, COVID-19 may have facilitated development of schizophrenia through neuroinflammation and volume reduction in the gray matter of the right medial temporal lobe. This case demonstrates that infectious diseases in adolescents should be carefully managed, to prevent schizophrenia.

Pancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and it has a recurrence rate of >70%, even in resectable cases. The treatment strategy for recurrent PDAC involves systemic chemotherapy, with gemcitabine (GEM) monotherapy historically serving as the standard of care. The present study describes the case of a patient with PDAC and postoperative liver metastases that maintained clinical complete remission (cCR) for >7 years following GEM monotherapy. A 63-year-old woman with upper abdominal pain was diagnosed with resectable PDAC and underwent pancreaticoduodenectomy. The patient was treated with GEM + S-1 as adjuvant chemotherapy for 6 months. Multiple liver metastases were detected 15 months post-operation and the patient was administered GEM alone. After 12 cycles, computed tomography showed cCR and GEM monotherapy was discontinued after 15 cycles. The patient has had no signs or symptoms of recurrence >7 years after the first recurrence. In addition, the present study analyzed PDAC resection specimens from four patients, including this case, to determine the expression levels of hENT1 protein in the tumor tissues. hENT1 is a transmembrane protein that acts as a nucleoside transporter and is a major mediator of GEM uptake into human cells. In the present case, hENT1 staining exhibited low frequency and weak positivity in the central region, whereas a strong positive reaction was observed in nearly all cell membranes at the invasive front of the cancer. The location, intensity, and frequency of hENT1 staining varied among cases. In conclusion, the efficacy of GEM may be predicted prior to treatment by evaluating hENT1 expression., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Mayuko et al.)

Adjuvant chemotherapy is usually not considered for pT1a pN0 human epidermal growth factor receptor 2 (HER2)-positive breast cancer due to its low recurrence rate. The present report describes a case of pT1a hormone receptor-positive HER2-positive breast cancer with multiple recurrences in the axillary lymph nodes and liver within 1 year after radical surgery. A 58-year-old woman underwent left total mastectomy and sentinel lymph node biopsy for left breast cancer with pathological stage IA (pT1a pN0). The subtype corresponded to luminal B-like breast cancer with a nuclear grade of 3 and a Ki-67 labeling index of 37%. An aromatase inhibitor (letrozole) was planned to be administered for 5 years after surgery, but the patient was diagnosed with multiple liver and axillary lymph node metastases 11 months after surgery. After 1 year of chemotherapy (paclitaxel) in combination with anti-HER2 therapy (pertuzumab and trastuzumab), liver metastases resolved. A complete response of the liver lesion has been maintained 4 years after the anti-HER2 therapy initiation. The present case exhibited two poor prognostic factors: High Ki-67 labeling index and nuclear grade 3. Based on the 'Predict' tool, the present case would be expected to have a cancer-related mortality rate of 6% 10 years after surgery with adjuvant endocrine therapy. Although this value may be controversial for postoperative anti-HER2 therapy, the present case should not be considered to be a low-risk case. When the identification of high-risk pT1a pN0 HER2-positive breast cancer is possible, postoperative anti-HER2 therapy plus chemotherapy would be effective in decreasing the rate of recurrence., Competing Interests: TY received honoraria from Eli Lilly Japan K.K. The other authors declare that they have no competing interests., (Copyright: © 2024 Suzuki et al.)

Mitochondria-ER membrane contact sites (MERCS) represent a fundamental ultrastructural feature underlying unique biochemistry and physiology in eukaryotic cells. The ER protein PDZD8 is required for the formation of MERCS in many cell types, however, its tethering partner on the outer mitochondrial membrane (OMM) is currently unknown. Here we identified the OMM protein FKBP8 as the tethering partner of PDZD8 using a combination of unbiased proximity proteomics, CRISPR-Cas9 endogenous protein tagging, Cryo-Electron Microscopy (Cryo-EM) tomography, and correlative light-EM (CLEM). Single molecule tracking revealed highly dynamic diffusion properties of PDZD8 along the ER membrane with significant pauses and capture at MERCS. Overexpression of FKBP8 was sufficient to narrow the ER-OMM distance, whereas independent versus combined deletions of these two proteins demonstrated their interdependence for MERCS formation. Furthermore, PDZD8 enhances mitochondrial complexity in a FKBP8-dependent manner. Our results identify a novel ER-mitochondria tethering complex that regulates mitochondrial morphology in mammalian cells.

Psychopharmacotherapy for patients with schizophrenia in Japan has a long history of polypharmacy, which is rare worldwide but remains a critical problem. One reason for this is that clozapine was not available in Japan until 2009. We aimed to investigate the changes in psychopharmacotherapy in patients with schizophrenia over 12 years pre- and post-introduction of clozapine to clarify how psychopharmacotherapy for patients with schizophrenia has changed with the introduction of clozapine. We retrospectively collected data from the medical records of inpatients diagnosed with schizophrenia at the Okayama Psychiatric Medical Center. Chlorpromazine equivalent (CP-eq) decreased from 1276.6 mg/day in 2009 to 613.9 mg/day in 2020. The prescribed daily dose/defined daily dose (PDD/DDD) decreased from 3.0 in 2009 to 1.2 in 2020. The monotherapy rate increased from 24.4 % in 2009 to 74.6 % in 2020. Our institution began using clozapine in 2010, and the prescription rate for clozapine increased to 37.3 % in 2020. The prescription rate for more than three antipsychotics decreased from 27.8 % in 2009 to 0.8 % in 2020. The increase in clozapine prescription has contributed to an increased rate of antipsychotic monotherapy and a decreased rate of polypharmacy, promoting the optimization of schizophrenia medication. Clozapine therapy should be further promoted in Japan to reduce treatment-resistant schizophrenia due to polypharmacy as much as possible., Competing Interests: Declaration of Competing Interest Mr. Kitagawa has received research grants from the Policy-Based Medical Services Foundation, Japan Society for the Promotion of Science; speaker’s honoraria from Novartis Pharma and Otsuka; and manuscript fees from the Japanese Society of Psychiatric Pharmacy, the Pharmaceutical Society of Japan, Jiho, and Nanzando., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chronic spontaneous urticaria (CSU), characterized by the recurrence of pruritic hives and/or angioedema for >6 weeks with no identifiable trigger, has a negative impact on health-related quality of life (HRQoL). Methods: The objective of this web-based cross-sectional study was to evaluate disease control, disease burden, and treatment satisfaction in Japanese adults with CSU using the Urticaria Control Test (UCT), HRQoL outcomes, and the Treatment Satisfaction Questionnaire for Medication-9 items (TSQM-9). Results: In total, 529 adults were included in the analysis (59.9% female), with a mean ± standard deviation (SD) in CSU duration of 13.2 ± 13.0 years. Based on UCT scores, two-thirds of patients had poor (score of 0-7; 23.6%) or insufficient (score of 8-11; 43.3%) symptom control, and one-third had good control (score of 12-16; 33.1%). Overall treatment satisfaction was not high, with mean ± SD TSQM-9 scores of 55.5 ± 17.6% for effectiveness, 68.2 ± 18.8% for convenience, and 59.2 ± 18.4% for global satisfaction. No apparent differences in TSQM-9 scores were observed between patients receiving different medications. HRQoL outcomes were worse among patients with poor/insufficient symptom control. Conclusions: Japanese adults with CSU have a high disease burden, and better treatment options are needed to increase treatment satisfaction., Competing Interests: A.F. has received research funding from Taiho Pharmaceutical Co., Ltd.; and lecture fees from Sanofi K.K., Y.K., K.A. and H.F. are employees of Sanofi K.K., and may hold shares in the company. The funding source was involved in study design, data interpretation, and manuscript preparation.

Tumor resectability, which is increasingly determined based on preoperative chemotherapy, is critical in determining the best treatment for pancreatic cancers. The present study evaluated the usefulness of serum carbohydrate antigen 19-9 (CA19-9) and the preoperative 8F-fluorodeoxyglucose positron emission tomography/computed tomography standardized uptake value (SUV) percentage change (SUVmax%=[(SUVmax2-SUVmax1)/SUVmax1] ×100, where SUVmax1 and SUVmax2 represent the initial and delayed phases, respectively) as biological factors indicative of tumor resectability. The present study included patients with resectable pancreatic cancer who underwent complete surgical resection, for whom both CA19-9 and SUVmax% were documented using cut-off values of 500 U/ml and 24.25%, respectively. Patients were classified as follows: i) High CA19-9 and SUVmax%: both CA19-9 and SUVmax% were elevated; ii) high CA19-9 or SUVmax%: either CA19-9 or SUVmax% were elevated; or iii) low CA19-9 and SUVmax%: neither value met the cut-off. Relapse-free survival (RFS) and overall survival (OS) were calculated, for which univariate and multivariate analyses were performed. Of the 86 patients included, 39 were classified as high CA19-9 or SUVmax% and 12 as high CA19-9 and SUVmax%, with the former group having a significantly worse RFS (vs. low CA19-9 and SUVmax%; P<0.001; vs. high CA19-9 or SUVmax%; P=0.011) and OS (vs. low CA19-9 and SUVmax%, P=0.002; vs. high CA19-9 or SUVmax%, P<0.001). Therefore, high CA19-9 and SUVmax% was an independent predictor of worse RFS (P<0.001) and OS (P=0.003). In conclusion, CA19-9 and SUVmax% can be utilized as biological indicators of resectability., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Kobayashi et al.)

GABAergic inhibitory interneurons, originating from the embryonic ventral forebrain territories, traverse a convoluted migratory path to reach the neocortex. These interneuron precursors undergo sequential phases of tangential and radial migration before settling into specific laminae during differentiation. Here, we show that the developmental trajectory of FoxG1 expression is dynamically controlled in these interneuron precursors at critical junctures of migration. By utilizing mouse genetic strategies, we elucidate the pivotal role of precise changes in FoxG1 expression levels during interneuron specification and migration. Our findings underscore the gene dosage-dependent function of FoxG1 , aligning with clinical observations of FOXG1 haploinsufficiency and duplication in syndromic forms of autism spectrum disorders. In conclusion, our results reveal the finely tuned developmental clock governing cortical interneuron development, driven by temporal dynamics and the dose-dependent actions of FoxG1 ., Competing Interests: Competing interests statement:The authors declare no competing interest.

E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.

If our visual system has a distinct computational process for motion trajectories, such a process may minimize redundancy and emphasize variation in object trajectories by adapting to the current statistics. Our experiments show that after adaptation to multiple objects traveling along trajectories with a common tilt, the trajectory of an object was perceived as tilting on the repulsive side. This trajectory aftereffect occurred irrespective of whether the tilt of the adapting stimulus was physical or an illusion from motion-induced position shifts and did not differ in size across the physical and illusory conditions. Moreover, when the perceived and physical tilts competed during adaptation, the trajectory aftereffect depended on the perceived tilt. The trajectory aftereffect transferred between hemifields and was not explained by motion-insensitive orientation adaptation or attention. These findings provide evidence for a trajectory-specific adaptable process that depends on higher-order representations after the integration of position and motion signals., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Aims: In order to uphold and enhance the emergency psychiatric care system, a thorough comprehension of the characteristics of patients who require a high-acuity psychiatry unit is indispensable. We aimed to clarify the most important predictors of the need for a high-acuity psychiatry unit using a random forest model., Methods: This cross-sectional study encompassed patients admitted to psychiatric emergency hospitals at 161 medical institutions across Japan between December 8, 2022, and January 31, 2023. Questionnaires were completed by psychiatrists, with a maximum of 30 patients assessed per medical institution. The questionnaires included psychiatrists' assessment of the patient's condition (exposure variables) and the need for a high-acuity psychiatry unit (outcome variables). The exposure variables consisted of 32 binary variables, including age, diagnoses, and clinical condition (i.e., factors on the clinical profile, emergency treatment requirements, and purpose of hospitalization). The outcome variable was the need for a high-acuity psychiatry unit, scored from 0 to 10. To identify the most important predictors of the need for a high-acuity psychiatry unit, we used a random forest model. As a sensitivity analysis, multivariate linear regression analysis was performed., Results: Data on 2,164 patients from 81 medical institutions were obtained (response rate, 50.3%). After excluding participants with missing values, this analysis included 2,064 patients. Of the 32 items, the top-5 predictors of the need for a high-acuity psychiatry unit were the essentiality of inpatient treatment (otherwise, symptoms will worsen or linger), need for 24-hour professional care, symptom severity, safety ensured by specialized equipment, and medication management. These items were each significantly and positively associated with the need for a high-acuity psychiatry unit in linear regression analyses (p < 0.001 for all). Conversely, items on age and diagnosis were lower in the ranking and were not statistically significant in linear regression models., Conclusion: Items related to the patient's clinical profile might hold greater importance in predicting the need for a high-acuity psychiatry unit than do items associated with age and diagnosis., 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 © 2024 Iwanaga, Yamaguchi, Hashimoto, Hanaoka, Kaneyuki, Fujita, Kishi, Hirata, Fujii and Sugiyama.)

Background: Locally recurrent rectal cancer (LRRC) involving the upper sacrum is typically incurable, and palliative treatment is the only option for most patients, resulting in a poor prognosis and reduced quality of life. Carbon ion radiotherapy (CIRT) has emerged as a promising modality for treating LRRC. This report presents a case of LRRC with sacral involvement that was managed via multidisciplinary therapy incorporating CIRT., Case Presentation: A 55-year-old male was diagnosed with an anastomotic recurrence of rectal cancer 15 months after undergoing anterior resection. Computed tomography (CT) suggested that the lesion was at an anastomosis site and broadly adherent to the upper sacrum, and colonoscopy confirmed the diagnosis of LRRC. Histopathological examination of the biopsy specimens revealed adenocarcinoma cells and that lesion was genetically RAS-wild. Induction chemotherapy with mFOLFOX6 and panitumumab was used as the first treatment. The recurrent lesion shrank and no signs of distant metastasis were observed after 11 cycles, although the range of the lesions attached to the sacrum remained unchanged. Therefore, we provided CIRT for this inoperable lesion and prophylactically removed the radiation-exposed bowel including the recurrent lesion, because radiation-induced ulcers can cause bleeding and perforation. Despite the presence of considerable fibrosis in the irradiated region, the operation was successful and the postoperative course had no untoward incidents. He is still recurrence-free 24 months following surgery, despite the lack of adjuvant chemotherapy. This is the first report of CIRT followed by CIRT-irradiated bowel removal for an unresectable anastomosis recurrent lesion., Conclusions: The clinical course of this case suggests that CIRT could be a potentially effective therapeutic option for LRRC involving the bowel, as long as the prophylactic removal of the irradiated bowel is performed at the optimal time. Further research involving larger sample sizes is warranted to validate the findings and conclusions of this case report., (© 2024. The Author(s).)

Background: Antipsychotics are commonly used to treat delirium but can adversely affect the extrapyramidal and cardiac conduction systems. Antipsychotic use has also been reported to be associated with increased mortality in older adults. Therefore, alternative and adjunct medications for delirium are necessary. We retrospectively assessed the efficacy and safety of gabapentin (GBP) as an alternative and adjunct medication for delirium., Methods: We retrospectively investigated the records of patients with delirium treated with GBP (71 patients; median age, 81 years; interquartile range, 76-87.5 years; 54.9% males) at a general hospital. We examined duration to delirium improvement, as assessed by the Intensive Care Delirium Screening Checklist (ICDSC) and DSM-5 criteria, as well as adverse events., Results: The median (interquartile range) GBP dose was 200 mg (150-350 mg) /day. A total of 71.8% and 85.9% of the patients failed to meet the diagnostic criteria for delirium at 2 days and 5 days after initial administration, respectively (p<0.05). In subgroup analysis, patients with a history of epilepsy or cerebrovascular disease responded better to GBP than did those without such histories, suggesting that patients with abnormal/borderline neuronal activity respond to GBP even though they do not exhibit seizures. GBP did not induce extrapyramidal symptoms, cardiac conduction disturbances, hyperglycemia, or epilepsy but caused sleepiness and myoclonus., Conclusions: GBP may improve delirium with fewer adverse effects and may be a safe alternative or adjunct treatment for delirium. Dosage adjustment may be necessary to prevent sleepiness.

Objective: The relationship between retention index calculated from dual-time point 18F-fluorodeoxyglucose positron emission tomography-computed tomography and oesophageal cancer prognosis remains unknown. This study aimed to determine usefulness of retention index as a predictor of long-term prognosis of oesophageal cancer and neoadjuvant chemotherapy efficacy., Methods: A total of 151 patients with oesophageal cancer who underwent esophagectomy were evaluated retrospectively in this study. We acquired positron emission tomography scans 60 and 120 min (SUVmax1 and SUVmax2, respectively) after the intravenous administration of 3.7 Mbq/kg 18F-fluorodeoxyglucose. The patients were divided into two groups: high-retention index (retention index ≥29%, 107 patients) and low-retention index (retention index <29%, 44 patients). Retention index was calculated as follows: retention index (%) = [(SUVmax2 - SUVmax1)/SUVmax1] × 100., Results: The overall survival and relapse-free survival rates in the high-retention index group were significantly lower than those in the low-retention index group (P < 0.001). Our multivariate analysis identified that the high-retention index group contained independent risk factors for overall survival (hazard ratio: 2.44, P = 0.009) and relapse-free survival (hazard ratio: 2.61, P = 0.002). The high-retention index group exhibited a lower partial response rate to neoadjuvant chemotherapy evaluated by computed tomography (P < 0.001) and a lower pathological therapeutic effect in the resected specimen (P = 0.019) than the low-retention index group., Conclusions: The retention index was associated with neoadjuvant chemotherapy responses and long-term prognosis for oesophageal cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tumor size (TS) is a well-established prognostic factor of pancreatic ductal adenocarcinoma (PDAC). However, whether a uniform treatment strategy can be applied for all resectable PDACs (R-PDACs) and borderline resectable PDACs (BR-PDACs), regardless of TS, remains unclear. This study aimed to investigate the impact of preoperative TS on surgical outcomes of patients with R-PDACs and BR-PDACs., Methods: Chart data from three institutions were reviewed to select patients who underwent pancreatectomy for R-PDACs and BR-PDACs between January 2006 and December 2020. The patients were divided into TS small and TS large groups according to a TS cutoff value determined for each of R- and BR-PDAC using the minimum P value approach for the risk of R1 resection., Results: TS of 35 mm and 24 mm was the best cutoff value in R-PDAC and BR-PDAC, respectively. The R1 rate was higher in the TS large than TS small group, in both R- (n = 35, 37% versus n = 294, 19%; P = 0.011) and BR-PDAC (n = 89, 37% versus n = 27, 15%; P = 0.030). Overall survival was significantly better in the TS small than TS large group in R-PDAC (38.2 versus 12.1 months; P < 0.001), but comparable between the two groups in BR-DPAC (21.2 versus 22.7 months; P = 0.363). Multivariate analysis revealed TS > 35 mm as an independent predictor of worse survival in patients with R-PDAC., Conclusion: Larger TS was associated with a higher R1 rate and is a worse prognostic factor in patients with R-PDAC., (© 2023. Society of Surgical Oncology.)

Introduction: No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine., Methods: This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use., Results: Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28-4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68-16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73-2.70; p = 0.30)., Conclusion: The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Intraorbital wooden foreign bodies are sometimes difficult to diagnose because of nonspecific clinical manifestations and diversity of imaging characteristics. We herein report a case involving a 72-year-old woman with a history of trauma induced by a coated wooden chopstick 3 years prior. Two years after the incident, computed tomography (CT) scan revealed an intraorbital mass that was initially diagnosed as an intraorbital hemangioma. The patient presented with hyperemia, impairment of ocular movement, and optic neuropathy in her right eye. Magnetic resonance imaging (MRI) showed granulation tissue and an abscess around a foreign body, which was compressing the eyeball. Surgical extraction of the foreign body was performed, leading to resolution of symptoms. The depiction of wooden foreign bodies by imaging is complicated and affected by several factors, increasing the risk of delayed diagnosis. To avoid permanent sequelae, MRI might be helpful because its imaging capabilities are superior to those of CT.

Identification of factors that regulate chromatin condensation is important for understanding of gene regulation. High-mobility group AT-hook (HMGA) proteins 1 and 2 are abundant nonhistone chromatin proteins that play a role in many biological processes including tissue stem-progenitor cell regulation, but the nature of their protein function remains unclear. Here we show that HMGA2 mediates direct condensation of polynucleosomes and forms droplets with nucleosomes. Consistently, most endogenous HMGA2 localized to transposase 5- and DNase I-inaccessible chromatin regions, and its binding was mostly associated with gene repression, in mouse embryonic neocortical cells. The AT-hook 1 domain was necessary for chromatin condensation by HMGA2 in vitro and in cellulo, and an HMGA2 mutant lacking this domain was defective in the ability to maintain neuronal progenitors in vivo. Intrinsically disordered regions of other proteins could substitute for the AT-hook 1 domain in promoting this biological function of HMGA2. Taken together, HMGA2 may regulate neural cell fate by its chromatin condensation activity., (© 2023. Springer Nature Limited.)

Neurons decline in their functionality over time, and age-related neuronal alterations are associated with phenotypes of neurodegenerative diseases. In nonneural tissues, an infolded nuclear shape has been proposed as a hallmark of aged cells and neurons with infolded nuclei have also been reported to be associated with neuronal activity. Here, we performed time-lapse imaging in the visual cortex of Nex-Cre;SUN1-GFP mice. Nuclear infolding was observed within 10 min of stimulation in young nuclei, while the aged nuclei were already infolded pre-stimulation and showed reduced dynamics of the morphology. In young nuclei, the depletion of the stimuli restored the nucleus to a spherical shape and reduced the dynamic behavior, suggesting that nuclear infolding is a reversible process. We also found the aged nucleus to be stiffer than the young one, further relating to the age-associated loss of nuclear shape dynamics. We reveal temporal changes in the nuclear shape upon external stimulation and observe that these morphological dynamics decrease with age., (© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Rationale: The long-term effectiveness of olanzapine and aripiprazole in real clinical conditions at flexible doses in patients after hospital discharge has not been evaluated yet., Objectives: This study was a multicenter retrospective cohort study. Patients with schizophrenia (n = 398) were prescribed olanzapine (n = 303) or aripiprazole (n = 95) at hospital discharge. The continuation of olanzapine or aripiprazole at 26, 52, or 104 weeks after the hospital discharge were compared using a Cox proportional hazards model and adjusted for possible confounders., Results: The Kaplan-Meier survival curves revealed that the continuation of olanzapine at 26 (P = 0.001) and 52 weeks (P = 0.018) was significantly higher than that of aripiprazole but not at 104 weeks. Olanzapine was better than aripiprazole in efficacy at 26 (hazard ratio: 0.321, 95% confidence interval: 0.159-0.645, P = 0.001), 52 (hazard ratio: 0.405, 95% confidence interval: 0.209-0.786, P = 0.008), and 104 weeks (hazard ratio: 0.438, 95% confidence interval: 0.246-0.780, P = 0.005). Aripiprazole was better than olanzapine in tolerability at 104 weeks (hazard ratio: 4.574, 95% confidence interval: 1.415-14.787, P = 0.011). Rates after two years continuation of olanzapine and aripiprazole were not significantly different in patients with less than five years' duration of illness, but olanzapine was more commonly maintained for more than two years in those patients who had been ill for over five years' due to its greater efficacy., Conclusion: Olanzapine treatment showed better continuation rates at 26 and 52 after hospital discharge than aripiprazole, whereas maintenance with the two antipsychotics did not differ significantly at 104 weeks, due reduced tolerability of long-term olanzapine treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer have recently revised the clinical practice guidelines for delirium in adult cancer patients. This article reports the process of developing the revised guidelines and summarizes the recommendations made., Methods: The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multi-disciplinary members, created three new clinical questions: non-pharmacological intervention and antipsychotics for the prevention of delirium and trazodone for the management of delirium. In addition, systematic reviews of nine existing clinical questions have been updated. Two independent reviewers reviewed the proposed articles. The certainty of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development, and Evaluation system. The modified Delphi method was used to validate the recommended statements., Results: This article provides a compendium of the recommendations along with their rationales, as well as a short summary., Conclusions: These revised guidelines will be useful for the prevention, assessment and management of delirium in adult cancer patients in Japan., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Among the five human senses, light, sound, and force perceived by the eye, ear, and skin, respectively are physical phenomena, and therefore can be easily measured and expressed as objective, univocal, and simple digital data with physical quantity. However, as taste and odor molecules perceived by the tongue and nose are chemical phenomena, it has been difficult to express them as objective and univocal digital data, since no reference chemicals can be defined. Therefore, while the recording, saving, transmitting to remote locations, and replaying of human visual, auditory, and tactile information as digital data in digital devices have been realized (this series of data flow is defined as DX (digital transformation) in this review), the DX of human taste and odor information is not yet in the realization stage. Particularly, since there are at least 400,000 types of odor molecules and an infinite number of complex odors that are mixtures of these molecules, it has been considered extremely difficult to realize "human olfactory DX" by converting all odors perceived by human olfaction into digital data. In this review, we discuss the current status and future prospects of the development of "human olfactory DX", which we believe can be realized by utilizing odor sensors that employ the olfactory receptors (ORs) that support human olfaction as sensing molecules (i.e., human OR sensor).

Background: Anorectal function deteriorates with age. The diagnostic performance of the endoscopic pressure study integrated system (EPSIS), an endoscopic carbon dioxide (CO 2 ) insufflation stress test of the lower esophageal sphincter has been previously evaluated as a diagnostic tool for gastroesophageal reflux disease. We aimed to evaluate the applicability of EPSIS in improving anorectal function. We hypothesized that EPSIS can be applied to the diagnosis of lower gastrointestinal tract disorders., Methods: This was a pilot, single-center, retrospective study using prospectively collected data between December 2021 and March 2022. It was designed to evaluate the differences in EPSIS rectal pressure measurements between older (≥80 years) and younger (<80 years) patients. At the end of the screening colonoscopy, the colonoscope was fixed in a retroflex position. When bowel movement was observed, CO 2 was insufflated to the point where gas leakage occurred through the anus. The measured maximum pressure was defined as EPSIS-rectal pressure max (EPSIS-RP max) and compared between the groups., Results: Overall, 30 patients were included and examined. The median ages of the <80 and ≥80 years' groups were 53 (range: 27-79) and 82 (range: 80-94) years, respectively, with corresponding median measured EPSIS-RP max of 18.7 (range: 8.5-30.2) and 9.8 (range: 5.4-22.3) mmHg (P<0.001)., Conclusions: Measurement of maximum rectal pressure illustrates the age-related decline in physiological anorectal function. Future studies should consider a loading test using EPSIS to quantify the decline in anorectal function and use it as a routine tool for screening and adjunctive diagnosis of anorectal hypofunction., Competing Interests: Conflict of Interest: Haruhiro Inoue is an advisor to Olympus Corporation and Top Corporation. He has also received educational grants from Takeda Pharmaceutical Company and Olympus Corporation. The other co-authors have no conflict of interests to disclose, (Copyright: © Hellenic Society of Gastroenterology.)

Aim: This study aimed to examine the prognostic value of desmoplastic reaction (DR) in esophageal squamous cell carcinoma (ESCC), particularly in patients who received neoadjuvant therapy, such as chemotherapy (NAC) or chemoradiotherapy (NACRT)., Method: In total, 153 patients with pStage II/III ESCC were included in this study. Ninety-one patients received neoadjuvant therapy (NAC, 70; NACRT, 21). Patients were classified according to three DR categories based on the presence of keloid-like collagen and/or myxoid stroma., Results: In total, 50, 50, and 53 patients were classified as having mature, intermediate, and immature DR, respectively. The weighted kappa coefficient was 0.623 in the patients with preoperative treatments and 0.782, in those without. The 5-year disease-specific survival (DSS) rates in patients with intermediate/immature DR was significantly worse than those with mature DR (40.7% vs. 73.3%, p < 0.001). Similarly, the 5-year DSS rate in patients with intermediate/immature DR was significantly worse than those with mature DR in a study of patients who received neoadjuvant therapy (46.7% vs. 71.2%, p = 0.009). Multivariate analysis revealed that DR (hazard ratio [HR]: 3.15, 95% confidence interval [CI] 1.58-6.27, p = 0.001), along with N factors, was an independent risk factor for DSS. Moreover, multivariate analysis of patients who received neoadjuvant therapy revealed only DR (HR: 2.47, 95% CI 1.02-5.96, p = 0.045) as independent risk factors for DSS., Conclusion: The DR classification was a valuable prognostic factor not only in the ESCC patients without neoadjuvant therapy but also in those with neoadjuvant therapy., (© 2023. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Periostin (POSTN) is a matricellular protein that was originally identified in osteoblasts. Past studies have shown that POSTN is also preferentially expressed in cancer-associated fibroblasts (CAFs) in various types of cancer. We previously demonstrated that the increased expression of POSTN in stromal tissues is associated with an unfavorable clinical outcome in esophageal squamous cell carcinoma (ESCC) patients. In this study, we aimed to elucidate the role of POSNT in ESCC progression and its underlying molecular mechanism. We found that POSTN is predominantly produced by CAFs in ESCC tissues, and that CAFs-cultured media significantly promoted the migration, invasion, proliferation, and colony formation of ESCC cell lines in a POSTN-dependent manner. In ESCC cells, POSTN increased the phosphorylation of ERK1/2 and stimulated the expression and activity of a disintegrin and metalloproteinase 17 (ADAM17), which is critically involved in tumorigenesis and tumor progression. The effects of POSTN on ESCC cells were suppressed by interfering with the binding of POSTN to integrin αvβ3 or αvβ5 using neutralizing antibody against POSTN. Taken together, our data show that CAFs-derived POSTN stimulates ADAM17 activity through activation of the integrin αvβ3 or αvβ5-ERK1/2 pathway and thereby contributes to the progression of ESCC., 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 © 2023 Elsevier B.V. All rights reserved.)

There are various types of gel materials used in a wide range of fields, and their gelation mechanisms are extremely diverse. Furthermore, in the case of hydrogels, there exist some difficulties in understanding complicated molecular mechanisms especially with water molecules interacting through hydrogen bonding as solvents. In the present work, the molecular mechanism of the structural formation of fibrous super-molecular gel by the low molecular weight gelator, N-oleyl lactobionamide/water mixture was elucidated using the broadband dielectric spectroscopy (BDS) method. The dynamic behaviors observed for the solute and water molecules indicated hierarchical structure formation processes in various time scales. The relaxation curves obtained at various temperatures in the cooling and heating processes showed relaxation processes respectively reflecting the dynamic behaviors of water molecules in the 10 GHz frequency region, solute molecules interacting with water in MHz region, and ion-reflecting structures of the sample and electrode in kHz region. These relaxation processes, characterized by the relaxation parameters, showed remarkable changes around the sol-gel transition temperature, 37.8 °C, determined by the falling ball method and over the temperature range, around 53 °C. The latter change suggested a structure formation of rod micelles appearing as precursors before cross-linking into the three-dimensional network of the supramolecular gels. These results clearly demonstrate how effective relaxation parameter analysis is for understanding the gelation mechanism in detail., Competing Interests: The authors declare no conflict of interest.

Background: The 3 core domains of delirium (cognitive, higher level thinking, circadian) do not include the less common noncore psychotic symptoms. However, psychosis might inform about perturbations of neural circuitry, outcomes, or suggest tailored clinical management., Objective: We assessed relationships between psychosis and other characteristics of delirium in patients without dementia or antipsychotics treatment., Methods: Cross-sectional analysis of 366 adults with delirium per the Delirium Rating Scale Revised-98, whose items distinguish hallucinations and delusions from other types of misperceptions and abnormal thought content, assessed during the preceding 24 hours to capture symptom severity fluctuation. The relationship of psychosis with other delirium characteristics was assessed using bivariate comparisons and analysis of variance as appropriate for groups with no psychosis and any psychosis (hallucinations and/or delusions), and subgroups with only hallucinations, only delusions, or both. A discriminant logistic model assessed variables associated with presence of any psychotic features versus none., Results: Delirium with any psychotic features occurred in 44.5% (163 of 366). Of the 366, 119 (32.5%) had only hallucinations (Hall), 14 (3.8%) had only delusions (Del), and 30 (8.2%) had both (Both). In the psychotic group (n = 163), 73.0% were Hall, 8.6% Del, and 18.4% Both. All psychotic patient groupings had significantly greater delirium severity on the Delirium Rating Scale Revised-98. Delusions and hallucinations were discordant for occurring together. The discriminant model found increased odds of having psychosis as 3 symptom severities increased (visuospatial ability, thought process, and sleep-wake cycle) where these each represented a delirium core domain. The noncore symptom of lability of affect had high odds ratio for psychosis, while motor retardation reduced odds of psychosis in this model., Conclusions: Consistent with prior reports, psychosis occurred in less than half of delirious patients with delusions being infrequent, and an association with affective lability was found. Given that previous functional magnetic resonance imaging research found a correlation between neural network dysconnectivity with greater severity of delirium, psychotic symptoms might be a clinical marker for greater underlying cerebral cortical neural circuitry dysfunction., (Copyright © 2022 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

A 72-year-old female had persistent severe chest pain while climbing stairs. She was diagnosed as having acute coronary syndrome, and underwent an emergency coronary angiography (CAG). The right coronary artery (RCA) ostium was sub-totally occluded. Echocardiography revealed a 10 mm mobile mass at the right coronary cusp of the aortic valve. To avoid total obustruction on two drug eluting stents were placed at the RCA ostium so as to have the proximal end protrude into the right Valsalva sinus. Thus, her hemodynamic condition was stabilized. The tumor was surgically resected and the stents were easily removed. Pathologically, the tumor was papillary fibroelastoma. Postoperative aortic regurgitation was minimal echocardiography, and CAG showed normal RCA.

Background: Postoperative subcutaneous emphysema (SE) is a possible complication of thoracoscopic or laparoscopic surgery. This study investigated the risk factors and clinical significance of SE after video-assisted thoracoscopic surgery for esophageal cancer (VATS-e)., Methods: This study included 135 patients who underwent VATS-e with artificial CO 2 pneumothorax. Based on the X-ray images on the first postoperative day, patients were divided into two groups: N/L group (no SE or SE localized at the thoracic area, n = 65) and SE group (SE extended to the cervical area, n = 70). We compared clinicopathological features, surgical findings, and short-term outcomes between the two groups., Results: In SE group, there were more patients who received neoadjuvant chemotherapy compared to N/L group. SE group had significantly lower preoperative body mass index. SE group had more frequently two-lung ventilation than N/L group. Multivariate analysis demonstrated that low BMI, NAC, and two-lung ventilation were independent risk factors for SE extended to the cervical area. Although pulmonary complication was relatively frequent in SE group, there were no significant differences in surgical outcomes between two groups, and all patients had SE disappeared within 21 days without serious complications., Conclusions: Despite extension to the cervical area, SE had a modest impact on the short-term result of VATS-e with artificial CO 2 pneumothorax., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Although conversion surgery has increasingly been performed for initially unresectable advanced pancreatic ductal adenocarcinoma (PDAC), the rate of conversion, including that for patients who do not undergo resection, remains unclear. Patients with PDAC who were treated between January 2013 and December 2018 were classified into three groups: resectable (R), borderline resectable (BR), and unresectable (UR). We analyzed patient outcomes, including the rate of surgical resection and survival, in each of these groups. In total, 211 patients (R, 118; BR, 22; UR, 81) were selected. Among them, 117 (99%), 18 (82%), and 15 (19%) patients in the R, BR, and UR groups, respectively, underwent surgical resection. R0 resection rates were 88, 78, and 67%, whereas median overall survival (OS) from treatment initiation were 31, 18, and 11 months ( p < 0.0001) in the R, BR, and UR groups, respectively. In patients who underwent surgical resection, relapse-free survival (RFS) and OS were similar among the three groups (R vs. BR vs. UR; median RFS (months), 17 vs. 13 vs. 11, p = 0.249; median OS (months), 31 vs. 26 vs. 32, p = 0.742). Lymph node metastases and incomplete adjuvant chemotherapy were identified as independent prognostic factors for OS. Although the surgical resection rate was low, particularly in the BR and UR groups, the prognosis of patients who underwent surgical resection was similar irrespective of the initial resectability status.

Changes in extracellular pH affect the homeostasis and survival of unicellular organisms. Supplementation of culture media with amino acids can extend the lifespan of budding yeast, Saccharomyces cerevisiae, by alleviating the decrease in pH. However, the optimal amino acids to use to achieve this end, and the underlying mechanisms involved, remain unclear. Here, we describe the specific role of serine metabolism in the regulation of pH in a medium. The addition of serine to synthetic minimal medium suppressed acidification, and at higher doses increased the pH. CHA1, which encodes a catabolic serine hydratase that degrades serine into ammonium and pyruvate, is essential for serine-mediated alleviation of acidification. Moreover, serine metabolism supports extra growth after glucose depletion. Therefore, medium supplementation with serine can play a prominent role in the batch culture of budding yeast, controlling extracellular pH through catabolism into ammonium and acting as an energy source after glucose exhaustion., (© 2023 John Wiley & Sons Ltd.)

Recent studies have demonstrated that epigenetic modifications are deeply involved in neurogenesis; however, the precise mechanisms remain largely unknown. To determine the role of UTX (also known as KDM6A), a demethylase of histone H3K27, in neural development, we generated Utx-deficient mice in neural stem/progenitor cells (NSPCs). Since Utx is an X chromosome-specific gene, the genotypes are sex-dependent; female mice lose both Utx alleles (Utx Δ/Δ ), and male mice lose one Utx allele yet retain one Uty allele, the counterpart of Utx on the Y chromosome (Utx Δ/Uty ). We found that Utx Δ/Δ mice exhibited fetal ventriculomegaly and died soon after birth. Immunofluorescence staining and EdU labeling revealed a significant increase in NSPCs and a significant decrease in intermediate-progenitor and differentiated neural cells. Molecular analyses revealed the downregulation of pathways related to DNA replication and increased H3K27me3 levels around the transcription start sites in Utx Δ/Δ NSPCs. These results indicate that UTX globally regulates the expression of genes required for proper neural development in NSPCs, and UTX deficiency leads to impaired cell cycle exit, reduced differentiation, and neonatal death. Interestingly, although Utx Δ/Uty mice survived the postnatal period, most died of hydrocephalus, a clinical feature of Kabuki syndrome, a congenital anomaly involving UTX mutations. Our findings provide novel insights into the role of histone modifiers in neural development and suggest that Utx Δ/Uty mice are a potential disease model for Kabuki syndrome., (© 2022 Federation of American Societies for Experimental Biology.)

Background/aim: This study aimed to evaluate the prognostic value of modified geriatric nutritional risk index (mGNRI) in patients with unresectable/recurrent esophageal cancer (EC)., Patients and Methods: We included 143 patients aged >65 years with unresectable/recurrent EC. The mGNRI was calculated as (1.489/CRP in mg/dl) + (41.7 × body mass index/22). Participants were divided into two groups: low-mGNRI (mGNRI <80, n=90) and high-mGNRI (mGNRI ≥80, n=53). We retrospectively examined the relationship between mGNRI and the prognosis of EC., Results: Median survival time in the low-mGNRI group was significantly lower than that in the high-mGNRI group (5.1 vs. 16.9 months, p<0.001). Multivariate analysis revealed that low mGNRI [hazard ratio (HR)=3.85, p<0.001] and absence of chemotherapy or chemoradiotherapy (HR=2.69, p<0.001) were independent and unfavorable prognostic factors of overall survival. Among patients who received chemotherapy or chemoradiotherapy, the mGNRI-low group had a significantly poorer prognosis than the mGNRI-high group (p<0.001). The mGNRI was the most appropriate prognostic index compared with other immune-inflammatory markers by the Akaike and Bayesian information criteria., Conclusion: In patients with unresectable/recurrent EC, low mGNRI was correlated with unfavorable prognosis and was a useful independent prognostic factor., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)