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Background/aim: Ischemic stroke is a major health concern globally and developing reliable animal models is crucial for understanding its pathophysiology. This study evaluated the relationship between cerebral angiographic findings and neurologic dysfunction in an acute non-human primate thromboembolic stroke model and determined the minimum clot length for suitable middle cerebral artery (MCA) occlusion., Materials and Methods: A thromboembolic stroke model was developed by injecting autologous blood clots (length: 1, 2, 3, 4, 5, and 10 cm, n=1 to 3, 14 monkeys in total) into the internal carotid artery of male cynomolgus monkeys. Digital subtraction angiography (DSA) and neurologic deficit observation were performed pre-; immediately after (DSA only); and 1, 3, 6, and 24 h after embolization, and the relationship between clot length, neurologic deficits, and cerebral infarction was assessed., Results: DSA confirmed MCA occlusion in all animals after the clot injection. Recanalization of the MCA was observed within 6 h post-embolization in animals with shorter clots (≤3 cm). Neurologic deficits were evident in animals with MCA occlusion and correlated with the clot length. Larger clots (≥5 cm) led to permanent MCA occlusion, significant neurologic deficits, and extensive cerebral infarction. Histopathological examination revealed ischemic damage in brain regions corresponding to the infarcted areas., Conclusion: Clot length is critical in determining the extent of neurologic dysfunction and cerebral infarction, with larger clots producing more severe outcomes. Furthermore, the minimum clot length required for model creation is 5 cm., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In this study, we investigated the application of distributed learning, including federated learning and cyclical weight transfer, in the development of computer-aided detection (CADe) software for (1) cerebral aneurysm detection in magnetic resonance (MR) angiography images and (2) brain metastasis detection in brain contrast-enhanced MR images. We used datasets collected from various institutions, scanner vendors, and magnetic field strengths for each target CADe software. We compared the performance of multiple strategies, including a centralized strategy, in which software development is conducted at a development institution after collecting de-identified data from multiple institutions. Our results showed that the performance of CADe software trained through distributed learning was equal to or better than that trained through the centralized strategy. However, the distributed learning strategies that achieved the highest performance depend on the target CADe software. Hence, distributed learning can become one of the strategies for CADe software development using data collected from multiple institutions., (© 2024. The Author(s).)

Purpose: Post-operative infectious complication (IC) is a well-known negative prognostic factor, while showing neoadjuvant chemotherapy (NAC) may cancel out the negative influence of IC. This analysis compared the clinical impacts of IC according to the presence or absence of NAC in gastric cancer patients enrolled in the phase III clinical trial (JCOG0501) which compared upfront surgery (arm A) and NAC followed by surgery (arm B) in type 4 and large type 3 gastric cancer., Methods: The subjects were 224 patients who underwent R0 resection out of 316 patients enrolled in JCOG0501. The prognoses of the patients with or without ICs in each arm were investigated by univariable and multivariable Cox regression analyses., Results: There were 21 (20.0%) IC occurrences in arm A and 15 (12.6%) in arm B. In arm A, the overall survival (OS) of patients with ICs was slightly worse than those without IC (3-year OS, 57.1% in patients with ICs, 79.8% in those without ICs; adjusted hazard ratio (95% confidence interval), 1.292 (0.655-2.546)). In arm B, patients with ICs showed a trend of better survival than those without ICs (3-year OS, 80.0% in patients with IC, 74.0% in those without IC; adjusted hazard ratio, 0.573 (0.226-1.456))., Conclusion: This study could not indicate the negative prognostic influence of ICs in gastric cancer patients receiving NAC, which might be canceled by NAC. To build exact evidence, further investigation with prospective and large numbers of data might be expected., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Total gastrectomy with D2 dissection including splenectomy (TGS) is usually selected for locally resectable scirrhous gastric cancer (SGC), which was established in the era of surgery alone. However, it remains unclear whether TGS for SGC is justified in the era of effective adjuvant chemotherapy., Methods: This study included 112 SGC patients, consisting of 60 cases treated between January 2000 and December 2006 (Former group), and 52 cases treated between January 2007 and December 2016 (Latter group). We collected clinicopathological data and then examined the survival and the therapeutic value indexes., Results: The background characteristics were well-balanced, except for sex and physical status. The Latter group might be characterized by frequent female (P = 0.037) and poorer physical status (P = 0.048). Adjuvant chemotherapy was administered to 86.5% of the Latter group and was 11.7% of the Former group (P < 0.001). The 5-year-overall survival rate of the Latter group was 58.7% (95% confidence interval: 43.5-71.1), seems better than that of the Former group (44.5%; 95% confidence interval 31.7-56.6) (hazard ratio = 0.758, P = 0.291). Improvement of the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between two groups was 1.42 at the D1 station and 1.67 at the D2 station. Index of splenic hilar node ranked similarly high in both groups., Conclusion: The therapeutic value index was improved in almost all nodal stations by S-1 adjuvant chemotherapy, especially in D2 nodes. TGS would be more important for locally resectable SGC in the era of effective adjuvant chemotherapy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab., Methods: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup., Results: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT., Conclusions: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Molecular-targeted drugs and immune checkpoint inhibitors have been developed for various malignant diseases, thereby improving clinical outcomes. However, these drugs are expensive, and few studies have assessed their actual use and costs in Japan. This study aimed to survey the use and costs of first-line chemotherapy for advanced/recurrent gastric cancer (AGC) in real-world settings., Methods: The survey included patients with human epidermal growth factor receptor type2 (HER2)-negative AGC who initiated first-line chemotherapy from January 2022 to December 2022 at the participating 92 institutions in the Japan Clinical Oncology Group. Data on the regimens were collected using Google Forms. A regimen that costs >500 000 Japanese yen (JPY) per month was defined as expensive., Results: Data on chemotherapy regimens were collected from 2173 patients at all 92 institutions between March 2023 and May 2023. We analyzed 2113 patients who underwent the chemotherapy with recommended regimens and conditionally recommended regimens according to the Japanese Gastric Cancer Treatment Guidelines sixth edition. The expensive regimens were triplet chemotherapy with fluoropyrimidine (S-1 or capecitabine or 5-fluorouracil/levofolinate), oxaliplatin, and nivolumab. Their monthly costs ranged from 767 648 to 771 046 JPY. Nivolumab-containing regimens cost more than 20 times the price of conventional chemotherapy with fluoropyrimidine and oxaliplatin. These regimens were used in 1416 (67%) of 2113 patients: in 71% of patients aged ≤74 years and in 59% of patients aged ≥75 years., Conclusion: The regimens with >20-fold cost of conventional chemotherapy were used as first-line chemotherapy in two-thirds of patients and more than half even in the elderly population with HER2-negative AGC. This finding is important for future health economic studies on drug cost-efficacy., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Till date, only few studies have detailed the reality of overwork-related disorders among seafarers. Therefore, in this study, we aimed to evaluate the prevalence of overwork-related disorders among seafarers and assess factors such as patient attributes, diseases diagnosed at the time of determination, workload factors, and other aspects, thereby suggesting relevant preventative measures., Methods: Among all the patients identified with overwork-related disorders from April 2010 to March 2017, 2,280 cases of cerebrovascular and cardiovascular diseases and 3,517 cases of mental disorders were selected. To identify seafarer-related cases, keywords related to seafarers were extracted. Subsequently, 33 cases of cardiovascular disease and 19 cases of mental disorders were obtained., Results: The average age of the patients with cerebrovascular and cardiovascular diseases was 56.7 years; for those with mental disorders, it was 45.2 years. The patients were most commonly engaged in fishing, transportation, and postal services. Most patients were employed in the deck department or were captains. The most common types of vessels were fishing and cargo ships. Among the diseases diagnosed at the time of determination, cerebrovascular diseases accounted for 20 cases (60.6%) and cardiovascular diseases accounted for 13 cases (39.4%), with cerebral and myocardial infarctions being the most frequent conditions. Among mental disorders, "mood disorders" accounted for 7 cases (36.8%), and "neurotic disorders, stress-related disorders, and somatoform disorders" accounted for 12 cases (63.2%), with major depressive episodes, post-traumatic stress disorder, and adjustment disorders being the most common. The most common workload factor for patients with cerebrovascular and cardiovascular diseases was "long-term excessive work," and among non-workload factors, "long working hours" and "irregular working hours" were prevalent. For mental disorders, 8 cases were attributed to "extreme psychological stress." Specific events leading to these diseases included "interpersonal relationships," "experiencing accidents or disasters," and "work quantity and quality.", Conclusions: Both cerebrovascular and cardiovascular diseases, as well as mental disorders, showed a notable aging trend among seafarers. Thus, measures that consider the characteristics of elderly workers, such as their physical function, are important. Additionally, as seafarers are distributed across various industries and occupations, measures should be specifically tailored to their industry and job type. Our study confirmed that long working hours and irregular working hours were prevalent in both cases. Therefore, there is an urgent need for further efforts to prevent and mitigate overwork-related deaths among seafarers, including organizational support from onshore workplaces and enhancement of medical and operational support using information and communication technology.

Background and Purpose: The rise of large language models such as generative pretrained transformers (GPTs) has sparked considerable interest in radiology, especially in interpreting radiologic reports and image findings. While existing research has focused on GPTs estimating diagnoses from radiologic descriptions, exploring alternative diagnostic information sources is also crucial. This study introduces the use of GPTs (GPT-3.5 Turbo and GPT-4) for information retrieval and summarization, searching relevant case reports via PubMed, and investigates their potential to aid diagnosis., Materials and Methods: From October 2021 to December 2023, we selected 115 cases from the "Case of the Week" series on the American Journal of Neuroradiology website. Their Description and Legend sections were presented to the GPTs for the 2 tasks. For the Direct Diagnosis task, the models provided 3 differential diagnoses that were considered correct if they matched the diagnosis in the diagnosis section. For the Case Report Search task, the models generated 2 keywords per case, creating PubMed search queries to extract up to 3 relevant reports. A response was considered correct if reports containing the disease name stated in the diagnosis section were extracted. The McNemar test was used to evaluate whether adding a Case Report Search to Direct Diagnosis improved overall accuracy., Results: In the Direct Diagnosis task, GPT-3.5 Turbo achieved a correct response rate of 26% (30/115 cases), whereas GPT-4 achieved 41% (47/115). For the Case Report Search task, GPT-3.5 Turbo scored 10% (11/115), and GPT-4 scored 7% (8/115). Correct responses totaled 32% (37/115) with 3 overlapping cases for GPT-3.5 Turbo, whereas GPT-4 had 43% (50/115) of correct responses with 5 overlapping cases. Adding Case Report Search improved GPT-3.5 Turbo's performance ( P  = .023) but not that of GPT-4 ( P  = .248)., Conclusions: The effectiveness of adding Case Report Search to GPT-3.5 Turbo was particularly pronounced, suggesting its potential as an alternative diagnostic approach to GPTs, particularly in scenarios where direct diagnoses from GPTs are not obtainable. Nevertheless, the overall performance of GPT models in both direct diagnosis and case report retrieval tasks remains not optimal, and users should be aware of their limitations., (© 2024 by American Journal of Neuroradiology.)

Background: Recently, patients with supra-normal left ventricular ejection fraction (snEF) are reported to have high risk of adverse outcomes, especially in women. We sought to evaluate sex-related differences in the association between LVEF and long-term outcomes in heart failure (HF) patients., Methods: The multicenter WET-HF Registry enrolled all patients hospitalized for acute decompensated HF (ADHF). We analyzed 3943 patients (age 77 years; 40.1% female) registered from 2006 to 2017. According to LVEF the patients were divided into the 3 groups: HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF) and preserved EF. The primary endpoint was defined as the composite of cardiac death and ADHF rehospitalization after discharge., Results: In HFmrEF, implementation of guideline-directed medical therapy (GDMT) such as the combination of renin-angiotensin-system inhibitor (RASi) and β-blocker at discharge was significantly lower in women than men even after adjustment for covariates (p = 0.007). There were no such sex-related differences in HFrEF. Female sex was associated with higher incidence of the primary endpoint and ADHF rehospitalization after adjustment for covariates exclusively in HFmrEF. Restricted cubic spline analysis demonstrated a U-shaped relationship between LVEF and the hazard ratio of the primary endpoint showing higher event rate in HFmrEF and HFsnEF in women, but such relationship was not observed in men (p for interaction = 0.037)., Conclusions: In women, mrEF and snEF were associated with worse long-term outcomes. Additionally, sex-related differences in the GDMT implementation for HFmrEF highlight the need for further exploration, which might lead to creation of sex-specific guidelines to optimize HF management., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Renin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear., Methods: We analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30-60 mL/min/1.73 m 2 ). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30-44, 45-59 mL/min/1.73 m 2 ), systolic blood pressure (<120, ≥120 mmHg), LVEF (41-49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use., Results: Among patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74-86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43-0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups., Conclusions: Approximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: No efficient treatment has yet been established for epidermolytic ichthyosis (EI), which is caused by pathogenic variants of KRT1 or KRT10. Patients with ichthyosis with confetti (IWC) have multiple normal-appearing spots, caused by the revertant somatic recombination of pathogenic variants that occurs at each spot independently. Additionally, some patients with EI have large areas of normal skin due to revertant postzygotic mosaicism., Objectives: To assess the feasibility of transplanting cultured epidermal autografts (CEAs) produced from revertant epidermal keratinocytes in patients with EI and IWC., Methods: We performed a clinical trial of treatment with CEAs produced from each patient's own revertant epidermal keratinocytes as a proof-of-concept study. This was a single-arm, open, unmasked, uncontrolled, single-assignment, treatment-purpose study. The primary outcome was the percentage area that lacked recurrence of ichthyosis lesions 4 weeks after the final transplant. The secondary outcome was the percentage area lacking recurrence of ichthyosis lesions 24 weeks after the initial transplantation. The trial was registered with the Japan Registry of Clinical Trials (jRCTb041190097)., Results: We successfully produced CEAs from genetically confirmed revertant skin from two patients with mosaic EI and from one patient with IWC and confirmed by amplicon sequencing and droplet digital polymerase chain reaction analysis that the CEAs mainly consisted of revertant wild-type cells. Single-cell RNA sequencing analysis confirmed the normal proliferation and safety profiling of CEAs. CEAs were transplanted onto desquamated lesional sites in the patients. Four weeks post-transplantation, the percentage area lacking recurrence of ichthyosis lesions in the three patients was 40%, 100% and 100% respectively, although recurrence of ichthyosis lesions was seen at the site of CEA transplantation in all three patients at 24 weeks post-transplantation., Conclusions: CEAs from normal skin have the potential to be a safe and local treatment option for EI and IWC., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Study Objectives: Light information crucially influences sleep initiation and continuity. The purpose of this study was to compare daily light exposure between patients with Parkinson's disease (PD) and non-PD older adults and evaluate the association of daily light exposure with objective sleep measures in patients with PD., Methods: In this cross-sectional study of 189 outpatients with PD and 1101 community-dwelling older adults (controls), daily light exposure was measured using wrist light meters during the daytime and light meters set in the bedrooms during the nighttime, and objective sleep quality was measured by wrist actigraphy., Results: The median duration of exposure to ≥ 1000 lux light was significantly shorter in patients with PD than in controls. The median nighttime light intensity was higher in patients with PD than in controls. Among patients with PD, multivariable analysis suggested that the highest quartile of exposure to ≥ 1000 lux light during the daytime was linked to significantly higher sleep efficiency (SE) by 8.0% and shorter wake after sleep onset (WASO) by 36.9 minutes than the lowest quartile. During the nighttime, the highest quartile of mean light intensity had significantly lower SE by 6.8%, longer WASO by 24.1 minutes, longer sleep onset latency, and higher fragmentation index, than the lowest quartile. Importantly, daytime and nighttime light levels were independently associated with objective sleep measures., Conclusions: The present study illustrated that greater daytime light exposure and lower nighttime light exposure are significantly associated with better objective sleep measures in patients with PD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Background: Theoretically, a rapid urease test (RUT) using a swab of the gastric wall (Swab-RUT) for Helicobacter pylori (H. pylori) is safe. However, the validity and utility of Swab-RUT remain unclear. Therefore, we assessed the validity and utility of Swab-RUT compared to RUT using mucosal forceps of the gastric wall (Forceps-RUT) and 13 C-urea breath test (UBT)., Methods: This study was a multicenter prospective observational study. When the examinees were suspected of H. pylori infection during esophagogastroduodenoscopy, we performed Swab-RUT and Forceps-RUT continuously. When the examinees were not suspected of H. pylori infection, we performed Swab-RUT alone. We validated the status of H. pylori infection using UBT., Results: Ninety-four examinees were enrolled from four institutions between May 2016 and December 2020 (median age [range], 56.5 [26-88] years). In this study, the sensitivity, specificity, and accuracy of Swab-RUT to UBT were 0.933 (95% confidence interval: 0.779-0.992), 0.922 (0.827-0.974), and 0.926 (0.853-0.970), respectively. The Kappa coefficient of Swab-RUT to UBT was 0.833, and that of Swab-RUT to forceps-RUT was 0.936. No complications were observed in this study., Conclusions: Swab-RUT is a valid examination for the status of H. pylori infection compared to the conventional Forceps-RUT., (© 2024. The Author(s).)

Chronic kidney disease (CKD) is a global health concern with high morbidity and mortality. Acute kidney injury (AKI) is a pivotal risk factor for the progression of CKD, and the rate of AKI-to-CKD progression increases with aging. Intrarenal inflammation is a fundamental mechanism underlying AKI-to-CKD progression. Tertiary lymphoid structures (TLSs), ectopic lymphoid aggregates formed in nonlymphoid organs, develop in aged injured kidneys, but not in young kidneys, with prolonged inflammation and maladaptive repair, which potentially exacerbates AKI-to-CKD progression in aged individuals. Dysregulated immune responses are involved in the pathogenesis of various kidney diseases, such as IgA nephropathy, lupus nephritis, and diabetic kidney diseases, thereby deteriorating kidney function. TLSs also develop in several kidney diseases, including transplanted kidneys and renal cell carcinoma. However, the precise immunologic mechanisms driving AKI-to-CKD progression and development of these kidney diseases remain unclear, which hinders the development of novel therapeutic approaches. This review aims to describe recent findings from single-cell analysis of cellular heterogeneity and complex interactions among immune and renal parenchymal cells, which potentially contribute to the pathogenesis of AKI-to-CKD progression and other kidney diseases, highlighting the mechanisms of formation and pathogenic roles of TLSs in aged injured kidneys., Competing Interests: Disclosure Statement M.Y. received research grants from Mitsubishi Tanabe Pharma and Boehringer Ingelheim., (Copyright © 2024. Published by Elsevier Inc.)

Background: With the recent advent of technology, it is important to confirm the health and safety of the youth. This study aimed to prospectively evaluate the relationship between Wi-Fi, cordless phones, and mobile phone usage patterns and behavioral problems., Methods: This study involved 2465 children aged 8-17 years from the Hokkaido Study on Environment and Children's Health from October 2020 to January 2021, with a follow-up from September 2021 to March 2022. The mother-child dyad provided information on the presence of residential Wi-Fi and cordless phones, cordless phone call duration, and mobile phone usage pattern (duration of calls using mobile network and internet, online audio streaming, online video streaming, and playing online games) via a baseline questionnaire. Based on the scores on Strength and Difficulties Questionnaire at baseline and follow-up, the children were categorized into four groups: normal, persistent, improved, and concurrent., Results: No significant association was found between Wi-Fi, mobile phone calls via mobile networks, and behavioral problems. Cordless phone at home had higher odds for improvement in total difficulty scores, and cordless phone for calling more than 4 min per week had lower odds of persistent problematic prosocial behavior. Longer duration of mobile phone calling via the internet (>40 min/week) had higher odds of concurrent total difficulties. Mobile phone calling via mobile network for <5 min per week had higher odds for improved total difficulty scores. Audio streaming via mobile phones for 60-120 min had lower odds of persistent total difficulties., Conclusion: Our results showed sporadic findings between residential RF-EMF indoor sources and mobile phone usage pattern. These observed findings could be affected by residual confounding and chance findings. Ongoing follow-up studies are necessary to further explore this association through detailed exposure assessment and addressing the potential limitations of our study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Reiko Kishi reports financial support was provided by Japanese Ministry of Internal Affairs and Communications. If there are other authors, they 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. Published by Elsevier Inc.)

Herpes simplex encephalitis (HSE) is an acute form of encephalitis that can lead to poor neurological outcomes. Although the exact pathogenesis of HSE remains elusive, recent reports suggest a significant role for postinfectious immune-inflammatory processes in the central nervous system (CNS). This study aimed to clarify the association between CNS autoimmune responses and clinical presentation in patients with HSE, focusing on cerebrospinal fluid (CSF) characteristics, particularly the IgG index. We retrospectively analyzed 176 consecutive patients suspected of having aseptic meningitis /encephalitis for chronological changes in CSF findings and clinical presentations. These patients underwent PCR screening for herpesviruses (HV) in their CSF. We identified seven patients positive for herpes simplex virus type 1 (HSV-1), 20 patients positive for varicella-zoster virus, and 17 patients who met the criteria for aseptic meningitis but were PCR-negative for HV. Patients in the HSV-1-positive group exhibited a significant increase in the IgG index at the time of PCR-negative conversion compared with on admission (p = 0.0156), while such a change was not observed in the other two groups. Additionally, all patients in the HSV-1-positive group tested negative for anti-neural autoantibodies in CSF and serum samples collected approximately 3 weeks after onset. This study, therefore, highlights that CSF IgG index elevation occurs even after PCR-confirmed HSV-1 clearance, which might indicate immunopathogenesis that is independent of antibody-mediated mechanisms., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

To elucidate the seroprevalence and rate of asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japanese children, serological analysis was performed using serum samples collected from March 2020 to February 2023. A total of 1493 serum samples were collected during the first study period (March 2020 to February 2021). None of the serum samples was positive for SARS-CoV-2 antibody. In the second period (March 2021 to February 2022), seven of the 1055 patients (0.7%) experienced SARS-CoV-2 infection. The third period (March 2022 to February 2023) was divided into three terms: from March to June 30, 2022; from July to October 2022; and from November 2022 to February 2023. The seroprevalence gradually increased throughout this period, with rates of 6.0%, 18.6%, and 30.4% in the three terms, respectively. Pediatric cases of asymptomatic SARS-CoV-2 infection occurred after the surge of Omicron variants. Since none of the SARS-CoV-2 antibody-positive patients had a previous history of coronavirus disease 2019, the seroprevalence rate in this study may represent the rate of asymptomatic infection., (© 2024 Wiley Periodicals LLC.)

Background/aim: The sex-specific effect of the visceral-to-subcutaneous fat ratio (VSR) before gastrectomy on postoperative survival in patients with gastric cancer (GC) remains unclear. This study measured the preoperative VSR in patients with GC and analyzed its relationship with 5-year overall survival (OS) and relapse-free survival (RFS) by sex., Patients and Methods: This prospective study included 540 patients with GC undergoing gastrectomy. Preoperative visceral and subcutaneous fat volumes were measured using computed tomography, and the VSR was calculated. A cutoff value for the VSR was established using 5-year survival data, and its association with survival was analyzed using the Kaplan-Meier method, log-rank tests, and multivariate regression analysis., Results: Among the 459 patients analyzed (300 males and 159 females), OS and RFS were significantly lower in the low-VSR group than in the high-VSR group in males (OS: 76.2% vs. 88.1%, p=0.01; RFS: 74.6% vs. 86.0%, p=0.02). In females, no difference in OS was observed between the groups, whereas the high-VSR group had significantly lower RFS than that of the low-VSR group (RFS: 74.7% vs. 88.9%, p=0.01). Multivariate analysis showed that a low VSR was an independent poor predictor of OS in males and a high VSR was an independent poor predictor of RFS in females., Conclusion: In patients with GC, the sex-dependent preoperative VSR was a potentially useful predictor of postoperative survival., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The quality and bias of annotations by annotators (e.g., radiologists) affect the performance changes in computer-aided detection (CAD) software using machine learning. We hypothesized that the difference in the years of experience in image interpretation among radiologists contributes to annotation variability. In this study, we focused on how the performance of CAD software changes with retraining by incorporating cases annotated by radiologists with varying experience., Methods: We used two types of CAD software for lung nodule detection in chest computed tomography images and cerebral aneurysm detection in magnetic resonance angiography images. Twelve radiologists with different years of experience independently annotated the lesions, and the performance changes were investigated by repeating the retraining of the CAD software twice, with the addition of cases annotated by each radiologist. Additionally, we investigated the effects of retraining using integrated annotations from multiple radiologists., Results: The performance of the CAD software after retraining differed among annotating radiologists. In some cases, the performance was degraded compared to that of the initial software. Retraining using integrated annotations showed different performance trends depending on the target CAD software, notably in cerebral aneurysm detection, where the performance decreased compared to using annotations from a single radiologist., Conclusions: Although the performance of the CAD software after retraining varied among the annotating radiologists, no direct correlation with their experience was found. The performance trends differed according to the type of CAD software used when integrated annotations from multiple radiologists were used., (© 2024. The Author(s).)

Objectives: 18 F-fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG-PET/CT) is a diagnostic imaging method that is based on the Warburg effect, which is the increased uptake of glucose through aerobic glycolysis in cancer cells. The diagnostic value of 18 F-FDG-PET/CT for thyroid cancer is controversial. However, uptake of 18 F-FDG and the corresponding maximum standardized uptake value (SUVmax) is expected to reflect the metabolic status of cancer cells. In the present study, we sought to determine the relationship between 18 F-FDG uptake and tumor metabolism- associated factors., Methods: This was a single-center retrospective study. In the present study, SUVmax was compared with the expression of hexokinase 2 (HK2), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), and glutaminase 1 (GLS1) in 41 patients with thyroid cancer., Results: GLS1 expression was found to be moderately correlated with SUVmax (p < 0.001, r = 0.51), whereas HK2 and VEGF expression were weakly correlated (p = 0.011, r = 0.28, p = 0.008, r = 0.29, respectively) and GLUT1 did not correlate with SUVmax (p = 0.62, r = 0.06)., Conclusion: Our findings suggest 18 F-FDG PET/CT reflects GLS1 expression in thyroid cancer and could be used to select suitable candidates for GLS1 inhibitor treatment., Competing Interests: Declaration of competing interest No conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To assess the performance of GPT-4 Turbo with Vision (GPT-4TV), OpenAI's latest multimodal large language model, by comparing its ability to process both text and image inputs with that of the text-only GPT-4 Turbo (GPT-4 T) in the context of the Japan Diagnostic Radiology Board Examination (JDRBE)., Materials and Methods: The dataset comprised questions from JDRBE 2021 and 2023. A total of six board-certified diagnostic radiologists discussed the questions and provided ground-truth answers by consulting relevant literature as necessary. The following questions were excluded: those lacking associated images, those with no unanimous agreement on answers, and those including images rejected by the OpenAI application programming interface. The inputs for GPT-4TV included both text and images, whereas those for GPT-4 T were entirely text. Both models were deployed on the dataset, and their performance was compared using McNemar's exact test. The radiological credibility of the responses was assessed by two diagnostic radiologists through the assignment of legitimacy scores on a five-point Likert scale. These scores were subsequently used to compare model performance using Wilcoxon's signed-rank test., Results: The dataset comprised 139 questions. GPT-4TV correctly answered 62 questions (45%), whereas GPT-4 T correctly answered 57 questions (41%). A statistical analysis found no significant performance difference between the two models (P = 0.44). The GPT-4TV responses received significantly lower legitimacy scores from both radiologists than the GPT-4 T responses., Conclusion: No significant enhancement in accuracy was observed when using GPT-4TV with image input compared with that of using text-only GPT-4 T for JDRBE questions., (© 2024. The Author(s).)

Congenital cytomegalovirus (cCMV) infection is the most common congenital infection in developed countries. Although a standard therapy has not yet been established, evidence for the management of cCMV infection has been accumulating. The first edition of the "Clinical Practice Guidelines for the Management of Congenital Cytomegalovirus Infection" was published in Japan in 2023. This summary outlines the clinical questions (CQs) in the guidelines, with reference to the Japanese Medical Information Distribution Service Manual. Overall, 20 CQs with statements regarding prenatal risk assessment, prevention and management at diagnosis (CQs 1-1-1-3), diagnosis (CQs 2-1-2-6), treatment (CQs 3-1-3-7) and follow-up requirements (CQs 4-1-4-4) have been discussed. For each statement, the levels of recommendation, evidence and consensus rates were determined. These guidelines will assist in the management of patients with cCMV infection., Competing Interests: This research was supported by the Japan Agency for Medical Research and Development (No. JP19gk0110037). The authors have no other funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The live attenuated human rotavirus vaccine strain RIX4414 (Rotarix ® ) is used worldwide to prevent severe rotavirus-induced diarrhea in infants. This strain was attenuated through the cell culture passaging of its predecessor, human strain 89-12, which resulted in multiple genomic mutations. However, the specific molecular reasons underlying its attenuation have remained elusive, primarily due to the absence of a suitable reverse genetics system enabling precise genetic manipulations. Therefore, we first completed the sequencing of its genome and then developed a reverse genetics system for the authentic RIX4414 virus. Our experimental results demonstrate that the rescued recombinant RIX4414 virus exhibits biological characteristics similar to those of the parental RIX4414 virus, both in vitro and in vivo. This novel reverse genetics system provides a powerful tool for investigating the molecular basis of RIX4414 attenuation and may facilitate the rational design of safer and more effective human rotavirus vaccines.

The association of computed tomography (CT)-derived skeletal muscle index (SMI) and skeletal muscle radiodensity (SMD) with postoperative prognosis in patients with gastric cancer (GC) remains unknown. Therefore, the present study aimed to assess the association between SMI and SMD with 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with GC. SMI and SMD were measured preoperatively in patients who underwent gastrectomy. Patients were categorized into Groups 1 (high SMI and SMD), 2 (high SMI or SMD) and 3 (low SMI and SMD). OS and RFS rates were assessed using Kaplan-Meier analysis and the log-rank test. Among 459 patients, OS and RFS rates were significantly lower in the low-SMD group than in the high-SMD group (OS, 83.4% vs. 88.8%, respectively; P=0.04 and RFS, 80.5% vs. 87.2%, respectively; P=0.02). OS and RFS rates were also significantly lower in Group 3 than in Groups 2 and 1 (P=0.006). Multivariate analysis revealed that a low SMI and SMD (Group 3) was a significant independent prognostic factor for OS [hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.17-4.59; P=0.016] and RFS (HR, 2.28; 95% CI, 1.19-4.37; P=0.013). In summary, low SMI and SMD values may be useful postoperative prognostic indicators for patients with GC., Competing Interests: The authors declared that they have no competing interests., (Copyright: © 2024 Hashimoto et al.)

Intraspecific variations in specialized metabolites play a crucial role in the adaptive response to diverse environments. Two major subspecies, japonica and indica, are observed in Asian cultivated rice (Oryza sativa L.). Previously, we identified (3R)-β-tyrosine, a novel nonproteinogenic β-amino acid in plants, along with the enzyme tyrosine aminomutase (TAM1), required for β-tyrosine biosynthesis, in the japonica cultivar Nipponbare. Notably, TAM1 and β-tyrosine preferentially distributed in japonica cultivars compared with indica cultivars. Considering its phytotoxicity and antimicrobial activity, intraspecific variations in β-tyrosine may contribute to defensive potentials of japonica rice. Investigation of the evolutionary trajectory of TAM1 and β-tyrosine should enhance our understanding of evolution of rice defense. However, their distribution patterns in Oryza rufipogon, the direct ancestor of O. sativa, remain unclear. Therefore, in this study, we extensively examined TAM1 presence/absence and β-tyrosine contents involving 110 genetically and geographically diverse O. rufipogon and revealed that they are characteristically observed in the ancestral subpopulation of japonica rice, while being absent or slightly accumulated in other subpopulations. Thus, we conclude that TAM1 and β-tyrosine in japonica rice are likely derived from its ancestral subpopulation. Furthermore, the high and low TAM1 possession rates and β-tyrosine contents in japonica and indica rice, respectively, could be attributed to distribution patterns of TAM1 and β-tyrosine in their ancestral subpopulations. This study provides fundamental insights into evolution of rice defense.

Severe fever with thrombocytopenia syndrome (SFTS) virus, a tick-borne bunyavirus, causes a severe/fatal disease termed SFTS; however, the viral virulence is not fully understood. The viral non-structural protein, NSs, is the sole known virulence factor. NSs disturbs host innate immune responses and an NSs-mutant SFTS virus causes no disease in an SFTS animal model. The present study reports a novel determinant of viral tropism as well as virulence in animal models, within the glycoprotein (GP) of SFTS virus and an SFTS-related tick-borne bunyavirus. Infection with mutant SFTS viruses lacking the N-linked glycosylation of GP resulted in negligible usage of calcium-dependent lectins in cells, less efficient infection, high susceptibility to a neutralizing antibody, low cytokine production in macrophage-like cells, and reduced virulence in Ifnar-/- mice, when compared with wildtype virus. Three SFTS virus-related bunyaviruses had N-glycosylation motifs at similar positions within their GP and a glycan-deficient mutant of Heartland virus showed in vitro and in vivo phenotypes like those of the SFTS virus. Thus, N-linked glycosylation of viral GP is a novel determinant for the tropism and virulence of SFTS virus and of a related virus. These findings will help us understand the process of severe/fatal diseases caused by tick-borne bunyaviruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shimojima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Many large radiographic datasets of lung nodules are available, but the small and hard-to-detect nodules are rarely validated by computed tomography. Such difficult nodules are crucial for training nodule detection methods. This lack of difficult nodules for training can be addressed by artificial nodule synthesis algorithms, which can create artificially embedded nodules. This study aimed to develop and evaluate a novel cost function for training networks to detect such lesions. Embedding artificial lesions in healthy medical images is effective when positive cases are insufficient for network training. Although this approach provides both positive (lesion-embedded) images and the corresponding negative (lesion-free) images, no known methods effectively use these pairs for training. This paper presents a novel cost function for segmentation-based detection networks when positive-negative pairs are available., Methods: Based on the classic U-Net, new terms were added to the original Dice loss for reducing false positives and the contrastive learning of diseased regions in the image pairs. The experimental network was trained and evaluated, respectively, on 131,072 fully synthesized pairs of images simulating lung cancer and real chest X-ray images from the Japanese Society of Radiological Technology dataset., Results: The proposed method outperformed RetinaNet and a single-shot multibox detector. The sensitivities were 0.688 and 0.507 when the number of false positives per image was 0.2, respectively, with and without fine-tuning under the leave-one-case-out setting., Conclusion: To our knowledge, this is the first study in which a method for detecting pulmonary nodules in chest X-ray images was evaluated on a real clinical dataset after being trained on fully synthesized images. The synthesized dataset is available at https://zenodo.org/records/10648433 ., (© 2024. The Author(s).)

Hypochlorous acid (HOCl) is an endogenous oxidant and chlorinating agent in mammals that is effective against a broad range of microorganisms. However, the effects of exogenous HOCl on biological processes have not been reported. In this study, the effects of highly purified slightly acidic hypochlorous acid water (HP-HAW) were investigated. After the safety of oral administration of HP-HAW was confirmed, the effects of HP-HAW on glucose homeostasis were assessed in mice. HP-HAW treatment significantly improved blood glucose levels in hyperglycemic condition. Based on the 16S rRNA sequencing, HP-HAW treatment significantly increased the diversity and changed the composition of gut microbiota by decreasing the abundance of genus Romboutsia in mice fed normal chow. In obese mice, HP-HAW administration tended to improve glucose tolerance. HP-HAW also attenuated memory impairments and changes N-methyl-d-aspartate (NMDA) receptor mRNA expression in obese mice. HP-HAW treatment suppressed Il-6 mRNA expression in the hippocampus in type 2 diabetic mice. Overall, these results support HP-HAW as a potential therapeutic agent to improve or prevent glucose tolerance and memory decline via gut microbiota alteration., (© 2024. The Author(s).)

Daily rest period (DRP) refers to the interval between the end of one workday and the start of the next. This study examined the joint association of DRP and sleep duration with subsequent sick leave among Japanese daytime employees. Participants (n=5,593) were measured for DRP and sleep duration at baseline and for sick leave at 1-year follow-up. They were categorized into 10 groups based on their DRP and daily sleep duration. Logistic regression analyses for individuals experiencing sick leave for longer than a month showed that the combination of short DRP (<11 h) and sleep duration (<6 h) had a higher odds ratio (4.981, 95% confidence interval [CI] = 1.126-22.046) than the reference group. Furthermore, the combination of short DRP and normal sleep duration had a higher odds ratio (8.152, 95% CI = 1.801-36.902) than the reference group. Short DRP was associated with subsequent long sick leave.

We report a simple and atom-efficient method for the synthesis of bithiophene-fused isoquinolines by iridium-catalyzed [2 + 2 + 2] cycloaddition of bithiophene-linked diynes with nitriles. All three structural isomers of bithiophene-linked diynes underwent [2 + 2 + 2] cycloaddition, and the trend in the reactivity for cycloaddition was diyne 1 = diyne 3 > diyne 2 . Dibenzothiophene-linked diyne also reacted with nitriles to form a variety of cycloadducts. Cycloaddition of bithiophene-linked diynes with alkynes and an isocyanate formed naphthodithiophenes and a 2-pyridone derivative, respectively. Cycloadducts bearing a 2-aminopyridine moiety and benzothiophene rings showed intense fluorescence at around 530 nm and gave a fluorescence quantum yield of 0.44. Furthermore, quantum chemical calculations provided insight into the origin of the difference in reactivity of three bithiophene-linked diynes. The different reactivities of the three diynes 1-3 are believed to originate from the step where an iridacyclopentadiene reacts with a coordinated nitrile to form azairidabicyclo[3.2.0]heptatriene. HOMOs of iridacyclopentadiene play a decisive role in this step.

The prevalence of chronic kidney disease (CKD) is increasing owing to the elderly population. Here, we investigated the effects of heat-treated Enterococcus faecalis (FK-23) and lysozyme-treated FK-23 (LFK) on the progression of CKD in rats. A CKD model was established using male Wistar rats by subjecting them to right nephrectomy (1K), followed by ischemia and reperfusion (IR). FK-23 or LFK was fed ad libitum as a mixed diet after right nephrectomy. Animals subjected to renal ischemia-reperfusion injury (IRI) showed increased plasma creatinine and blood urea nitrogen levels. Furthermore, in the kidneys, collagen accumulation and α-smooth muscle actin, indicative of fibroblast activation and fibrosis-related gene and protein expression, increased 3 weeks after IRI. FK-23 and LFK suppressed the increase in the mRNA levels of some of these genes. The increase in oxidative stress markers, 4-hydroxy-2-nonenal, endothelial nitric oxide synthase, and nitrotyrosine in the kidney, as well as increased plasma uremic toxins after IRI, were also ameliorated by FK-23 and LFK. Metagenomic analysis of fecal samples revealed that gut microbial alteration caused by IRI was also ameliorated by LFK treatment. These results suggest that Enterococcus faecalis ingredients may improve CKD progression by suppressing oxidative stress and correcting the balance of the intestinal microflora., Competing Interests: ST, YM, and TY received an unrestricted grant from Nichinichi Pharmaceutical Co., Ltd. (Mie, Japan). NI is supported by Nichinichi Pharmaceutical Co., Ltd. as an outside work in this study. The funders had no role in the data analysis and interpretation. KN is employed by Nichinichi Pharmaceutical Co., Ltd. The remaining authors declare no competing interests., (Copyright © 2024 JCBN.)

Purpose: Despite annual endoscopy, patients with metachronous remnant gastric cancer (MRGC) following proximal gastrectomy (PG) are at times ineligible for endoscopic resection (ER). This study aimed to clarify the clinical risk factors for ER inapplicability., Materials and Methods: We reviewed the records of 203 patients who underwent PG for cT1 gastric cancer between 2006 and 2015. The remnant stomach was categorized as a pseudofornix, corpus, or antrum., Results: Thirty-two MRGCs were identified in the 29 patients. Twenty MRGCs were classified as ER (ER group, 62.5%), whereas 12 were not (non-ER group, 37.5%). MRGCs were located in the pseudo-fornix in 1, corpus in 5, and antrum in 14 in the ER group, and in the pseudo-fornix in 6, corpus in 4, and antrum in 2 in the non-ER group (P=0.019). Multivariate analysis revealed that the pseudo-fornix was an independent risk factor for non-ER (P=0.014). In the non-ER group, MRGCs at the pseudo-fornix (n=6) had more frequent undifferentiated-type histology (4/6 vs. 0/6), deeper (≥pT1b2; 6/6 vs. 2/6) and nodal metastasis (3/6 vs. 0/6) than non-pseudo-fornix lesions (n=6). We examined the visibility of the region developing MRGC on an annual follow-up endoscopy one year before MRGC detection. In seven lesions at the pseudofornix, visibility was only secured in two (28.6%) because of food residues. Of the 25 lesions in the non-pseudo-fornix, visibility was secured in 21 lesions (84%; P=0.010)., Conclusions: Endoscopic visibility increases the chances of ER applicability. Special preparation is required to ensure the complete clearance of food residues in the pseudo-fornix., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Gastric Cancer Association.)

The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents' decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents' decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89-0.99; Model 2: 0.95 0.90-0.997). Critical disease (5.25; 1.09-25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21-14.53; Model 2: 5.47, 1.50-19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14-2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility., (© 2024. The Author(s).)

Ca 2+ /calmodulin-dependent protein kinase IIα (CaMKIIα) is widely expressed in the brain and is involved in various functions, including memory formation, mood and sleep. We previously reported that CaMKIIα is involved in the circadian molecular clock. Mice lacking functional CaMKIIα (K42R mice) exhibited a gradual increase in activity time (α decompression) of running-wheel (RW) activity due to a lengthened circadian period (τ) of activity offset under constant darkness (DD). In the present study, to investigate the functional roles of CaMKIIα in behavioural rhythms, we measured RW and general movements simultaneously under prolonged DD. Tau became longer as the relative intensity of behaviour activity within an activity time shifted from activity onset towards activity offset. In some K42R mice, α was gradually expanded with a marked reduction of RW activity, while general movements persisted without noticeable decline, which was followed by an abrupt shortening of α (α compression) with differential phase shifts of the activity onset and offset and recovery of RW activity. These results suggest that an internal coupling between the oscillators controlling activity onset and offset is bidirectional but with different strengths. The α compression occurred recurrently in 38% of K42R mice examined with an average interval of 37 days in association with attenuation of RW activity but never in the wild-type (WT) mice. Consistent with behavioural rhythms, the circadian period of the PER2::LUC rhythm in the cultured suprachiasmatic nucleus (SCN) slice was significantly longer in K42R than in WT. These findings are best interpreted by assuming that a loss of functional CaMKIIα attenuates the coupling between the onset and offset oscillators., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: This study examined temporal shifts in adjuvant therapy patterns in Japanese patients with resectable gastric cancer (GC) and treatment patterns of first-line and subsequent therapy among those with recurrent disease., Methods: This retrospective analysis of hospital-based administrative claims data (April 1, 2008 to March 31, 2022) included adults (aged ≥ 20 years) with GC who started adjuvant therapy on or after October 1, 2008 (adjuvant cohort) and patients in the adjuvant cohort with disease recurrence (recurrent cohort), further defined by the time to recurrence (≤ 180 or > 180 days after adjuvant therapy)., Results: In the adjuvant cohort (n = 17,062), the most common regimen during October 2008-May 2016 was tegafur/gimeracil/oteracil potassium (S-1; 95.7%). As new standard adjuvant regimen options were established, adjuvant S-1 use decreased to 65.0% and fluoropyrimidine plus oxaliplatin or docetaxel plus S-1 use increased to 15.0% and 20.0%, respectively, in September 2019-March 2022. In the recurrent cohort with no history of trastuzumab/trastuzumab deruxtecan treatment (n = 1257), the most common first-line regimens were paclitaxel plus ramucirumab (34.0%), capecitabine plus oxaliplatin (CapeOX; 17.0%), and nab-paclitaxel plus ramucirumab (10.1%) in patients with early recurrence, and S-1 plus oxaliplatin (26.3%), S-1 plus cisplatin (15.3%), CapeOX (14.0%), S-1 (13.2%), and paclitaxel plus ramucirumab (10.8%) in those with late recurrence., Conclusions: This study demonstrated temporal shifts in adjuvant treatment patterns that followed the establishment of novel regimens, and confirmed that post-recurrent treatment patterns were consistent with the Japanese Gastric Cancer Association guideline recommendations., (© 2024. The Author(s).)

Background: The EORTC QLQ-STO22 (QLQ-STO22) is a firmly established and validated measure of health-related quality of life (HRQoL) for people with gastric cancer (GC), developed over two decades ago. Since then there have been dramatic changes in treatment options for GC. Also, East Asian patients were not involved in the development of QLQ-STO22, where GC is most prevalent and the QLQ-STO22 is widely used. A review with appropriate updating of the measure was planned. This study aims to capture HRQoL issues associated with new treatments and the perspectives of patients and health care professionals (HCPs) from different cultural backgrounds, including East Asia., Methods: A systematic literature review and open-ended interviews were preformed to identify potential new HRQoL issues relating to GC. This was followed by structured interviews where HCPs and patients reviewed the QLQ-STO22 alongside new issues regarding relevance, importance, and acceptability., Results: The review of 267 publications and interviews with 104 patients and 18 HCPs (48 and 9 from East Asia, respectively) generated a list of 58 new issues. Three of these relating to eating small amounts, flatulence, and neuropathy were recommended for inclusion in an updated version of the QLQ-STO22 and covered by five additional questions., Conclusions: This study supports the content validity of the QLQ-STO22, suggesting its continued relevance to patients with GC, including those from East Asia. The updated version with additional questions and linguistic changes will enhance its specificity, but further testing is required., (© 2024. The Author(s).)

Introduction: Insurance coverage for oral valganciclovir (VGCV) began in Japan in April 2023 on the basis of results, including our clinical trials for symptomatic congenital cytomegalovirus (CMV) disease. The VGCV treatment is available throughout Japan, so clinicians must consider the likelihood of hearing improvement and the possibility of neutropenia before dosing., Materials and Methods: We performed a substudy of an investigator-initiated, single-arm, prospective, multicenter, clinical trial in which 24 infants with symptomatic congenital CMV disease were orally administered 16 mg/kg VGCV twice daily for 6 months as an intervention. We examined the infants' baseline characteristics associated with improved hearing impairment or a severely reduced neutrophil count., Results: Of the 24 patients, 4 had normal hearing on assessment of their ear with the best hearing. Hearing impairment improved in 14 patients and did not respond to VGCV treatment in 6 patients at the 6-month hearing assessment. CMV DNA levels in plasma at baseline were higher in patients in whom hearing did not respond to treatment. A neutrophil count <500/mm 3 occurred in 5 (21%) patients for the first 6 weeks and in 8 (33%) patients for the first 6 months. A neutrophil count at screening and the lowest neutrophil count over the 6 months showed the highest correlation (r = 0.477, p = 0.019)., Conclusions: Infants with a low plasma viral load at screening tend to have an improvement in hearing impairment. Clinicians should be aware of neutropenia during VGCV treatment particularly in patients with a low neutrophil count during screening., Competing Interests: Declaration of competing interest Mitsubishi Tanabe Pharm Corp. provided Valixa™ dry syrup during the study period for treatment, but this company had no role in this clinical trial. None of the authors have any conflict of interest to declare., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The authors previously developed a divide-and-conquer (DC)-based non-local excited-state calculation method for large systems using dynamical polarizability [Nakai and Yoshikawa, J. Chem. Phys. 146, 124123 (2017)]. This method evaluates the excitation energies and oscillator strengths using information on the dynamical polarizability poles. This article proposes a novel analysis of the previously developed method to obtain further configuration information on excited states, including excitation and de-excitation coefficients of each excitation configuration. Numerical applications to simple molecules, such as ethylene, hydrogen molecule, ammonia, and pyridazine, confirmed that the proposed analysis could accurately reproduce the excitation and de-excitation coefficients. The combination with the DC scheme enables both the local and non-local excited states of large systems with an excited nature to be treated., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose., Methods: Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP)., Results: The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose., Conclusions: The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications., (© 2024. The Author(s).)

The efficient generation of chimeric antigen receptor (CAR) T cells is highly influenced by the quality of apheresed T cells. Healthy donor-derived T cells usually proliferate better than patients-derived T cells and are precious resources to generate off-the-shelf CAR-T cells. However, relatively little is known about the determinants that affect the efficient generation of CAR-T cells from healthy donor-derived peripheral blood mononuclear cells (PBMCs) compared with those from the patients' own PBMCs. We here examined the efficiency of CAR-T cell generation from multiple healthy donor samples and analyzed its association with the phenotypic features of the starting peripheral blood T cells. We found that CD62L expression levels within CD8+ T cells were significantly correlated with CAR-T cell expansion. Moreover, high CD62L expression within naïve T cells was associated with the efficient expansion of T cells with a stem cell-like memory phenotype, an indicator of high-quality infusion products. Intriguingly, genetic disruption of CD62L significantly impaired CAR-T cell proliferation and cytokine production upon antigen stimulation. Conversely, ectopic expression of a shedding-resistant CD62L mutant augmented CAR-T cell effector functions compared to unmodified CAR-T cells, resulting in improved antitumor activity in vivo. Collectively, we identified the surface expression of CD62L as a concise indicator of potent T-cell proliferation. CD62L expression is also associated with the functional properties of CAR-T cells. These findings are potentially applicable to selecting optimal donors to massively generate CAR-T cell products., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Many promising study results as well as technical advances for chest magnetic resonance imaging (MRI) have demonstrated its academic and clinical potentials during the last few decades, although chest MRI has been used for relatively few clinical situations in routine clinical practice. However, the Fleischner Society as well as the Japanese Society of Magnetic Resonance in Medicine have published a few white papers to promote chest MRI in routine clinical practice. In this review, we present clinical evidence of the efficacy of chest MRI for 1) thoracic oncology and 2) pulmonary vascular diseases., Competing Interests: Disclosure Y. Ozawa, T. Ueda, Y. Oshima, N. Hamabuchi, T. Yoshikawa, D. Takenaka: Nothing to disclosure. H. Nagata, Y. Ohno: Research grant from Canon Medical Systems Corporation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To generate synthetic medical data incorporating image-tabular hybrid data by merging an image encoding/decoding model with a table-compatible generative model and assess their utility. We used 1342 cases from the Stony Brook University Covid-19-positive cases, comprising chest X-ray radiographs (CXRs) and tabular clinical data as a private dataset (pDS). We generated a synthetic dataset (sDS) through the following steps: (I) dimensionally reducing CXRs in the pDS using a pretrained encoder of the auto-encoding generative adversarial networks (αGAN) and integrating them with the correspondent tabular clinical data; (II) training the conditional tabular GAN (CTGAN) on this combined data to generate synthetic records, encompassing encoded image features and clinical data; and (III) reconstructing synthetic images from these encoded image features in the sDS using a pretrained decoder of the αGAN. The utility of sDS was assessed by the performance of the prediction models for patient outcomes (deceased or discharged). For the pDS test set, the area under the receiver operating characteristic (AUC) curve was calculated to compare the performance of prediction models trained separately with pDS, sDS, or a combination of both. We created an sDS comprising CXRs with a resolution of 256 × 256 pixels and tabular data containing 13 variables. The AUC for the outcome was 0.83 when the model was trained with the pDS, 0.74 with the sDS, and 0.87 when combining pDS and sDS for training. Our method is effective for generating synthetic records consisting of both images and tabular clinical data., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)