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Yoichi Hamai, Manabu Emi, Yuta Ibuki, Tomoaki Kurokawa, Toru Yoshikawa, Manato Ohsawa, Ryosuke Hirohata, Nao Kitasaki, Morihito Okada Department of Surgical Oncology, Hiroshima University, Hiroshima, JapanCorrespondence: Yoichi Hamai, Department of Surgical Oncology, Hiroshima University, 1-2-3 Kasumi, Minami-Ku, Hiroshima, 734-8551, Japan, Tel +81 822575869, Fax +81 822567109, Email yyhamai@hiroshima-u.ac.jpPurpose: Various blood cell parameters have been identified as predictive markers of tumor responses and the survival of patients with cancer treated with immune checkpoint inhibitors. The purpose of this study is to assess the ability of various blood cell parameters to predict therapeutic effects and survival in patients with esophageal squamous cell carcinoma (ESCC) treated with nivolumab monotherapy.Patients and Methods: We evaluated neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR) and lymphocyte-to-monocyte (LMR) ratios as predictive markers of patients’ survival and effects of nivolumab monotherapy after one or more prior chemotherapies for unresectable advanced or recurrent ESCC.Results: The objective response and disease control rates were 20.3% and 47.5%, respectively. The LMRs before, and 14 and 28 days after nivolumab initiation were significantly higher in patients with complete response (CR)/partial response (PR)/stable disease (SD) than those with progressive disease (PD). The NLRs at 14 and 28 days after nivolumab initiation were significantly lower in patients with CR/PR/SD than with PD. The optimal cutoffs for these parameters significantly discriminated patients with CR/PR/SD and PD. Univariate and multivariate analyses identified pretreatment NLRs as a significant independent factor for progression-free and overall survival (hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.07– 1.32, and HR 1.23, 95% CI: 1.11– 1.37, respectively; p ≤ 0.001 for both).Conclusion: The pretreatment LMRs, and NLR and LMR at 14 and 28 days after starting nivolumab monotherapy were significantly associated with the clinical therapeutic effect. The pretreatment NLR was significantly associated with patients’ survival. These blood cell parameters before and during the early days of nivolumab monotherapy can help to identify patients with ESCC who would most likely benefit from nivolumab monotherapy.Keywords: biomarkers, cancer, esophagus, immunotherapy, response, survival

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.)