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The author focuses on the Hepatitis G virus. The article reveals that since the 1960s, 5 hepatitis viruses have been identified and named A, B, C, D, and E. Hepatitis A and E viruses are transmitted enterically and induce acute hepatitis, but they rarely cause chronic hepatitis. Hepatitis B Virus and hepatitis C virus are primarily blood-borne, cause acute as well as chronic hepatitis, and can lead to cirrhosis and hepatocellular carcinoma. The author reports on the role of HGV in post-transfusion hepatitis and community-acquired acute hepatitis. The study of community-acquired hepatitis identified non-E hepatitis in 3% of patients, and among 45 of these patients 9% were positive for HGV. The author argues that because post-transfusion non-E hepatitis was mild and the patients had no jaundice, the community-acquired hepatitis in these patients may not really be attributable to HGV.

A letter to the editor is presented which is concerned with transient selective C4 deficiency in infancy.

In clinical clerkship (CC), medical students can practice evidence-based medicine (EBM) with their assigned patients. Although CC can be a valuable opportunity for EBM education, the impact of EBM training, including long-term behavioral changes, remains unclear. One hundred and nine fourth- and fifth-year medical students undergoing CC at a medical school in Japan attended a workplace-based learning program for EBM during CC (WB-EBM), which included the practice of the five steps of EBM. The program's effect on the students' attitudes toward EBM in CC was assessed through questionnaires. A total of 88 medical students participated in the program. Responses to the questionnaire indicated high satisfaction with the WB-EBM program. The most common theme in students' clinical problems with their assigned patients was the choice of treatment, followed by its effect. Based on the responses in the post-survey for the long-term effects of the program, the frequency of problem formulation and article reading tended to increase in the 'within six months' group comprising 18 students who participated in the WB-EBM program, compared with the control group comprising 34 students who did not. Additionally, the ability to self-assess problem formulation was significantly higher, compared with the control group. However, among 52 students who participated in the WB-EBM program more than six months later, EBM-related behavioral habits in CC and self-assessments of the five steps of EBM were not significantly different from those in the control group. The WB-EBM program was acceptable for medical students in CC. It motivated them to formulate clinical questions and enhanced their critical thinking. Moreover, the WB-EBM program can improve habits and self-evaluations about EBM. However, as its effects may not last more than six months, it may need to be repeated across departments throughout CC to change behavior in EBM practice.

The relationship between early childhood phthalate exposure and early adiposity rebound (EAR) is unclear. This study aimed to investigate the association between 1.5- and 3-year phthalate exposure and EAR and overweight/obesity in 7.5-year-old Japanese children. A total of 452 mother-child pairs were enrolled from the Aichi Regional Cohort of the Japan Environment and Children's Study. The children were followed up at birth and at 1.5, 2, 3, 4, 5, 6, and 7.5 years of age for physical examination. Human biomonitoring of 16 urinary metabolites of eight phthalates was performed at 1.5 and 3 years of age. Latent class mixed models, binary logistic regression, and quantile g-computation were performed to identify body mass index (BMI) trajectories and investigate the relationships of single or mixed phthalate exposure with EAR and overweight/obesity. A one-unit increase in log 10 -transformed 3-year-old Σdi(2-ethylhexyl) phthalate (ΣDEHP) exposure levels was significantly associated with 6-year-old BMI in girls. The 1.5-year mono-iso-butyl phthalate and 3-year Σdi-isodecyl phthalate exposure levels were significantly associated with the repeated measures of longitudinal BMIs in girls. Single phthalate exposure showed null associations with EAR or overweight/obesity in the 7.5-year-old children. Σdi-isononyl phthalate, ΣDEHP, and mono-n-butyl phthalate exhibited the highest proportion of partial positive weights of being in the EAR trajectory after confounder adjustment. Phthalate mixture exposure in 1.5- and 3-year-old children was not significantly associated with EAR. Early childhood phthalate exposure was not related to EAR or overweight/obesity in 7.5-year-old Japanese children. However, few phthalates were positively associated with longitudinal BMIs in girls., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The suitability of high-power short-duration (HPSD) cavo-tricuspid isthmus ablation (CTI-Abl) for electrophysiology (EP) trainees, as well as the underlying mechanisms of its efficacy, remain unknown. The aim of this study was to clarify the efficacy and safety of HPSD CTI-Abl performed by EP trainees and assess lesion characteristics between HPSD and moderate-power long duration (MPLD) ablations., Methods: Study 1: CTI-Abl was performed by first- to fourth-year EP trainees in consecutive 113 patients (67 ± 11 years, 27.2% female). Study cohort was historically divided into three groups: MPLD (30-35 W for up to 30 s) using TactiCath (TC-MPLD, N = 38) and MPLD and HPSD (50 W for 12 s) using TactiFlex (TF-MPLD, N = 23; TF-HPSD, N = 52). Primary endpoint was first-pass bidirectional isthmus block (BIB). Study 2: lesion geometries created by each ablation strategy were compared using an ex-vivo model., Results: Study 1: TF-HPSD ablation strategy demonstrated a higher success rate of first-pass BIB than MPLD protocol (TC-MPLD, 58%; TF-MPLD, 48%; TF-HPSD, 94%, p < 0.001), without any complications. TF-HPSD group was associated with shorter total procedure and RF application times, as well as fewer ablation points and gaps, compared to the MPLD groups. Study 2: TF-HPSD created greater lesion surface length, width, and area than MPLD strategies., Conclusion: HPSD CTI-Abl performed by EP trainees using TactiFlex SE catheter demonstrated a higher first-pass BIB rate, shorter total procedure and RF application times, and fewer ablation points and gaps compared to the conventional method, without increasing complication rates., (© 2024 Wiley Periodicals LLC.)

Background: Effective management with second-line therapy with the lenvatinib + pembrolizumab regimen for patients with advanced endometrial cancer is necessary., Methods: This retrospective study enrolled patients with endometrial cancer treated with the lenvatinib + pembrolizumab regimen. We evaluated progression-free survival (PFS), overall survival (OS), safety for patients non-eligible for the KEYNOTE775 trial, aged ≥65 years, or with ECOG performance status 1-2., Results: Forty-five patients were analyzed: 21 (47%) were aged ˃ 65 years, 16 (36%) had performance status 1-2, and 15 (33%) were non-eligible for KEYNOTE775 trial participation. Overall, the median PFS was 8.5 months (95% confidence interval [CI] 4.6-12.4), and the median OS was 15.6 months (95% CI 9.4-NA). Median PFS was significantly shorter in patients not eligible for KEYNOTE775 participation and with performance status 1-2. The median OS was significantly shorter in patients with performance status 1-2. Grade ˃3 adverse events (AEs) occurred in 78% of patients who received the lenvatinib + pembrolizumab regimen. AEs resulted in lenvatinib dose reductions in 35 patients (78%) and lenvatinib and pembrolizumab discontinuation in 3 (7%) and 5 (11%), respectively. The median time to the first lenvatinib dose reduction was 1.5 (0.92-2.3) months in all patients and was significantly shorter in patients aged >65 years., Conclusions: The current regimen has favorable efficacy and manageable safety with appropriate dose reduction of lenvatinib in the real world. However, the efficacy may be inferior in patients with performance status 1 or 2, heavily treated patients, and those with organ dysfunction. The current treatment status should reflect real-world data relative to the medical environment and management., Competing Interests: Declarations. Conflict of interest: The authors declare no conflicts of interest., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Lead (Pb) exposure negatively impacts fertility in both males and females, pregnancy outcomes, and child brain development. We investigated the reproductive and neurological effects of Pb exposure on male and female mice via Pb-contaminated soil for 4 weeks. Breeding was conducted after completion of exposure, in four groups; group 1 consisted of exposed dams and unexposed sires, group 2 consisted of exposed sires and unexposed dams, group 3 consisted of exposed sires and exposed dams and group 4 was the control. Generally, Pb exposure reduced observed conception rates, with a cumulative decrement observed when both males and females are exposed. Gene expression of the testes revealed oxidative stress as the cause of reduced conception rates. Neurological tests: Morris water maze and rotarod were conducted on F1 generation offspring. Maternally and paternally exposed F1 mice performed poorly in the Morris water maze when compared to the control. The severity of the neurological effects was also parent-dependent and sex-dependent. Paternal Pb exposure effects were more pronounced in female offspring. A comparison of gene expression changes of the hippocampus and prefrontal cortex showed paternal Pb-exposure resulted in more prefrontal cortex changes than in the hippocampus, a trend also recorded in the exposed sires. The pronounced effects in female offspring of paternal Pb exposure may suggest that Pb neurological effects may be X-chromosome-linked., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A 36-year-old man presented with sudden onset of severe abdominal pain. A CT scan was performed first, which showed marked thickening of the gastric wall. Gastric anisakiasis was suspected because he had eaten sashimi (a raw fish dish), including salmon and tuna, the night before. An upper gastrointestinal endoscopy revealed three Anisakis larvae invading the gastric wall. All larvae were removed by the biopsy forceps. His symptoms were resolved after the removal. Anisakiasis is a gastrointestinal parasitic infection of humans caused by ingestion of raw or undercooked seafood containing Anisakis larvae, resulting in severe gastrointestinal disorders and allergic reactions. Salmon, herring, cod, mackerel, squid, and flounder are known intermediate hosts. Cases of anisakidosis are increasing globally. Although gastric anisakiasis is a relatively common disease in Japan, it is unusual to find marked thickening of the gastric wall on CT scans and multiple anisakiasis on upper endoscopy, as shown in this case. Our case highlights the importance of a careful history leading to prompt diagnosis and treatment of gastric anisakiasis in cases presenting with acute onset of severe abdominal pain several hours after ingestion of raw or undercooked seafood. Healthcare professionals and edible seafood handlers should increase their awareness of fish parasites. Proper freezing or cooking of seafood is an important prophylactic measure.

Background and Aim: Werner syndrome (WS) is an autosomal recessive, adult-onset, progeroid syndrome caused by WRN mutations. As refractory skin ulcers significantly affect the quality of life of patients with WS, this study identified ulcer risk factors and assessed prevention methods., Methods: We analyzed the data of 51 patients with WS enrolled in the Japanese Werner Syndrome Registry between 2016 and 2022. A cross-sectional analysis was performed to determine the association with skin ulcers at baseline. Statistical analyses were conducted, including Welch's and Pearson's chi-square tests. Age was adjusted using a logistic regression model., Results: The mean patient age was 48.8±7.6 years, and 66.7% of patients presented with skin ulcers. Univariate analysis showed that patients with skin ulcers were older than those without ulcers. Systolic blood pressure (SBP) was higher in patients with skin ulcers. Patients without skin ulcers received metformin and pioglitazone treatment significantly more often than those with ulcers. Logistic regression analysis adjusted for age showed that higher SBP remained a significant risk factor for skin ulcers. Patients administered pioglitazone had lower ulcer morbidity., Conclusions: Age and SBP are risk factors for skin ulcers in patients with WS. Moreover, pioglitazone treatment may prevent skin ulcers.

Competing Interests: The authors declare that they have no conflict of interest.

Introduction: Preeclamptic patients, both lean and obese, present with elevated leptin levels which are associated with the development of maternal endothelial dysfunction and adverse fetal outcomes, such as growth restriction, leading to low birth weight. Recent studies in pregnant mice demonstrate that mid-late gestation leptin infusion induces clinical characteristics of preeclampsia, including elevated maternal blood pressure, maternal endothelial dysfunction and fetal growth restriction. However, whether leptin triggers placental stress responses that contribute to adverse fetal outcomes as in preeclampsia is unknown., Methods: In the current study we measured the expression of proteins involved in the endoplasmic reticulum (UPR er ) and mitochondrial (UPR mt ) unfolded protein responses in placentas of wild-type sham normal pregnant and leptin-infused preeclamptic mice., Results: The data show that mid-late gestation leptin infusion induced activation of indices of placental UPR er and UPR mt , while reducing placental repair mechanisms to UPR mt in preeclamptic mice. Mid-late gestation infusion with leptin upregulated markers of placental oxidative stress, reduced the placental expression levels of mitochondrial electron transport chain complexes I and II and increased the expression of placental endothelin-1 (ET-1) in preeclamptic mice. The leptin-induced activation of several placental UPR mt markers as well as ET-1 levels correlated with fetal growth restriction and impaired maternal endothelial function in preeclamptic mice., Discussion: Collectively, these data indicate that elevated levels of leptin in mid-late pregnancy in mice promote placental stress responses, akin to those in pregnant women with preeclampsia., Competing Interests: Declaration of competing interest This work was supported by NIH1R01HL169576, 4R00HL146948 to JLF, AHA24PRE1196923 to DM and by the British Heart Foundation PG/14/5/30,547 to DAG. This work was partially supported by Department of Obstetrics and Gynecology, Toho University Faculty of Medicine., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To control spoilage by lactic acid bacteria (Leuconostoc spp.) in cooked deli food, various combinations of environmental and/or intrinsic factors have been employed based on hurdle technology. Since many factors and their combinations greatly influence Leuconostoc spp. growth, this study aimed to develop a machine learning model based on the experimentally obtained growth kinetic data using extreme gradient boosting tree algorithm to quantitatively and flexibly predict Leuconostoc spp. growth. In particular, the effects of sodium acetate (0-1.5%) and glycine (0-1.5%), which are frequently used food additives in the Japanese food industry, on the growth of Leuconostoc spp. in cooked deli foods were examined with a combination of temperature (5-25 °C) and pH (5.0-6.0) conditions. The developed machine learning model to predict the number of Leuconostoc spp. over time successfully demonstrates comparable accuracy in culture media to the conventional Baranyi model-based prediction. Furthermore, while the accuracy of the prediction by the machine learning model for cooked deli foods such as potato salad, Japanese simmered hijiki, and unohana evaluated by the proportion of relative error within the acceptable prediction range was 98%, the accuracy of the conventional Baranyi model-based prediction was 89%. The developed machine learning model successfully and flexibly predicted the growth of Leuconostoc spp. in various cooked deli foods incorporating the effect of food additives, with an accuracy comparable to or better than that of the conventional kinetic-based model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Palonosetron, a second-generation 5-HT 3 receptor antagonist (5-HT 3 RA), is more effective than first-generation 5-HT 3 RA. Several studies have investigated whether dexamethasone (DEX), when combined with palonosetron as a 5-HT 3 RA, can be spared in the delayed phase after moderately emetogenic chemotherapy (MEC). In this systematic review, we aimed to determine which between 1- and 3-day DEX administration, when combined with palonosetron, is more useful in patients receiving MEC., Methods: The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant studies published between 1990 and 2020. We included studies that compared the efficacy of 1- and 3-day DEX administration in preventing nausea and vomiting associated with MEC. Outcomes were "prevention of vomiting (complete response rate and no vomiting rate)," "prevention of nausea" (complete control rate, total control rate, no nausea rate, and no clinically significant nausea rate)" in the delayed phase, "prevention of blood glucose level elevation," and "prevention of osteoporosis.", Results: Eight studies were included in this systematic review. The no vomiting rate was significantly higher in the 3-day DEX group than in the 1-day DEX group. However, the other efficacy items did not significantly differ between the two groups. Meanwhile, insufficient evidence was obtained for "prevention of blood glucose level elevation" and "prevention of osteoporosis.", Conclusions: No significant differences in most antiemetic effects were found between 1- and 3-day DEX administration. Thus, DEX administration could be shortened from 3 days to 1 day when used in combination with palonosetron., Competing Interests: Declarations. Conflict of interest: Kazuhisa Nakashima received honoraria from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K. Michiyasu Murakami received honoraria from Taiho Pharmaceutical Co., Ltd. Eriko Satomi received honoraria from Shionogi & Co., Ltd. Masayuki Takeda received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., and Bayer. Takako Eguchi Nakajima received research funding from KBBM, Inc. and Takeda Pharmaceutical Co., Ltd. Junichi Nishimura received honoraria from Taiho Pharmaceutical Co., Ltd. Narikazu Boku received honoraria from Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan K.K. Koji Matsumoto received honoraria from MSD K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd. as well as research funding from Daiichi Sankyo Co., Ltd., MSD K.K., Gilead Sciences, Inc., and Eli Lilly Japan K.K. Nobuyuki Yamamoto received honoraria from MSD K.K., Accuray Japan K.K., AstraZeneca K.K., Abbvie Inc., Amgen Inc., Ono Pharmaceutical Co., Ltd., Guardant Health Japan Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Foundation for Innovative Drug Discovery Science, Lao Tsumura Co., Ltd., Terumo Corporation, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Novartis AG, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd, Pfzer Global Supply Japan Inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., and USACO Corporation, as well as legal fees in case of lawsuit from Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Prime Research Institute for Medical RWD, Inc., AstraZeneca K.K., and A2 Healthcare Corporation. Other authors declare that they have no conflict of interest. Ethical approval: Not applicable. Informed consent: Formal consent was not required for this type of study. Consent to participate: Not applicable. Consent for publication: All authors consented to the publication of this study., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Introduction: Behçet's disease (BD) with intestinal, neurological (NBD), and vascular (VBD) manifestations often leads to poor outcomes. Infliximab is approved for the treatment of intestinal BD, NBD, and VBD in Japan; however, evidence regarding its safety and effectiveness in these patients is limited. We conducted a 2-year post-marketing surveillance to evaluate the safety and effectiveness of infliximab in patients with intestinal BD, NBD, and VBD in Japan., Methods: This 2-year, multicenter, prospective, observational study included all patients with intestinal BD, NBD, or VBD, who had experienced an insufficient response to conventional therapies (e.g., glucocorticoids and immunosuppressants/immunomodulators), and initiated infliximab for the first time at participating medical institutions. The safety endpoints included adverse events and adverse drug reactions (ADRs), and the effectiveness endpoints included global improvement, and for patients with acute NBD, acute attacks., Results: Between October 2015 and August 2018, 255 patients (171 intestinal BD, 49 NBD, and 51 VBD; including 16 with two disease types) were enrolled from 133 medical centers and treated with infliximab. Adverse events, ADRs, and serious ADRs occurred in 100 (39.2%), 72 (28.2%), and 38 (14.9%) patients, respectively; incidences were generally similar across intestinal BD, NBD, and VBD groups. No new safety concerns were identified. At the final evaluation, 68.8% of patients with intestinal BD showed improvement, most patients with chronic progressive NBD and VBD had not worsened (100% and 91.7%, respectively), and 93.3% of patients with acute NBD had no new acute attacks during the observation period., Conclusion: These results confirmed the safety and effectiveness of infliximab in clinical practice in 255 patients with intestinal BD, NBD, and VBD. There were no new safety concerns., (© 2024. The Author(s).)

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Competing Interests: The authors declare that they have no conflict of interest.

In Japan, the myth of motherhood, the idea that every woman harbours maternal love and that a woman only becomes a full-fledged woman after giving birth, has existed for a long time. However, there has been a limited number of studies concerning this motherhood myth in patients with recurrent pregnancy loss (RPL). The present study aimed to examine the experiences of maternal myths in patients with RPL and to determine whether maternal myths affect depression. Participants in the study included 61 patients in 1995, 71 patients in 2002, 503 patients from 2008 to 2012, and 318 patients and 1210 pregnant women from 2017 to 2020. Patients who sought an examination of their RPL visited Nagoya City University Hospital, while pregnant women requiring a prenatal checkup visited Nagoya City West Medical Center. Both groups completed a questionnaire concerning seven maternal myths and how they rated their level of depression (K6). It was found that not only patients with RPL but also pregnant women with no pregnancy loss had encountered maternal myths and many of them felt some discomfort. It has become clear that exposure to such myths has decreased over the 25 years from 1995 to 2020 (p < 0.05). Additionally, opportunities for exposure to maternal myths clearly had an impact on depression (p < 0.05). It is imperative that we recognize the distress caused by these myths. One potential solution to this problem is to improve education on gender issues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: To evaluate the image quality of ultra-high-resolution CT (U-HRCT) images reconstructed using an improved deep-learning-reconstruction (DLR) method. Additionally, we assessed the utility of U-HRCT in visualizing gastric wall structure, detecting gastric cancer, and determining the depth of invasion., Methods: Forty-six patients with resected gastric cancer who underwent preoperative contrast-enhanced U-HRCT were included. The image quality of U-HRCT reconstructed using three different methods (standard DLR [AiCE], improved DLR-AiCE-Body Sharp [improved AiCE-BS], and hybrid-IR [AIDR3D]) was compared. Visualization of the gastric wall's three-layered structure in four regions and the visibility of gastric cancers were compared between U-HRCT and conventional HRCT (C-HRCT). The diagnostic ability of U-HRCT with the improved AiCE-BS for determining the depth of invasion of gastric cancers was assessed using postoperative pathology specimens., Results: The mean noise level of U-HRCT with the improved AiCE-BS was significantly lower than that of the other two methods (p < 0.001). The overall image quality scores of the improved AiCE-BS images were significantly higher (p < 0.001). U-HRCT demonstrated significantly better conspicuity scores for the three-layered structure of the gastric wall than C-HRCT in all regions (p < 0.001). In addition, U-HRCT was found to have superior visibility of gastric cancer in comparison to C-HRCT (p < 0.001). The correct diagnostic rates for determining the depth of invasion of gastric cancer using C-HRCT and U-HRCT were 80%., Conclusions: U-HRCT reconstructed with the improved AiCE-BS provides clearer visualization of the three-layered gastric wall structure than other reconstruction methods. It is also valuable for detecting gastric cancer and assessing the depth of invasion., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: The work environment during work from home (WFH) may have a negative impact on workers' health. We investigated the effects of the physical work environment during WFH on sleep., Methods: We conducted a 1-year cohort study of 2099 Japanese WFH workers. We used eight questions about the physical work environment during WFH as independent variables and the Athens Insomnia Scale as the dependent variable. We performed multilevel logistic regression with residence as a random effect., Results: With the exception of one item, nonconformity with recommendations for the physical work environment during WFH was significantly associated with sleep problems. Further, the number of nonconformities and sleep problems showed a graded relationship., Conclusion: An inappropriate physical work environment during WFH may be associated with sleep problems., Competing Interests: Conflict of interest: All authors declare no conflicts of interest for this article. Okawara, Hirashima, Tateishi, Eguchi, Tsuji, Ogami, Mori, Matsuda, and Fujino, for the CORoNaWork Project have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Background: Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation., Methods: The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC., Results: Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months., Conclusion: Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients., (© 2024. Society of Surgical Oncology.)

Although breastfeeding has various benefits for mothers and children, there are several barriers to continuing breastfeeding practices. However, little is known about the relationship between breastfeeding in Japan and maternal socioeconomic circumstances. Based on data from the Japan Environment and Children's Study ( n = 75,742), we evaluated maternal socioeconomic factors associated with breastfeeding 1 year after giving birth. Socioeconomic status (education, employment status, and household income), working hours, and breastfeeding were assessed using a self-administered questionnaire. After descriptive analysis, a logistic regression analysis was conducted with adjustments for age, educational level, employment status, and household income. Mothers with higher education and full-time homemakers were more likely to breastfeed one-year-old children. Mothers working long hours (both part-time and full-time) were less likely to breastfeed their one-year-old children. To improve breastfeeding among working mothers, it may be helpful to promote awareness of breastfeeding for every mother as well as to make the workplace environment conducive for working mothers to breastfeed., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

N-myc downstream regulated gene 1 (NDRG1) is a member of the NDRG family, of which four members (NDRG1, NDRG2, NDRG3, and NDRG4) have been identified. NDRG1 is repressed by c-MYC and N-MYC proto-oncogenes. NDRG1 is translated into a 43 kDa protein that is associated with the regulation of cellular stress responses, proliferation, and differentiation. In this study, we aimed to clarify the relationship between progression of glioblastoma (GB) IDH-wildtype and NDRG1 expression in tumor cells. We assessed the expression of NDRG1 in 41 GBs using immunostaining and evaluated its prognostic significance. NDRG1 expression by GBs was evaluated using Histoscore, which showed high and low scores in 23 and 18 cases, respectively. NDRG1-positive cells were strongly expressed in Ki-67 labeled proliferating tumor cells and CD105 positive proliferating microvessels around the area of palisading necrosis. Statistical analyses showed lower survival rates in the high-score group than the low-score group (P < 0.01). This study indicated that overexpression of NDRG1 by GB reflects tumor angiogenesis and poor patient prognosis., (© 2024 Japanese Society of Neuropathology.)

Competing Interests: The authors declare that they have no conflict of interest.

SARS-CoV-2 undergoes budding within the lumen of the endoplasmic reticulum-Golgi intermediate compartment (ERGIC), and the progeny virions are delivered to the cell surface via vesicular transport. However, the molecular mechanisms remain poorly understood. Using three-dimensional electron microscopic analysis, such as array tomography and electron tomography, we found that virion-transporting vesicles possessed protein coats on their membrane and demonstrated that the protein coat was coatomer complex I (COPI). During the later stages of SARS-CoV-2 infection, we observed a notable alteration in the distribution of COPI and ERGIC throughout the cytoplasm, suggesting their potential involvement in virus replication. Depletion of COPB2, a key component of COPI, led to the confinement of SARS-CoV-2 progeny virions within the ERGIC at the perinuclear region. While the expression levels of viral proteins within cells were comparable, this depletion significantly reduced the efficiency of virion release, leading to the significant reduction of viral replication. Hence, our findings suggest COPI as a critical player in facilitating the transport of SARS-CoV-2 progeny virions from the ERGIC. Thus, COPI could be a promising target for the development of antivirals against SARS-CoV-2., Importance: SARS-CoV-2 virions are synthesized within the ERGIC and are transported to the cell surface via vesicular transport for release. However, the precise mechanisms remain unclear. Through various electron microscopic techniques, we identified the presence of COPI on virion-transporting vesicles. Alterations in the distribution of COPI and ERGIC in SARS-CoV-2 infected cells are evident, suggesting their involvement in virus replication. When COPB2, a component of COPI, is depleted, progeny virions become trapped within the ERGIC, leading to a reduction in the efficiency of virion release. These findings highlight COPI's crucial role in mediating SARS-CoV-2 vesicular transport from the ERGIC and suggest it as a potential antiviral target.

Significant sociocultural barriers to sexual and reproductive health (SRH) information influence what is acceptable to discuss and learn within the Malaysian community. To address gaps in their knowledge, adolescents routinely turn to the Internet. This study identifies the ways they navigate SRH information found online. One-on-one interviews were conducted with 17 Malaysian adolescents. The data were analysed with reflexive thematic analysis. Participants navigate SRH information using intuitive strategies, known locally as pandai-pandai. This important cultural concept involves balancing between adherence to social norms and resourcefulness in problem-solving. Pandai-pandai strategies were observed in three domains: (1) navigating SRH sources, (2) evaluating and verifying SRH information, and (3) processing SRH information. Malaysian adolescents' strategies for evaluating SRH information extend beyond traditional critical evaluation models and are driven by emotional, social, and cultural criteria, requiring a reconsideration of what constitutes critical evaluation in this context., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article:June Low reports work experience in the field of sexual health as a sex educator since 2010. Occasionally, she receives income from teaching sex education and providing sex education solutions.Yoshitaka Nishikawa reports the following outside the submitted work: a grant from Japan Medical Association and donations from Datack Inc and Cancerscan Inc.Takeo Nakayama reports the following outside the submitted work: grants from I&H Co., Ltd, Cocokarafine Group Co., Ltd, Konica Minolta, Inc, and NTT DATA; consulting fees from Ohtsuka Pharmaceutical Co., Takeda Pharmaceutical Co., Johnson & Johnson K.K., AstraZeneca plc., and Nippon Aoki Pharmaceutical Co., Ltd.; honoraria from Pfizer Japan Inc, MSD K.K., Chugai Pharmaceutical Co., Takeda Pharmaceutical Co., Janssen Pharmaceutical K.K., Boehringer Ingelheim International GmbH, Eli Lilly Japan K.K., Maruho Co., Ltd, Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Allergan Japan K.K., Novo Nordisk Pharma Ltd, Toa Eiyo Ltd, Dentsu Co., Ono Pharmaceutical Co., Ltd, GSK, Alexion Pharmaceuticals, Inc, Cannon Medical Systems Co., Kowa Company Ltd, and Araya; stock option from BonBon Inc; and donation from Cancerscan and JMDC Inc.All the other authors have no conflicts of interests to declare.

Development of efficient electrocatalysts for hydrogen evolution reactions (HERs) is necessary to achieve environmentally friendly and sustainable hydrogen production. To reduce cost and to circumvent the scarcity of platinum, the most efficient catalyst for HER, it is essential to develop catalysts using ubiquitous base metals or minimal amounts of precious metals. Bis(diimino)metal (MDI) coordination nanosheets are potential HER catalysts because their electric conductivities, two-dimensionality, and porous structures provide large surface areas and efficient mass and electron transfer. In addition, with sparse metal arrangements in their chemical structures, nanosheets can reduce the amount of metal needed. We synthesized bis(diimino)palladium coordination nanosheets (PdDI) as a coordination polymer composed of bis(diimino)palladium, with semiconducting characteristics, using gas-liquid interfacial synthesis and electrochemical oxidation. These electrochemically synthesized PdDIs exhibit remarkable catalytic performance with overpotential reaching 10 mA cm -2 of 34 mV, a Tafel slope of 47 mV dec -1 , and an exchange current density of 2.1 mA cm -2 after appropriate activation. This performance is closely comparable to that of metallic platinum. An ex-situ investigation of the activation process revealed that reduction of the divalent Pd center in bis(diimino)palladium produced a composite of Pd(0) species and PdDI, combining high catalytic activity with smooth electron transfer., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Objective: Long COVID is a global health concern. While various risk factors are known, the link between workplace factors and Long COVID is underexplored. We conducted a cohort study to examine the impact of pre-infection workplace stressors on Long COVID among Japanese workers, with the aim of improving understanding of its disease process and inform workplace management., Methods: This prospective cohort study used online survey data collected in December 2020 and December 2022 from 1,539 participants with no initial infection history but later reported COVID-19. Workplace stressors were assessed at baseline using the Job Content Questionnaire, which measured job demands, job control, and social support. At the follow-up survey, COVID-19 infection was determined by self-reported positive SARS-CoV-2 test by PCR or antigen, and development of Long COVID was defined as symptoms persisting for over two months. Univariate and multivariate logistic regression analyses estimated odds ratios for the association between workplace stressors and the development of Long COVID., Results: Of the participants, 248 reported Long COVID. Univariate analysis showed that both high job demands (OR: 1.55, 95% CI: 1.09-2.20) and poor job control (OR: 1.50, 95% CI: 1.04-2.18) increased the odds. Poor supervisor support (OR: 1.73, 95% CI: 1.16-2.58) and co-worker support (OR: 1.59, 95% CI: 1.13-2.23) were also significant. On multivariate analysis, job demands remained significantly associated with Long COVID., Conclusions: Our findings indicate that pre-infection workplace stressors may contribute to Long-COVID development in workers. Managing workplace stressors effectively could be a preventive measure., (© The Author(s) [2024]. Published by Oxford University Press.)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder. Some children with ASD show enhanced cortisol response to stress. BTBR T + Itpr3 tf /J (BTBR) mice, an ASD model, display behavior consistent with the three diagnostic categories of ASD and exhibit an exaggerated response to stress in adulthood. However, it remains unclear how basal corticosterone levels change and how the hypothalamic-pituitary-adrenal axis responds to stress during the early life stages in BTBR mice. In this study, we found that basal corticosterone levels showed characteristic changes, peaking at weaning during postnatal development in both BTBR and control C57BL/6J (B6J) mice. Furthermore, we observed higher corticosterone and corticotropin-releasing hormone levels in BTBR mice than in B6J mice following acute stress exposure during weaning; however, adrenocorticotropic hormone levels were lower in BTBR mice. Glucocorticoid receptor mRNA expression levels in the hippocampus and lateral septum after stress were higher in BTBR mice than in B6J mice. This study documented changes in corticosterone levels at baseline during postnatal development in mice and showed that BTBR mice exhibited disrupted stress responses at weaning., (© 2024 The Author(s). Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

The innate immune system, which eliminates pathogens and abnormal cells, is involved in the pathogenesis of various diseases and infections, where Toll-like receptors (TLRs) play a critical regulatory role. In this study, we investigated the potential of chitin nanofiber (CtNF) to induce an immune response, which is expected to act as an agonist of TLR2. Crab-derived CtNF, surface-deacetylated CtNF, and surface-carboxylated cellulose NF were employed as TLR2-mediated immune stimulator, signal regulator, and cell adhesion promoter, respectively, to fabricate cell culture scaffolds for HEK293 cells with TLR2 and human monocyte THP-1 cells with or without TLR2. Surface deacetylation of CtNF drastically diminished the immunological response of HEK293 cells, suggesting that the N-acetyl groups on the solid CtNF surface were pivotal for TLR2-mediated stimulation. A comparison of wild-type and TLR2-KO THP-1 cells on cell culture substrates with N-acetyl groups ranging from 0 to 1.39 mmol g -1 revealed that immune signaling for nuclear factor-κB and interferon regulatory factor pathways was strongly dependent on the surface N-acetyl group content. The immunostimulatory level at the interface of solid CtNF and immune cells could be regulated by simply mixing CtNF and surface-deacetylated CtNF, which is a significant advantage for its potential use as a novel immunostimulant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, a draft genome sequence of Zygosaccharomyces siamensis kiy1 isolated from unpasteurized honey in Japan was analyzed. This strain was reported to be a promising arabitol-producing strain, and this report contributes to a better understanding of arabitol production in yeasts.

Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of the lysosomal enzyme ⍺-galactosidase-A (⍺-Gal A), resulting in widespread accumulation of terminal galactose-containing glycosphingolipids (GSLs) and the impairment of multiple organ systems. Thrombotic events are common in Fabry patients, with strokes and heart attacks being significant contributors to a shortened lifespan in patients of both genders. Previously, we developed an ⍺-Gal A-knockout (KO) murine model that recapitulates most Fabry symptomologies and demonstrated that platelets from KO males become sensitized to agonist-mediated activation. In the current report, we used mass spectrometry, platelet-based assays and histology to define further the mechanisms linking GSL accumulation with thrombotic phenotypes in both sexes. Sera and platelets from ⍺-Gal A-KO females have elevated levels of Fabry-associated GSLs relative to wild-type females, but accumulated less of these GSLs than KO males. Correspondingly, KO females demonstrate a less severe thrombotic phenotypes than KO males. Notably, treatment of platelets from wild-type animals with globotriaosylceramide (Gb3) increased baseline platelet activation and aggregation. In contrast, several control GSLs did not stimulate platelet responses. These data suggest that chronically high concentrations of the Fabry-associated GSL, Gb3, contributes to the prothrombotic phenotypes experienced by Fabry patients by directly stimulating platelet activation., Competing Interests: Declaration. Competing interests: NMD is a member of the scientific advisory board of M6P Therapeutics. AJK, EP, MI-A, and KA declare no competing interests., (© 2024. The Author(s).)

Cardiovascular disease (CVD) is becoming prevalent among younger people who have dual roles at both work and home. A possible contributor to CVD is conflict between work and home life. Thus, this study investigated the impact of work-to-family conflict (WFC) and family-to-work conflict (FWC) on metabolic risk factors. We used longitudinal data with a 4-yr interval from the Midlife in Japan study. 152 participants who were employed at baseline without missing variables of interest were included. We assessed the associations of baseline WFC and FWC with changes in metabolic risk factors between baseline and follow-up using Generalized Estimating Equations. After adjusting for baseline sociodemographic, work and family-related, and lifestyle factors, the fully adjusted model showed WFC was significantly associated with changes in low-density lipoprotein cholesterol (LDL-C) and Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. However, FWC was not significantly associated with changes in any metabolic risk factors. Our findings indicated a significant impact of WFC on LDL-C and TC/HDL-C ratio but no significant impact of FWC on metabolic health. Since these metabolic risk factors cause CVD, understanding the physiological responses to occupational psychosocial stress could help create primary prevention interventions and assess their effects on workers' metabolic health.

Background: We examined the effectiveness of a community-based intervention package that targeted pregnant women for increasing utilization of maternal health services. The intervention package was implemented in Suhum Municipality, Ghana, from March 2019 to April 2022. The package consisted of: (i) maternal health education by female and male peers; (ii) training existing health workers on maternal health; and (iii) strengthening the local community health management committees., Methods: A cross-sectional household survey was conducted in May 2022. We sampled four groups of women: (i) intervention at baseline; (ii) intervention at follow-up; (iii) control at baseline; and (iv) control at follow-up. Three outcome variables were set, i.e., the proportions of women having utilized: (i) at least four antenatal care (ANC) services; (ii) facility-based delivery (FBD) services; and (iii) post-partum care (PPC) services. To estimate the effectiveness of the intervention package in increasing the service coverages, both crude and adjusted difference-in-differences (DID) estimates were calculated. Significance levels were set at the values of 0.10, 0.05, and 0.01, since the aforementioned service coverages had already been too high to have room for an increase at the significance level of 0.05., Results: The proportion of women completing at least four ANC services displayed significant DID in both crude and adjusted analyses. The proportions of women utilizing facility-based delivery services and post-partum care services did not display significant DID., Conclusions: Of the three outcome variables set, only the proportion of women having utilized at least four ANC services significantly increased in the intervention group, compared with the control group. Ghana has been in the transition process of shifting the minimum number of ANC visits from four to eight. Thus, nationwide scaling up of the intervention package is expected to help the transition be smooth by increasing the number of ANC visits., Competing Interests: EO, FTA, KF and EY were partially engaged either in planning or in implementing the Program. All the other authors (HA, YK, NK, FO and MO) declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare. Authors’ acronyms: Hirotsugu Aiga (HA); Yoshito Kawakatsu (YK); Nobuhiro Kadoi (NK); Emmanuel Obeng (EO); Frank Tabi Addai (FTA); Frederick Ofosu (FO); Kazuki Fujishima (KF); Mayumi Omachi (MO); and Etsuko Yamaguchi (EY)., (Copyright: © 2024 Aiga 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.)

Plant membrane-bound prenyltransferases (PTs) catalyse the transfer of prenyl groups to acceptor substrates, phenols, using prenyl diphosphates as the donor substrate. The presence of prenyl residues in the reaction products, prenylated phenols, is key to the expression of a variety of physiological activities. Plant PTs generally exhibit high specificities for both substrate recognition and prenylation sites, while the molecular mechanism involved in these enzymatic properties is largely unknown. In this study, we performed a systematic biochemical analysis to elucidate the catalytic mechanism responsible for the reaction specificity of plant PTs. Using two representative PTs, PsPT1 and PsPT2, from parsnip (Pastinaca sativa, Apiaceae), which differ only in the regiospecificity of the prenylation site, we performed domain swapping and site-directed mutagenesis of these PTs, followed by detailed enzymatic analysis combined with three-dimensional modelling. As a result, we discovered the domains that control prenylation site specificity and further defined key amino acid residues responsible for the catalytic mechanism. In addition, we showed that the control mechanism of prenylation specificity revealed here is also highly conserved among coumarin-substrate PTs. These data suggest that the regulatory domain revealed here is commonly involved in prenylation regiospecificity in Apiaceae PTs., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

Cell immunotherapy is a promising therapeutic modality to combat unmet medical needs. Macrophages offer a prominent cell therapy modality since their phenotypic plasticity allows them to perform a variety of roles including defending against pathogens, inducing/suppressing adaptive immunity, and aiding in wound healing. At the same time, this plasticity is a major hurdle in implementation of macrophage therapy. This hurdle can be overcome by cellular backpacks (BPs), discoidal particles that adhere on the macrophage surface and regulate M1/M2 phenotypic shift in an environment-independent manner. In this study, we engineered IL-4 BPs for maintaining macrophages in the M2 phenotype to regulate excess inflammation in periodontitis, a major oral infectious disease. IL-4 BPs induced and maintained M2 phenotype in macrophages in vitro for several days. After injection of macrophages carrying IL-4 BPs into the gingiva, the cells stayed in the tissue for over 5 days and maintained the M2 phenotype in the disease sites. Furthermore, treatment with IL-4 BP-macrophages significantly suppressed the disease progression. Altogether, a treatment with BP-carrying macrophages offers a promising local therapy against periodontitis., Competing Interests: Declaration of competing interest S.M., N.Ka. N. Ku, S·P and L.L.W. are inventors on patent applications related to backpacks (owned and managed by Harvard University)., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study aims to develop a population pharmacokinetic (PK) model of mycophenolic acid (MPA) in pediatric patients with different diseases., Methods: To develop the PK model, electronic medical records (EMR) of pediatric patients with different diseases who received mycophenolic acid mofetil (MMF) at the National Center for Child Health and Development from February 2013 to May 2022 and the results of the MMF pharmacokinetic study of pediatric complicated frequently relapsing steroid-dependent nephrotic syndrome under the Advanced Medical Care B protocol (JSKDC09 study) from October 2015 to June 2019 were integrated and analyzed. Non-linear mixed-effects modeling was used to 1) develop a cross-disease population PK model and 2) estimate PK parameters (apparent clearance CL/F and Q/F; apparent volume of distribution Vc/F and Vp/F; absorption rate constant Ka) by post-hoc Bayesian methods. Patient backgrounds, concomitant medications, and laboratory data were included in the covariate analysis. Visual predictive checks with bootstrap and predictive correction were performed to evaluate the final model., Results: A total of 249 patients with 1495 measurements were used in the analysis, including 68 with post-liver transplant, 65 with nephrotic syndrome, 28 with post-renal transplant, 31 with autoimmune diseases (17 with lupus nephritis and 14 with other collagen diseases), 13 with hematopoietic stem cell transplantation, and 5 with others from EMR and 39 with nephrotic syndrome from the JSKDC09 study. A two-compartment model with a first-order rate absorption process best explained the PK of MPA. A nonlinear relationship between dose and MPA exposure was observed and described by the power function of the model. The final population mean PK parameter estimates (95 % confidence interval) for non-renal transplant patients and average albumin levels were CL/F 15.2 (13.3, 18.0) L/h/70 kg, Vc/F 15.4 (14.4, 17.2) L, Vp/F 246.8 (159.1, 332.1) L, Q/F 7.0 (5.0, 9.0) L/h, and Ka (without proton pump inhibitor [PPI]) 4.4 (2.4, 4.9) h -1 . Weight, disease (post-renal transplant), and serum albumin level were significant covariates for CL/F, and serum albumin level for Vc/F. The use of PPIs also affected Ka., Conclusions: An integrated population PK model of MPA was developed in children with the following conditions: post-solid organ transplantation, post-HSCTx, autoimmune disease, and nephrotic syndrome. Estimated parameters and parameter covariates were similar to those previously reported. This model is expected to provide useful information for using MPA in various diseases in the Japanese population., Competing Interests: Declarations of competing interest KI reports a research grant for clinical trials and clinical research from Zenyaku Kogyo Co., Ltd. to his institution; consulting fees from Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd.; honoraria for manuscript writing from Zenyaku Kogyo Co., Ltd.; payment for expert testimony to his institution from Zenyaku Kogyo Co., Ltd.; and serves as a member of the advisory board of Kyowa Kirin Co., Ltd. and Chugai Pharmaceutical Co., Ltd.. KN is a member of advisory groups for Kyowa Kirin Co., Ltd., Toa Eiyo Co., Ltd., Zenyaku Kogyo Co., Ltd., and Taisho Pharmaceutical Co., Ltd.; Lecture fee from Ono Pharmaceutical Co., Ltd., Astellas Pharma Inc., Novo Nordisk Pharma Ltd., Alexion Pharmaceuticals Inc., Sumitomo Pharma Co., Ltd., Sanofi K.K., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., and Miyarisan Pharmaceutical Co., Ltd.; Speaker's bureaus from Sumitomo Pharma Co., Ltd., Chugai Pharmaceutical Co. Ltd., JCR Pharmaceuticals Co., Ltd., Sanofi K.K., Zenyaku Kogyo Co. Ltd., and Kyowa Kirin Co. Ltd.. HN reports grants for regulatory science on facilitating pediatric drug development from Japan Agency for Medical Research and Development; Consulting fees from Tohoku University, Daiichi Sankyo Company, Limited, and Pfizer R&D Japan G.K.; Honoraria for lectures from Japan Pharmaceutical Manufacturers Association, Pfizer Global Supply Japan Inc., Bristol Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Shionogi & Co., Ltd., and Northern Science Consulting Inc.; and serves as a member of advisory board of Taisho Pharmaceutical Holdings Co., Ltd. for drug development for diabetes, a member of advisory board of Sato Pharmaceutical Co., Ltd. for drug development for dermatology, Chairman of the Committee on Pharmaceutical Affairs of Japan Pediatric Society, and Chairman of the Steering Committee of Japan Society on Developmental Pharmacology and Therapeutics., (Copyright © 2024. Published by Elsevier B.V.)

Oncogenic programs regulate the proliferation and maintenance of cancer stem cells, and can define pharmacologic dependencies. In acute myeloid leukemia (AML) with the chromosome inversion 16 (inv(16)), the fusion oncoprotein CBFβ::MYH11 regulates pathways associated with leukemia stem cell activity. Here we demonstrate that expression of Neuropilin-1 (NRP1) is regulated by the fusion oncoprotein, and promotes AML expansion. Mechanistically, we show that the NRP1 locus has open chromatin in inv(16) AML, and that CBFβ::MYH11 modulates the local function of the transcription factors ERG, GATA2 and RUNX1 to sustain NRP1 levels. We found that ERG activates NRP1 expression, and that CBFβ::MYH11 knockdown represses ERG expression, thereby allowing the repressive activity of GATA2/RUNX1 at three NRP1 enhancers. Functionally, we demonstrate that NRP1 enhances the expansion of leukemic cells in vitro and in mice, and that this activity is dependent on its VEGFR-associated FV/FVIII domain. Finally, we show that treatment with VEGF inhibitor axitinib reduces AML cell growth and delays median leukemia latency in vivo. Our findings reveal that the NRP1/VEGF axis mediates proliferation in inv(16) AML blasts, and suggest that targeting NRP1 function could be promising in combination AML therapy., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Olanzapine is an atypical antipsychotic drug used for chemotherapy-induced nausea and vomiting. It is particularly effective in preventing delayed nausea and vomiting induced by highly emetogenic chemotherapy (HEC). However, it has side effects, such as hyperglycemia and somnolence, the efficacy and safety of adding olanzapine to triplet antiemetic therapy (5-HT 3 receptor antagonist, NK 1 receptor antagonist, and dexamethasone) must be verified., Methods: We performed a systematic review and meta-analysis to compare the effectiveness of olanzapine combined with triplet antiemetic therapy and triplet antiemetic therapy in preventing nausea and vomiting for HEC. We set five items (hyperglycemia, prevention of vomiting, prevention of nausea, adverse events, and cost (drug costs)) as outcomes and conducted a systematic review., Results: Five randomized controlled trials was extracted and they showed that the addition of olanzapine was effective in control of nausea and vomiting, especially in the delayed phase. Complete response of acute and delayed phase were significantly higher in the olanzapine group. Risk difference was - 0.14 [95% CI - 0.26, - 0.03; p = 0.02] and - 0.14 [95% CI - 0.19, -0.09; p < 0.00001], respectively. Additionally, we evaluated hyperglycemia and somnolence, which are typical side effects of olanzapine. However, the incidence of grade ≥ 2 was low in both events, and there was no significant difference between olanzapine and control groups., Conclusions: Adding olanzapine to triplet antiemetic therapy is useful in preventing nausea and vomiting induced by HEC and there would be minimal adverse effects from the combination use., Competing Interests: Declarations. Conflicts of interest: Michiyasu Murakami received honoraria from Taiho Pharmaceutical Co. Ltd. Kazuhisa Nakashima received honoraria from Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., AstraZeneca K.K., and Eli Lilly Japan K.K. Junichi Nishimura received honoraria from Taiho Pharmaceutical Co. Ltd. Eriko Satomi received honoraria from Shionogi & Co. Ltd. Masayuki Takeda received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., and Bayer. Narikazu Boku received honoraria from Ono Pharmaceutical Co., Ltd., Bristol Myers Squibb, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., and Eli Lilly Japan K.K. Koji Matsumoto received honoraria from MSD K.K., Kyowa Kirin Co., Ltd., and Chugai Pharmaceutical Co., Ltd., as well as research funding from Daiichi Sankyo Co., Ltd., MSD K.K., Gilead Sciences, Inc., and Eli Lilly Japan K.K. Nobuyuki Yamamoto received honoraria from MSD K.K., Accuray Japan K.K., AstraZeneca K.K., Abbvie Inc., Amgen Inc., Ono Pharmaceutical Co., Ltd., Guardant Health Japan Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Chugai Foundation for Innovative Drug Discovery Science, Lao Tsumura Co., Ltd., Terumo Corporation, Eli Lilly Japan K.K., Nippon Kayaku Co., Ltd., Novartis AG, Pfizer Global Supply Japan Inc., Merck Biopharma Co., Ltd, Pfizer Global Supply Japan Inc., Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., and USACO Corporation, as well as legal fees in case of iawsuit from Taiho Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Nippon Kayaku Co., Ltd., Prime Research Institute for Medical RWD, Inc., AstraZeneca K.K., and A2 Healthcare Corporation. Takako Eguchi Nakajima received research funding from KBBM, Inc. and Takeda Pharmaceutical Co., Ltd. Ethical approval: Not applicable. Informed consent: Formal consent was not required for this type of study. Consent to participate: Not applicable. Consent for publication: All authors consented to the publication of this study., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: To determine the clinical outcomes of endoscopic submucosal dissection (ESD) for colorectal tumors in older patients and predictors of mortality., Methods: We retrospectively evaluated 207 lesions in 195 consecutive older patients aged ≥ 75 years who underwent ESD for colorectal tumors between January 2007 and December 2018. Outcomes of ESD were evaluated, and the prognosis was assessed in terms of both curability and the patient's baseline physical condition as determined by several indices. Cox regression analyses were performed to identify factors associated with reduced overall survival (OS)., Results: Treatment outcomes included a median procedure time of 55 min, en bloc resection rate of 97%, histological en bloc resection rate of 92%, postoperative bleeding rate of 2.4%, and intraoperative perforation rate of 3.4%. Postoperative bleeding and intraoperative perforation could be treated conservatively. Delayed perforation occurred in one patient and required emergency surgery. Three-year OS was 99.4% and 5-year OS was 95.8%. Overall, three patients experienced recurrence (one local, two distant metastasis), and one patient died of primary cancer. Multivariate analysis identified the Charlson Comorbidity Index (CCI) score ≥ 3 as the only independent predictor of reduced OS (hazard ratio 4.26; 95% confidence interval 1.60-11.38; P = 0.004)., Conclusion: Our results suggest that colorectal ESD is safe and effective in older patients aged ≥ 75 years. There was a significant independent association of reduced OS with high CCI score, but not with curability by ESD. The CCI score should be considered when determining the indications for ESD in older patients., Competing Interests: Declarations. Ethics approval: The study protocol was approved by the institutional review board at North Medical Center Asa Citizens Hospital (approval no. 05–3-31) and was conducted in accordance with the tenets of the Declaration of Helsinki. Informed consent: All patients were informed of the risks and benefits of ESD, and each patient provided written informed consent for the use of their data for publication. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Primary lung cancer is among the cancers with the poorest prognosis, having the highest mortality rate among men and the second highest among women in Japan. While surgery is the primary treatment, advanced stages often require pharmacotherapy. Recently, ferroptosis, an iron-dependent form of cell death caused by lipid peroxidation, has gained attention as a potential therapeutic strategy. This study investigated the prognostic impact of lipid peroxidation marker and regulators involved in ferroptosis in lung adenocarcinoma. Methods : We analyzed 207 patients who underwent resection surgery for lung adenocarcinoma at Tokyo Medical and Dental University Hospital. Immunohistochemistry was used to evaluate the expression levels of glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and 4-hydroxy-2-nonenal (4-HNE). The association between these markers and clinicopathological factors was assessed, and in vitro experiments were conducted to examine the effects of these markers on cell death. Results : Low cytoplasmic accumulation of 4-HNE and low expression of GPX4 were associated with a worse prognosis, and low FSP1 expression was associated with unfavorable relapse-free survival. In vitro experiments demonstrated that 4-HNE inhibited cell proliferation, and combined inhibition of GPX4 and FSP1 induced ferroptosis. Conclusions : These findings suggest that lipid peroxidation markers and regulators can serve as prognostic biomarkers and therapeutic targets in lung adenocarcinoma.

Striving to build an exhaustive guidebook of the types and properties of human cells, the Human Cell Atlas' (HCA) success relies on the sampling of diverse populations, developmental stages, and tissue types. Its open science philosophy preconizes the rapid, seamless sharing of data - as openly as possible. In light of the scope and ambition of such an international initiative, the HCA Ethics Working Group (EWG) has been working to build a solid foundation to address the complexities of data collection and sharing as part of Atlas development. Indeed, a particular challenge of the HCA is the diversity of sampling scenarios (e.g., living participants, deceased donors, pediatric populations, culturally diverse backgrounds, tissues from various developmental stages, etc.), and associated ethical and legal norms, which vary across countries contributing to the effort. Hence, to the extent possible, the EWG set out to provide harmonised, international and interoperable policies and tools, to guide its research community. This paper provides a high-level overview of the types of challenges and approaches proposed by the EWG., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To ascertain whether psychotherapies combined with medication are more efficacious than those without medication and determine which combinations yield the best results., Methods: We conducted a network meta-analysis of randomised controlled trials (RCTs) comparing behavioural activation (BA), psychoanalytic/psychodynamic psychotherapy (DYN), interpersonal psychotherapy (IPT), individual face-to-face cognitive behavioural therapy (CBT (ftf)), group cognitive behavioural therapy (gCBT), and computerised or internet cognitive behavioural therapy (iCBT) with each other, or with treatment-as-usual (TAU) and wait list control (WLC) among adults formally diagnosed with depression. The psychotherapy arms were categorised as either psychotherapy alone or psychotherapy combined with medication (+ p ). Treatment efficacy was assessed based on depression severity. We used a random-effects model to conduct a pairwise meta-analysis., Results: A total of 100 RCTs with 9,873 participants were included. The most common treatment was CBT (ftf) alone. All treatment arms were compared with TAU. Most psychotherapies combined with medication were superior to psychotherapy alone. In the subgroup analyses according to the baseline severity of depression, most psychotherapies combined with medication were more effective than psychotherapy alone in moderate-to-severe depression, whereas in mild depression, such differences were not observed. Among psychotherapies with medication, gCBT + p was significantly more effective than TAU and other psychotherapies in both the main and subgroup analyses., Conclusion: The efficacy of depression treatment varied depending on the severity of the depressive condition. Notably, gCBT + p was identified as the most effective approach for treating adult depression.

Competing Interests: Declaration of competing interest The authors certify that all of their affiliations and/or financial involvement with any organization, or any financial conflicts with the subject matter discussed in the manuscript are disclosed in the Acknowledgement section of the manuscript.

Subtropical Asia has a rich diversity of reptiles and ticks, though the role of reptiles in the sylvatic cycles of medically important ticks in the region is poorly known. Habu vipers (Protobothrops flavoviridis) are widespread and common in the Japanese subtropics but their role as hosts for ticks has not been carefully explored. For 15 months in 2023/24, habu vipers were screened for ticks and were found to be important hosts for immature stages of the tick Amblyomma testudinarium, with a 22 % infestation rate. Amblyomma testudinarium was found to have weak attachment site preferences on P. flavoviridis and host body length was found to have no relationship with either the risk of infestation or the tick load in infested snakes. The phenological profile of A. testudinarium was mapped for the first time in the subtropics based on mean tick loads on P. flavoviridis and historical flagging data. March-April were identified as the period of highest activity, May to July was a period of declining activity, August-September was a period of almost complete inactivity, and October to February was a periods of increasing activity. The role of habu vipers in the sylvatic cycle of A. testudinarium in subtropical Asia is discussion. Additionally, the potential of habu vipers to serve as reservoirs of pathogens or as dilution hosts is also explored., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Mucin-producing adenocarcinoma is a less common variant of lung adenocarcinoma. Adenocarcinoma cells with mucin can spread through the airspace via mucus-mediated extension, leading to their implantation in distant normal lungs. Consequently, post-operative intrapulmonary recurrence frequently occurs. Mucin-producing adenocarcinomas include not only invasive mucinous adenocarcinoma but also papillary, acinar, and other subtypes. Despite increasing reports on surgical outcomes for invasive mucinous adenocarcinomas, the outcomes for total mucin-producing adenocarcinoma remain unclear., Methods: We clinically and pathologically evaluated 511 patients who underwent curative resection for lung adenocarcinoma at our institution. The patients were divided into adenocarcinoma with mucin and without mucin groups. Based on pathological findings, the adenocarcinoma with mucin was further classified into intracellular, extracellular, and mucus extension types. Additionally, the CT value of the tumor mass was analyzed using SYNAPSE VINCENT software., Results: The 5 year overall survival after surgery was 81.5% and 75.9% for patients with adenocarcinoma with versus without mucin (P = 0.774), respectively. The 5 year intrapulmonary recurrence rate in patients with adenocarcinoma with mucin was 29.2%, significantly higher than 12.9% for patients without mucin. Mucus extension was a strong indicator (hazard ratio: 3.03) of intrapulmonary recurrence after surgery. According to SYNAPSE VINCENT analysis, a high volume rate of - 400 HU indicated mucus extension., Conclusion: Our results demonstrated that intrapulmonary recurrence occurs approximately 2.3 times more often in adenocarcinoma with mucin than in adenocarcinoma without mucin. Mucus extension is a significant risk factor for intrapulmonary recurrence, and surgeons can predict it using SYNAPSE VINCENT analysis., Competing Interests: Declarations Conflict of interest The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

The reaction of γ -stannylated propargyl esters in the presence of a cationic gold(I) catalyst affords vinylidenecyclopropane derivatives as a mixture of diastereomers. The cis -geometry of the alkenes is almost entirely retained in the product. DFT calculations suggest the involvement of the gold(I)-stabilized propargyl cation as a resonance form of gold(I)-coordinated allenylidene species.

Institute for Radiological Science (NIRS), National Institutes for Quantum Science and Technology (QST), and Institute for Environmental Sciences (IES) have conducted large-scale animal experiments for radiation risk analyses in terms of life shortening and cancer prevalence. It is important to store data and biological samples from these large-scale experiments for sharing and future use since the economic and practical limitations, as well as the ethical considerations, make it difficult. QST/NIRS established an archive called the Japan Storehouse of Animal Radiobiology Experiments (J-SHARE) for the purpose of storing and sharing these historic collections. We plan to integrate the data and tissue specimen images obtained at the IES into J-SHARE by standardizing the archive format, with the aim of maximizing the results of radiation biology research. This integration is expected to contribute to the generation of new knowledge for radiation risk assessment and the provision of scientifically based information on radiation protection., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: To evaluate the feasibility of a high-precision single-shot fast spin-echo (SS-FSE) sequence using the deep learning-based Precise IQ Engine (PIQE) algorithm in comparison with standard SS-FSE for T2-weighted MR imaging of the abdomen, and to compare the image quality with a multi-shot (MS)-FSE sequence using the PIQE algorithm., Methods: This retrospective study included 105 patients who underwent abdominal MR including T2-weighted sequences using the PIQE reconstruction algorithm. The image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) in high-precision SS-FSE sequences using PIQE were compared to those in standard SS-FSE without PIQE and MS-FSE sequences using PIQE., Results: The scores for all qualitative parameters were significantly higher in high-precision SS-FSE sequence using PIQE than in standard SS-FSE sequence without PIQE (all p < 0.001). In the comparison between two high-precision sequences using PIQE, the SS-FSE sequence showed significantly better scores for the blurring, ghosts or motion/flow artifacts, conspicuity of intrahepatic structures, focal nonsolid hepatic and pancreatic cystic lesions, and overall image quality, in comparison to the MS-FSE sequence (all p < 0.001). Additionally, the SS-FSE sequence using PIQE showed significantly higher SNR of the liver and CNR of nonsolid hepatic lesions than the MS-FSE sequence using PIQE (p < 0.001)., Conclusions: A high-precision SS-FSE sequence using the PIQE algorithm is a feasible alternative to the standard FSE sequence in T2-weighted MR imaging of the abdomen. It can improve image quality, the SNR of the liver, and the ability to visualize nonsolid focal liver lesions and pancreatic cystic lesions in comparison to a high-precision MS-FSE sequence using PIQE although this study was limited by single-center design and lack of pathological confirmation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)