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Competing Interests: Declarations. Informed consent: Written informed consent was obtained from the patient before using her anonymized data and images.

Objective: To examine the association between adjuvant chemotherapy and survival outcomes in patients with stage I uterine leiomyosarcoma (uLMS)., Methods: This comprehensive systematic review and meta-analysis through December 31, 2023 (PROSPERO registration number: CRD42024504776) investigated studies that examined survival outcomes in patients with stage I uLMS using 4 public search engines (PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials). Two investigators searched the studies independently, and survival outcomes (overall survival [OS] and disease-free survival [DFS]) were compared between the adjuvant chemotherapy and observation groups. Utilization rate of adjuvant chemotherapy and the regimens used were also assessed. Kaplan-Meier survival curves in the two treatment groups were evaluated using ImageJ software., Results: From 1988 to 2022, 16 eligible studies including a total of 5690 patients met the inclusion criteria and evaluated the effect of adjuvant chemotherapy on survival outcomes in patients with stage I uLMS. Adjuvant chemotherapy was utilized in 38.5 % of patients (range, 14.8 % to 70.0 %). Eight studies from 2017 to 2022 compared the survival outcomes between adjuvant chemotherapy and observation. OS was comparable between the two groups in both unadjusted (n = 6, hazard ratio [HR] 1.02, 95 % confidence interval [CI] 0.77-1.35, P = 0.88) and adjusted (n = 4, HR 0.90, 95 %CI 0.56-1.43, P = 0.65) pooled analyses. DFS was also similar between adjuvant chemotherapy and observation in both unadjusted (n = 4, HR 0.78, 95 %CI 0.53-1.13, P = 0.18) and adjusted (n = 2, HR 1.14, 95 %CI 0.67-1.94, P = 0.64) pooled analyses. Adjuvant chemotherapy regimens utilized included doxorubicin, ifosfamide, cisplatin, gemcitabine, and docetaxel as monotherapies or combination therapies., Conclusions: In this contemporaneous systematic review and meta-analysis, less than 40 % of patients received adjuvant chemotherapy for stage I uLMS and adjuvant chemotherapy which was not associated with improved survival. These results support the current National Comprehensive Cancer Network clinical practice guidelines that recommends de-escalating adjuvant chemotherapy in stage I uLMS after complete resection., Competing Interests: Declaration of competing interest Research funding, MSD (S.M.); consultant, Cardiff Oncology, Nutcracker, participation in the Steering Committee for the Global Coalition of Adaptive Research (L.D.R.); consultant, research grant, Merck, royalties, UpToDate, honorarium, American College of Obstetrics and Gynecology (J.D.W.); none for others., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Despite significant advances in the treatment of cutaneous melanoma (hereafter melanoma), the prognosis remains less favorable due to therapeutic resistance, which is presumably linked to epigenetic dysregulation. We hypothesized that the histone lysine demethylase KDM4B could play a pivotal role in controlling therapy-resistant melanoma. To validate our hypothesis, we retrieved RNA sequencing data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) program and observed upregulation of KDM4B in both primary and metastatic melanoma, which was associated with poor survival. To explore its role, we used murine B16, human SK-MEL-5, and G-361 melanoma cells as in vitro models of melanoma. We found that KDM4B inhibition using NCGC00244536 increased global levels of H3K9me3 and downregulated the expressions of cell cycle progression-related genes Cdk1, Cdk4, Ccnb1, and Ccnd1. Moreover, genetic ablation of KDM4B or its chemical inhibition using NCGC00244536 reduced p53 production by upregulating MDM2, which enhances the proteolytic degradation of p53. Interestingly, despite the reduction of p53, these interventions augmented apoptosis and senescence-induced cell death by activating pathways downstream of p53, as evidenced by reduced levels of pro-survival Bcl-2 and Bcl-xL proteins and increased production of pro-apoptotic cleaved caspase-3, caspase-7, Bax, and the senescence inducer Cdkn1a. Compared to the FDA-approved anti-melanoma agent dacarbazine, NCGC00244536 exhibited more pronounced cytotoxic and antiproliferative effects in melanoma cells. Importantly, NCGC00244536 demonstrated minimal cytotoxicity to low Kdm4b-expressing mouse embryonic fibroblasts. In conclusion, our findings suggest that KDM4B inhibition can override the antitumor effect of p53, and potentially serve as a therapeutic strategy for melanoma., (© 2024 Wiley Periodicals LLC.)

This study investigated the applicability of fluorescent chromophores for exciton-coupled circular dichroism (ECCD) exploiting fluorescence-detected circular dichroism (FDCD). FDCD had been previously reported useful in allowing the sensitive detection of ECCD in favorable conditions. However, fluorescence detection may prevent applications of the combined method especially when solutions are polarized in emission. Even without polarization of emission, FDCD deviates from circular dichroism (CD) in some cases when the fluorophore of interest interacts with nonfluorescent chromophore. Herein, it was confirmed that employing 6-methoxy-2-naphthoate always yielded interpretable exciton-coupled FDCD spectra even when coupling with nonfluorescent p-substituted benzoates. The 6-methoxy-2-naphthoate chromophore (6-MN) is prescribed in special cases when only a small amount of sample is available for determining the absolute stereochemistry by the CD exciton chirality method observed by FDCD., (© 2024 The Author(s). Chirality published by Wiley Periodicals LLC.)

Objectives: To evaluate the prevalence of ultrasound (US)-detected knee synovitis in patients with rheumatoid arthritis (RA) with a history of total knee arthroplasty (TKA) and to explore its association with RA disease activity and clinical outcomes., Methods: The present, retrospective, cross-sectional study retrieved the data from electronic medical records of patients with RA who were followed up for TKA and had musculoskeletal ultrasound assessment at the study center from January 1, 2021, through December 31, 2021., Results: Forty-two patients with 67 post-TKA knee joints were enrolled in the present study. US-detected synovitis of the post-TKA knee was present in 15 knees (22.4%) and 12 patients (28.6%). There was no difference in disease activity scores or the pain domain of Knee Injury and Osteoarthritis Outcome Score between the patients with (n=12) and without (n=30) US-detected knee synovitis. The proportion of patients with the intensification of anti-rheumatic drugs after musculoskeletal ultrasound assessment was significantly higher in patients with US-detected synovitis compared to those without US-detected synovitis (41.7% vs. 6.7%, p = 0.01)., Conclusions: US-detected synovitis of the knee was present at 22.4% of post-TKA knee joints. Patients with US-detected synovitis of post-TKA knees were likely to receive an intensification of anti-rheumatic drugs., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Every year an estimated two million tonnes of waste electrical and electronic equipment (WEEE) are discarded by householders and companies in the United Kingdom (UK). While the UK has left the European Union (EU), its waste-related policies still mirror those of the EU, including the WEEE-related policies. Motivated by the recent introduction the so-called 'Right to Repair' policy for electrical and electronic equipment (EEE) across the EU and UK, this paper aims to demonstrate that, depending on the commitment and behavioural changes by the consumers and the government, the future of the WEEE management of the UK will vary. To this end, focusing on landfilled WEEE reduction we develop a generic system dynamics model and apply it to eleven WEEE categories. They depict the flow of EEE and WEEE representing the interaction among the stakeholders (e.g., consumers and producers of EEE) and relevant government regulations of the UK. Our four scenario analyses find that longer use of EEE and better WEEE collection seem to be effective in reducing landfilled WEEE, while more reuse and more recycling and recovery have negligible impacts, despite excluding the additional generation of landfilled WEEE as a result of recycling and recovery. Comparing with the business-as-usual scenario, one year longer EEE use and 10% more of WEEE collection could at maximum reduce landfilled WEEE by 14.05% of monitoring and control instruments and 93.93% of display equipment respectively. Backcasting scenario analyses reveal that significant efforts are required to reduce the targeted amounts., 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 Ltd.. All rights reserved.)

Although a Western diet has been identified as a risk factor for Crohn's disease (CD), there is still controversy surrounding the specific foods that may contribute to the development of the disease. In this study, we examined the association between food intake and the prevalence of CD in Japan, as Japanese patients with CD are known to have limited genetic involvement. We identified changes in food intake associated with an increase in the number of patients with CD by analyzing the per capita consumption of food types from 1981 to 2014. Additionally, we examined the association between CD prevalence and food intake in each prefecture. Finally, the relationship between food intake and estimated age at CD onset was also investigated. Between 1981 and 2014, we observed Increased consumption of meat, eggs, milk and dairy products, oil, and potatoes and decreased consumption of grains, beans, vegetables, fruit, fish, sugar, and seaweed. The annual incidence of CD increased by 1388% over the same period. We found that meat consumption was significantly associated with CD prevalence (β = 0.503, p = 0.0003), while a significant negative correlation was observed between CD prevalence and fruit and vegetable consumption (fruit, β = 0.464, p = 0.0012; vegetables, β = 0.404, p = 0.0023). Furthermore, we estimated that the peak consumption of more meat and less fruit and vegetables and the peak age of CD onset occurred within the age range of 20-24 years. Our study identified a clear correlation between the consumption of meat, fruits, and vegetables and the prevalence of CD in Japan. Additionally, we found an association between meat, fruit, and vegetable consumption and the age at CD onset., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kodama 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.)

Background: Frozen shoulder (FS) is a common disorder causing shoulder pain and limited motion. Magnetic resonance imaging (MRI) is expected to help diagnose FS and realize the disease stage if stage-specific features are present. We aimed to survey stage-related MRI findings of FS in the literature., Methods: MEDLINE, SCOPUS, and Google Scholar databases were searched with search terms "frozen shoulder" or "adhesive capsulitis" combined with "magnetic resonance imaging." Studies that discussed MRI findings in relation to FS stages were retrieved. The course of FS was divided into stages 1 to 4 according to Hannafin and Chiaia., Results: Two of the noncontrast-enhanced MRI findings were stage-related. T2 signal hyperintensity of the joint capsule was more frequent in stages 1 and 2. The axillary capsule thickness was greater in stages 1 and 2. However, these findings were also seen in the later stages to a lesser degree. Effusion around the long head of biceps, subcoracoid fat obliteration, and coracohumeral ligament thickening were common in FS but their relation to the stages was not evident. Signal enhancement on contrast-enhanced MRI was not consistently linked to stages., Conclusion: T2 signal hyperintensity and axillary capsule thickening are characteristic of the early stages of FS, although MRI alone cannot completely define the disease stage., (© 2024 The Author(s).)

Nanodots composed of multiferroic cobalt-substituted BiFeO 3 , a ferroelectric ferromagnet at room temperature, are fabricated by pulsed laser deposition using anodized porous alumina as masks. The obtained nanodots are approximately 60 nm in diameter, more than 10 nm in thickness, and approximately 70 Gbit/in. 2 in density. Piezoresponse and magnetic force microscopies show both ferroelectricity and ferromagnetism with a single-domain nature. It is also found that the dot with 190 nm diameter had multidomain vortex ferroelectric and magnetic structures indicating the strong magnetoelectric coupling. The single-domain cobalt-substituted BiFeO 3 nanodots are suitable for verifying magnetization reversal by the electric field, which is the first step in the development of low-power-consumption nonvolatile magnetic memory devices.

Frozen shoulder (FS) is a common disorder characterized by spontaneous onset of shoulder pain accompanied by progressive loss of range-of-motions. The cause of FS is still unclear, and radical therapy has not been established. With the final aim of preventing or curing FS at an earlier stage, we reviewed the pathological and biological features of this disease. Many studies indicate that the main pathology of FS is inflammation initially and fibrosis later. There are inflammatory cytokines, immune cells, fibrotic growth factors, and type-III collagen in the synovium and the joint capsule. The immune cell landscape switches from the macrophages to T cells. Activated fibroblasts seem to regulate the inflammatory and fibrotic processes. The imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteases might promote fibrosis. Additionally, advanced glycation end-products are noted in the FS synovium. Diabetes mellitus and hypothyroidism are closely related to the development of FS. In terms of nonsurgical treatment, oral or intra-articular glucocorticoids are the only drugs that provide early benefit. Some other anti-inflammatory or antifibrotic drugs may potentially control the FS, but have not been proven effective in the clinical setting. Future studies should be targeted to develop steroid-sparing agents that inhibit biological events in FS., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Progressive supranuclear palsy (PSP) is a rapidly progressive neurodegenerative disorder characterized by Parkinsonism, supranuclear ophthalmoplegia, postural instability, and cognitive impairment., Patients: This case series describes three patients initially diagnosed with late-life mood disorders (depression and bipolar disorder) who were later diagnosed with PSP because of the development of typical neurological symptoms., Result: The diagnostic challenge of PSP is highlighted in this case report, particularly in the early stages, when characteristic symptoms may not be present. The importance of considering PSP in the differential diagnosis of late-life mood disorders, especially in the absence of response to standard antidepressant therapy, is also emphasized. The heterogeneity of PSP is described, with various subtypes and atypical variants presenting with different clinical features. The psychiatric symptoms of PSP include apathy, disinhibition, depression, and anxiety, whereas hallucinations and delusions are less frequent. Tau positron emission tomography imaging is discussed as a potential biomarker for atypical PSP., Conclusion: Early diagnosis and intervention are crucial for improved outcomes in PSP, necessitating further research to enhance the diagnostic and treatment strategies for PSP and other neurodegenerative diseases., Competing Interests: Keisuke Takahata is an Editorial Board member of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication. The remaining authors declare no conflict of interest., (© 2024 The Authors. Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Lipolysis-stimulated lipoprotein receptor (LSR) is known as a lipoprotein receptor. LSR is expressed in various solid tumors, including epithelial ovarian, gastric, and colon cancers. High LSR expression is significantly associated with poor prognosis, but its role in cancer has not been fully elucidated. LSR belongs to the Ig protein superfamily, which is conserved in B7 family. Here, we assessed LSR as a novel immune checkpoint molecule. We developed a novel anti-LSR antibody (#27-6 mF-18) that defects antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity. The #27-6 mF-18 cross-reacts with both human and mouse LSR. We found that LSR was expressed on 4T1 murine breast cancer cell line. The #27-6 mF-18 exhibited antitumor effects against the 4T1 syngeneic tumor model, a poor immunogenic model refractory to treatment with anti-PD-1 or anti-CTLA-4 antibodies. Compared with control antibody-treated mice, mice treated with #27-6 mF-18 showed significantly increased numbers of CD8 + T cells and a ratio of activated CD8 + T cells infiltrated in the tumor tissue. This antitumor effect was abrogated by CD8 + T-cell depletion through anti-CD8 antibody treatment, indicating that LSR negatively regulates tumor immunity by repressing CD8 + T cells. These findings show that LSR negatively regulates T-cell immune activity. LSR targeting could provide immune checkpoint inhibitors for cancer immunotherapy., (© 2023 UICC.)

BRCA1/2 mutations are robust biomarkers for platinum-based chemotherapy in epithelial ovarian cancers. However, BRCA1/2 mutations in clear cell ovarian carcinoma (CCC) are less frequent compared with high-grade serous ovarian cancer (HGSC). The discovery of biomarkers that can be applied to CCC is an unmet need in chemotherapy. Schlafen 11 (SLFN11) has attracted attention as a novel sensitizer for DNA-damaging agents including platinum. In this study, we investigated the utility of SLFN11 in HGSC and CCC for platinum-based chemotherapy. SLFN11 expression was analyzed retrospectively by IHC across 326 ovarian cancer samples. The clinicopathologic significance of SLFN11 expression was analyzed across 57 advanced HGSC as a discovery set, 96 advanced HGSC as a validation set, and 57 advanced CCC cases, all of whom received platinum-based chemotherapy. BRCA1/2 mutation was analyzed using targeted-gene sequencing. In the HGSC cohort, the SLFN11-positive and BRCA mutation group showed significantly longer whereas the SLFN11-negative and BRCA wild-type group showed significantly shorter progression-free survival and overall survival. Moreover, SLFN11-positive HGSC shrunk significantly better than SLFN11-negative HGSC after neoadjuvant chemotherapy. Comparable results were obtained with CCC but without consideration of BRCA1/2 mutation due to a small population. Multivariate analysis identified SLFN11 as an independent factor for better survival in HGSC and CCC. The SLFN11-dependent sensitivity to platinum and PARP inhibitors were validated with genetically modified non-HGSC ovarian cancer cell lines. Our study reveals that SLFN11 predicts platinum sensitivity in HGSC and CCC independently of BRCA1/2 mutation status, indicating that SLFN11 assessment can guide treatment selection in HGSC and CCC., (©2023 American Association for Cancer Research.)

Objectives: Pain causal attribution is the attribution of pain causes to self or others, which may depend on one's choice of actions. The study aimed to examine how the cognitive processes of pain causal attribution as one aspect of the sense of agency change in healthy individuals based on free or forced choice, using a temporal binding (TB) experimental task., Methods: Participants pressed keys (action) in a combined TB task, with one key having a high probability of delivering pain (with tone). In fact, only the bias between the free-choice and the forced choice conditions was manipulated. Participants estimated the time between their action and tone, with shorter intervals indicating internal attribution., Results: Interval estimation was significantly longer in the forced-choice condition than in the free-choice condition when a pain stimulus was delivered., Conclusions: Explicit complaints of pain being caused by others may be represented in implicit cognitive processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the trend of joint destruction patterns on knee radiographs of patients with rheumatoid arthritis (RA) undergoing total knee arthroplasty (TKA) over the past 16 years., Method: Medial joint space, lateral joint space, medial spur area, lateral spur area (L-spur), and femoro-tibial angle were obtained from 831 preoperative knee radiographs of patients with RA who underwent TKA between 2006 and 2021 using software capable of automatic measurements. Non-hierarchical clustering was performed based on these five parameters. Trends in the five individual radiographic parameters and the ratio of each cluster were investigated during the target period. Moreover, clinical data from 244 cases were compared among clusters to identify factors associated with this trend., Results: All parameters, except for L-spur, showed significant increasing trends from 2006 to 2021. The radiographs were clustered into groups according to the characteristic pattern of radiographic findings: cluster 1 (conventional RA type), with bicompartmental joint space narrowing (JSN), less spur formation, and valgus alignment; cluster 2 (osteoarthritis type), with medial JSN, medial osteophytes, and varus alignment; and cluster 3 (less destructive type), with mild bicompartmental JSN, less spur formation, and valgus alignment. The ratio of cluster 1 showed a significantly decreasing trend contrary to the significantly increasing trend in clusters 2 and 3. The DAS28-CRP of cluster 3 was higher than those of clusters 1 and 2., Conclusions: Radiographs of TKA recipients with RA are increasingly presenting osteoarthritic features in recent decades. Key Points • Using automated measurement software, morphological parameters were measured from radiographs of 831 patients with rheumatoid arthritis who had undergone TKA in the past 16 years. • Cluster analysis based on the radiographic parameters revealed that the radiographs of patients with end-stage knee arthritis requiring total knee arthroplasty were classified into three groups. • In patients with rheumatoid arthritis who have undergone total knee arthroplasty in the past 16 years, the proportion of clusters with features of osteoarthritis and difficult-to-treat rheumatoid arthritis has increased, while the proportion of conventional rheumatoid arthritis has decreased., (© 2023. The Author(s).)

Introduction: Tumor cell spillage during the colpotomy has been suspected as one reason for poor oncologic outcomes in laparoscopic radical hysterectomy (LRH) for cervical cancer. To prevent such tumor spillage in LRH, we focused on use of a Gutclamper which is a device originally designed to clamp the colon and rectum during colorectal resections., Materials and Surgical Technique: A woman with stage IB1 cervical cancer underwent LRH using the Gutclamper. The Gutclamper was inserted into the abdominal cavity via 5-mm trocar, the vagina was clamped, and an intracorporeal colpotomy was performed caudal to this device., Discussion: The Gutclamper can be used to clamp the vaginal canal and avoid the exposure of cervical tumor, regardless of the surgeon's skills or patient conditions. An intracorporeal colpotomy using the Gutclamper can contribute to the standardization of LRH., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Bile acids are major components of bile; they emulsify dietary lipids for efficient digestion and absorption and act as signaling molecules that activate nuclear and membrane receptors. The vitamin D receptor (VDR) is a receptor for the active form of vitamin D and lithocholic acid (LCA), a secondary bile acid produced by the intestinal microflora. Unlike other bile acids that enter the enterohepatic circulation, LCA is poorly absorbed in the intestine. Although vitamin D signaling regulates various physiological functions, including calcium metabolism and inflammation/immunity, LCA signaling remains largely unknown. In this study, we investigated the effect of the oral administration of LCA on colitis in a mouse model using dextran sulfate sodium (DSS). Oral LCA decreased the disease activity of colitis in the early phase, which is a phenotype associated with the suppression of histological injury, such as inflammatory cell infiltration and goblet cell loss. These protective effects of LCA were abolished in VDR-deleted mice. LCA decreased the expression of inflammatory cytokine genes, but this effect was at least partly observed in VDR-deleted mice. The pharmacological effect of LCA on colitis was not associated with hypercalcemia, an adverse effect induced by vitamin D compounds. Therefore, LCA suppresses DSS-induced intestinal injury in its action as a VDR ligand.

Circulating fatty acid composition is assumed to play an important role in metabolic dysfunction-associated fatty liver disease (MAFLD) pathogenesis. This study aimed to investigate the association between the overall balance of serum fatty acid composition and MAFLD prevalence. This cross-sectional study involved 400 Japanese individuals recruited from a health-screening program. We measured fatty acids in serum lipids using gas chromatography-mass spectrometry. The serum fatty acid composition balance was evaluated using fuzzy c-means clustering, which assigns individual data points to multiple clusters and calculates the percentage of data points belonging to multiple clusters, and serum fatty acid mass%. The participants were classified into four characteristic subclasses (i.e., Clusters 1, 2, 3, and 4), and the specific serum fatty acid composition balance (i.e., Cluster 4) was associated with a higher MAFLD prevalence. We suggest that the fuzzy c-means method can be used to determine the circulating fatty acid composition balance and highlight the importance of focusing on this balance when examining the relationship between MAFLD and serum fatty acids.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually., (© 2022 Japan Society of Obstetrics and Gynecology.)

Objectives: Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab., Methods: This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era., Results: After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months)., Conclusions: Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab., (© 2022 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Mucosal hypoxia is detected in the mucosa of ulcerative colitis (UC), however the mechanism and the cause of hypoxia is not fully understood, while a dense infiltration of plasma cells is observed in the inflamed mucosa of UC. When differentiating from a B cell to a plasma cell, the energy metabolism dramatically shifts from glycolysis to oxidative phosphorylation, which results in a large amount of oxygen consumption of the plasma cell. We hypothesized that the plasma cell infiltration into the inflamed mucosa contributes to the mucosal hypoxia in UC in part. We examined the association between mucosal hypoxia and plasma cell infiltration in UC. More IgG plasma cells (but not IgA plasma cells) were distributed, and the nuclear and cell sizes were enlarged in hypoxic mucosa compared to normoxic mucosa in UC. Oxidative phosphorylation signature genes of these IgG plasma cells were markedly upregulated compared to those of other lymphoid cells infiltrating the lamina propria of inflamed mucosa of UC. Enlarged IgG plasma cells, which increase in number in the inflamed mucosa of UC, can be related to the hypoxic state of the inflamed mucosa of UC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In Japan, the government suspended HPV vaccine recommendation in 2013, resulting in dropping vaccination uptake to almost zero. We conducted four serial surveys on our colleague' attitude to HPV vaccination between 2014 and 2021. Here, we evaluate the result of the survey in 2021 and compare it to previous surveys., Methods: The subjects were 567 obstetricians and gynecologists who had been trained in our university hospital or our affiliated hospitals. We used a questionnaire similar in format to those used in 2014, 2017, and 2019., Results: A total of 340 doctors (60.0%) completed the survey. Among them, 93.2% (317/340) of respondents thought that the government should restart HPV vaccination recommendation, and that 63.2% (215/340) think male teenagers should also vaccinate against HPV. The percentage of teenaged daughters inoculated with HPV vaccination after Japanese government had suspended its recommendation was 43.5% (20/46), an increasing trend from the previous surveys. 39 out of the 46 daughters (84.8%) would be expected to receive full HPV vaccination after they take junior high school entrance examination or after 9-valent HPV vaccination is designated as a national routine-immunization., Conclusion: This study revealed increasing number of our colleagues think HPV vaccination is necessary for prevention of cervical cancer. The Japanese government's decision to resume its recommendation of the HPV vaccine in November 2021 will lead to a change in the public's thinking and behavior toward the HPV vaccine., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Abnormal cord insertion (ACI) is associated with adverse obstetric outcomes; however, the relationship between ACI and assisted reproductive technology (ART) has not been examined in a meta-analysis. This study examines the association between ACI and ART, and delivery outcomes of women with ACI. A systematic review was conducted, and 16 studies (1990-2021) met the inclusion criteria. In the unadjusted pooled analysis ( n = 10), ART was correlated with a higher rate of velamentous cord insertion (VCI) (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.64-2.79), marginal cord insertion ( n = 6; OR 1.58, 95%CI 1.26-1.99), and vasa previa ( n = 1; OR 10.96, 95%CI 2.94-40.89). Nevertheless, the VCI rate was similar among the different ART types (blastocyst versus cleavage-stage transfer and frozen v ersus fresh embryo transfer). Regarding the cesarean delivery (CD) rate, women with VCI were more likely to have elective ( n = 3; OR 1.13, 95%CI 1.04-1.22) and emergent CD ( n = 5; OR 1.93, 95%CI 1.82-2.03). In conclusion, ART may be correlated with an increased prevalence of ACI. However, most studies could not exclude confounding factors; thus, further studies are warranted to characterize ART as a risk factor for ACI. In women with ACI, elective and emergent CD rates are high.

The purpose of this study was to develop a robotic hand to assist with large organs, instead of using a surgeon, in laparoscopic surgery. Grasping, pinching, and exclusion were performed by three subjects with no medical knowledge. The results indicate that the proposed system can perform surgical operations in hand-assisted laparoscopic surgery when the subjects are proficient. However, the thumb mechanism and the wrist control method were required improvement because it was difficult to approach organs. Surgeons were asked to operate the robotic hand while watching the laparoscope image, and they were able to grasp and pinch with little practice.

Background: Endometrial cancer (EC) is a common gynecologic malignancy and patients with advanced and recurrent EC have a poor prognosis. Although chemotherapy is administered for those patients, the efficacy of current chemotherapy is limited. Therefore, it is necessary to develop novel therapeutic agents for EC. In this study, we focused on lipolysis-stimulated lipoprotein receptor (LSR), a membrane protein highly expressed in EC cells, and developed a chimeric chicken-mouse anti-LSR monoclonal antibody (mAb). This study investigated the antitumor effect of an anti-LSR mAb and the function of LSR in EC., Methods: We examined the expression of LSR in 228 patients with EC using immunohistochemistry and divided them into two groups: high-LSR (n = 153) and low-LSR groups (n = 75). We developed a novel anti-LSR mAb and assessed its antitumor activity in an EC cell xenograft mouse model. Pathway enrichment analysis was performed using protein expression data of EC samples. LSR-knockdown EC cell lines (HEC1 and HEC116) were generated by transfected with small interfering RNA and used for assays in vitro., Results: High expression of LSR was associated with poor overall survival (hazard ratio: 3.53, 95% confidence interval: 1.35-9.24, p = 0.01), advanced stage disease (p = 0.045), deep myometrial invasion (p = 0.045), and distant metastasis (p < 0.01). In EC with deep myometrial invasion, matrix metalloproteinase (MMP) 2 was highly expressed along with LSR. Anti-LSR mAb significantly inhibited the tumor growth in EC cell xenograft mouse model (tumor volume, 407.1 mm 3 versus 726.3 mm 3 , p = 0.019). Pathway enrichment analysis identified the mitogen-activated protein kinase (MAPK) pathway as a signaling pathway associated with LSR expression. Anti-LSR mAb suppressed the activity of MAPK in vivo. In vitro assays using EC cell lines demonstrated that LSR regulated cell proliferation, invasion, and migration through MAPK signaling, particularly MEK/ERK signaling and membrane-type 1 MMP (MT1-MMP) and MMP2. Moreover, ERK1/2-knockdown suppressed cell proliferation, invasion, migration, and the expression of MT1-MMP and MMP2., Conclusions: Our results suggest that LSR contributes to tumor growth, invasion, metastasis, and poor prognosis of EC through MAPK signaling. Anti-LSR mAb is a potential therapeutic agent for EC., (© 2022. The Author(s).)

To investigate the trend and factors related to the occurrence of osteoarthritis (OA)-like features on knee radiographs of rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA) in the recent decades. To classify antero-posterior knee radiographs into 'RA' and 'OA-like RA' groups, a deep learning model was developed by training the network using knee radiographs of end-stage arthropathy in RA patients obtained during 2002-2005 and in primary OA patients obtained during 2007-2009. We used this model to categorize 796 knee radiographs, which were recorded in RA patients before TKA during 2006-2020, into 'OA-like RA' and 'RA' groups. The annual ratio of 'OA-like RA' was investigated. Moreover, univariate and multivariate analyses were performed to identify the factors associated with the classification as OA-like RA using clinical data from 240 patients. The percentage of 'OA-like RA' had significant increasing trend from 20.9% in 2006 to 67.7% in 2020. Higher body mass index, use of biologics, and lower level of C-reactive protein were identified as independent factors for 'OA-like RA'. An increasing trend of knee radiographs with OA-like features was observed in RA patients in the recent decades, which might be attributed to recent advances in pharmacotherapy., (© 2022. The Author(s).)

From genetic and etiological studies, autoimmune mechanisms underlying schizophrenia are suspected; however, the details remain unclear. In this study, we describe autoantibodies against neural cell adhesion molecule (NCAM1) in patients with schizophrenia (5.4%, cell-based assay; 6.7%, ELISA) in a Japanese cohort (n = 223). Anti-NCAM1 autoantibody disrupts both NCAM1-NCAM1 and NCAM1-glial cell line-derived neurotrophic factor (GDNF) interactions. Furthermore, the anti-NCAM1 antibody purified from patients with schizophrenia interrupts NCAM1-Fyn interaction and inhibits phosphorylation of FAK, MEK1, and ERK1 when introduced into the cerebrospinal fluid of mice and also reduces the number of spines and synapses in frontal cortex. In addition, it induces schizophrenia-related behavior in mice, including deficient pre-pulse inhibition and cognitive impairment. In conclusion, anti-NCAM1 autoantibodies in patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice. These antibodies may be a potential therapeutic target and serve as a biomarker to distinguish a small but treatable subgroup in heterogeneous patients with schizophrenia., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Background: The present study aimed prospectively to investigate the effect of a combination of tumour necrosis factor inhibitors and bisphosphonates (TNFi with BP) on bone mineral density (BMD) and bone and cartilage biomarkers compared to that of BP alone at 1 year in patients with rheumatoid arthritis (RA)., Methods: Two groups of patients with RA and osteoporosis were enrolled. One group (37 patients) had already received BP, while the other group (37 patients) had already received TNFi with BP. The serum bone resorption and formation markers, cartilage markers, BMD in the lumbar spine, femoral neck, and distal radius were prospectively investigated at the beginning of the study and at 6 and 12 months., Results: The percentages of change recorded for the various assessment categories were as follows in the TNFi with BP group: (1) tartrate-resistant acid phosphatase-5b had significantly decreased and osteocalcin had increased; (2) matrix metalloproteinase-3 and cartilage oligomeric matrix protein had significantly decreased; and (3) each BMD did not differ significantly between the groups., Conclusion: Our data suggested that TNFi with BP therapy not only suppressed cartilage degradation and bone resorption but also increased bone formation; however, this treatment did not affect the BMD at 1 year., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Endometriosis is a common benign gynecological disorder; however, delivery outcomes concerning pregnancies with endometriosis remain understudied. This study aimed to assess the effect of endometriosis on delivery outcomes, including the rate of instrumental delivery, cesarean delivery (CD), postpartum hemorrhage (PPH), and perioperative complications during CD. A systematic literature review was conducted using multiple computerized databases, and 28 studies met the inclusion criteria. Pooled analysis showed that histologically diagnosed endometriosis was associated with an increased rate of instrumental delivery (odds ratio [OR] 1.26, 95% confidence interval [CI] 1.02-1.56) and an increased risk of CD (adjusted OR 2.59, 95%CI 1.32-5.07). In our analysis, histologically diagnosed endometriosis was not associated with an increased rate of PPH; however, one retrospective study reported that endometriosis increased the rate of PPH during CD (adjusted OR 1.7, 95%CI 1.5-2.0). Two studies examined perioperative complications during CD, and women with deep endometriosis had a higher rate of bowel resection or bladder injury than those without endometriosis. Our findings suggest that endometriosis is a significant risk factor for instrumental delivery and CD and may be associated with a higher rate of PPH and intraoperative complications during CD.

This study aimed to assess the relationship between placenta accreta spectrum disorder (PASD) and endometriosis. The relationships among pregnancy, assisted reproductive technology (ART), placenta previa, ART-conceived pregnancy and PASD were also determined. A systematic literature review was conducted using multiple computerized databases. Forty-eight studies (1990-2021) met the inclusion criteria. According to the adjusted pooled analysis ( n = 3), endometriosis was associated with an increased prevalence of PASD (adjusted odds ratio [OR] 3.39, 95% confidence interval [CI] 1.96-5.87). In the included studies, the ART rate ranged from 18.2% to 37.2% for women with endometriosis. According to the adjusted pooled analysis, women who used ART were more likely to have placenta previa ( n = 13: adjusted OR 2.96, 95%CI, 2.43-3.60) and PASD ( n = 4: adjusted OR 3.54, 95%CI 1.86-6.76) than those who did not use ART. According to the sensitivity analysis using an unadjusted analysis accounting for the type of ART, frozen embryo transfer (ET) was associated with an increased risk of PASD ( n = 4: OR 2.79, 95%CI, 1.22-6.37) compared to fresh ET. Endometriosis may be associated with an increased rate of PASD. Women with placenta previa complicated with endometriosis who conceived using frozen ET may be a high risk for PASD.

Background: Automated medical history-taking systems that generate differential diagnosis lists have been suggested to contribute to improved diagnostic accuracy. However, the effect of these systems on diagnostic errors in clinical practice remains unknown., Objective: This study aimed to assess the incidence of diagnostic errors in an outpatient department, where an artificial intelligence (AI)-driven automated medical history-taking system that generates differential diagnosis lists was implemented in clinical practice., Methods: We conducted a retrospective observational study using data from a community hospital in Japan. We included patients aged 20 years and older who used an AI-driven, automated medical history-taking system that generates differential diagnosis lists in the outpatient department of internal medicine for whom the index visit was between July 1, 2019, and June 30, 2020, followed by unplanned hospitalization within 14 days. The primary endpoint was the incidence of diagnostic errors, which were detected using the Revised Safer Dx Instrument by at least two independent reviewers. To evaluate the effect of differential diagnosis lists from the AI system on the incidence of diagnostic errors, we compared the incidence of these errors between a group where the AI system generated the final diagnosis in the differential diagnosis list and a group where the AI system did not generate the final diagnosis in the list; the Fisher exact test was used for comparison between these groups. For cases with confirmed diagnostic errors, further review was conducted to identify the contributing factors of these errors via discussion among three reviewers, using the Safer Dx Process Breakdown Supplement as a reference., Results: A total of 146 patients were analyzed. A final diagnosis was confirmed for 138 patients and was observed in the differential diagnosis list from the AI system for 69 patients. Diagnostic errors occurred in 16 out of 146 patients (11.0%, 95% CI 6.4%-17.2%). Although statistically insignificant, the incidence of diagnostic errors was lower in cases where the final diagnosis was included in the differential diagnosis list from the AI system than in cases where the final diagnosis was not included in the list (7.2% vs 15.9%, P=.18)., Conclusions: The incidence of diagnostic errors among patients in the outpatient department of internal medicine who used an automated medical history-taking system that generates differential diagnosis lists seemed to be lower than the previously reported incidence of diagnostic errors. This result suggests that the implementation of an automated medical history-taking system that generates differential diagnosis lists could be beneficial for diagnostic safety in the outpatient department of internal medicine., (©Ren Kawamura, Yukinori Harada, Shu Sugimoto, Yuichiro Nagase, Shinichi Katsukura, Taro Shimizu. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 27.01.2022.)

Inhaler devices play an important role in the management of obstructive lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Some of these patients show suboptimal inhaler techniques; however, time for inhaler instruction by pharmacists is limited in daily clinical practice. Therefore, sufficient education regarding inhaler device handling should be provided within a limited time frame. The current study aimed to investigate the instruction methods provided by community pharmacists and their influence on inhaler device handling techniques in outpatient clinical care settings. We retrospectively collected the data of outpatients with obstructive lung diseases who were referred to our hospital and who underwent inhalation technique assessments conducted by community pharmacists. The prevalence of handling errors, clinical characteristics of patients, and instruction methods were analyzed. In total, 138 patients (170 devices) were included in this study. Approximately 70.0% of patients received verbal explanations combined with leaflets about inhaler instructions. In a device-based analysis, 63 (37.1%) of 170 devices had at least one technical error and 18 (10.6%) of the devices had critical errors. Patients without critical errors received practical demonstration instructions from pharmacists combined with leaflets and verbal explanations more frequently than those with critical errors (22.8 vs. 0%, p < 0.01). This study revealed that patients with obstructive lung diseases commonly present with inhaler device handling errors and critical errors were observed with non-negligible frequency in daily practice in Japan. Combined instruction with leaflet, verbal explanation, and pharmacist demonstration may be effective in improving proper inhaler treatment.