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jPOST (https://jpostdb.org/) comprises jPOSTrepo (https://repository.jpostdb.org/) (over 2000 projects), a repository for proteome mass spectrometry data, the reanalysis of raw proteome data based on a standardised protocol using UniScore, and jPOSTdb (https://globe.jpostdb.org/) (over 600 datasets), a database that integrates the reanalysed data. The jPOST reanalysis protocol rescores MS/MS spectra using a new scale, UniScore, to evaluate the extent to which the spectral peaks correspond to the amino acid sequences identified by search engines. However, the metadata registered in the repository database is insufficient for conducting the reanalysis. To address this issue, the Japanese Proteomics Society launched a data journal, the Journal of Proteome Data and Methods (JPDM), which accepts data descriptor articles detailing metadata that can be reanalysed. Within jPOST, raw proteome data is reanalysed based on the metadata described in the JPDM data descriptor articles, utilising UniScore. The reanalysed data is deposited in jPOSTdb, and a link to the JPDM articles is added to jPOSTrepo. These reanalysis accelerations within the jPOST environment will promote FAIR data principles and open science., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

A 64-year-old Japanese woman presented with gross hematuria and was diagnosed with stage IVB cervical cancer. Renal dysfunction was observed following chemoradiation therapy, and a renal biopsy revealed renal thrombotic microangiopathy (TMA) and tubulointerstitial nephritis (TIN), which are atypical features of radiation nephropathy. Contrast-enhanced computed tomography revealed wedge-shaped areas of high contrast, consistent with areas of high radiation dose in the kidneys, thus leading to the diagnosis of radiation nephropathy. This case underscores the importance of integrating clinical, pathological, and radiological findings for the diagnosis of radiation nephropathy, atypical renal biopsy findings, and a combination of TIN and renal TMA.

Background: Addressing the shortage of healthcare professionals in rural Japan poses significant challenges. At Sanmu Medical Center, incorporating resident physicians into a general medicine training program has proved effective in retaining them as supervising physicians. This study aims to identify the key factors contributing to the success of such programs., Methods: We used a qualitative research design to comprehensively understand the factors contributing to physician retention in regional community hospitals in areas with physician shortages. Interviews were conducted with four experienced physicians, including the center director, who participated in the general or family medicine training programs at Sanmu Medical Center. Using a semi-structured questionnaire, we explored the factors influencing physician retention in community-based hospitals experiencing shortages. Two physicians specializing in community medicine conducted a content analysis under the supervision of three experts in community-oriented medical education and qualitative research. This approach helped compare retention factors perceived by physicians and the center director., Results: Content analysis revealed 10 categories and 47 subcategories. The analysis revealed that "Educational activity" and "Supervising physicians and guidance system" are crucial for physician retention in rural hospitals in Japan. The study highlighted key educational factors contributing to retention: engagement in educational activities led to personal and professional growth, creating a rewarding experience for the physicians. Furthermore, a structured supervising physician system provided essential guidance and mentorship, improving the educational environment. Diverse learning opportunities and protected learning times were identified as critical for fostering a sustainable commitment among physicians to work in rural settings. These findings contribute to existing literature by detailing how structured educational activities and mentorship programs in rural hospital settings can significantly impact physician retention., Conclusions: Community-based medical education programs that focus on diverse clinical settings, mentorship, and a supportive work environment can enhance physician retention in rural areas. By fostering such educational and professional environments, healthcare institutions can address physician maldistribution and improve care quality in underserved communities. Our study offers practical insights that can be replicated or adapted by other rural hospitals facing similar challenges. It offers targeted strategies to address the unique challenges faced by female physicians in rural healthcare settings., (© 2024. The Author(s).)

Background: Report writing in class provides basic training for academic writing. However, report writing education in medical schools in Japan has rarely been reported and no teaching strategy has been established for it., Methods: This study developed a report writing program using peer review for first-year medical students consisting of two 120-minute classes. The goal of being able to write reports appropriately was established and presented to students at the beginning of the program. In session 1, students decided on a topic, gathered information, and structured their report. In session 2, students' written reports were peer reviewed. The reports were improved based on the peer reviews. The responses of the pre- and post-program questionnaires were evaluated to determine the program's effectiveness. The other reports that were assigned one month after the program were used as comparison with the reports of students who did not participate. Furthermore, the long-term effects of the program were also evaluated by comparing the results of students from the previous year who did not participate in the program with those of program participants six months after the program., Results: A total of 106 students completed the questionnaire evaluation. The program was rated as being acceptable for the students. Self-assessment of report writing significantly improved after the program. The report scores of program participants (n = 99) were significantly higher overall and in all domains than were those of non-participants (n = 99). The self-assessment of students who participated (n = 96) was significantly higher than that of non-participants (n = 109). No difference was observed for students' sense of burden in report writing., Conclusions: The report writing skills of medical students can be improved by clearly establishing the goals of report writing and practicing the basic skills of report writing step-by-step. Moreover, the use of peer review may enhance the effectiveness of learning opportunities for report writing., (© 2024. The Author(s).)

The construction industry is actively developing remote-controlled excavators to address labor shortages and improve work safety. However, visually induced motion sickness (VIMS) remains a concern in the remote operation of construction machinery. To predict the occurrence and severity of VIMS, we developed a prototype system that acquires multiple physiological signals with different mechanisms under a low burden and detects VIMS from the collected data. Signals during VIMS were recorded from nine healthy adult males operating excavator simulators equipped with multiple displays and a head-mounted display. Light gradient-boosting machine-based VIMS detection binary classification models were constructed using approximately 30,000 s of time-series data, comprising 23 features derived from the physiological signals. These models were validated using leave-one-out cross-validation on seven participants who experienced severe VIMS and evaluated through area under the curve (AUC) scores. The mean receiver operating characteristic curve AUC score was 0.84, and the mean precision-recall curve AUC score was 0.71. All features were incorporated into the models, with saccade frequency and skin conductance response identified as particularly important. These trends aligned with subjective assessments of VIMS severity. This study contributes to advancing the use of remote-controlled machinery by addressing a critical challenge to operator performance and safety.

α-Actinin-4 (ACTN4) expression levels are correlated with the invasive and metastatic potential of cancer cells; however, the underlying mechanism remains unclear. Here, we identified ACTN4-localized ruffle-edge lamellipodia using live-cell imaging and correlative light and electron microscopy (CLEM). BSC-1 cells expressing EGFP-ACTN4 showed that ACTN4 was most abundant in the leading edges of lamellipodia, although it was also present in stress fibers and focal adhesions. ACTN4 localization in lamellipodia was markedly diminished by phosphoinositide 3-kinase inhibition, whereas its localization in stress fibers and focal adhesions remained. Furthermore, overexpression of ACTN4, but not ACTN1, promoted lamellipodial formation. Live-cell analysis demonstrated that ACTN4-enriched lamellipodia are highly dynamic and associated with cell migration. CLEM revealed that ACTN4-enriched lamellipodia exhibit a characteristic morphology of multilayered ruffle-edges that differs from canonical flat lamellipodia. Similar ruffle-edge lamellipodia were observed in A549 and MDA-MB-231 invasive cancer cells. ACTN4 knockdown suppressed the formation of ruffle-edge lamellipodia and cell migration during wound healing in A549 monolayer cultures. Additionally, membrane-type 1 matrix metalloproteinase was observed in the membrane ruffles, suggesting that ruffle-edge lamellipodia have the ability to degrade the extracellular matrix and may contribute to active cell migration/invasion in certain cancer cell types., 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.)

Background and Aims: EUS-guided biliary drainage (EUS-BD) has shown promising procedural outcomes in high-volume centers. Although inferior procedural outcomes were reported in inexperienced centers during the early days of EUS-BD, the current outcomes are unknown. This study aimed to clarify the feasibility and safety of EUS-BD in centers that recently introduced EUS-BD., Methods: This multicenter retrospective study was conducted at 22 centers that introduced EUS-BD between 2017 and 2022. A maximum of 20 initial EUS-BD cases at each center were evaluated. The clinical outcomes and experience of 84 endoscopists who performed these procedures were examined. Primary outcomes were the rate of technical success and adverse events (AEs), whereas secondary outcomes were risk factors associated with technical failure and procedure-related AEs., Results: Two hundred fifty-five patients were enrolled. The technical success rate was 91.4% (233/255). Among 22 technical failure cases, guidewire manipulation failure was the most common cause (n = 12) followed by tract dilation failure (n = 5). The AE rate was 10.2% (26/255). Multivariate analysis identified a puncture target diameter of <5 mm (odds ratio, 3.719; 95% CI, 1.415-9.776; P = .008) and moderate ascites extending to the liver surface (odds ratio, 3.25; 95% CI, 1.195-8.653; P = .021) as independent risk factors for technical failure and procedure-related AEs, respectively. Endoscopists' procedural experience was not a risk factor for technical failure or procedure-related AEs., Conclusions: The feasibility and safety of EUS-BD were maintained during the induction phase at inexperienced centers. These data will be helpful to better understand the current status of EUS-BD. (Clinical trial registration number: UMIN 000053615.)., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Acquired idiopathic generalized anhidrosis (AIGA) leads to heat intolerance due to the loss or reduction in thermoregulatory sweating over an extensive area of the body. The pathomechanism of AIGA is still unclear but is believed to be autoimmune., Objectives: We investigated the clinical and pathological features of inflammatory AIGA (InfAIGA) and noninflammatory AIGA (non-InfAIGA) within the skin., Methods: We compared anhidrotic and normohidrotic skin samples from 30 patients with InfAIGA and non-InfAIGA, as well as skin samples of melanocytic nevus as a negative control. We conducted morphometric analysis and immunohistochemical analysis of cell types and expression of inflammatory molecules (TIA1, CXCR3 and MxA). MxA expression was used as a proxy for type 1 interferon activity., Results: We found that tissue samples from patients with InfAIGA exhibited inflammation within the sweat duct and atrophy of the sweat coil, whereas patients with non-InfAIGA exhibited only atrophy of the sweat coil. Cytotoxic T lymphocyte infiltration and MxA expression were only observed in the sweat ducts of patients with InfAIGA., Conclusions: InfAIGA is associated with increased sweat duct inflammation and sweat coil atrophy, whereas non-InfAIGA is only associated with sweat coil atrophy. These data suggest that inflammation leads to epithelial destruction of sweat ducts associated with the sweat coil atrophy and subsequent loss of function. Non-InfAIGA may be regarded as a postinflammatory state of InfAIGA. These observations indicate the contribution of both type 1 and type 2 interferons to sweat gland injury. The mechanism involved is similar to the pathomechanism of alopecia areata (AA)., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Phagocytosis is an important immune response that protects the host from pathogen invasion. Rit1 GTPase is known to be involved in diverse cellular processes. However, its role in FcγR-mediated phagocytosis remains unclear. Our live-cell imaging analysis revealed that Rit1 was localized to the membranes of F-actin-rich phagocytic cups in RAW264 macrophages. Rit1 knockout and expression of the GDP-locked Rit1 mutant suppressed phagosome formation. We also found that TBC1D10B, a GAP for the Rab family GTPases, colocalizes with Rit1 in the membranes of phagocytic cups. Expression and knockout studies have shown that TBC1D10B decreases phagosome formation in both Rab-GAP activity-dependent and -independent manners. Notably, the expression of the GDP-locked Rit1 mutant or Rit1 knockout inhibited the dissociation of TBC1D10B from phagocytic cups. In addition, the expression of the GTP-locked Rit1 mutant promoted the dissociation of TBC1D10B in phagocytic cups and restored the rate of phagosome formation in TBC1D10B-expressing cells. These data suggest that Rit1-TBC1D10B signaling regulates FcγR-mediated phagosome formation in macrophages., (© 2024 Egami et al.)

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Multiple system atrophy (MSA) is a progressive, incurable, life-threatening neurodegenerative disease uniquely characterized by the risk of sudden death, which makes diagnosis delivery challenging for neurologists. Empirical studies on breaking a diagnosis of MSA are scarce, with no guidelines currently established. This study aimed to investigate neurologists' current practices and experiences in delivering the diagnosis of MSA., Methods: We conducted a multicenter online survey and employed a mixed-methods (quantitative and qualitative) study design in which responses to open-ended questions were analyzed qualitatively using critical incident technique., Results: Among the 194 neurologists surveyed, 166 opened the survey (response rate = 85.6%), of whom 144 respondents across various Japanese regions completed the survey. Accordingly, 92.3% and 82.8% of the participating neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, respectively. Factors independently associated with difficulties in diagnosis delivery included explaining the importance of the family decision making process in life-prolonging treatment, perceived difficulties in delivering information regarding the risk of sudden death, and perceived difficulties in differential diagnosis of MSA., Conclusions: Our findings showed that the majority of neurologists perceived delivering the diagnosis of MSA and explaining the risk of sudden death as difficult, which could have been associated with the difficulty of breaking the diagnosis of MSA. Difficulty in conveying bad news in MSA are caused by various factors, such as empathic burden on neurologists caused by the progressive and incurable nature of MSA, the need to explain complex and important details, including the importance of the family decision-making process in life-prolonging treatment, difficulty of MSA diagnosis, and communication barriers posed by mental status and cognitive impairment in patients or their family members. Neurologists consider various factors in explaining the risk of sudden death (e.g., patient's personality, mental state, and degree of acceptance and understanding) and adjust their manner of communication, such as limiting their communication on such matters or avoiding the use of the term "sudden death" in the early stages of the disease. Although neurologists endeavor to meet the basic standards of good practice, there is room for the multiple aspects for improvement., (© 2024. The Author(s).)

Purpose: We compared cerebrospinal fluid (CSF) leak conspicuity and image quality as visualized using 3D versus 2D magnetic resonance (MR) myelography in patients with spinal CSF leaks., Methods: Eighteen patients underwent spinal MR imaging at 3 Tesla. Three board-certified radiologists independently evaluated CSF leak conspicuity and image quality on a 4-point scale; the latter assessed by scoring fat suppression, venous visualization, and severity of CSF flow artifacts. Additionally, the evaluators ranked the overall performances of 2D versus 3D MR myelography upon completing side-by-side comparisons of CSF leak conspicuity. Inter-reader agreement was determined using the Gwet's AC1., Results: The quality of 3D MR myelography images was significantly better than that of 2D MR myelography with respect to CSF leak conspicuity (mean scores: 3.3 vs. 1.9, p < 0.0001) and severity of CSF flow artifacts on the axial view (mean scores: 1.0 vs. 2.5, p = 0.0001). Inter-reader agreement was moderate to almost perfect for 2D MR myelography (AC1 = 0.55-1.00), and almost perfect for 3D MR myelography (AC1 = 0.85-1.00). Moreover, 3D MR myelography was judged to be superior to 2D acquisition in 78 %, 83 %, and 83 % of the samples per readers 1, 2 and 3, respectively; the inter-reader agreement was almost perfect (AC1: reader 1 vs. 2; 0.98, reader 2 vs. 3; 0.96, reader 3 vs. 1; 0.98)., Conclusion: CSF leaks are more conspicuous when using 3D MR myelography than when using its 2D counterpart; therefore, the former is more reliable for identifying such leaks., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Authors.)

Glioma stem cell/glioma-initiating cell (GIC) and their niches are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanisms of GIC maintenance/differentiation, we performed a unique integrated proteogenomics utilizing GIC clones established from patient tumors having the potential to develop glioblastoma. After the integration and extraction of the transcriptomics/proteomics data, we found that chondroitin sulfate proteoglycan 4 (CSPG4) and its glycobiosynthetic enzymes were significantly upregulated in GICs. Glyco-quantitative PCR array revealed that chondroitin sulfate (CS) biosynthetic enzymes, such as xylosyltransferase 1 (XYLT1) and carbohydrate sulfotransferase 11, were significantly downregulated during serum-induced GIC differentiation. Simultaneously, the CS modification on CSPG4 was characteristically decreased during the differentiation and also downregulated by XYLT1 knockdown. Notably, the CS degradation on CSPG4 by ChondroitinaseABC treatment dramatically induced GIC differentiation, which was significantly inhibited by the addition of CS. GIC growth and differentiation ability were significantly suppressed by CSPG4 knockdown, suggesting that CS-CSPG4 is an important factor in GIC maintenance/differentiation. To understand the molecular function of CS-CSPG4, we analyzed its associating proteins in GICs and found that CSPG4, but not CS-CSPG4, interacts with integrin αV during GIC differentiation. This event sequentially upregulates integrin-extracellular signal-regulated kinase signaling, which can be inhibited by cyclic-RGD (Arg-Gly-Asp) integrin αV inhibitor. These results indicate that CS-CSPG4 regulates the GIC microenvironment for GIC maintenance/differentiation via the CS moiety, which controls integrin signaling. This study demonstrates a novel function of CS on CSPG4 as a niche factor, so-called "glyco-niche" for GICs, and suggests that CS-CSPG4 could be a potential target for malignant glioma., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Changes in protein glycosylation have been reported in various diseases, including cancer; however, the consequences of altered glycosylation in meningiomas remains undefined. We established two benign meningioma cell lines-SUT-MG12 and SUT-MG14, WHO grade I-and demonstrated the glycan and glycosyltransferase profiles of the mucin-type O-linked glycosylation in the primary benign meningioma cells compared with two malignant meningioma cell lines-HKBMM and IOMM-Lee, WHO grade III. Changes in O-linked glycosylation profiles in malignant meningiomas were proposed., Methods: Primary culture technique, morphological analysis, and immunocytochemistry were used to establish and characterize two benign meningioma cell lines. The glycan profiles of the primary benign and malignant meningiomas cell lines were then analyzed using lectin cytochemistry. The gene expression of O-linked glycosyltransferases, mucins, sialyltransferases, and fucosyltransferases were analyzed in benign and malignant meningioma using the GEO database (GEO series GSE16581) and quantitative-PCR (qPCR)., Results: Lectin cytochemistry revealed that the terminal galactose (Gal) and N-acetyl galactosamine (GalNAc) were highly expressed in primary benign meningioma cells (WHO grade I) compared to malignant meningioma cell lines (WHO grade III). The expression profile of mucin types O-glycosyltransferases in meningiomas were observed through the GEO database and gene expression experiment in meningioma cell lines. In the GEO database, C1GALT1-specific chaperone ( COSMC ) and mucin 1 ( MUC1 ) were significantly increased in malignant meningiomas (Grade II and III) compared with benign meningiomas (Grade I). Meanwhile, in the cell lines, Core 2 β1,6-N-acetylglucosaminyltransferase-2 ( C2GNT2 ) was highly expressed in malignant meningiomas. We then investigated the complex mucin-type O-glycans structures by determination of sialyltransferases and fucosyltransferases. We found ST3 β-galactoside α-2,3-sialyltransferase 4 ( ST3GAL4) was significantly decreased in the GEO database, while ST3GAL1, ST3GAL3 , α1,3 fucosyltransferases 1 and 8 ( FUT1 and FUT8 ) were highly expressed in malignant meningioma cell lines-(HKBMM)-compared to primary benign meningioma cells-(SUT-MG12 and SUT-MG14)., Conclusion: Our findings are the first to demonstrate the potential glycosylation changes in the O-linked glycans of malignant meningiomas compared with benign meningiomas, which may play an essential role in the progression, tumorigenesis, and malignancy of meningiomas., Competing Interests: The authors have declared that no competing interest exists., (© 2024 Talabnin et al.)

Multiple system atrophy with predominant parkinsonism (MSA-P) can hardly be distinguished from Parkinson's disease (PD) clinically in the early stages. This study investigated whether a standardized T1-weighted/T2-weighted ratio (sT1w/T2w ratio) can effectively detect degenerative changes in the middle cerebellar peduncle (MCP) associated with MSA-P and PD and evaluated its potential to distinguish between these two diseases. We included 35 patients with MSA-P, 32 patients with PD, and 17 controls. T1w and T2w scans were acquired using a 1.5-T MR system. The MCP sT1w/T2w ratio was analyzed via SPM12 using a region-of-interest approach in a normalized space. The diagnostic performance of the MCP sT1w/T2w ratio was compared between the MSA-P, PD, and controls. Patients with MSA-P had significantly lower MCP sT1w/T2w ratios than patients with PD and controls. Furthermore, MCP sT1w/T2w ratios were lower in patients with PD than in the controls. The MCP sT1w/T2w ratio showed excellent or good accuracy for differentiating MSA-P or PD from the control (area under the curve (AUC) = 0.919 and 0.814, respectively) and substantial power for differentiating MSA-P from PD (AUC = 0.724). Therefore, the MCP sT1w/T2w ratio is sensitive in detecting degenerative changes in the MCP associated with MSA-P and PD and is useful in distinguishing MSA-P from PD.

We encountered a-27-year-old female patient who developed refractory severe headache and photophobia after the first dose of COVID-19 vaccine. Despite her prior history of migraine, we diagnosed COVID-19 vaccine-induced aseptic meningitis. Symptoms were significantly resolved after methylprednisolone therapy. On reviewing the literature, we could find only nine similar cases, with over half of them affecting women aged 20-40 years. Although uncommon, aseptic meningitis should be suspected in patients with persistent or delayed onset of headache following COVID-19 vaccination.

The phospholipase A and acyltransferase (PLAAT) family is a protein family consisting of five members (PLAAT1-5), which acts as phospholipid-metabolizing enzymes with phospholipase A1/A2 and N-acyltransferase activities. Since we previously reported that the overexpression of PLAAT3 in mammalian cells causes the specific disappearance of peroxisomes, in the present study we examined a possible effect of PLAAT1 on organelles. We prepared HEK293 cells expressing mouse PLAAT1 in a doxycycline-dependent manner and found that the overexpression of PLAAT1 resulted in the transformation of mitochondria from the original long rod shape to a round shape, as well as their fragmentation. In contrast, the overexpression of a catalytically inactive point mutant of PLAAT1 did not generate any morphological change in mitochondria, suggesting the involvement of catalytic activity. PLAAT1 expression also caused the reduction of peroxisomes, while the levels of the marker proteins for ER, Golgi apparatus and lysosomes were almost unchanged. In PLAAT1-expressing cells, the level of dynamin-related protein 1 responsible for mitochondrial fission was increased, whereas those of optic atrophy 1 and mitofusin 2, both of which are responsible for mitochondrial fusion, were reduced. These results suggest a novel role of PLAAT1 in the regulation of mitochondrial biogenesis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Background: Generative artificial intelligence (GAI), represented by large language models, have the potential to transform health care and medical education. In particular, GAI's impact on higher education has the potential to change students' learning experience as well as faculty's teaching. However, concerns have been raised about ethical consideration and decreased reliability of the existing examinations. Furthermore, in medical education, curriculum reform is required to adapt to the revolutionary changes brought about by the integration of GAI into medical practice and research., Objective: This study analyzes the impact of GAI on medical education curricula and explores strategies for adaptation., Methods: The study was conducted in the context of faculty development at a medical school in Japan. A workshop involving faculty and students was organized, and participants were divided into groups to address two research questions: (1) How does GAI affect undergraduate medical education curricula? and (2) How should medical school curricula be reformed to address the impact of GAI? The strength, weakness, opportunity, and threat (SWOT) framework was used, and cross-SWOT matrix analysis was used to devise strategies. Further, 4 researchers conducted content analysis on the data generated during the workshop discussions., Results: The data were collected from 8 groups comprising 55 participants. Further, 5 themes about the impact of GAI on medical education curricula emerged: improvement of teaching and learning, improved access to information, inhibition of existing learning processes, problems in GAI, and changes in physicians' professionality. Positive impacts included enhanced teaching and learning efficiency and improved access to information, whereas negative impacts included concerns about reduced independent thinking and the adaptability of existing assessment methods. Further, GAI was perceived to change the nature of physicians' expertise. Three themes emerged from the cross-SWOT analysis for curriculum reform: (1) learning about GAI, (2) learning with GAI, and (3) learning aside from GAI. Participants recommended incorporating GAI literacy, ethical considerations, and compliance into the curriculum. Learning with GAI involved improving learning efficiency, supporting information gathering and dissemination, and facilitating patient involvement. Learning aside from GAI emphasized maintaining GAI-free learning processes, fostering higher cognitive domains of learning, and introducing more communication exercises., Conclusions: This study highlights the profound impact of GAI on medical education curricula and provides insights into curriculum reform strategies. Participants recognized the need for GAI literacy, ethical education, and adaptive learning. Further, GAI was recognized as a tool that can enhance efficiency and involve patients in education. The study also suggests that medical education should focus on competencies that GAI hardly replaces, such as clinical experience and communication. Notably, involving both faculty and students in curriculum reform discussions fosters a sense of ownership and ensures broader perspectives are encompassed., (©Ikuo Shimizu, Hajime Kasai, Kiyoshi Shikino, Nobuyuki Araki, Zaiya Takahashi, Misaki Onodera, Yasuhiko Kimura, Tomoko Tsukamoto, Kazuyo Yamauchi, Mayumi Asahina, Shoichi Ito, Eiryo Kawakami. Originally published in JMIR Medical Education (https://mededu.jmir.org), 30.11.2023.)

Objectives: Some surgical cases of pleural empyema lead to death despite multidisciplinary treatment. The purpose of this study was to identify prognostic factors in cases treated surgically for pneumonia-associated pleural effusions and empyema caused by common bacteria., Methods: We conducted a retrospective cohort study of 108 surgical patients of empyema who encountered at our hospital between 2011 and 2021. Patients were divided into surviving and non-surviving cases. Factors on admission (age, sex, body mass index, presence of fistula, performance status, pleural fluid culture results, HbA1c, albumin, leukocytes, hemoglobin, body temperature, heart rate, respiratory rate, systolic blood pressure, prognostic nutritional index, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and RAPID score) were compared between the two groups., Results: There were 87 cases of pleural empyema caused by pneumonia due to common bacteria. Variables that differed significantly in univariate analysis between the surviving and non-surviving cases in patients' characteristics on admission were fistula (p value < 0.001, odds ratio 20.000, 95% confidence interval 3.478-115.022), positive pleural fluid culture (0.016, 6.591, 1.190-36.502), body mass index < 18.5 (0.001, 16.857, 1.915-148.349), performance status 0-1 (0.007, 11.778, 1.349-102.858), and hemoglobin (0.024, 1.768, 1.077-2.904). Multivariate analysis showed significant differences in the presence of fistula (p = 0.036, CI 1.174-125.825). The odds ratio was 12.154. The mortality rate was 3.8% for non-fistulous empyema and 44.4% for fistulous empyema. In 6 of 9 cases of fistulous empyema, the fistula could be closed., Conclusion: Fistula was a significant independent prognostic factor for pneumonia-associated pleural effusions and empyema caused by common bacteria., (© 2023. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

In Japan, only single-unit cord blood transplantations (CBTs) are typically performed, and their number has increased over the last 23 years, with ongoing improvement in results. In most cases, CBTs with multiple HLA mismatches are used, owing to a low HLA barrier, and lower engraftment rate is a problem that must be overcome. Here, as part of an effort to improve guidelines for the selection and processing of CB units for transplantation, we sought to assess the present status of CBT in Japan and to elucidate factors contributing to the favorable outcomes, focusing in particular on selection by cell components of CB unit and HLA allele matching. We conducted a nationwide study analyzing 13,443 patients who underwent first CBT between in Japan between December 1997 and December 2019 using multivariate regression analysis. Both patient- and transplantation-related variables, such as age and Hematopoietic Cell Transplantation Comorbidity Index, as well as selected CB unit characteristics, were included in the analysis. The interaction analysis elucidated that CB unit selection favoring higher counts of CD34 + cells and granulocyte macrophage colony-forming units (GM-CFU)/kg, but not of total nucleated cells, contributed to improved engraftment after transplantation. Moreover, a higher CD34 + cell dose was associated with improved overall survival (OS). Distinctive HLA allele matching was observed. A 0 or 1 HLA allele mismatch between patient and donor had favorable engraftment and carried significantly lower risks of acute GVHD and chronic GVHD but had a significantly higher leukemia relapse rate, compared with a 3-HLA allele mismatch. HLA-DRB1 mismatches were associated with reduced risk of leukemia relapse. Notably, the number of HLA allele mismatches had no incremental effect on engraftment, acute and chronic GVHD, or relapse incidence. As a result, 5-year overall survival did not differ significantly among patients receiving CB units with 0 to 7 HLA allele mismatches. The main points of CB unit selection are as follows. First, selection according to a higher number of CD34 + cells/kg and then of CFU-GM/kg is recommended to obtain favorable engraftment. A unit with .5 × 10 5 CD34 + cells/kg is minimally acceptable. For units with a CD34 + cell dose of .5 to 1.0 × 10 5 cells/kg, applying the parameter of ≥20 to 50 × 10 3 GM-CFU/kg (66.5% of transplanted CB units in this cohort) is associated with a neutrophil engraftment rate of approximately 90%. A unit with ≥1.0 × 10 5 CD34 + cells/kg can achieve a ≥90% mean neutrophil engraftment rate. Subsequently, HLA allele matching of HLA-A, -B, -C, and -DRB1 at the 2-field level should be searched for units with 0 or 1 HLA allele mismatch in the host-versus-graft direction for favorable engraftment. Units with 2 to 6 HLA allele mismatches are acceptable in patients age ≥15 years and units with 2 to 4 HLA allele mismatches are acceptable in patients age ≤14 years. Units with HLA-DRB1 and/or -B allele mismatch(es) might not be preferable owing to an increased GVHD risk. Our analysis demonstrates that single-unit CBT with the selection of adequate CD34 + /kg and GM-CFU/kg and HLA allele matching showed favorable outcomes in both pediatric and adult patients., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Nitric oxide (NO) is involved in the pathogenesis of cerebral ischemic injury. Here, we investigated the effects of aging on NO production during cerebral ischemia-reperfusion (IR). Male Wister rats (WRs) were assigned to 12-month-old (older; n = 5) and 3-month-old (younger; n = 7) groups. Similarly, male spontaneous hypertensive rats (SHRs) were allocated to 12-month-old (older; n = 6) and 3-month-old (younger; n = 8) groups. After anesthesia, their NO production was monitored using in vivo microdialysis probes inserted into the left striatum and hippocampus. Forebrain cerebral IR injuries were produced via ligation of the bilateral common carotid arteries, followed by reperfusion. The change in the NO 3 - of the older rats in the SHR groups in the striatum was less compared to that of the younger rats before ischemia, during ischemia, and after reperfusion ( p < 0.05). In the hippocampus, the change in the NO 3 - of the older rats in the SHR groups was lower compared to that of the younger rats after reperfusion ( p < 0.05). There were no significant differences between the two WR groups. Our findings suggested that aging in SHRs affected NO production, especially in the striatum, before and during cerebral ischemia, and after reperfusion. Hypertension and aging may be important factors impacting NO production in brain IR injury.

Cholangiocarcinoma (CCA) is an aggressive malignant tumor of bile duct epithelia. Recent evidence suggests the impact of cancer stem cells (CSC) on the therapeutic resistance of CCA; however, the knowledge of CSC in CCA is limited due to the lack of a CSC model. In this study, we successfully established a stable sphere-forming CCA stem-like cell, KKU-055-CSC, from the original CCA cell line, KKU-055. The KKU-055-CSC exhibits CSC characteristics, including: (1) the ability to grow stably and withstand continuous passage for a long period of culture in the stem cell medium, (2) high expression of stem cell markers, (3) low responsiveness to standard chemotherapy drugs, (4) multilineage differentiation, and (5) faster and constant expansive tumor formation in xenograft mouse models. To identify the CCA-CSC-associated pathway, we have undertaken a global proteomics and functional cluster/network analysis. Proteomics identified the 5925 proteins in total, and the significantly upregulated proteins in CSC compared with FCS-induced differentiated CSC and its parental cells were extracted. Network analysis revealed that high mobility group A1 (HMGA1) and Aurora A signaling through the signal transducer and activator of transcription 3 pathways were enriched in KKU-055-CSC. Knockdown of HMGA1 in KKU-055-CSC suppressed the expression of stem cell markers, induced the differentiation followed by cell proliferation, and enhanced sensitivity to chemotherapy drugs including Aurora A inhibitors. In silico analysis indicated that the expression of HMGA1 was correlated with Aurora A expressions and poor survival of CCA patients. In conclusion, we have established a unique CCA stem-like cell model and identified the HMGA1-Aurora A signaling as an important pathway for CSC-CCA., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: This single-center retrospective analysis investigated the number of days required for postoperative 6-minute walk distance (6MWD) to recover to preoperative values after coronary artery bypass grafting (CABG) and the factors influencing this recovery. Methods and Results: The 6MWD was measured in 101 patients (median age 69 years; 18 women) before and every day after CABG. Univariate and multivariate analyses were performed to identify factors affecting 6MWD recovery to preoperative values after CABG. The median number of days required for recovery of 6MWD after CABG was 9 (interquartile range 7-11 days). Patients were divided into 2 groups based on the median number of days required for recovery of 6MWD; there were 60 patients in the early recovery group (<9 days) and 41 in the "non-early" recovery group (38 who recovered after the median 9 days, and 3 who did not recover during hospitalization). Using univariate logistic regression analysis, diabetes (P=0.01), stroke (P=0.26), left ventricular ejection fraction (P=0.27), and grip strength (P=0.13) were selected for multivariate analysis. Multivariate logistic regression analysis revealed that diabetes (odds ratio 2.955; 95% confidence interval 1.208-7.229; P=0.02) was the only independent predictor of 6MWD recovery. Conclusions: Diabetes was the single factor influencing the recovery of postoperative 6MWD in patients undergoing CABG., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023, THE JAPANESE CIRCULATION SOCIETY.)

Purpose: Although the Palliative Prognostic Index (PPI) has been used to predict survival in various cancers, to our knowledge, no study has examined its applicability in gastric cancer. This study aimed to determine the baseline PPI cutoff value for recommending single-fraction radiotherapy in patients with bleeding gastric cancer., Materials and Methods: This was a secondary analysis of the Japanese Radiation Oncology Study Group (JROSG) 17-3, a multicenter prospective study of palliative radiotherapy for bleeding gastric cancer. Discrimination was evaluated using a time-dependent receiver operating characteristic curve, and the optimal cutoff value was determined using the Youden index. A calibration plot was used to assess the agreement between predicted and observed survival., Results: We enrolled 55 patients in JROSG 17-3. The respective median survival times were 6.7, 2.8, and 1.0 months (p = 0.021) for patients with baseline PPI scores of ≤ 2, 2 < PPI ≤ 4, and PPI > 4. The areas under the curve for predicting death within 2, 3, 4, and 5 months were 0.813, 0.787, 0.775, and 0.721, respectively. The negative predictive value was highest when survival < 2 months was predicted and the Youden index was highest when the cutoff PPI value was 2. The calibration curve showed a reasonable agreement between the predicted and observed survival., Conclusion: Baseline PPI is useful for estimating short-term prognosis in patients treated with palliative radiotherapy for gastric cancer bleeding. A cutoff PPI value of 2 for estimating survival ≤ 2 months should be used to recommend single-fraction radiotherapy., Competing Interests: 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., (© 2023 The Authors.)

Natural waterways are contaminated due to industrialization, urbanization, population growth etc., degrading their quality. Contaminated waterways cause numerous health and environmental hazards. Therefore, it is imperative to remove contaminants. Coagulation is one of the efficient primary chemical treatment methods that could be used to treat such contaminants. Natural coagulants have gained popularity in the water and wastewater treatment industry due to their advantage over chemical coagulants. Natural coagulants are derived from either plants, animals, or microorganisms. This study has elaborated on the nature and mechanisms, and types of natural coagulants. In this review work, many studies have proposed several types of natural coagulants. However, plant-based natural coagulants extracted from different plant components have been extensively discussed and compared based on their application and efficiency in water and waste treatment. The primary purpose of this review is to refine the knowledge on the potential use and optimization of the effectiveness of eco-friendly and sustainable natural coagulants. Besides, the development efforts and the barriers reported by recent findings for the commercialization of natural coagulants are also discussed. Further, few modified natural coagulants have also been presented for exploring the other possible approaches to promote their usage in water and wastewater treatment in the future studies.. [ABSTRACT FROM AUTHOR]