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The majority of genetic Primary progressive aphasia (PPA) patients harbor mutations in the granulin ( GRN ) gene. The present case showed impaired performances in single-word retrieval in spontaneous speech and naming, and repetition. Head MRI revealed marked lateral atrophy in the left parietal cortex. A diagnosis of logopenic variant PPA (lvPPA) was established. Genetic analysis showed a heterozygous 10-bp frameshift deletion in exon 4 of the GRN gene (NM_002087.4), leading to transformation of cysteine into alanine at amino acid 92 and creation of a premature stop codon at position 161. This patient represented a rare case of GRN -associated lvPPA. A new mutation site was detected in exon 4 of GRN gene.

Effective and efficient detection of pavement distress is very important for the normal use and maintenance of roads. To achieve this goal, a new road damage detection method based on YOLOv8 is proposed in this article. Firstly, omni-dimensional dynamic convolution (ODConv) block is employed to better grasp the complex and diverse features of damage objects by making dynamic adjustment according to the features of input images. Secondly, to extract the global and local feature information simultaneously to better improve the feature extraction ability of the model, BoTNet is added to the end of the backbone, which can combine the advantages of convolutional neural network (CNN) and Transformer. Finally, the coordinate attention mechanism (CA) is incorporated into the Neck section to make more accurate speculations and enhance detection accuracy further which can effectively mitigate irrelevant feature interference. The new proposed model is named OBC-YOLOv8 and the experimental results on the RDD2022-China dataset demonstrate its superiority compared with baselines, with 1.8% and 1.6% increases in mean average precision 50 (mAP@0.5) and F1-score, respectively., Competing Interests: The authors declare that they have no competing interests., (© 2025 Zhang et al.)

Objective: The diagnosis and prognosis of hepatocellular carcinoma (HCC) present significant challenges in clinical practice. This study aimed to evaluate the clinical utility of tumor abnormal protein (TAP), Prothrombin induced by vitamin K absence-II (PIVKA-II), and alpha-fetoprotein (AFP) in diagnosing HCC as well as to investigate their prognostic significance in patients with HCC undergoing transarterial chemoembolization., Methods: A total of 93 HCC patients were enrolled and 101 healthy individuals served as controls. Fresh venous blood samples were collected, and TAP, PIVKA-II, and AFP levels were measured by chemiluminescence immunoassay., Results: Significant differences in TAP, PIVKA-II, and AFP levels were found between HCC patients and healthy individuals. The combined assay of TAP, AFP, and PIVKA-II showed better diagnostic performance for HCC. Patients who underwent transarterial chemoembolization and achieved complete response (CR) had lower levels of prechemotherapy serum TAP, AFP, and PIVKA-II. There are significant differences in levels of TAP, AFP, and PIVKA-II between CR and partial response (PR), CR and stable disease (SD), and CR and progressive disease (PD)., Conclusion: Combined detection of TAP, PIVKA-II, and AFP has better diagnostic performance for HCC. Higher levels of prechemotherapy serum TAP, AFP, and PIVKA-II are significantly associated with poor clinical chemoresponse., (© The Author(s) 2025. Published by Oxford University Press on behalf of American Society for Clinical Pathology. 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.)

Introduction and Hypothesis: The objective was to explore the efficacy of micro-radiofrequency (micro-RF) therapy for treating non-Hunner interstitial cystitis (NHIC)., Methods: Forty female NHIC patients were enrolled in this retrospective study from December 2021 to December 2023, with 20 receiving intravesical micro-RF therapy and 20 undergoing hydrodistension (HD). The primary evaluation index was the treatment success rate using the Global Response Assessment (GRA) scale. Secondary indexes included changes from baseline in the visual analog scale (VAS) for pain, Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale, and urination parameters. Outcomes were analyzed via t or nonparametric tests., Results: All 40 patients completed the treatment and follow-up; the treatment success rate of the micro-RF group (70%, 14 out of 20) was slightly higher than that of the HD group (50%, 10 out of 20) at 12 weeks post-treatment, with no significant difference (20%, p = 0.197). The VAS, ICSI, ICPI, PUF, day-time frequency, urgency episodes, and nocturia significantly decreased in both groups after treatment (p < 0.05). Further, the median decline ranges of VAS (-4.0 vs -3.0; p = 0.017; 95% CI -1.45, -0.15) and ICPI (-5.0 vs -4.0; p = 0.011; 95% CI -2.02, -0.283) were significantly larger in the micro-RF group. There were no significant differences in ICSI (-6.5 vs -6.0, p = 0.407), PUF (-10.0 vs. -8.0; p = 0.071), and urgency episodes (-5.5 vs -4.5; p = 0.570)., Conclusions: Our study showed that the short-term overall efficacy of micro-RF therapy was better than hydrodistension, particularly in managing pain, and might be a new alternative treatment option for patients with NHIC., Competing Interests: Declarations. Ethics Statement: All procedures of this study were in accordance with the Declaration of Helsinki (revised 2013) and were approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. Written informed consent to release patient information was obtained. Conflicts of Interest: None., (© 2024. The International Urogynecological Association.)

Cerebral infarction is the main cause of death and long-term disability worldwide. Neuronal degeneration and limp sensory dysfunction are the secondary damages induced by cerebral infarction. This study aimed to investigate the roles of activating transcription factor 4 (ATF4) in cerebral infarction and the underlying molecular mechanisms. Middle cerebral artery occlusion (MCAO) surgery was applied to establish a cerebral infarction model in vivo. Histological analysis was performed using Nissl assay. Gene expression was determined using immunohistochemistry, immunofluorescence, and Western blot. Gene interaction was confirmed by co-immunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP), and luciferase assays. Cellular functions were determined using Cell Counting Kit assay (CCK-8), propidium iodide (PI) staining, and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assays. ATF4 was overexpressed in cerebral infarction models in vivo and in vitro. However, ATF4 knockdown decreased ischemic foci and volume and restored sensory functions in vivo. ATF4 knockdown suppressed lipid peroxidation and neuronal ferroptosis in vitro. Moreover, ATF4 activated DNA methyltransferase 1 (DNMT1), which induced glutathione peroxidase 4 (GPX4) DNA methylation and decreased its expression. GPX4 knockdown alleviated the effects of shATF4 and promoted neuronal ferroptosis. Overall, ATF4 knockdown protected against cerebral infarction and sensory dysfunction by promoting DNMT1-mediated DNA methylation of GPX4.

This study is to analyse the failure patterns and long-term survival after stereotactic body radiotherapy (SBRT) in patients with T1-3N0M0 inoperable non-small cell lung cancer (NSCLC). Early-stage NSCLC patitents who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary endpoint were the patterns of disease progression, which were divided into local recurrence, regional failure, and distant metastasis. Kaplan-Meier method survival analysis was used to calculate overall survival (OS), progression-free survival (PFS). Cox model was used for univariate analysis and multivariate analysis. A total of 215 patients with 224 lesions were enrolled. After the median follow-up time of 50.8 months (1.0-117.9 months), 76 (35.3%) patients progressed, with regional progression occurring in 4 cases (1.8%), local and local-regional progression in 17 cases (7.9%), various distant metastases developing in 55 cases (25.6%). The OS rates at 1, 3, and 5 years were 97.1%, 80.9%, and 63.8%, respectively, with a median OS of 92.2 months (95%CI, 61.5-122.9 months). The PFS rates at 1, 3, and 5 years were 87.5%, 65.9%, and 50.8%, respectively, with a median PFS of 62.2 months (95% CI, 45.0-59.4 months). There was no significant difference in OS (P = 0.832) and PFS (P = 0.672) between the two groups with or without pathology. Multivariate analysis showed that BED and patient age were independent prognostic factors affecting early-stage lung cancer survival (all P < 0.05). Distant metastasis was the main failure pattern of inoperable early-stage NSCLC after SBRT, and the high-risk population should be selected for further systemic treatment., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study has been approved by the Ethics Committee of Zhejiang Cancer Hospital (IRB-2023-588) with the informed consent of all participants and/or their legal guardians., (© 2024. The Author(s).)

Background: The role of gasdermin D (GSDMD) in bloodstream infection (BSI) diagnosis is unknown., Methods: Serum GSDMD levels were measured in patients with BSI. Endothelial cells and peripheral blood mononuclear cells were isolated and infected with bacteria/fungi, and intracellular/extracellular GSDMD concentrations were measured. An animal model was established to investigate the association between serum GSDMD levels and BSI incidence or progression., Results: Receiver operating characteristic curve analysis indicated that GSDMD could be a potential early diagnostic biomarker for BSI (area under the curve [AUC], .9885). Combining GSDMD with procalcitonin improved the differential diagnosis of gram-positive and gram-negative bacteria (AUC, 0.6699; 66.15% specificity) and early diagnosis of gram-positive bacteria (98.46% sensitivity), while procalcitonin was not significantly elevated. The combined GSDMD and (1-3)-β-D glucan test (G test) had higher sensitivity (AUC, 0.7174) for differential diagnosis of bacterial and fungal infections and early detection of fungal infections (98.44% sensitivity). In vitro and in vivo experiments confirmed that GSDMD levels increased significantly within 2 hours, peaked at 16 hours, and exhibited a time-dependent upward trend., Conclusions: Serum GSDMD, alone or combined with other biomarkers, has potential for early diagnosis and differential diagnosis of BSI caused by various pathogens. This finding offers a new strategy for early detection and treatment of BSI., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Dysregulation of SMAD4 (i.e. somatic mutation) is strongly associated with poor pancreatic ductal adenocarcinoma (PDAC) prognosis, yet the molecular mechanisms remain underlying this relationship obscure. Previously, we discovered that SMAD4 mutation renders pancreatic cancer resistant to radiotherapy via promotion of autophagy. In the current work, we observed a downregulation of the protein level of SMAD4 in PDAC as compared with adjacent normal tissue, and that such SMAD4 low PDAC failed to benefit from chemotherapy. Furthermore, we observed that SMAD4 depletion dramatically enhanced DNA repair capacity in response to irradiation (IR) or a radiomimetic chemical. Interestingly, we found the radiomimetic chemical having induced a robust translocation of SMAD4 into the nucleus, where a direct interaction was shown to occur between the MH1 domain of SMAD4 and the DBD domain of PARP1. Functionally, the SMAD4-PARP1 interaction was found to perturb the recruitment of PARP1 to DNA damage sites. Accordingly, the combination of olaparib and radiotherapy was indicated in vivo and in vitro to specifically reduce the growth of SMAD4-deficient PDAC by attenuating PARP1 activity. Collectively, our results revealed a novel molecular mechanism for the involvement of the SMAD4-PARP1 interaction in DNA repair with a vital role in radiotherapy response in PDAC. Based on our set of findings, our findings offer a new combined therapeutic strategy for SMAD4 deficient PDAC that can significantly reduce pancreatic cancer radiotherapy resistance., Competing Interests: Competing interests The authors declare no competing interests. Ethics approval and consent to participate The care and use of the animals were approved by the ethical review board at Shanghai Tenth People’s Hospital (under references SHDSYY-2023-2532). All methods were performed in accordance with the relevant guidelines and regulations at Tongji University and Shanghai Tenth People’s Hospital., (© 2024. The Author(s).)

This paper introduces a novel retaining wall structure that integrates a traditional mechanically stabilized earth (MSE) retaining wall with foamed lightweight soil (FLS) as the fill material. To evaluate the performance of the structure, a numerical approach based on the finite difference method was employed. Firstly, numerical models were developed based on a centrifuge test model designed by previous researchers, and the results were compared with the measured data. The close agreement between the experimental values and simulations demonstrates the reliability and validity of the proposed numerical models. Subsequently, a series of parametric studies were conducted to reveal the effect of key parameters on the performance of the newly proposed retaining wall. Furthermore, this paper proposes a modified harmonic search algorithm (MHSA), which is based on the original harmonic search algorithm (OHSA), to optimize the design of the proposed retaining wall structure. The results indicate that the proposed retaining wall structure can effectively reduce the differential settlement between the existing road and the newly constructed road at a relatively lower cost. The MHSA can serve as a practical design guidebook for engineers and potential users, enabling rapid and efficient design.

Background: A phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed., Objectives: The aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials., Methods: MET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups., Results: H9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting., Conclusions: We confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Long-term survival varies among hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer patients and is seriously impaired by metastasis. Chromosomal instability (CIN) was one of the key drivers of breast cancer metastasis. Here we evaluate CIN and 10-year invasive disease-free survival (iDFS) and overall survival (OS) in HR+/HER2-- breast cancer. In this large-scale, multiple-site, retrospective study, 354 HR+/HER2- breast cancer patients were recruited. Of these, 204 patients were used for internal training, 70 for external validation, and 80 for cross-validation. All medical records were carefully reviewed to obtain the disease recurrence information. Formalin-fixed paraffin-embedded tissue samples were collected, followed by low-pass whole-genome sequencing with a median genome coverage of 1.86X using minimal 1 ng DNA input. CIN was then assessed using a customized bioinformatics workflow. Three or more instances of CIN per sample was defined as high CIN and the frequency was 42.2% (86/204) in the internal cohort. High CIN correlated significantly with increased lymph node metastasis, vascular invasion, progesterone receptor negative status, HER2 low, worse pathological type, and performed as an independent prognostic factor for HR+/- breast cancer. Patients with high CIN had shorter iDFS and OS than those with low CIN [10-year iDFS 11.1% versus 82.2%, hazard ratio (HR) = 11.12, p < 0.01; 10-year OS 45.7% versus 94.3%, HR = 14.17, p < 0.01]. These findings were validated in two external cohorts with 70 breast cancer patients. Moreover, high CIN could predict the prognosis more accurately than Adjuvant! Online score (10-year iDFS 11.1% versus 48.6%, HR = 2.71, p < 0.01). Cross-validation analysis found that high consistency (83.8%) was observed between CIN and MammaPrint score, while only 45% between CIN and Adjuvant! Online score. In conclusion, high CIN is an independent prognostic indicator for HR+/HER2- breast cancer with shorter iDFS and OS and holds promise for predicting recurrence and metastasis., (© 2024 The Author(s). The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition., Competing Interests: The authors declare no conflict of interest.

The expression of some genes regulated by their DNA methylation is involved in pathogenesis and disease progression of myelodysplastic syndrome (MDS), which is characterised by abnormal differentiation and development of myeloid cells. Therefore, it is significant for us to work on investigating what factors regulate U2AF1 expression and hydroxymethylation in MDS patients. However, the members of TET protein family can change 5-methylcytosine (5mC) into 5-hydroxymethylcytosine5-methyl cytosine (5hmC). In general, 5mC and 5hmC levels maintain dynamic equilibrium, and their imbalance is associated with the onset and progression of some tumors. In this study, the expression and 5mC and 5hmC levels of U2AF1 gene decreased significantly after the treatment by decitabine in Mutz-1 cells. The decreased degree of 5hmC is far greater than that of 5mC. IDH2 expression decreased significantly followed by U2AF1 5hmC levels. However, the expression of other hydroxymethylation-related genes such as IDH1, TET1 and TET2 also decreased, but the difference did not achieve significance. Compared with IDH2 or U2AF1 wild-type MDS patients, U2AF1 expression and 5hmC level in patients with these two gene mutations were both significantly reduced.

Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75-0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates., (© 2024. The Author(s).)

Background: In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored., Method: The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model., Results: In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC., Conclusion: This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection., (© 2024. The Author(s).)

Introduction: Chronic ankle instability (CAI) carries a high risk of progression to talar osteochondral lesions and post-traumatic osteoarthritis. It has been clinically hypothesized the progression is associated with abnormal joint motion and ligament elongation, but there is a lack of scientific evidence. Methods: A total of 12 patients with CAI were assessed during level walking with the use of dynamic biplane radiography (DBR) which can reproduce the in vivo positions of each bone. We evaluated the uninjured and CAI side of the tibiotalar and subtalar joint for three-dimensional kinematics differences. Elongation of the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL) were also calculated bilaterally. Results: For patients with CAI, the dorsiflexion of the tibiotalar joint had reduced (21.73° ± 3.90° to 17.21° ± 4.35°), displacement of the talus increased (2.54 ± 0.64 mm to 3.12 ± 0.55 mm), and the inversion of subtalar joint increased (8.09° ± 2.21° to 11.80° ± 3.41°). Mean ATFL elongation was inversely related to mean dorsiflexion angle (CAI: rho = -0.82, P < 0.001; Control: rho = -0.92, P < 0.001), mean ATFL elongation was related to mean anterior translation (CAI: rho = 0.82, P < 0.001; Control: rho = 0.92, P < 0.001), mean CFL elongation was related to mean dorsiflexion angle (CAI: rho = 0.84, P < 0.001; Control: rho = 0.70, P < 0.001), and mean CFL elongation was inversely related to mean anterior translation (CAI: rho = -0.83, P < 0.001; Control: rho = -0.71, P < 0.001). Furthermore, ATFL elongation was significantly (CAI: rho = -0.82, P < 0.001; Control: rho = -0.78, P < 0.001) inversely correlated with CFL elongation. Discussion: Patients with CAI have significant changes in joint kinematics relative to the contralateral side. Throughout the stance phase of walking, ATFL increases in length during plantarflexion and talar anterior translation whereas the elongation trend of CFL was the opposite. This understanding can inform the development of targeted therapeutic exercises aimed at balancing ligament tension during different phases of gait. The interrelationship between two ligaments is that when one ligament shortens, the other lengthens. The occurrence of CAI didn't change this trend. Surgeons might consider positioning the ankle in a neutral sagittal plane to ensure optimal outcomes during ATFL and CFL repair., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ruan, Wang, Zhang, Jiang, Mei, Li, Ren, Qian and Chang.)

Background: Myopia is a significant public health problem across the globe. This study aimed to examine the regional disparity in prevalence and correlated factors of myopia in children and adolescents in two typical regions, Gannan Tibetan Autonomous Prefecture (Gannan Prefecture for short, a Tibetan residential area) and Wuwei City (a Han residential area) in Gansu Province, China, and to provide a reference for the prevention and control of regional myopia., Methods: The study was a cross-sectional study of children and adolescents in Gansu Province, China. A total of 6,187 (Wuwei City: 3,266, Gannan Tibetan Autonomous Prefecture: 2,921) students were selected by stratified cluster sampling. Eye examinations and questionnaires were administered to the participants. Myopia is defined as a condition in which the spherical equivalent refractive error of an eye is less than or equal to -0.50 D when ocular accommodation is relaxed. The χ 2 test and multivariate logistic regression analysis were used to analyze the correlated factors of myopia., Results: The myopia rate of 6,187 students was 71.4%, and students had a higher rate of myopia (77.5%) in Wuwei City compared to Gannan Prefecture (64.6%) ( p  < 0.001). The results of multivariate analysis in Wuwei City showed that girls (odds ratio ( OR ) = 1.325), junior students ( OR  = 2.542), senior students( OR  = 4.605), distance between eyes and book less than one foot ( OR  = 1.291), and parents with myopia (one, OR  = 2.437; two, OR  = 4.453) had higher risks of myopia (all, p  < 0.05). For Gannan Prefecture, girls ( OR  = 1.477), senior students ( OR  = 1.537), daily time spent doing homework ≥2 h (OR = 1.420), the distance between eyes and book less than one foot ( OR  = 1.205), mean time continuous eye use (0.25-<0.5 h, OR  = 1.345, 0.5-<1 h, OR  = 1.317, ≥1 h, OR  = 1.313), average daily sleep duration <8 h ( OR  = 1.399), and parents with myopia (one, OR  = 1.852; two, OR  = 2.913) had higher risks of myopia (all, p  < 0.05)., Conclusion: The prevalence of myopia is at a relatively high level in Gansu Province. The prevalence and risk factors for myopia vary by region., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, He, Feng and Li.)

Purpose: Our study aimed to develop and validate a homologous recombination deficiency (HRD) scoring algorithm in the Chinese breast cancer population., Methods and Materials: Ninety-six in-house breast cancer (BC) samples and 6 HRD-positive standard cells were analyzed by whole-genome sequencing (WGS). Besides, 122 BCs from the TCGA database were down-sampled to ~ 1X WGS. We constructed an algorithm named AcornHRD for HRD score calculated based on WGS at low coverage as input data to estimate large-scale copy number alteration (LCNA) events on the genome. A clinical cohort of 50 BCs (15 cases carrying BRCA mutation) was used to assess the association between HRD status and anthracyclines-based neoadjuvant treatment outcomes., Results: A 100-kb window was defined as the optimal size using 41 in-house cases and the TCGA dataset. HRD score high threshold was determined as HRD score ≥ 10 using 55 in-house BCs with BRCA mutation to achieve a 95% BRCA-positive agreement rate. Furthermore, the HRD status agreement rate of AcornHRD is 100%, while the ShallowHRD is 60% in standard cells. BRCA mutation was significantly associated with a high HRD score evaluated by AcornHRD and ShallowHRD (p = 0.008 and p = 0.003, respectively) in the TCGA dataset. However, AcornHRD showed a higher positive agreement rate than did the ShallowHRD algorithm (70% vs 60%). In addition, the BRCA-positive agreement rate of AcornHRD was superior to that of ShallowHRD (87% vs 13%) in the clinical cohort. Importantly, the high HRD score assessed by AcornHRD was significantly correlated with a residual cancer burden score of 0 or 1 (RCB0/1). Besides, the HRD-positive group was more likely to respond to anthracycline-based chemotherapy than the HRD-negative group (pCR [OR = 9.5, 95% CI 1.11-81.5, p = 0.040] and RCB0/1 [OR = 10.29, 95% CI 2.02-52.36, p = 0.005])., Conclusion: Using the AcornHRD algorithm evaluation, our analysis demonstrated the high performance of the LCNA genomic signature for HRD detection in breast cancers., (© 2024. The Author(s).)

Sunitinib, a primary treatment for clear cell renal cell carcinoma (ccRCC), frequently encounters the challenge of resistance development. Metabolic reprogramming, a characteristic change in ccRCC, is likely linked to this resistance. Our research revealed a notable decrease in the expression of the key metabolic gene ABAT in ccRCC, which contributed to diminished sensitivity to sunitinib. Downregulation of ABAT led to an increase in the intracellular level of gamma-aminobutyric acid (GABA), triggering abnormal activation of the G-protein-coupled receptor GABA-B. This activation resulted in increased transactivation of the tyrosine kinase receptors SYK and LYN, thereby reducing the antitumor and antiangiogenic properties of sunitinib. However, the application of SYK and LYN inhibitors successfully inhibited this effect. The transactivation of SYK and LYN caused resistance to the antiangiogenic effects of sunitinib through the upregulation of PGF protein levels. Furthermore, the combined application of an LYN inhibitor with sunitinib has been shown to enhance therapeutic efficacy., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined., Methods: In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells., Results: Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes., Conclusions: Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC., (© 2024. The Author(s).)

Polyadenylation [Poly(A)] is an essential process during messenger RNA (mRNA) maturation in biological eukaryote systems. Identifying Poly(A) signals (PASs) from the genome level is the key to understanding the mechanism of translation regulation and mRNA metabolism. In this work, we propose a deep dual-dynamic context-aware Poly(A) signal prediction model, called multiscale convolution with self-attention networks (MCANet), to adaptively uncover the spatial-temporal contextual dependence information. Specifically, the model automatically learns and strengthens informative features from the temporalwise and the spatialwise dimension. The identity connectivity performs contextual feature maps of Poly(A) data by direct connections from previous layers to subsequent layers. Then, a fully parametric rectified linear unit (FP-RELU) with dual-dynamic coefficients is devised to make the training of the model easier and enhance the generalization ability. A cross-entropy loss (CL) function is designed to make the model focus on samples that are easy to misclassify. Experiments on different Poly(A) signals demonstrate the superior performance of the proposed MCANet, and an ablation study shows the effectiveness of the network design for the feature learning and prediction of Poly(A) signals.

Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years., Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening., Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p  < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable., Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Ding, Kong, Zhu, Li, Tian and Zhang.)

Territorial space conflicts (TSCs) in coastal zones stem from the intricate interaction between the land-sea dual system, significantly impacting the sustainable development of these areas. To accurately identify TSCs, our study proposed a theoretical framework based on a land-sea interaction perspective. We also assessed TSCs using the territorial space conflicts index and a social network analysis model. We demonstrated the proposed spatial conflicts assessment methodology through a case study of Wenzhou, a typical city on the east coast of China. Our results indicate that the distribution of TSCs gradually decreased from the coastal zone to the inland zone, with significant variation in the distribution of different conflict types across different zones. The findings also reveal that territorial space use had diverse impacts on the space conflict network, making it urgent to take targeted measures. In the future, it is crucial to comprehensively consider the overall pattern and distribution characteristics of current TSCs, as well as the spatial spillover effect of the overall network, to develop targeted coping strategies and regulation mechanisms that promote the integration and high-quality development of coastal territorial space systems. To maintain a sustainable coastal zone process, we proposed a set of optimization paths for alleviating TSCs and promoting the coordinated development of land and sea regions in China based on our study., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chaotic waveforms with Gaussian distributions are significant for laser-chaos-based applications such as random number generation. By exploring the injection parameter space of the optical injection semiconductor lasers, we numerically investigate the associated probability density functions of the generated chaotic waveforms when different high-pass filters with different cutoff frequencies are used. Our results demonstrate that the chaotic waveforms with Gaussian probability density functions can be obtained once the cutoff frequency of the high-pass filter is larger than the laser relaxation resonance frequency. Especially, we find that the Gaussian probability density function can reach a superhigh coefficient of determination R 2  ≥ 99.5% and an ultralow skewness |S|<0.1 in a large parameter space by jointly controlling the injection parameter and cutoff frequency.

Efficient obstacle-avoidance path planning is critical for orchards with numerous irregular obstacles. This paper presents a continuous bidirectional Quick-RRT* (CBQ-RRT*) algorithm based on the bidirectional RRT (Bi-RRT) and Quick-RRT* algorithms and proposes an expansion cost function that evaluates path smoothness and length to overcome the limitations of the Quick-RRT* algorithm for non-holonomic mobile robot applications. To improve the zigzag between dual trees caused by the dual-tree expansion of the Bi-RRT algorithm, CBQ-RRT* proposes the CreateConnectNode optimization method, which effectively solves the path smoothness problem at the junction of dual trees. Simulations conducted on the ROS platform showed that the CBQ-RRT* outperformed the unidirectional Quick-RRT* in terms of efficiency for various orchard layouts and terrain conditions. Compared to Bi-RRT*, CBQ-RRT* reduced the average path length and maximum heading angle by 8.5% and 21.7%, respectively. In addition, field tests confirmed the superior performance of the CBQ-RRT*, as evidenced by an average maximum path lateral error of 0.334 m, a significant improvement over Bi-RRT* and Quick-RRT*. These improvements demonstrate the effectiveness of the CBQ-RRT* in complex orchard environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ye, Li and Li.)

Effective marine oil spill responses are vital to reduce environmental, societal, and economic damage. This study developed a Multi-Criteria Emergency Response System (MC-ERS) to comprehensively evaluate response efficiency, operational costs, and environmental losses. The proposed system integrates dynamic multiphase simulation of oil weathering and oil cleanup processes and further provides effective planning for multi-stage resource allocation through system optimization. The developed weight-sum model improved the performance of response operations by reducing the complexity of multi-criteria decision-making. Particle Swarm Optimization (PSO) was chosen as the foundational optimization algorithm due to its efficiency in rapid convergence and suitability for complex problems. From extensive comparisons of PSO variants across benchmark functions and inertia strategies, the C-PSO algorithm was developed, demonstrating enhanced optimization performance for MC-ERS. The developed modelling system performance was demonstrated and evaluated through a representative case study. The optimization plan coordinated resource allocation from onshore warehouses to harbors and spill sites, balancing oil recovery efficiency, costs, and ecological losses. Optimized results indicate an oil recovery of up to 76.50% in five days. Additionally, the system cuts costs by 3.45% and environmental losses by 15.75%. The findings enhance the efficiency of marine oil spill emergency response and provide support for such incidents., 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 B.V. All rights reserved.)

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited., Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China., Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China., Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations., Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers ( p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy., Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Aim: To identify the differential methylation sites (DMS) and their according genes associated with diabetic retinopathy (DR) development in type 1 diabetes (T1DM) children., Methods: This study consists of two surveys. A total of 40 T1DM children was included in the first survey. Because no participant has DR, retina thinning was used as a surrogate indicator for DR. The lowest 25% participants with the thinnest macular retinal thickness were included into the case group, and the others were controls. The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay, and compared between the case and control groups. Four DMS with a potential role in diabetes were identified. The second survey included 27 T1DM children, among which four had DR. The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing., Results: In the first survey, the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls (|Δβ|>0.1 and Adj. P <0.05), and 328 of these were identified with a significance of Adj. P <0.01. Among these, 319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls. Pyrosequencing revealed that the transcription elongation regulator 1 like ( TCERG1L , cg07684215) gene was hypermethylated in the four T1DM children with DR ( P =0.018), which was consistent with the result from the first survey. The methylation status of the other three DMS (cg26389052, cg25192647, and cg05413694) showed no difference (all P >0.05) between participants with and without DR., Conclusion: The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM., Competing Interests: Conflicts of Interest: Qian Y, None; Xiao Y, None; Lin QR, None; Xiang ZY, None; Cui LP, None; Sun JQ, None; Li SC, None; Qin XR, None; Zou HD, None; Yang CH, None; Jin PY, None., (International Journal of Ophthalmology Press.)

Random bit generators are critical for information security, cryptography, stochastic modeling, and simulations. Speed and scalability are key challenges faced by current physical random bit generation. Herein, we propose a massively parallel scheme for ultrafast random bit generation towards rates of order 100 terabit per second based on a single micro-ring resonator. A modulation-instability-driven chaotic comb in a micro-ring resonator enables the simultaneous generation of hundreds of independent and unbiased random bit streams. A proof-of-concept experiment demonstrates that using our method, random bit streams beyond 2 terabit per second can be successfully generated with only 7 comb lines. This bit rate can be easily enhanced by further increasing the number of comb lines used. Our approach provides a chip-scale solution to random bit generation for secure communication and high-performance computation, and offers superhigh speed and large scalability., (© 2024. The Author(s).)

Radical scavengers were employed to evaluate the influence of various active species (•OH, •O, and H 2 O 2 ) on the rheological properties, antioxidant activity, and molecular conformation of chitosan under solution plasma process (SPP) degradation. ESR analysis showed that •OH and •O radicals played important roles in SPP degradation. The results of rheological properties and antioxidant activity indicated that the •OH scavenger (tert-butanol), •O scavenger (1, 4-benzoquinone), and H 2 O 2 scavenger (MnO 2 ) remarkably inhibited the decrease of G' and G" of the degraded chitosan, the formation of gel structure, and the increase of antioxidant activity. The analysis of molecular conformation of the chitosan by particle size analysis, atomic force microscopy (AFM), and high performance size exclusion chromatography coupled with multi-angle laser light scattering (HPSEC-MALLS) revealed that the decrease of particle size, molecular aggregation, and molecular weight of chitosan was inhibited after the addition of radical scavengers. An evident effect of radical scavengers on the hard sphere conformation of chitosan was observed. It was found that the above effects were strongly dependent on the scavenger concentration. These results proved that •OH, •O, and H 2 O 2 played important roles in SPP treatment. For the rheological properties and molecular conformation, H 2 O 2 exhibited the greatest impact. For the antioxidant activity and molecular weight, •OH presented the biggest influence. Besides, •O expressed the weakest effect. This study will be beneficial to reveal the action mechanisms of SPP technology to the degradation of chitosan., 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 B.V. All rights reserved.)

Tunable composition of perovskite micro/nanostructures are perfect candidate for the designing of multifunctional optoelectronic circuits. Especially, integrated polychromatic luminescence based on the perovskite materials along a single substrate or chip is essential to the integrated photonic devices and multicolor displays. Here, we reported a synthesis of composition tunable CsPbI 3(1- x ) Br 3 x (X = 0.65-0.9) perovskite microstructures on a single substrate via a magnetic-pulling CVD method. The PL emissions can be changed gradually from green (558 nm, 2.23 eV) to red (610 nm, 2.03 eV) under a focused 375 nm laser illumination. Furthermore, these composition-graded alloyed perovskite microcrystals show stable emissions after six months in air, which may find applications in multicolor display and broad band light sources in the future., (© 2024 IOP Publishing Ltd.)

Introduction: The type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii . However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed., Methods: The importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii , namely, tssB , tssD ( hcp ), and tssM was elucidated., Results: A higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The Δ tssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM -lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the Δ tssM mutant. Moreover, the Δ tssM strain, followed by the Δ tssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella ., Discussion: The above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii , especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhang, Wang, Al-Shamiri, Luo, Liu, Mi, Wu, Liu, Tian, Han, Lei, Han and Han.)

Objectives: To determine the clinical significance of Ro52 protein/tripartite motif-containing 21 antibody and specific antinuclear antibody patterns using indirect immunofluorescence technique., Methods: The retrospective study was conducted at the clinical laboratory of the First Affiliated Hospital of Chongqing Medical University, China, and comprised data from January 2017 to December 2021 of patients who underwent antinuclear antibody and anti-extractable nuclear antigen antibody detection. Inpatients with Ro52 antibody-positive status were taken as the cases, while anti-Ro52 negative patients with clear clinical diagnosis were taken as the controls. Data was analysed using SPSS 19., Results: There were 1802 cases and 1211 controls. Positive Ro52 showed significantly greater frequency in patients with primary Sjogren's syndrome, systemic lupus erythematosus, inflammatory myositis, dry eyes and interstitial lung disease (p<0.05). Ro52 antibody showed high positive predictive value for primary Sjogren's syndrome 25(96.15%), systemic lupus erythematosus 259(91.20%), connective tissue disease-associated interstitial lung disease 45(86.67%) and inflammatory myositis 60(86.67%). Antinuclear antibody indirect immunofluorescence patterns most frequently detected were nuclear speckled 128(40.89%) and cytoplasmic speckled 126(40.26%) (p<0.05). Interstitial lung disease was associated with the presence of cytoplasmic speckled antinuclear antibody indirect immunofluorescence pattern 24(19.2%), while tumours 47(36.5%) and hepatitis B 26(20.3%) seemed to be more frequent with nuclear speckled pattern (p<0.05). The simultaneous reactivity extractable nuclear antigen antibodies most frequently detected were antinuclear antibody+Ro52+anti-Sjogren's syndrome A+ 558(33.96%)., Conclusions: Ro52 antibody positivity was found to be associated with Sjogren's syndrome, systemic lupus erythematosus, inflammatory myositis, dry eye and interstitial lung disease. The antinuclear antibody immunofluorescence pattern of Ro52 positive was single and primarily granular cytoplasm type. Antinuclear antibody negative and Ro52 positive in the serum of patients also had certain significance in auxiliary disease diagnosis.

A novel "off-on" ratiometric fluorescent aptasensor was established for adenosine detection based on fluorescence resonance energy transfer (FRET) between CdS QDs, DNA QDs as donor and graphene oxide (GO) as acceptor. Amino-riched DNA QDs covalently bonded to the carboxyl group on the edge of the GO, and with the absorption of the TGA-modified CdS QDs with aptamer (CdS QDs-apt) onto the GO surface via the π-π stacking interaction. The fluorescence of both CdS QDs and DNA QDs were efficiently quenched due to FRET (turn off). When adenosine was present, the specific binding of the aptamer to the target preferentially that released the CdS QDs-apt from GO. The process would inhibit the FRET which contribute to the fluorescence of CdS QDs-apt recovery again (turn on), while the fluorescence intensity of DNA QDs only slightly altered and acted as the reference signal. Thus, a novel "off-on" ratiometric fluorescent aptasensor for adenosine detection was constructed accordingly. There was a good linearity relationship between the ratio of the FL intensity (F 595 nm/F 464 nm) and the concentration of adenosine in the range of 20.00-180.0 nmol/L with a detection limit of 1.3 nmol/L (S/N = 3, n = 9). Importantly, the feasibility of the developed aptasensor for selective detection of adenosine in serum and urine samples with satisfactory results. The recoveries were observed to be 97.04-100.2 %., 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. Published by Elsevier B.V.)

The ubiquity of plastics in our environment has brought about pressing concerns, with their aging processes, photo-oxidation, mechanical abrasion, and biodegradation, being at the forefront. Microplastics (MPs), whether originating from plastic degradation or direct anthropogenic sources, further complicate this landscape. This review delves into the intricate aging dynamics of plastics in aquatic environments under various influential factors. We discuss the physicochemical changes that occur in aged plastics and the release of oxidation products during their degradation. Particular attention is given to their evolving environmental interactions and the resulting ecotoxicological implications. A rigorous evaluation is also conducted for methodologies in the analysis and quantification of plastics aging, identifying their merits and limitations and suggesting potential avenues for future research. This comprehensive review is able to illuminate the complexities of plastics aging, charting a path for future research and aiding in the formulation of informed policy decisions., 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 Ltd. All rights reserved.)

BRCA2-mutated carriers have a high lifetime risk of breast cancer (BC), an early age of onset, and an increased risk of other cancers (including ovarian, pancreatic, and prostate cancer). Almost 70-80% of BRCA2-mutated BC are estrogen receptor (ER)-positive, which is a particular type of ER-positive BC that differs from sporadic ER-positive BC. This article reviews the clinicopathological features, treatment, and prognosis of ER-positive and BRCA2-mutated BC to provide a reference for clinical decision-making., (© 2024. The Author(s).)

Greater superficial petrosal nerve (GSPN) schwannomas are an exceedingly rare nerve sheath tumor. The current literature search was conducted using Medline and Embase database by key search terms. Only 31 cases have been reported in the literature so far. Facial palsy, hearing loss, and xerophthalmia accounted for 48.4% (15), 41.9% (13), and 29% (9) of all cases, respectively. The middle cranial fossa approach was used in all previous reports. A retrospective review of 2 GSPN schwannomas patients treated by endoscopic endonasal approach (EEA) in our center was collected. Clinical records, including clinical features, pre- and postoperative images, surgery, and follow-up information, were reviewed. In all cases, clinical features including facial numbness and headache were found, with tinnitus in case 1, hearing loss, xerophthalmia in case 2. Imaging studies showed a solid mass that originated in the anterior of the petrous bone. Two patients were treated by EEA. Furthermore, no recurrence was found during the follow-up period (15-29 months) in both of the 2 cases after the operation. Complete resection of GSPN schwannomas can be achieved via the pure EEA. Endoscopic endonasal approach for radical removal of tumors is safe and feasible., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study aimed to reveal harm of exposure to indoor air pollution to cognitive function through "gut-brain-axis" among rural elderly residents. There were 120 participants recruited in rural villages of northwest China from December 2021 to February 2022. The cognitive level was assessed by eight-item ascertain dementia (AD) questionnaire, and indoor air pollution exposure was measured by air quality sensor. Inflammatory cytokines and oxidative stress-related index were detected in blood serum. Fecal samples were collected for gut microbiota analysis. The 120 participants were divided into impaired cognition (AD8) (81/67.5%) and cognition normal (NG) (39/32.5%). And there had more female in AD8 (FAD) (55/67.9%) than NG (FNG) (18/46.2%) (P = 0.003). Exposure of air pollution in FAD was higher than FNG (PM 1 , PM 2.5 , PM 10 , P < 0.001; NO 2 , P < 0.001; CO, P = 0.014; O 3 , P = 0.002). The risk of cognitive impairment increases 6.8%, 3.6%, 2.6%, 11%, and 2.4% in female for every 1 μg/m 3 increased in exposure of PM 1 , PM 2.5 , PM 10 , NO 2 , and O 3 , separately. And GSH-Px and T-SOD in FAD were significantly lower than the FNG group (P = 0.011, P = 0.019). Gut microbiota in FAD is disordered with lower richness and diversity. Relative abundance of core bacteria Faecalibacterium (top 1 genus) in FAD was reduced (13.65% vs 19.81%, P = 0.0235), while Escherichia&#95;Shigella and Akkermansia was increased. Correlation analysis showed Faecalibacterium was negatively correlated with age, and exposure of O 3 , PM 1 , PM 2.5 , and PM 10 ; Akkermansia and Monoglobus were positively correlated with exposure of PM 1 , PM 2.5 and PM 10 ; Escherichia&#95;Shigella was significantly positively correlated with NO 2 . Indoor air pollution exposure impaired cognitive function in elderly people, especially female, which may cause systemic inflammation, dysbiosis of the gut microbiota, and ultimately leading to early cognitive impairment through the gut-brain axis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: To assist doctors in making better treatment decisions and improve patient prognosis, it is important to determine which therapy modalities are suitable for various forms of idiopathic hypertrophic cranial pachymeningitis (IHCP)., Methods: All cases were received from the hospital medical record system, and some follow-up information was gathered through telephone follow-up., Results: A total of 26 patients, 14 men and 12 women, with ages ranging from 20 to 73 years and a mean of 47.42 years, were included in the research. Regular types were less likely to recur than irregular and nodular types, focal types were less likely to recur than diffuse types, and corticosteroid-refractory types were more likely to recur than corticosteroid-sensitive types., Conclusions: The extent and shape of the lesion and susceptibility to corticosteroids are potential factors that could influence recurrence. Futhermore, this paper also proposes the fibroblasts as a new therapeutic target which may improve the quality of prognostic survival of patients., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prostate cancer is a common solid tumor that affects a significant number of men worldwide. Conventional androgen deprivation therapy (ADT) increases the risk of developing castration-resistant prostate cancer (CRPC). Effective clinical management of patients with CRPC is challenging due to the limited understanding., Methods: In this study, transcriptomic and metabolomic profiles of androgen-dependent prostate cancer cell line LNCaP and the androgen-independent cells developed from LNCaP cells (LNCaP-ADR) were investigated using RNA-sequencing and LC-MS/MS, respectively. The differentially expressed genes and metabolites were analyzed, and integrative analysis of transcriptomic and metabolomic data was further conducted to obtain a comprehensive understanding of the metabolic characteristics in LNCaP-ADR cells. Quantitative real-time PCR (QPCR) was employed to ascertain the mRNA expression levels of the selected differentially expressed genes., Results: The arginine and proline metabolism pathway was identified as a commonly altered pathway at both the transcriptional and metabolic levels. In the LNCaP-ADR cells, significant upregulation was observed for metabolites including 5-Aminopentanoic acid, L-Arginine, L-Glutamic acid, N-Acetyl-L-alanine, and Pyrrole-2-carboxylic acid at the metabolic level. At the transcriptional level, MAOA, ALDH3A2, ALDH2, ARG1, CKMT2, and CNDP1 were found to be significantly upregulated in the LNCaP-ADR cells. Gene set enrichment analysis (GSEA) identified various enriched gene sets in the LNCaP-ADR cells, encompassing inflammatory response, 9plus2 motile cilium, motile cilium, ciliary plasm, cilium or flagellum-dependent cell motility, cilium movement, cilium, response to endoplasmic reticulum stress, PTEN DN.V1 DN, SRC UP.V1 UP, IL15 UP.V1 DN, RB DN.V1 DN, AKT UP MTOR DN.V1 UP, VEGF A UP.V1 UP, and KRAS.LUNG.BREAST UP.V1 UP., Conclusions: These findings highlight the substantial association between the arginine and proline metabolism pathway and CRPC, emphasizing the need to prioritize strategies that target dysregulated metabolites and differentially expressed genes as essential interventions in the clinical management of CRPC., (© 2023. The Author(s).)

As one of the common plasticizers, di-n-butyl phthalate (DBP) has been using in various daily consumer products worldwide. Since it is easily released from products and exists in the environment for a long time, it has a lasting impact on human health, especially male reproductive health. However, the detailed mechanism of testicular damage from DBP and the protection strategy are still not clear enough. In this study, we found that DBP could induce dose-dependent ferroptosis in testicular tissue. Mechanism dissection indicates that DBP can upregulate SP1 expression, which could directly transcriptionally upregulate PRDX6, a negative regulator of ferroptosis. Overexpression of PRDX6 or adding SP1 agonist curcumin could suppress the DBP-induced ferroptosis on testicular cells. In vivo, rats were given 500 mg/kg/day DBP orally for 3 weeks; elevated levels of ferroptosis were detected in testicular tissue. When the above-mentioned doses of DBP and curcumin at a dose of 300 mg/kg/day were administered intragastrically simultaneously, the testicular ferroptosis induced by DBP was alleviated. Immunohistochemistry and quantitative real-time PCR of testis tissue showed that the expression of PRDX6 was upregulated under the action of DBP and curcumin. These findings suggest a spontaneous self-protection mechanism of testicular tissue from DBP damage by upregulating SP1 and PRDX6. However, it is not strong enough to resist the DBP-induced ferroptosis. Curcumin can strengthen this self-protection mechanism and weaken the level of ferroptosis induced by DBP. This study may help us to develop a novel therapeutic option with curcumin to protect the testicular tissue from ferroptosis and function impairment by DBP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Antibiotics are widely prescribed among children and pregnant women, but their safety profile is controversial. This study aimed to summarize and appraise current evidence for the potential impact of antibiotic exposure on pregnancy outcomes and children's health., Methods: PubMed, Embase, Web of Science and the Cochrane Database of Systematic Reviews were searched from inception to June 2022. Meta-analyses of any study design comparing the impact of antibiotic exposure with nonexposure among children, pregnant women and prepregnant women on adverse health outcomes of children and pregnancy were retrieved. The quality of evidence was assessed by a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR2) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Data were reanalyzed, and the credibility of the evidence was determined., Results: Out of 2956 studies identified, 19 articles with 39 associations were included. Totally 19 of the associations (48.72%) were statistically significant with a P value ≤ 0.05, while only six were supported by highly suggestive evidence. Children with postnatal antibiotic exposure had a higher risk of developing asthma odds ratio (OR): 1.95, 95% confidence interval (CI): 1.76-2.17, wheezing (OR: 1.81, 95% CI 1.65-1.97) and allergic rhinoconjunctivitis (OR: 1.66, 95% CI 1.51-1.83), with prediction intervals excluding the nulls. Quality assessed by both AMSTAR2 and GRADE of included meta-analyses were very low in general., Conclusions: Antibiotic exposure in early life was associated with children's long-term health, especially in cases of allergic diseases. Prenatal exposure might also influence children's health in some aspects but requires more high-quality evidence. Potential adverse effects of antibiotics on pregnancy outcomes were not observed in our study. Studies with higher quality and better quantification of antibiotic exposure are needed in the future., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Photodegradation significantly influences marine oil spill behavior, yet its role remains underrepresented in current models, impairing predictive accuracy. Addressing this, our study rigorously examined oil properties and environmental determinants affecting marine oil spill photodegradation through laboratory simulations. We identified and quantified key factors and their interactions, noting particularly the positive influence of asphaltene and negative implications of oil density. We also discerned a negative correlation between n-alkane degradation and carbon numbers. Our findings underscored the pivotal roles of temperature and irradiance in photodegradation. All tested oils adhered to first-order kinetics, with rate constants ranging from 0.0348 to 0.0645 day -1 . Finally, we introduced a novel model incorporating temperature, irradiance and their interactions, ensuring reasonable simulations for marine oil spill photodegradation, fortifying marine oil spill management strategies., 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 Ltd. All rights reserved.)

Based on DNA bio-dots-induced aggregation of gold nanoparticles (AuNPs), a methionine (Met) photoelectrochemical (PEC) sensor with CS-GSH-CuNCs/TiO 2 NPs as the photoelectric conversion element and AuNPs as the specific recognition element was constructed. First, a TiO 2 NPs/ITO electrode and CS-GSH-CuNCs were prepared, and then the CS-GSH-CuNCs/TiO 2 NPs/ITO photosensitive electrode was obtained by self-assembly. Next, DNA bio-dots were modified to the upper surface of the electrode using a coupling reaction to assemble the DNA bio-dots/CS-GSH-CuNCs/TiO 2 NPs electrode. Amino-rich DNA bio-dots were used to induce the aggregation of AuNPs on the electrode surface via Au-N interactions and prepare the AuNPs/DNA bio-dots/CS-GSH-CuNCs/TiO 2 NPs electrode. Due to the fluorescence resonance energy transfer (FRET) between CS-GSH-CuNCs and AuNPs, the complexation chance of electron-hole (e - -h + ) pair in CS-GSH-CuNCs increased, which, in turn, led to a decrease in photocurrent intensity. When Met was present, AuNPs aggregated on the electrode surface were shed and bound to Met since the Au-S interaction is stronger than the Au-N interaction, resulting in the recovery of the photocurrent signal. Under optimal conditions, the photocurrent intensity of the PEC sensor showed good linearity with the logarithm of Met concentration in the range of 25.0 nmol/L-10.0 μmol/L with the limit of detection (LOD) of 5.1 nmol/L (S/N = 3, n = 10).

Pyroptosis is a form of programmed cell death mediated by gasdermins, particularly gasdermin D (GSDMD), which is widely expressed in tissues throughout the body. GSDMD belongs to the gasdermin family, which is expressed in a variety of cell types including epithelial cells and immune cells. It is involved in the regulation of anti-inflammatory responses, leading to its differential expression in a wide range of diseases. In this review, we provide an overview of the current understanding of the major activation mechanisms and effector pathways of GSDMD. Subsequently, we examine the importance and role of GSDMD in different diseases, highlighting its potential as a pan-biomarker. We specifically focus on the biological characteristics of GSDMD in several diseases and its promising role in diagnosis, early detection, and differential diagnosis. Furthermore, we discuss the application of GSDMD in predicting prognosis and monitoring treatment efficacy in cancer. This review proposes a new strategy to guide therapeutic decision-making and suggests potential directions for further research into GSDMD.

Background: Maternal diabetes increases the risk for neural tube defects (NTDs). It is unclear if miRNAs, senescence, and DNA damage are involved in this process. In this study, we used neural stem cells as an in vitro proxy of embryonic neuroepithelium to investigate whether high glucose triggers neural stem cell senescence and DNA damage by upregulating miR-200c, which may be responsible for NTDs., Methods: C17.2 neural stem cells were cultured with normal glucose (5 mM) or high glucose (≥16.7 mM) at different doses and time points for detecting miR-200c levels, markers of senescence and DNA damage. Neural stem cells were exposed to antioxidant SOD1 mimetic Tempol and high glucose for 48 h to test roles of oxidative stress on the miR-200c, senescence, and DNA damage levels. An miR-200c mimic and an inhibitor were transfected into neural stem cells to increase or decrease miR-200c activities., Results: High glucose upregulated miR-200c in neural stem cells. A time course study of the effect of high glucose revealed that miR-200c initially increased at 12 h and reached its zenith at 18 h. Tempol reduced miR-200c levels caused by high glucose. High glucose induced markers of senescence and DNA damage in neural stem cells. Tempol abolished high glucose-induced markers of senescence and DNA damage. The miR-200c inhibitor suppressed high glucose-induced markers of senescence and DNA damage. Treatment with miR-200c mimic imitates high glucose-induced markers of senescence and DNA damage., Conclusions: We show that high glucose increases miR-200c, which contributes to cellular senescence and DNA damage in neural stem cells and provides a potential pathway for maternal diabetes-induced neural tube defects., (© 2023 Wiley Periodicals LLC.)

Background: Four Fanconi anemia (FA) genes (BRCA1, BRCA2, PALB2 and RAD51C) are defined as breast cancer (BC) susceptibility genes. Other FA genes have been inconsistently associated with BC. Thus, the role of other FA genes in BC should be explored in specific populations., Methods: Mutations in 16 FA genes were screened with a 98-gene panel sequencing assay in a cohort of 1481 Chinese patients with high-risk hereditary BC. The association between mutations and clinicopathological characteristics as well as prognosis was analyzed. The risk of BC in carriers of FA gene mutations was assessed in the Genome Aggregation Database and the Westlake Biobank for Chinese cohort., Results: A total of 2.57% (38/1481) BC patients were identified who had 12 other FA gene germline mutations. Among them, the most frequently mutated gene was FANCA (8/1481, 0.54%). These 38 patients carried 35 distinct pathogenic/likely pathogenic variants, of which 21 were novel. We found one rare FANCB deleterious variant (c.1327-3dupT) in our cohort. There was a statistically significant difference in lymph node status between FA gene mutation carriers and non-carriers (p = 0.041). We observed a trend that mutation carriers had larger tumor sizes, lower estrogen receptor (ER) and progesterone receptor (PR) positivity rates, and lower 3.5-year invasive disease-free survival (iDFS) and distant recurrence-free survival (DRFS) rates than non-carriers (tumor size > 2 cm: 51.43% vs. 45.63%; ER positivity rates: 51.43% vs. 60.81%; PR positivity rates: 48.57% vs. 55.16%; 3.5-year iDFS rates: 58.8% vs. 66.7%; 3.5-year DRFS rates: 58.8% vs. 68.8%). The frequency of the mutations in FANCD2, FANCM and BRIP1 trended to be higher among BC cases than that in controls (p = 0.055, 0.08 and 0.08, respectively)., Conclusion: This study comprehensively estimated the prevalence, clinicopathological characteristics, prognosis and risk of BC associated with deleterious variants in FA genes in Chinese high-risk hereditary BC patients. It enriches our understanding of the role of FA genes with BC., (© 2023. The Author(s).)

Introduction: An extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient., Methods: The effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated., Results: HKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H 2 O 2 , alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing., Discussion: Here, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Cheng, Ma, Wang, Li, Wang, Han, Hou, Ma, Jiang, Li, Lv, Han and Da.)

Background: Differences exist between high- and low-risk endometrial cancer (EC) in terms of whether lymph node dissection is performed. Factors such as tumor grade, myometrial invasion (MDI), and lymphovascular space invasion (LVSI) in the European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guidelines risk classification can often only be accurately assessed postoperatively. The aim of our study was to estimate the risk classification of patients with endometrial endometrioid adenocarcinoma before surgery and offer individualized treatment plans based on their risk classification., Methods: Clinical information and last preoperative pelvic magnetic resonance imaging (MRI) of patients with postoperative pathologically determined endometrial endometrioid adenocarcinoma were collected retrospectively. The region of interest (ROI) was subsequently plotted in T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI) MRI scans, and the traditional radiomics features and deep-learning image features were extracted. A final radiomics nomogram model integrating traditional radiomics features, deep learning image features, and clinical information was constructed to distinguish between low- and high-risk patients (based on the 2020 ESMO-ESGO-ESTRO guidelines). The efficacy of the model was evaluated in the training and validation sets of the model., Results: We finally included 168 patients from January 1, 2020 to July 29, 2021, of which 95 patients in 2021 were classified as the training set and 73 patients in 2020 were classified as the validation set. In the training set, the area under the curve (AUC) of the radiomics nomogram was 0.923 (95%CI: 0.865-0.980) and in the validation set, the AUC of the radiomics nomogram was 0.842 (95%CI: 0.762-0.923). The nomogram had better predictions than both the traditional radiomics model and the deep-learning radiomics model., Conclusion: MRI-based radiomics models can be useful for preoperative risk classification of patients with endometrial endometrioid adenocarcinoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Cao, Zhou, Li, Lv and Li.)