Search

Ya-Ming Xie,1 Wenfeng Lu,2 Jian Cheng,1 Mugen Dai,3 Si-Yu Liu,4 Dong-Dong Wang,1 Tian-Wei Fu,1 Tai-Wei Ye,1 Jun-Wei Liu,1 Cheng-Wu Zhang,1 Dong-Sheng Huang,1 Lei Liang1 1Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 3Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Lei Liang; Dong-Sheng Huang, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email liangl1992@hotmail.com; huangdshz88@hotmail.comBackground: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC.Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems.Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038– 3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358– 5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262– 3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586– 0.712, P < 0.05).Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.Keywords: hepatocellular carcinoma, Naples prognostic score, nutritional indicator, inflammatory indicator, prognostic performance

Shuang Xu,1 Yi Fu,2 Dan Xu,1 Shuang Han,1 Mingzhi Wu,3 Xinrong Ju,1 Meng Liu,1 De-Sheng Huang,4,5 Peng Guan4,6 1Library of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2School of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Library of Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China; 4Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, People’s Republic of China; 5Department of Intelligent Computing, School of Intelligent Medicine, China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: De-Sheng Huang; Peng Guan, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China, Email dshuang@cmu.edu.cn; pguan@cmu.edu.cnBackground: Before the COVID-19 pandemic, tuberculosis is the leading cause of death from a single infectious agent worldwide for the past 30 years. Progress in the control of tuberculosis has been undermined by the emergence of multidrug-resistant tuberculosis. The aim of the study is to reveal the trends of research on medications for multidrug-resistant pulmonary tuberculosis (MDR-PTB) through a novel method of bibliometrics that co-occurs specific semantic Medical Subject Headings (MeSH).Methods: PubMed was used to identify the original publications related to medications for MDR-PTB. An R package for text mining of PubMed, pubMR, was adopted to extract data and construct the co-occurrence matrix-specific semantic types. Biclustering analysis of high-frequency MeSH term co-occurrence matrix was performed by gCLUTO. Scientific knowledge maps were constructed by VOSviewer to create overlay visualization and density visualization. Burst detection was performed by CiteSpace to identify the future research hotspots.Results: Two hundred and eight substances (chemical, drug, protein) and 147 diseases related to MDR-PTB were extracted to form a specific semantic co-occurrence matrix. MeSH terms with frequency greater than or equal to six were selected to construct high-frequency co-occurrence matrix (42 × 20) of specific semantic types contains 42 substances and 20 diseases. Biclustering analysis divided the medications for MDR-PTB into five clusters and reflected the characteristics of drug composition. The overlay map indicated the average age gradients of 42 high-frequency drugs. Fifteen top keywords and 37 top terms with the strongest citation bursts were detected.Conclusion: This study evaluated the literatures related to MDR-PTB drug therapy, providing a co-occurrence matrix model based on the specific semantic types and a new attempt for text knowledge mining. Compared with the macro knowledge structure or hot spot analysis, this method may have a wider scope of application and a more in-depth degree of analysis.Keywords: multidrug-resistant tuberculosis, pulmonary tuberculosis, medication trends, specific semantic types, MeSH tree, pubMR

Nan Li,1,* Yi-Zhuo Wang,1,* Dong-Sheng Huang,1 Yi Zhang,1 Wei-Ling Zhang,1 Jian-Min Ma,2 Yan Zhou,1 Ting-Ting Liu1 1Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, 100176, People’s Republic of China; 2Department of Ophthalmic Oncology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong-Sheng HuangDepartment of Pediatrics, Beijing Tongren Hospital, Capital Medical University, No. 2, Xihuan South Road, Yizhuang Economic and Technological Development Zone, Beijing, 100176, People’s Republic of China, Email Hds5180@sina.comAim: This study aimed to summarize the clinical characteristics, treatment, and outcomes of distant metastatic retinoblastoma with event-free survival.Design: Retrospective interventional case series.Methods: We screened patients with retinoblastoma who survived without events after the comprehensive treatment of distant metastases from June 2015 to February 2021 and collected information regarding their basic characteristics, diagnosis, and treatment. All patients received systemic intravenous chemotherapy. Other treatments included surgical treatment, radiotherapy, intrathecal chemotherapy, and autologous stem cell transplantation.Results: Among 780 hospitalized patients with retinoblastoma in the pediatric ward, a total of 94 patients with retinoblastoma were diagnosed with distant metastases, and 16 patients with distant metastatic retinoblastoma who survived more than 6 months without events were screened, including eight male and eight female patients. The median age of onset was 29 (range, 11– 120) months. Among the 16 patients, central nervous system metastasis (8/16), bone metastasis (8/16), bone marrow infiltration (4/16), lymph node metastasis (4/16), and parotid gland metastasis (3/16) were presented. All patients received treatment for more than 6 months, completed their regimen by February 2021, and survived without events. The median survival time after the onset of retinoblastoma was 50.5 (range, 23– 102) months, the median survival time after metastasis was 43.5 (range, 16– 71) months, and the median event-free survival was 29.0 (range, 6– 59) months.Conclusion: Metastatic retinoblastoma may benefit from comprehensive treatments including systemic intravenous chemotherapy and hematopoietic stem cell transplantation. However, recurrence after treatment still needs attention, and patients in complete remission still need long-term follow-up.Keywords: retinoblastoma, distant metastasis, comprehensive treatment

Xiaochun Zhang,1 De-Sheng Huang,2,3 Peng Guan2 1Department of Pulmonary and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Department of Epidemiology, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, People’s Republic of China; 3Department of Mathematics, School of Fundamental Sciences, China Medical University, Shenyang, 110122, Liaoning, People’s Republic of ChinaCorrespondence: Peng GuanDepartment of Epidemiology, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, People’s Republic of ChinaEmail pguan@cmu.edu.cnIntroduction: Due to COVID-19 outbreak, since January 24, 2020, national medical teams from across the country and the armed forces have been dispatched to aid Hubei. The present review was designed to timely summarize the existing frontline information about nursing scheduling mode with special focus on the length of shifts with the aim to contribute to improve the nurses’ job satisfaction and the quality of nursing services.Methods: Articles from Jan 2020 to October 2020 were retrieved from China National Knowledge Infrastructure, Wanfang Data and Weipu Information, with the terms “COVID-19”, “designated hospital”, “Hubei-assisted”, “makeshift hospital”, “nursing”, “nursing shift”, “whole-system takeover” and variations of these, in the title and abstract fields and the Boolean combinations of these words as the retrieval strategy.Results: Seventeen journal articles have been included in the target field, from the nurses in aiding Hubei Province, four kinds of shift length, 2-hour (h), 3-h, 4-h and 6-h shift have been considered, the main nursing scheduling mode adopted in designated hospitals for COVID-19 patients was dynamic scheduling based on workload, flexible scheduling based on working hours, workload and the number of critically ill patients admitted, humanized scheduling based on the daily reported health status of the nurses, and professional-integrated scheduling according to the professional distribution of nurses on the basis of four-hour shift length, and in makeshift hospitals for mild patients, the scheduling mode was 6-h based correspondingly.Conclusion: The descriptive results of the present systematic review shed light on the challenges and practical solutions of nursing scheduling mode in the context of cross-regional medical assistance. Additionally, the present systematic review could provide the academic community of nurses, nurse managers and administrators with baseline information and scientific productions from the content’s points of view in the target field.Keywords: nursing scheduling, shift work, nursing management, systematic review

Lei Liang,1,2,* Ming-Da Wang,3,* Yao-Ming Zhang,4 Wan-Guang Zhang,5 Cheng-Wu Zhang,1 Wan Yee Lau,3,6 Feng Shen,3 Timothy M Pawlik,7 Dong-Sheng Huang,1,2,8 Tian Yang1– 3,8 1Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Zhejiang, People’s Republic of China; 2School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 4The 2nd Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Guangdong, People’s Republic of China; 5Department of Hepatic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 6Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong, China; 7Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA; 8The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People’ s Hospital (People’ s Hospital of Hangzhou Medical College), Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tian YangDepartment of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaEmail yangtiandfgd@hotmail.comDong-Sheng HuangDepartment of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, 310014, People’s Republic of ChinaEmail Huangdongshengsj@hotmail.comBackground: High alpha-fetoprotein (AFP) expressions (> 400 ng/mL) are associated with poor oncological characteristics for hepatocellular carcinoma (HCC). However, prognosis after liver resection for high-AFP HCC is poorly studied. To investigate long-term recurrence and survival after hepatectomy for high-AFP HCC, and to identify the predictive value of postoperative incomplete biomarker response (IBR) on overall survival (OS) and recurrence-free survival (RFS).Methods: Patients undergoing curative resection for high-AFP HCC were analyzed. According to the decline magnitude of serum AFP as measured at first follow-up (4∼ 6 weeks after surgery), all patients were divided into the complete biomarker response (CBR) and IBR groups. Characteristics, recurrence, and survival rates were compared. Univariate and Multivariate Cox-regression analyses were performed to identify independent predictors associated with poorer OS and RFS after liver resection for high-AFP HCC.Results: Among 549 patients, the overall and early recurrence rates in patients with IBR were significantly higher than patients with CBR (97.8%vs.56.4%, and 92.5%vs.33.3%, both P< 0.001). On multivariate analysis, postoperative IBR was the strongest risk factor with the highest hazard ratio in predicting poor OS (HR 2.97; 95% CI 2.49∼ 3.45; P< 0.001) and RFS (HR 4.29; 95% CI 3.31∼ 5.55; P< 0.001).Conclusion: Postoperative biomarker response of serum AFP can be used in predicting recurrence and survival for high-AFP HCC patients. Once postoperative IBR was identified at first follow-up, subsequent enhanced recurrence surveillance and available treatments against recurrence should actively be considered.Keywords: hepatocellular carcinoma, alpha-fetoprotein, hepatectomy, survival, recurrence

Ding-Siang Huang,1,* Hsuan-Yuan Lin,1,2,* Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li,1 Chung-Hsin Wu,1 Jung-Yaw Lin1,21Department of Life Science, National Taiwan Normal University, 2Institute of Biochemistry and Molecular Biology, National Taiwan University, Taipei City, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Spinocerebellar ataxia type 17 (SCA 17) is a polyglutamine disease caused by the expansion of CAG/CAA repeats in the TATA box-binding protein (TBP) gene. The Ginkgo biloba extract, EGb 761, contains flavonoids and terpenoids with a potential use for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. The neuroprotective effects of EGb 761 are obvious, but whether the EGb 761 has therapeutic effects in SCA 17 is still unclear. To manage our issues, we have generated TBP/79Q-expressing SH-SY5Y cells and SCA 17 transgenic mice with the mutant hTBP gene. In in vitro experiment, we observed that the EGb 761 treatment decreased the amount of sodium dodecyl sulfate-insoluble proteins in the TBP/79Q-expressing SH-SY5Y cells. We further found that the EGb 761 treatment could inhibit excitotoxicity and calcium influx and reduce the expression of apoptotic markers in glutamate-treated SH-SY5Y neuroblastoma cells. In in vivo experiment, we observed that the EGb 761 treatment (100 mg/kg intraperitoneal injection per day) could relieve the motor deficiencies of the SCA 17 transgenic mice. Our findings provide evidence that the EGb 761 treatment can be a remedy for SCA 17 via suppressing excitotoxicity and apoptosis in SCA 17 cell and animal models. Therefore, we suggest that EGb 761 may be a potential therapeutic agent for treating SCA 17.Keywords: spinocerebellar ataxia type 17, excitotoxicity, EGb 761, polyQ diseases, apoptosis

The average age of patients with BS was 52.29 ± 9.46 years, comprising 136 males and 31 females. Risk factors for BS include close contact with cattle and sheep and consumption of unpasteurized food. The positive detection rate using combined Rose Bengal Test (RBT) and Standard Agglutination Test (SAT) was 94.6%, whereas the positive rate for blood culture was only 7.8%. The most common clinical manifestations were fever (81.4%), back pain (88.6%), sweating (61.1%), fatigue (69.5%), and anorexia (65.3%). Hematological examinations often revealed decreased hemoglobin (18.0%), increased platelets (18.0%), elevated erythrocyte sedimentation rate (ESR) (88.0%), elevated C-reactive protein (CRP) (78.4%), elevated Alanine aminotransferase (ALT) (18.6%), and decreased K+(23.4%). The imaging examinations revealed that the lumbar spine, particularly L4/5 (41.3%), is the most frequently affected vertebral level in BS. After treatment, the overall recurrence rate was 3.0%. In endemic areas, clinicians should be vigilant for BS in patients presenting with back pain and unexplained fever, particularly those with a history of close contact with cattle and sheep. The RBT and SAT tests show a high positivity rate of 94.6%, establishing them as the preferred diagnostic methods. This study enhances clinicians' comprehension of BS characteristics and lays a robust theoretical groundwork for disease prevention and monitoring., (© 2024. The Author(s).)

Competing Interests: The authors have no conflicts of interest to declare.

Microscopic vascular invasion (MVI) has been demonstrated as a strong risk factor associated with tumor recurrence and poor overall survival among hepatocellular carcinoma (HCC) patients after resection, but the preoperative prediction of MVI is still challenging. We aimed to build and validate a novel model to predict MVI in the preoperative setting. We retrospectively collected 857 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection at Kaohsiung Chang Gung Hospital between January 2001 and June 2016. The patients were randomized into derivation (n = 648) and validation groups (n = 209). Logistic regression analysis was used to screen out independent risk factors for MVI and further constructed a predictive model for MVI. Prediction performance was compared by the area under the receiver operating characteristic curve (AUC). The multivariable logistic regression analysis of the training cohort found that alpha-fetoprotein (AFP) ≥ 20 ng/mL (OR = 1.96, 95% CI: 1.41-2.73, P < 0.001), albumin < 3.5 g/dL (OR = 1.48, 95% CI: 1.06-2.05, P = 0.019) and tumor burden score (TBS) ≥ 8.6 (OR = 2.54, 95% CI: 1.49-4.35, P = 0.001) to be independent risk factors for MVI. The three factors were chosen to build a model for prediction of MVI. The AUC for the training and validation group was 0.619 (95% CI: 0.575-0.663) and 0.642 (95% CI: 0.562-0.722), respectively, and the calibration plot showed good performance of the prediction model, with a low mean absolute error at 0.01. In conclusion, the new model comprised AFP, albumin, and TBS that can predict risk of MVI for early-stage HCC., Competing Interests: None., (AJCR Copyright © 2024.)

Background & Aims: The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B., Methods: Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD)., Results: Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378-0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379-0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results., Conclusion: Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation., (© 2024. The Author(s).)

The gene regulatory network (GRN) plays a vital role in understanding the structure and dynamics of cellular systems, revealing complex regulatory relationships, and exploring disease mechanisms. Recently, deep learning (DL)-based methods have been proposed to infer GRNs from single-cell transcriptomic data and achieved impressive performance. However, these methods do not fully utilize graph topological information and high-order neighbor information from multiple receptive fields. To overcome those limitations, we propose a novel model based on multiview graph attention network, namely, scMGATGRN, to infer GRNs. scMGATGRN mainly consists of GAT, multiview, and view-level attention mechanism. GAT can extract essential features of the gene regulatory network. The multiview model can simultaneously utilize local feature information and high-order neighbor feature information of nodes in the gene regulatory network. The view-level attention mechanism dynamically adjusts the relative importance of node embedding representations and efficiently aggregates node embedding representations from two views. To verify the effectiveness of scMGATGRN, we compared its performance with 10 methods (five shallow learning algorithms and five state-of-the-art DL-based methods) on seven benchmark single-cell RNA sequencing (scRNA-seq) datasets from five cell lines (two in human and three in mouse) with four different kinds of ground-truth networks. The experimental results not only show that scMGATGRN outperforms competing methods but also demonstrate the potential of this model in inferring GRNs. The code and data of scMGATGRN are made freely available on GitHub (https://github.com/nathanyl/scMGATGRN)., (© The Author(s) 2024. Published by Oxford University Press.)

The clinical data of five patients diagnosed with olfactory neuroblastoma (ONB) who were admitted to the Department of Pediatrics, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2012 to January 2024 were retrospectively analyzed. Two males and three females aged 6.2 (5.7-15.8) years were included. The symptoms mainly covered nasal congestion, increased nasal secretions, headache, decreased vision and so on. Pathological grade Ⅱ, Ⅲ and Ⅳ was identified in two cases, one case and two cases, respectively. Modified Kadish stage B, C and D was detected in one case, two cases and two cases, respectively. All patients underwent surgery, chemotherapy, and radiation therapy. Among the five patients, four survived and one died. The follow-up time was 22.3 (10.4-56.4) months, and the recurrence rate was 0. ONB should be suspected when tumors are presented in the upper and middle parts of the nasal cavity, especially dumbbell shaped masses that grow towards the nasal cavity and intracranial area based on imaging. The multimodality therapy of ONB comprising of surgery and chemotherapy, can achieve good therapeutic effects and prognosis, but long-term follow-up is required.

Cross-species prediction of TF binding remains a major challenge due to the rapid evolutionary turnover of individual TF binding sites, resulting in cross-species predictive performance being consistently worse than within-species performance. In this study, a novel Nucleotide-Level Deep Neural Network (NLDNN) is first proposed to predict TF binding within or across species. NLDNN regards the task of TF binding prediction as a nucleotide-level regression task, which takes DNA sequences as input and directly predicts experimental coverage values. Beyond predictive performance, it also assesses model performance by locating potential TF binding regions, discriminating TF-specific single-nucleotide polymorphisms (SNPs), and identifying causal disease-associated SNPs. The experimental results show that NLDNN outperforms the competing methods in these tasks. Then, a dual-path framework is designed for adversarial training of NLDNN to further improve the cross-species prediction performance by pulling the domain space of human and mouse species closer. Through comparison and analysis, it finds that adversarial training not only can improve the cross-species prediction performance between humans and mice but also enhance the ability to locate TF binding regions and discriminate TF-specific SNPs. By visualizing the predictions, it is figured out that the framework corrects some mispredictions by amplifying the coverage values of incorrectly predicted peaks., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Circular RNAs (circRNAs) play vital roles in transcription and translation. Identification of circRNA-RBP (RNA-binding protein) interaction sites has become a fundamental step in molecular and cell biology. Deep learning (DL)-based methods have been proposed to predict circRNA-RBP interaction sites and achieved impressive identification performance. However, those methods cannot effectively capture long-distance dependencies, and cannot effectively utilize the interaction information of multiple features. To overcome those limitations, we propose a DL-based model iCRBP-LKHA using deep hybrid networks for identifying circRNA-RBP interaction sites. iCRBP-LKHA adopts five encoding schemes. Meanwhile, the neural network architecture, which consists of large kernel convolutional neural network (LKCNN), convolutional block attention module with one-dimensional convolution (CBAM-1D) and bidirectional gating recurrent unit (BiGRU), can explore local information, global context information and multiple features interaction information automatically. To verify the effectiveness of iCRBP-LKHA, we compared its performance with shallow learning algorithms on 37 circRNAs datasets and 37 circRNAs stringent datasets. And we compared its performance with state-of-the-art DL-based methods on 37 circRNAs datasets, 37 circRNAs stringent datasets and 31 linear RNAs datasets. The experimental results not only show that iCRBP-LKHA outperforms other competing methods, but also demonstrate the potential of this model in identifying other RNA-RBP interaction sites., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH)., Methods: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors., Results: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF., Conclusion: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy., Competing Interests: Conflict of interest None to declare., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Patients may use crowdfunding to solicit donations, typically from multiple small donors using internet-based means, to offset the financial toxicity of cancer care., Objective: To describe crowdfunding campaigns by gynecologic cancer patients and to compare campaign characteristics and needs expressed between patients with cervical, uterine, and ovarian cancer., Study Design: We queried the public crowdfunding forum GoFundMe.com for "cervical cancer," "uterine cancer," and "ovarian cancer." The first 200 consecutive posts for each cancer type fundraising within the United States were analyzed. Data on campaign goals and needs expressed were manually extracted. Descriptive statistics and bivariate analyses were performed., Results: Among the 600 fundraising pages, the median campaign goal was $10,000 [IQR $5000-$23,000]. Campaigns raised a median of 28.6% of their goal with only 8.7% of campaigns reaching their goal after a median of 54 days online. On average, ovarian cancer campaigns had higher monetary goals, more donors, and larger donation amounts than cervical cancer campaigns and raised more money than both cervical and uterine cancer campaigns. Campaigns were fundraising to support medical costs (80-85%) followed by lost wages (36-56%) or living expenses (27-41%). Cervical cancer campaigns reported need for non-medical costs more frequently than uterine or ovarian cancer campaigns. States without Medicaid expansions (31% of the national population) were over-represented among cervical cancer and uterine cancer, but not ovarian cancer campaigns., Conclusions: Crowdfunding pages reveal patients fundraising for out-of-pocket costs in the thousands of dollars and a wide range of unmet financial needs based on cancer type., 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. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article. The authors have no conflicts of interest related to this work. This paper was presented as an oral presentation at the Western Association of Gynecologic Oncology in June 2023 in Monterey, CA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC., Methods: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves., Results: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis., Conclusions: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time., (© 2024. The Author(s).)

Background: The Albumin-Bilirubin (ALBI) score, widely used in predicting long-term prognosis for patients with hepatocellular carcinoma (HCC), has limitations due to serum albumin variability. This study aimed to develop and validate the Prealbumin-Bilirubin (preALBI) score as a reliable alternative., Methods: A multicenter cohort of HCC patients who underwent hepatectomy was randomly divided into the training and validation cohorts. The preALBI score was developed using Cox regression models within the training cohort, incorporating serum prealbumin and bilirubin levels as crucial determinants. The survival predictive accuracy was evaluated and compared between the preALBI score with two other staging systems, including the ALBI score and the Child-Pugh grade., Results: A total of 2409 patients were enrolled. In the training cohort, the preALBI score demonstrated superior performance in predicting long-term survival after hepatectomy. The preALBI score was associated with the best monotonicity of gradients (linear trend χ 2 : 72.84) and homogeneity (likelihood ratio χ 2 : 74.69), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.663, 0.654, and 0.644, respectively). In addition, the preALBI was the most informative staging system in predicting survival (Akaike information criterion: 11325.65).The results remained consistent in both training and validation cohorts, indicating its reliable performance across different populations., Conclusion: The preALBI score, leveraging the stability of prealbumin, represents a promising tool for better patient stratification, providing more accurate prognostic predictions than the ALBI score and the Child-Pugh grade., Competing Interests: Declaration of competing interest We confirm that this work is original and has not previously been published. None of the authors have any financial disclosures or conflict of interest. Approval for this study was obtained from the Ethics Committee of the participating hospitals. All the authors have been involved in the design, performance, and interpretation of data of this study, and in drafting the article and its critical revision., (Copyright © 2024 Elsevier Inc. All rights reserved.)

High-purity CO 2 rather than dilute CO 2 (15 vol %, CO 2 /N 2 /O 2 = 15:80:5, v/v/v) similar to the flue gas is currently used as the feedstock for the electroreduction of CO 2 , and the liquid products are usually mixed up with the cathode electrolyte, resulting in high product separation costs. In this work, we showed that a microporous conductive Bi-based metal-organic framework ( Bi-HHTP , HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) can not only efficiently capture CO 2 from the dilute CO 2 under high humidity but also catalyze the electroreduction of the adsorbed CO 2 into formic acid with a high current density of 80 mA cm -2 and a Faradaic efficiency of 90% at a very low cell voltage of 2.6 V. Importantly, the performance in a dilute CO 2 atmosphere was close to that under a high-purity CO 2 atmosphere. This is the first catalyst that can maintain exceptional eCO 2 RR performance in the presence of both O 2 and N 2 . Moreover, by using dilute CO 2 as the feedstock, a 1 cm -2 working electrode coating with Bi-HHTP can continuously produce a 200 mM formic acid aqueous solution with a relative purity of 100% for at least 30 h in a membrane electrode assembly (MEA) electrolyzer. The product does not contain electrolytes, and such a highly concentrated and pure formic acid aqueous solution can be directly used as an electrolyte for formic acid fuel cells. Comprehensive studies revealed that such a high performance might be ascribed to the CO 2 capture ability of the micropores on Bi-HHTP and the lower Gibbs free energy of formation of the key intermediate *OCHO on the open Bi sites.

Background & Aims: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases., Methods: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications., Results: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis., Conclusion: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR., (© 2024. The Author(s).)

Background and Aims: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy., Methods: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors., Results: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS., Conclusion: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Transformer-based models have revolutionized single cell RNA-seq (scRNA-seq) data analysis. However, their applicability is challenged by the complexity and scale of single-cell multi-omics data. Here a novel single-cell multi-modal/multi-task transformer (scmFormer) is proposed to fill up the existing blank of integrating single-cell proteomics with other omics data. Through systematic benchmarking, it is demonstrated that scmFormer excels in integrating large-scale single-cell multimodal data and heterogeneous multi-batch paired multi-omics data, while preserving shared information across batchs and distinct biological information. scmFormer achieves 54.5% higher average F1 score compared to the second method in transferring cell-type labels from single-cell transcriptomics to proteomics data. Using COVID-19 datasets, it is presented that scmFormer successfully integrates over 1.48 million cells on a personal computer. Moreover, it is also proved that scmFormer performs better than existing methods on generating the unmeasured modality and is well-suited for spatial multi-omic data. Thus, scmFormer is a powerful and comprehensive tool for analyzing single-cell multi-omics data., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Management guidelines and corresponding survival data for patients with recurrent retinoblastoma (RB) are lacking. This study aimed to summarize the clinical characteristics of patients with recurrent RB and analyze their survival outcomes., Methods: We retrospectively analyzed 68 patients with recurrent RB who underwent treatment in our institution from January 2016 to December 2020. Patients were grouped according to location of recurrence: intraocular, orbital, and distant metastasis., Results: The male:female ratio was 1.3:1 and the median age at recurrence was 37.5 months (range, 30.3-62.8). The number of patients in the intraocular recurrence, orbital recurrence, and metastasis groups was 13 (19.1%), 23 (33.8%), and 32 (47.1%), respectively. Thirty patients died, 36 were alive at last follow-up, and two were lost to follow-up. Eye enucleation was performed in 94.1% of patients. Five-year overall survival in patients with intraocular recurrence, orbital recurrence, and metastasis was 84.6%, 69.6%, and 31.3%, respectively (P = 0.001). Most deaths occurred within 2 years of recurrence. Presence of high-risk pathological factors, central nervous system invasion, and absence of combination therapy were independent predictors of worse 5-year overall survival., Conclusion: The rate of eye preservation in survivors of recurrent RB was very low. Although 5-year overall survival in patients who underwent treatment for intraocular and orbital recurrence was high, it was low in those with metastasis. RB patients may need lifelong follow-up for recurrence and secondary malignancy., (© 2024. The Author(s).)

With a growing body of evidence establishing circular RNAs (circRNAs) are widely exploited in eukaryotic cells and have a significant contribution in the occurrence and development of many complex human diseases. Disease-associated circRNAs can serve as clinical diagnostic biomarkers and therapeutic targets, providing novel ideas for biopharmaceutical research. However, available computation methods for predicting circRNA-disease associations (CDAs) do not sufficiently consider the contextual information of biological network nodes, making their performance limited. In this work, we propose a multi-hop attention graph neural network-based approach MAGCDA to infer potential CDAs. Specifically, we first construct a multi-source attribute heterogeneous network of circRNAs and diseases, then use a multi-hop strategy of graph nodes to deeply aggregate node context information through attention diffusion, thus enhancing topological structure information and mining data hidden features, and finally use random forest to accurately infer potential CDAs. In the four gold standard data sets, MAGCDA achieved prediction accuracy of 92.58%, 91.42%, 83.46% and 91.12%, respectively. MAGCDA has also presented prominent achievements in ablation experiments and in comparisons with other models. Additionally, 18 and 17 potential circRNAs in top 20 predicted scores for MAGCDA prediction scores were confirmed in case studies of the complex diseases breast cancer and Almozheimer's disease, respectively. These results suggest that MAGCDA can be a practical tool to explore potential disease-associated circRNAs and provide a theoretical basis for disease diagnosis and treatment.

Growing studies reveal that Circular RNAs (circRNAs) are broadly engaged in physiological processes of cell proliferation, differentiation, aging, apoptosis, and are closely associated with the pathogenesis of numerous diseases. Clarification of the correlation among diseases and circRNAs is of great clinical importance to provide new therapeutic strategies for complex diseases. However, previous circRNA-disease association prediction methods rely excessively on the graph network, and the model performance is dramatically reduced when noisy connections occur in the graph structure. To address this problem, this paper proposes an unsupervised deep graph structure learning method GSLCDA to predict potential CDAs. Concretely, we first integrate circRNA and disease multi-source data to constitute the CDA heterogeneous network. Then the network topology is learned using the graph structure, and the original graph is enhanced in an unsupervised manner by maximize the inter information of the learned and original graphs to uncover their essential features. Finally, graph space sensitive k-nearest neighbor (KNN) algorithm is employed to search for latent CDAs. In the benchmark dataset, GSLCDA obtained 92.67% accuracy with 0.9279 AUC. GSLCDA also exhibits exceptional performance on independent datasets. Furthermore, 14, 12 and 14 of the top 16 circRNAs with the most points GSLCDA prediction scores were confirmed in the relevant literature in the breast cancer, colorectal cancer and lung cancer case studies, respectively. Such results demonstrated that GSLCDA can validly reveal underlying CDA and offer new perspectives for the diagnosis and therapy of complex human diseases.

Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post-surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti-recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti-recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: TMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level., Methods: Based on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA)., Results: A signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion., Conclusions: Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management., (© 2024. The Author(s).)

The transcription factor binding site is a deoxyribonucleic acid sequence that binds to transcription factors. Transcription factors are proteins that regulate the transcription gene. Abnormal turnover of transcription factors can lead to uncontrolled cell growth. Therefore, discovering the relationships between transcription factors and deoxyribonucleic acid sequences is an important component of bioinformatics research. Numerous deep learning and machine learning language models have been developed to accomplish these tasks. Our goal in this work is to propose a GMean model for predicting unlabelled deoxyribonucleic acid sequences. The GMean model is a hybrid model with a combination of gated recurrent unit and K-mean clustering. The GMean model is developed in three phases. The labelled and unlabelled data are processed based on k-mers and tokenization. The labelled data is used for training. The unlabelled data are used for testing and prediction. The experimental data consists of deoxyribonucleic acid experimental of GM12878, K562 and HepG2. The experimental results show that GMean is feasible and effective in predicting deoxyribonucleic acid sequences, as the highest accuracy is 91.85% in predicting K562 and HepG2. This is followed by the prediction of the sequence between GM12878 and K562 with an accuracy of 89.13%. The lowest accuracy is the prediction of the sequence between HepG2 and GM12828, which is 88.80%., (© 2024. The Author(s).)

The advent of single-cell sequencing technologies has revolutionized cell biology studies. However, integrative analyses of diverse single-cell data face serious challenges, including technological noise, sample heterogeneity, and different modalities and species. To address these problems, we propose scCorrector, a variational autoencoder-based model that can integrate single-cell data from different studies and map them into a common space. Specifically, we designed a Study Specific Adaptive Normalization for each study in decoder to implement these features. scCorrector substantially achieves competitive and robust performance compared with state-of-the-art methods and brings novel insights under various circumstances (e.g. various batches, multi-omics, cross-species, and development stages). In addition, the integration of single-cell data and spatial data makes it possible to transfer information between different studies, which greatly expand the narrow range of genes covered by MERFISH technology. In summary, scCorrector can efficiently integrate multi-study single-cell datasets, thereby providing broad opportunities to tackle challenges emerging from noisy resources., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Evidence regarding the characteristics and prognosis of neuroblastoma (NBL) in China is limited. We aimed to investigate the characteristics and prognosis of intermediate- or high-risk NBL in children in China., Methods: We included 147 patients with intermediate- or high-risk NBL evaluated from January 2006 to March 2015. The patients were aged 1 month to 15.5 years, 66% of them were boys, and 117 (79.6%) were diagnosed with high-risk NBL., Results: After a median follow-up of 32.5 months, 80 (45.6%) patients survived, with a median survival time of 48 months (95% confidence interval [CI]: 36.41-59.59). High-risk patients (hazard ratio [HR]: 12.467; 95% CI: 11.029-12.951), partial response (PR) (HR: 1.200; 95% CI: 1.475-2.509) or progression disease (PD) (HR: 1.924; 95% CI: 1.623-3.012) after induction chemotherapy, and intracranial metastasis (HR: 3.057; 95% CI: 0.941-4.892) were independent risk factors for survival (p < 0.05) and postrelapse survival (p < 0.05). NBL relapse, male sex, and PR or PD after induction chemotherapy were risk factors for event-free survival (p < 0.05)., Conclusions: In addition to previously established independent risk factors, such as age, risk group, and relapse, efficacy of induction chemotherapy and intracranial metastasis play significant roles in the prognosis of NBL., (© 2023. The Author(s).)

Background: In this study, we aimed to analyze the clinical characteristics and prognosis of children with retinoblastoma (RB) in a single center in China with a large sample collection spanning 17 years., Methods: The clinical data of 2790 children with RB treated in Beijing Tongren Hospital from 2005 to 2021 were collected, and a retrospective analysis was conducted., Results: The median age of the participants was 28.3 months. There were 3624 affected eyes, 12.4% of which were in groups A-C, 67.1% in groups D-E and 16.2% were not specified. The primary symptom observed in most cases was a white pupil, accounting for 66.5%, followed by strabismus (12.8%). The median follow-up time was 59.7 months. The enucleation rate was 71.3% (703/986) in a single left eye and 72.5% (702/968) in a single right eye. The overall survival (OS) rate was 95.8% (2444/2552) because 237 patients dropped out, and 109 died. Kaplan‒Meier survival analysis showed that the median survival time (MST) was 125.92 months [95% confidence interval (CI) = 124.83-127.01]. Cox multivariate survival analysis showed that trilateral RB (P = 0.017), metastasis site (P = 0.001), and combined distant tissue metastasis (P = 0.001) were independent prognostic factors for RB. The OS of 44 cases of familial RB was 93.2% (41/44), with an MST of 80.62 months (95% CI = 67.70-93.54)., Conclusions: The timing of eye protection treatment and enucleation should be comprehensively judged to avoid worsening prognosis due to operation time delay. More importantly, the promotion and popularization of diagnosis and treatment technologies are necessary to further improve RB prognosis., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

Background: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy., Methods: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR., Results: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators., Conclusion: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment., (© 2023. The Author(s).)

Background: Human brucellosis continues to be a great threat to human health in China. The present study aimed to investigate the spatiotemporal distribution of human brucellosis in China from 2004 to 2019, to analyze the socioeconomic factors, meteorological factors and seasonal effect affecting human brucellosis incidence in different geographical regions with the help of spatial panel model, and to provide a scientific basis for local health authorities to improve the prevention of human brucellosis., Methods: The monthly reported number and incidence of human brucellosis in China from January 2004 to December 2019 were obtained from the Data Center for China Public Health Science. Monthly average air temperature and monthly average relative humidity of 31 provincial-level administrative units (22 provinces, 5 autonomous regions and 4 municipalities directly under the central government) in China from October 2003 to December 2019 were obtained from the National Meteorological Science Data Centre. The inventory of cattle, the inventory of sheep, beef yield, mutton yield, wool yield, milk yield and gross pastoral product of 31 provincial-level administrative units in China from 2004 to 2019 were obtained from the National Bureau of Statistics of China. The temporal and geographical distribution of human brucellosis was displayed with Microsoft Excel and ArcMap software. The spatial autocorrelation and hotspot analysis was used to describe the association among different areas. Spatial panel model was constructed to explore the combined effects on the incidence of human brucellosis in China., Results: A total of 569,016 cases of human brucellosis were reported in the 31 provincial-level administrative units in China from January 2004 to December 2019. Human brucellosis cases were concentrated between March and July, with a peak in May, showing a clear seasonal increase. The incidence of human brucellosis in China from 2004 to 2019 showed significant spatial correlations, and hotspot analysis indicated that the high incidence of human brucellosis was mainly in the northern China, particularly in Inner Mongolia, Shanxi, and Heilongjiang. The results from spatial panel model suggested that the inventory of cattle, the inventory of sheep, beef yield, mutton yield, wool yield, milk yield, gross pastoral product, average air temperature (the same month, 2-month lagged and 3-month lagged), average relative humidity (the same month) and season variability were significantly associated with human brucellosis incidence in China., Conclusions: The epidemic area of human brucellosis in China has been expanding and the spatial clustering has been observed. Inner Mongolia and adjacent provinces or autonomous regions are the high-risk areas of human brucellosis. The inventory of cattle and sheep, beef yield, mutton yield, wool yield, milk yield, gross pastoral product, average air temperature, average relative humidity and season variability played a significant role in the progression of human brucellosis. The present study strengthens the understanding of the relationship between socioeconomic, meteorological factors and the spatial heterogeneity of human brucellosis in China, through which 'One Health'-based strategies and countermeasures can be provided for the government to tackle the brucellosis menace., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To establish a patient-derived xenograft (PDX) humanized mouse model for hepatoblastoma in children. In addition, compare the biological consistency between successfully modeled PDX tumors and primary tumors in children while comparing and analyzing the influence of PDX model modeling success as a key factor. Methods: A PDX tumor model was constructed from fresh tumor tissue samples from 39 children with hepatoblastoma. The tumor growth time and volume size were recorded in detail. Simultaneously, 39 children's data were collected for experimental and clinical analysis. The difference in tumorigenesis rate between different parameters was analyzed by χ (2) test (categorical variable). Continuous variables with a normal distribution were compared using the t-test. Results: After cell passage and pathological diagnosis, 21 cases of hepatoblastoma PDX models were successfully constructed, with a success rate of 53.8% (21/39). Tumor samples from each generation of successfully modeled PDX models had pathology results that were consistent with those of the corresponding primary tumors. The analysis of the key factors affecting the tumor formation rate of PDX revealed that the metastasis rate was more successful in primary tumors than in liver in situ tumors (7/8 vs. 14/31, P = 0.049). However, there was no significant difference between tumor formation rates and pathological subtypes. According to the PDX tumor formation group comparison between the primary tumor and the metastatic tumor, there was no statistically significant difference between the two groups in terms of tumor formation time and tumor volume. Hematoxylin-eosin staining in hepatoblastoma's PDX mouse was consistent with the primary tumor. Immunohistochemistry positivity rates of four proteins, namely hepatocyte antigen (Hepatocyte), phosphatidylinositol glycan 3, β-catenin, and alpha-fetoprotein, in primary tumor tissues and PDX mouse models were 100% vs. 100%, 100% vs. 95.24%, 100% vs. 100%, and 95.24% vs. 85.71%, respectively. Conclusion: A PDX mouse model for hepatoblastoma has been successfully established in children. The tumor formation rate is high, with metastatic tumors having a higher tumor formation rate than primary tumors and transplanted tumors retaining the biological characteristics of primary tumors.

Transcription factors (TFs) play a part in gene expression. TFs can form complex gene expression regulation system by combining with DNA. Thereby, identifying the binding regions has become an indispensable step for understanding the regulatory mechanism of gene expression. Due to the great achievements of applying deep learning (DL) to computer vision and language processing in recent years, many scholars are inspired to use these methods to predict TF binding sites (TFBSs), achieving extraordinary results. However, these methods mainly focus on whether DNA sequences include TFBSs. In this paper, we propose a fully convolutional network (FCN) coupled with refinement residual block (RRB) and global average pooling layer (GAPL), namely FCNARRB. Our model could classify binding sequences at nucleotide level by outputting dense label for input data. Experimental results on human ChIP-seq datasets show that the RRB and GAPL structures are very useful for improving model performance. Adding GAPL improves the performance by 9.32% and 7.61% in terms of IoU (Intersection of Union) and PRAUC (Area Under Curve of Precision and Recall), and adding RRB improves the performance by 7.40% and 4.64%, respectively. In addition, we find that conservation information can help locate TFBSs.

Objective: This study aimed to investigate the effectiveness of doxofylline as an adjuvant in reducing severe exacerbation for different clinical subtypes of chronic obstructive pulmonary disease (COPD)., Methods: The clinical trial was an open-label non-randomized clinical trial that enrolled patients with COPD. The patients were divided into two groups (doxofylline group[DG] and non-doxofylline group[NDG]) according to whether the adjuvant was used. Based on the proportion of inflammatory cells present, the patients were divided into neutrophilic, eosinophilic, and mixed granulocytic subtypes. The rates of severe acute exacerbation, use of glucocorticoids, and clinical symptoms were followed up in the first month, the third month, and the sixth month after discharge., Results: A total of 155 participants were included in the study. The average age of the participants was 71.2  ±  10.1 years, 52.3% of the patients were male, and 29.7% of the participants had extremely severe cases of COPD. In the third month after discharge the numbers of patients exhibiting severe exacerbation among the neutrophilic subtype were 5 (6.6%) in the DG versus 17 (22.4%) in the NDG (incidence rate ratio[IRR] = 0.4 [95% CI: 0.2-0.9] P = 0.024). In the sixth month after discharge, the numbers were 3 (3.9%) versus 13 (17.1%; IRR = 0.3 [95%; CI: 0.1-0.9], P = 0.045), and those for the eosinophilic subtype were 0 (0.0%) versus 4 (14.8%), P = 0.02. In the eosinophilic subtype, the results for forced expiratory volume in the first second and maximal mid-expiratory flow were significantly higher in the DG. The mean neutrophil and eosinophil levels were significantly lower than in the NDG among the neutrophilic subtype, and the neutrophil percentage was lower than in the NDG among the eosinophilic subtype. At the six-month follow-up, the dose adjustment rates of the neutrophilic and eosinophilic subtypes showed a significant difference (P< 0.05)., Conclusions: As an adjuvant drug, doxofylline has a good therapeutic effect on patients with the neutrophilic and eosinophilic clinical subtypes of COPD. It can reduce the incidence of severe exacerbation, the use of glucocorticoids, and inflammatory reactions in the long term (when used for a minimum of 3 months)., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Accumulating evidence suggests that circRNAs play crucial roles in human diseases. CircRNA-disease association prediction is extremely helpful in understanding pathogenesis, diagnosis, and prevention, as well as identifying relevant biomarkers. During the past few years, a large number of deep learning (DL) based methods have been proposed for predicting circRNA-disease association and achieved impressive prediction performance. However, there are two main drawbacks to these methods. The first is these methods underutilize biometric information in the data. Second, the features extracted by these methods are not outstanding to represent association characteristics between circRNAs and diseases. In this study, we developed a novel deep learning model, named iCircDA-NEAE, to predict circRNA-disease associations. In particular, we use disease semantic similarity, Gaussian interaction profile kernel, circRNA expression profile similarity, and Jaccard similarity simultaneously for the first time, and extract hidden features based on accelerated attribute network embedding (AANE) and dynamic convolutional autoencoder (DCAE). Experimental results on the circR2Disease dataset show that iCircDA-NEAE outperforms other competing methods significantly. Besides, 16 of the top 20 circRNA-disease pairs with the highest prediction scores were validated by relevant literature. Furthermore, we observe that iCircDA-NEAE can effectively predict new potential circRNA-disease associations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Imbalances in gut microbes have been implied in many human diseases, including colorectal cancer (CRC), inflammatory bowel disease, type 2 diabetes, obesity, autism, and Alzheimer's disease. Compared with other human diseases, CRC is a gastrointestinal malignancy with high mortality and a high probability of metastasis. However, current studies mainly focus on the prediction of colorectal cancer while neglecting the more serious malignancy of metastatic colorectal cancer (mCRC). In addition, high dimensionality and small samples lead to the complexity of gut microbial data, which increases the difficulty of traditional machine learning models., Methods: To address these challenges, we collected and processed 16S rRNA data and calculated abundance data from patients with non-metastatic colorectal cancer (non-mCRC) and mCRC. Different from the traditional health-disease classification strategy, we adopted a novel disease-disease classification strategy and proposed a microbiome-based multi-view convolutional variational information bottleneck (MV-CVIB)., Results: The experimental results show that MV-CVIB can effectively predict mCRC. This model can achieve AUC values above 0.9 compared to other state-of-the-art models. Not only that, MV-CVIB also achieved satisfactory predictive performance on multiple published CRC gut microbiome datasets., Discussion: Finally, multiple gut microbiota analyses were used to elucidate communities and differences between mCRC and non-mCRC, and the metastatic properties of CRC were assessed by patient age and microbiota expression., 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 Cui, Wu, Zhang, Wang, He and Huang.)

Background: Non-cancer-specific death (NCSD) is an important factor that needs to be considered in patients with malignancy, as it can affect their long-term prognosis. In particular, the effect of age on patients with hepatocellular carcinoma (HCC) after hepatectomy requires clarification. This study aims to examine the impact of age on patients with HCC after hepatectomy and to identify independent risk factors of survival., Methods: Patients with HCC that fell within the Milan Criteria and had undergone curative hepatectomy were included in this study. The patients were divided into two groups: young patients (age <70) and elderly patients (age ≥70). Perioperative complications, cancer-specific death (CSD), recurrence, and NCSD were all recorded and analyzed. Multivariate analyses were performed to identify independent risk factors of survival using Fine and Gray's competing-risk regression model., Results: Among 1,354 analytic patients, 1,068 (78.7%) were stratified into the young group and 286 (21.3%) into the elderly group. The elderly group had a higher 5-year cumulative incidence of NCSD (12.6% vs. 3.7% for the young group, P < 0.001), but lower 5-year cumulative incidences of recurrence (20.3% vs. 21.1% for the young group, P = 0.041) and CSD (14.3% vs. 15.5% for the young group, P = 0.066). Multivariate competing-risk regression analyses revealed that age was independently associated with NCSD (subdistribution hazard ratio (SHR) 3.003, 95%CI: 2.082-4.330, P < 0.001), but not with recurrence (SHR 0.837, 95%CI: 0.659-1.060, P = 0.120) or CSD (SHR 0.736, 95%CI: 0.537-1.020, P = 0.158)., Conclusion: For patients with early-stage HCC after hepatectomy, older age was independently associated with NCSD, but not recurrence and CSD., 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 Masson SAS. All rights reserved.)

Several isostructural lanthanide metal-organic frameworks, viz. [Ln(DCHB) 1.5 phen] n ( Ln-MOFs , where Ln = Eu for 1 , Tb for 2 , Sm for 3 and Dy for 4 ), are successfully synthesized through the hydrothermal reactions of 4'-di(4-carboxylphenoxy)hydroxyl-2, 2'-bipyridyl (H 2 DCHB) and lanthanide nitrates as well as chelator 1,10-phenantroline (phen). These structures are characterized by single-crystal X-ray diffraction, and the representative Ln-MOF 1 is a fivefold interpenetrated framework with the uncoordinated Lewis base N sites form DCHB 2- ligands. The photoluminescence research studies reveal that Ln-MOFs 1 - 4 exhibit characteristic fluorescent emissions from ligand-induced lanthanide Ln(III) ions, while the single-component emission spectra of Ln-MOF 4 are all located in a white region under different excitations. The absence of coordinated water and the interpenetration property of the structures are conducive to the structure rigidity, and the results display that Ln-MOF 1 has high thermal/chemical stabilities in common solvents and a wide pH range as well as the boiling water. Notably, luminescent sensing studies reveal that Ln-MOF 1 with prominent fluorescence properties can perform in highly sensitive and selective sensing of vanillylmandelic acid (VMA) in aqueous systems ( K SV = 562.8 L·mol -1 ; LOD = 4.6 × 10 -4 M), which can potentially establish a detection platform for the diagnosis of pheochromocytoma via multiquenching mechanisms. Moreover, the 1 @MMMs sensing membranes comprised of Ln-MOF 1 and a poly(vinylidene fluoride) (PVDF) polymer can also be facilely developed for VMA detection in aqueous media, suggesting the enhanced convenience and efficiency of practical sensing applications.

Background & Aims: Although anatomical hepatectomy (AH) is widely used in the treatment of hepatocellular carcinoma (HCC), the prognosis is still unsatisfactory. The present study aimed to evaluate the survival benefit of adjuvant transcatheter arterial chemoembolization (TACE) for patients with HCC after AH., Methods: A total of 832 patients were stratified into with adjuvant TACE (443, 53.2%) and without adjuvant TACE group (389, 46.8%) AH. Propensity score matching (PSM) was performed to control for confounding factors, and multivariable Cox regression was performed to determine the independent risk factors., Results: After PSM, the results showed that the adjuvant TACE group had better overall survival (OS) and recurrence-free survival (RFS). Among the patients with tumor recurrence, adjuvant TACE was associated with a high rate of early-stage tumor at recurrence, a lower recurrence rate around the frontal margin and extrahepatic metastases, and a higher rate of receiving curative treatment. Multivariable Cox regression analysis showed that adjuvant TACE was an independent prognostic factor for OS (HR 0.673, P = 0.001) and RFS (HR 0.650, P = 0.001)., Conclusions: Patients with HCC after AH can benefit from postoperative adjuvant TACE. Therefore, adjuvant TACE should be considered for patients with a high risk of recurrence.