bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Clinical Validation of Novel 8-Gene Prognostic Signature Associated With the Proportion of Regulatory T Cells by Weighted Gene Co-Expression Network Analysis in Uterine Corpus Endometrial Carcinoma
Authors: Liu Jinhui , Geng Rui , Yang Sheng , Shao Fang , Zhong Zihang , Yang Min , Ni Senmiao , Cai Lixin , Bai Jianling 
Published: December 2021

BackgroundUterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with low survival rate and poor prognosis. The traditional clinicopathological staging is insufficient to estimate the prognosis of UCEC. It is necessary to select a more effective prognostic signature of UCEC to predict the prognosis and immunotherapy effect of UCEC.MethodsCIBERSORT and weighted correlation network analysis (WGCNA) algorithms were combined to screen modules related to regulatory T (Treg) cells. Subsequently, univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were used to identify the genes in key modules. The difference in overall survival (OS) between high- and low-risk patients was analyzed by Kaplan–Meier analysis. The Tregs-related risk signature (TRRS) was screened by uni- and multivariate Cox analyses. Afterward, we analyzed the expression difference of TRRS and verified its ability to predict the prognosis of UCEC and the effect of immunotherapy.ResultsRed module has the highest correlation with Tregs among all clustered modules. Pathways enrichment indicated that the related processes of UCEC were primarily associated to the immune system. Eight genes (ZSWIM1, NPRL3, GOLGA7, ST6GALNAC4, CDC16, ITPK1, PCSK4, and CORO1B) were selected to construct TRRS. We found that this TRRS is a significantly independent prognostic factor of UCEC. Low-risk patients have higher overall survival than high-risk patients. The immune status of different groups was different, and tumor-related pathways were enriched in patients with higher risk score. Low-risk patients are more likely take higher tumor mutation burden (TMB). Meanwhile, they are more sensitive to chemotherapy than patients with high-risk score, which indicated a superior prognosis. Immune checkpoints such as PD-1, CTLA4, PD-L1, and PD-L2 all had a higher expression level in low-risk group. TRRS expression really has a relevance with the sensitivity of UCEC patients to chemotherapeutic drugs.ConclusionWe developed and validated a TRRS to estimate the prognosis and reflect the immune status of UCEC, which could accurately assess the prognosis of patients with UCEC and supply personalized treatments for them.
Systemic Immune Activation and Responses of Irradiation to Different Metastatic Sites Combined With Immunotherapy in Advanced Non-Small Cell Lung Cancer
Authors: Wu Min , Liu Jie , Wu Shihao , Liu Jingru , Wu Hui , Yu Jinming , Meng Xue 
Published: December 2021

PurposeConsidering the limited data, we aimed to identify the greatest immune activation irradiated site of common metastases and response to immune checkpoint inhibitors simultaneously in non-small cell lung cancer (NSCLC).MethodsA total of 136 patients with advanced NSCLC who had received radiation to a primary or metastatic solid tumor were enrolled. We recorded blood cell counts in three time periods, before, during, and after radiotherapy (RT), and derived some blood index ratios including monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). The delta-IBs were calculated as medio-IBs ÷ pre-IBs − 1. We analyzed the changes before and during RT using Spearman rank correlation test, Kruskal–Wallis rank sum test, and logistic regression analyzing their correlation with efficacy.ResultsThe medians of delta-MLR and delta-PLR were both the lowest while the median of delta-L was the highest in brain. Therapeutic effect evaluation showed that the objective response rate (ORR) of 48.65% (18/37) in the brain irradiation group was the highest, compared with 17.07% (7/41) in bone and 41.94% (13/31) in lung.ConclusionsIn this study, results suggested that irradiation to brain has the best immune activation effect and patient outcome compared with other organs in NSCLC, and when the earlier-line ICIs were combined with RT, a better patient outcome was reached. Prospective studies are also necessary to provide more convincing evidence and standards for clinical irradiation metastases selection.
Clinical Features and Risk Factors Analysis for Hemorrhage in Adults on ECMO
Authors: Hu Wenwen , Zhang Jing , Wang Meifang , Chen Wei , Chai Lin , Leung Elaine Lai-Han , Tang Yijun 
Published: December 2021

Background: The use of extracorporeal membrane oxygenation (ECMO) to support critically ill patients with cardiorespiratory dysfunction has increased over the last decades. However, hemorrhagic complications occur frequently during ECMO support, and this has a significant impact on morbidity and mortality. Thus, this study aimed to identify the risk factors for hemorrhage in patients receiving ECMO.Methods: Our retrospective study included 60 patients, who were admitted to the Taihe Hospital in Shiyan City, Hubei Province, China from February 2017 to October 2020. About 18 patients developed hemorrhagic complications, and 42 patients did not demonstrate such complications. Data regarding patient demography, laboratory tests, and clinical manifestations prior to ECMO were collected to analyze their clinical features. Univariable and multivariable logistic analyses were used to explore the risk factors for hemorrhage in adults on ECMO. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the binary logistic model. The amount of blood transfusions was compared between the two groups, and the activated partial thromboplastin time (APTT), platelet count, and hemoglobin level before the initiation of ECMO.Results: Logistic analysis showed that a longer duration of ECMO support, higher APTT, and lower platelet count prior to ECMO were independent risk factors for hemorrhage in adults on ECMO. In addition, we found that the cannula site was the most common bleeding site. Most bleeding events occurred within the first 3 days of ECMO therapy. After the ECMO initiation, APTT was prolonged while the platelet count and hemoglobin levels were decreased. The amount of blood transfusion was significantly higher in the hemorrhage group than in the non-hemorrhage group.Conclusions: Clinicians should evaluate the risk of hemorrhage based on the coagulation function of patients, underlying disease, and the duration of ECMO support. In the first 3 days during ECMO support, special attention should be given to the cannula site, mucosal, and dermal regions, and digestive tract to detect any signs of hemorrhage. Moreover, increasing the platelet count transfusion threshold and accurately determining the amount of blood transfusion required may prevent bleeding events.
Impact of Computer-Assisted System on the Learning Curve and Quality in Esophagogastroduodenoscopy: Randomized Controlled Trial
Authors: Huang Li , Liu Jun , Wu Lianlian , Xu Ming , Yao Liwen , Zhang Lihui , Shang Renduo , Zhang Mengjiao , Xiong Qiutang , Wang Dawei , Dong Zehua , Xu Youming , Li Jia , Zhu Yijie , Gong Dexin , Wu Huiling , Yu Honggang 
Published: December 2021

Background and Aims: To investigate the impact of the computer-assisted system on esophagogastroduodenoscopy (EGD) training for novice trainees in a prospective randomized controlled trial.Methods: We have constructed a computer-aided system (CAD) using retrospective images based on deep learning which could automatically monitor the 26 anatomical landmarks of the upper digestive tract and document standard photos. Six novice trainees were allocated and grouped into the CAD group and control group. Each of them took the training course, pre and post-test, and EGD examination scored by two experts. The CAD group was trained with the assistance of the CAD system and the control group without.Results: Both groups achieved great improvements in EGD skills. The CAD group received a higher examination grading score in the EGD examination (72.83 ± 16.12 vs. 67.26 ± 15.64, p = 0.039), especially in the mucosa observation (26.40 ± 6.13 vs. 24.11 ± 6.21, p = 0.020) and quality of collected images (7.29 ± 1.09 vs. 6.70 ± 1.05). The CAD showed a lower blind spot rate (2.19 ± 2.28 vs. 3.92 ± 3.30, p = 0.008) compared with the control group.Conclusion: The artificial intelligence assistant system displayed assistant capacity on standard EGD training, and assisted trainees in achieving a learning curve with high operation quality, which has great potential for application.Clinical Trial Registration: This trial is registered at https:/clinicaltrials.gov/, number NCT04682821.
CalmBelt: Rapid SARS-CoV-2 Genome Characterization for Outbreak Tracking
Authors: Yingtaweesittikul Hatairat , Ko Karrie , Abdul Rahman Nurdyana , Tan Shireen Yan Ling , Nagarajan Niranjan , Suphavilai Chayaporn 
Published: December 2021

Background: The ongoing COVID-19 pandemic is a global health crisis caused by the spread of SARS-CoV-2. Establishing links between known cases is crucial for the containment of COVID-19. In the healthcare setting, the ability to rapidly identify potential healthcare-associated COVID-19 clusters is critical for healthcare worker and patient safety. Increasing sequencing technology accessibility has allowed routine clinical diagnostic laboratories to sequence SARS-CoV-2 in clinical samples. However, these laboratories often lack specialized informatics skills required for sequence analysis. Therefore, an on-site, intuitive sequence analysis tool that enables clinical laboratory users to analyze multiple genomes and derive clinically relevant information within an actionable timeframe is needed.Results: We propose CalmBelt, an integrated framework for on-site whole genome characterization and outbreak tracking. Nanopore sequencing technology enables on-site sequencing and construction of draft genomes for multiple SARS-CoV-2 samples within 12 h. CalmBelt's interactive interface allows users to analyse multiple SARS-CoV-2 genomes by utilizing whole genome information, collection date, and additional information such as predefined potential clusters from epidemiological investigations. CalmBelt also integrates established SARS-CoV-2 nomenclature assignments, GISAID clades and PANGO lineages, allowing users to visualize relatedness between samples together with the nomenclatures. We demonstrated multiple use cases including investigation of potential hospital transmission, mining transmission patterns in a large outbreak, and monitoring possible diagnostic-escape.Conclusions: This paper presents an on-site rapid framework for SARS-CoV-2 whole genome characterization. CalmBelt interactive web application allows non-technical users, such as routine clinical laboratory users in hospitals to determine SARS-CoV-2 variants of concern, as well as investigate the presence of potential transmission clusters. The framework is designed to be compatible with routine usage in clinical laboratories as it only requires readily available sample data, and generates information that impacts immediate infection control mitigations.
The Clinical Value of Explainable Deep Learning for Diagnosing Fungal Keratitis Using in vivo Confocal Microscopy Images
Authors: Xu Fan , Jiang Li , He Wenjing , Huang Guangyi , Hong Yiyi , Tang Fen , Lv Jian , Lin Yunru , Qin Yikun , Lan Rushi , Pan Xipeng , Zeng Siming , Li Min , Chen Qi , Tang Ningning 
Published: December 2021

Background: Artificial intelligence (AI) has great potential to detect fungal keratitis using in vivo confocal microscopy images, but its clinical value remains unclarified. A major limitation of its clinical utility is the lack of explainability and interpretability.Methods: An explainable AI (XAI) system based on Gradient-weighted Class Activation Mapping (Grad-CAM) and Guided Grad-CAM was established. In this randomized controlled trial, nine ophthalmologists (three expert ophthalmologists, three competent ophthalmologists, and three novice ophthalmologists) read images in each of the conditions: unassisted, AI-assisted, or XAI-assisted. In unassisted condition, only the original IVCM images were shown to the readers. AI assistance comprised a histogram of model prediction probability. For XAI assistance, explanatory maps were additionally shown. The accuracy, sensitivity, and specificity were calculated against an adjudicated reference standard. Moreover, the time spent was measured.Results: Both forms of algorithmic assistance increased the accuracy and sensitivity of competent and novice ophthalmologists significantly without reducing specificity. The improvement was more pronounced in XAI-assisted condition than that in AI-assisted condition. Time spent with XAI assistance was not significantly different from that without assistance.Conclusion: AI has shown great promise in improving the accuracy of ophthalmologists. The inexperienced readers are more likely to benefit from the XAI system. With better interpretability and explainability, XAI-assistance can boost ophthalmologist performance beyond what is achievable by the reader alone or with black-box AI assistance.
Associations of TFEB Gene Polymorphisms With Cognitive Function in Rural Chinese Population
Authors: Wei Yanfei , Liu Shuzhen , Cai Jiansheng , Tang Xu , Zhang Junling , Xu Min , Liu Qiumei , Wei Chunmei , Mo Xiaoting , Huang Shenxiang , Lin Yinxia , Mai Tingyu , Tan Dechan , Luo Tingyu , Gou Ruoyu , Lu Huaxiang , Qin Jian , Zhang Zhiyong 
Published: December 2021

Background: The study aimed to investigate the relationship between transcription factor EB (TFEB) gene polymorphisms, including their haplotypes, and the cognitive functions of a selected population in Gongcheng County, Guangxi.Methods: A case-control study approach was used. The case group comprised 339 individuals with cognitive impairment, as assessed by their Mini-Mental State Examination scores; the control population also comprised 339 individuals who were matched by sex and age (± 5 years) in a 1:1 ratio. TFEB gene polymorphisms were genotyped in 678 participants (190 men and 488 women, aged 30–91 years) by using the Sequenom MassARRAY platform.Results: Multifactorial logistic regression analysis showed that in the dominant model, the risk of developing cognitive impairment was 1.547 times higher in cases with the TFEB rs14063A allele (AG + AA) than in those with the GG genotype (adjusted odds ratio [OR] = 1.547, Bonferroni correction confidence interval = 1.021–2.345). Meanwhile, the presence of the TFEB rs1062966T allele (CT + TT) was associated with a lower risk of cognitive impairment in comparison with the presence of the CC genotype (adjusted OR = 0.636, Bonferroni correction confidence interval = 0.405–0.998). In the co-dominant model, the risk of developing cognitive impairment was 1.553 times higher in carriers of the TFEB rs14063AG genotype than in carriers of the GG genotype (adjusted OR = 1.553, Bonferroni correction confidence interval = 1.007–2.397). After the Bonferroni correction and adjustment for confounding factors, the association of TFEB rs1062966 with cognitive function persisted in the analyses stratified by education level. Ethnically stratified analysis showed a significant association between TFEB rs1062966 and cognitive function in the Yao population. The multilocus linkage disequilibrium analysis indicated that the identified single nucleotide polymorphisms were not inherited independently. The haplotype analysis suggested that the rs14063A–rs1062966C–rs2278068C–rs1015149T haplotype of the TFEB gene increased the risk of cognitive impairment (P &lt; 0.05) and that the rs14063G–rs1062966T–rs2278068C–rs1015149C haplotype was associated with a reduced risk of cognitive impairment (P &lt; 0.05).Conclusion:TFEB rs1062966 polymorphisms and their rs14063A–rs1062966C–rs2278068C–rs1015149T and rs14063G–rs1062966T–rs2278068C–rs1015149C haplotypes are genetic factors that may affect cognitive function among the rural Chinese population.
Intravenous Thrombolysis After Reversal of Dabigatran With Idarucizumab in Acute Ischemic Stroke: A Case Report
Authors: Xie Dan , Wang Xuefan , Li Yao , Chen Ruiling , Zhao Yingying , Xu Chunling , Zhang Qian , Zhang Yongbo 
Published: December 2021

Background: As there is a growing concern about the cerebral embolism events secondary to non-valvular atrial fibrillation (NVAF), novel oral anticoagulant (NOAC) has been more and more widely used as an anticoagulation treatment for the prevention of stroke. However, in the face of life-threatening bleeding or emergency surgery/treatment, NOAC-related antagonists such as idarucizumab need to be urgently used to reverse the NOAC. Using recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis for acute ischemic stroke requires a time window of 4.5 h. This case reports rt-PA intravenous thrombolysis after reversal of dabigatran anticoagulation with idarucizumab in patients with acute ischemic stroke.Case Presentation: We report the case of 62-year-old Chinese female with NVAF treated with dabigatran 110 mg twice daily, and missed a dose on the eve of the stroke. The patient presented with acute ischemic stroke causing the angle of mouth deviated to right side and left limb weakness in the early morning of the next day. However, the last dosing time of dabigatran was between 24 and 48 h, the patients were given rt-PA intravenous thrombolysis after reversal of dabigatran anticoagulation with idarucizumab, while any potential relative contraindication had been excluded by means of laboratory test and CT scan in the hospitalization services. National Institute of Health stroke scale (NIHSS) score was reduced from 4 to 1, and the patient was discharged after 2 weeks.Conclusion: Our case report adds to the evidence that idarucizumab administration is safe and effective in the setting of patients with atrial fibrillation treated with dabigatran who develop acute ischemic stroke requiring rt-PA intravenous thrombolysis.
Extracranial Carotid Plaque Hemorrhage Is Independently Associated With Poor 3-month Functional Outcome After Acute Ischemic Stroke—A Prospective Cohort Study
Authors: Che Fengli , Liu Yanfang , Gong Xiping , Wang Anxin , Bai Xiaoyan , Ju Yi , Sui Binbin , Jing Jing , Geng Xiaokun , Zhao Xingquan 
Published: December 2021

Background and Purpose: Carotid plaque hemorrhage (IPH) is a critical plaque vulnerable feature. We aim to elucidate the association between symptomatic extracranial carotid atherosclerotic IPH and poor 3-month functional outcome after acute ischemic stroke by high-resolution vessel wall MRI (HRVMRI).Methods: We prospectively studied consecutive patients with a recent stroke or transient ischemic attack (TIA) of carotid atherosclerotic origin. All patients underwent a High-Resolution (HR) VWMRI scan of ipsilateral extracranial carotid within 1 week after admission. The patients recruited were interviewed by telephone after 3 months after stroke onset. The primary outcome was a 3-month functional prognosis of stroke, expressed as a modified Rankin Scale (mRS) score. A poor prognosis was defined as a 3-month modified Rankin Scale (mRS) score ≥ of 3. Univariate analysis was used to analyze the correlation between risk factors and IPH. The relation between IPH and 3-month functional outcome was analyzed by Logistic regression analysis.Results: A total of 156 patients (mean age, 61.18 ± 10.12 years; 108 males) were included in the final analysis. There were significant differences in the age, gender, smoking history, national institutes of health stroke scale (NIHSS) on admission, and diastolic blood pressure (DBP) on admission between the IPH group and the non-IPH group (all p &lt; 0.05). During the follow-up, 32 patients (20.5%) had a poor functional outcome. According to the prognosis analysis of poor functional recovery, there was a significant difference between the two groups [36.7 vs. 16.7%; unadjusted odds ratio (OR), 2.32, 95% confidence interval (CI), 1.12–4.81, p = 0.024). Even after adjusting for confounding factors [such as age, gender, smoking history, National Institutes of Health Stroke Scale (NIHSS) on admission, DBP on admission, stenosis rate of carotid artery (CA), calcification, loose matrix, lipo-rich necrotic core (LRNC), and statins accepted at 3 months], IPH was still a strong predictor of poor 3-month outcome, and the adjusted OR was 3.66 (95% CI 1.68–7.94, p = 0.001).Conclusions: Extracranial carotid IPH is significantly associated with poor 3-month outcome after acute ischemic stroke and can predict the poor 3-month functional prognosis.
Correlation Between Retinal Microvascular Abnormalities and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes
Authors: Zhang Ying , Zhang Zhixiang , Zhang Min , Cao Yin , Yun Wenwei 
Published: December 2021

Background and Purpose: Diabetic retinopathy (DR) is one of the common microvascular complications in diabetes. The total magnetic resonance imaging (MRI) burden of cerebral small vessel disease (CSVD) tends to be increased in diabetic patients and is a marker of microvascular disease; however, the relationship between DR and CSVD is unclear. This study aimed to explore the relationship between retinal microvascular abnormalities and the total MRI burden of CSVD in patients with type 2 diabetes.Methods: Data were collected from patients with type 2 diabetes who were hospitalized between December 2019 and November 2020 in Changzhou Second People’s Hospital affiliated to Nanjing Medical University. All patients underwent retinal photography and cerebral MRI. The central retinal artery equivalent (CRAE), the central retinal venous equivalent (CRVE), and arteriole-to-venule ratio (AVR) were calculated using Image J software to determine the retinal vascular calibers for each patient. The total MRI burden score for CSVD was determined, and the relationship between retinal microvascular abnormalities and the total MRI burden of CSVD was analyzed.Results: Of the 151 diabetic patients included in the study, 84 (55.6%) had no diabetic retinopathy (NDR), 27 (17.9%) had mild DR, and 40 (26.5%) had moderate, or severe non-proliferative DR (grouped together for this study as “more than mild DR”). In patients with more than mild DR, the proportion of moderate to severe burden of CSVD was 75%, which was higher than in patients with mild DR (48.1%) or NDR (26.2%). Patients with moderate to severe burden of CSVD were more likely than those with mild burden of CSVD to have narrowed retinal arterioles (105.24 ± 8.42 μm vs. 109.45 ± 7.93 μm), widened retinal venules (201.67 ± 16.25 μm vs. 193.95 ± 13.54 μm), and lower arteriole-to-venule ratio (0.52 ± 0.05 vs. 0.57 ± 0.04) (P &lt; 0.05 for all). The degree of DR (r = 0.465, P &lt; 0.001) and CRVE (r = 0.366, P &lt; 0.001) were positively correlated with the total MRI burden of CSVD. Multivariate logistic regression analysis indicated that, after adjustments were made for age, smoking, alcohol consumption, hypertension, and other factors, more than mild DR (OR, 4.383; P = 0.028), CRAE (OR, 0.490; P = 0.031), and CRVE (OR, 1.475; P = 0.041) were independently associated with moderate to severe burden of CSVD.Conclusion: Retinal microvascular abnormalities in patients with type 2 diabetes are associated with the presence of cerebral small vessel lesions. The degree of DR and retinal vessel changes can be used as predictors of intracranial microcirculation lesions.