bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum LAG-3 Predicts Outcome and Treatment Response in Hepatocellular Carcinoma Patients With Transarterial Chemoembolization
Authors: Guo Mengzhou , Qi Feng , Rao Qianwen , Sun Jialei , Du Xiaojing , Qi Zhuoran , Yang Biwei , Xia Jinglin 
Published: October 2021

BackgroundTransarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment.MethodsA total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA).ResultsWe found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE.ConclusionBoth pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.
The Value of 18F-FDG PET/CT in Diagnosing Pancreatic Lesions: Comparison With CA19-9, Enhanced CT or Enhanced MR
Authors: Huang Shengyun , Chong Huanhuan , Sun Xun , Wu Zhijian , Jia Qing , Zhang Yongxue , Lan Xiaoli 
Published: October 2021

Objective: To investigate the value of 18F-FDG PET/CT in diagnosing pancreatic lesions, and compare it with CA19-9, contrast-enhanced CT (CECT), and contrast-enhanced MRI (CEMR).Methods: Cases of patients with suspected pancreatic lesions examined between January 1, 2011 and June 30, 2017 were retrospectively analyzed. CA19-9, CECT and CEMR within 2 weeks of PET/CT were evaluated. We compared the diagnostic efficacy of PET/CT with CA19-9, CECT and CEMR as well as combined tests.Results: A total of 467 cases were examined in this study, including 293 males and 174 females, with an average age of 57.79 ± 12.68 y (16–95 y). Cases in the malignant group (n = 248) had significantly higher SUVmax (7.34 ± 4.17 vs. 1.70 ± 2.68, P &lt; 0.001) and CA19-9 (663.21 ± 531.98 vs. 87.80 ± 218.47, P &lt; 0.001) than those in the benign group (n = 219). The sensitivity, specificity and accuracy of PET/CT were 91.9, 96.3, and 94.0%, respectively. Those for CECT were 83.6, 77.8, 81.2%, respectively; and 91.2, 75.0, 81.7% were for CEMR. PET/CT corrected 14.7% (28/191) CECT diagnoses and 12.2% (10/82) CEMR diagnoses. Although the diagnostic efficiency of CA19-9 was acceptable (80.0, 69.0, 74.9% respectively), the joint application of PET/CT and CA19-9 could significantly enhance the diagnostic efficiency compared with PET/CT alone (sen 97.4 vs. 90.5%, P = 0.0003; spe 100.0 vs. 95.2%, P = 0.0047).Conclusions: PET/CT has sensitivity similar to CECT, CEMR and significantly higher specificity and accuracy, helping reduce false diagnoses of morphological images. Combining PET/CT with CA19-9 could enhance diagnostic efficiency.
Association of Cytomegalovirus Infection With Anti-MDA5 Antibody-Positive Dermatomyositis: A Prospective Cohort Study
Authors: Huang Linlin , Zhu Wenbo , Ye Yan , Wu Xiaoping , Yan Qingran , Wang Zhiqing , Lin Yanwei , Chen Sheng 
Published: October 2021

Objectives: To investigate whether cytomegalovirus (CMV) infection plays a role in the pathogenesis and prognosis of idiopathic inflammatory myopathy (IIM), particularly in anti-MDA5 antibody-positive (anti-MDA5+) dermatomyositis (DM).Methods: A prospective cohort of 204 newly diagnosed IIM patients and 50 healthy individuals were enrolled in the study. CMV-IgM and CMV-IgG antibody concentrations and lymphocyte counts were analyzed. Differences in categorical data were compared using Fisher's exact test and the chi-square test. One-year survival rates were analyzed in MDA5+ DM patients with and without CMV infection.Results: In IIM patients, the median CMV-IgM level was significantly higher than in healthy controls (6 U/mL vs. 0 U/mL, p &lt; 0.05) as was the median CMV-IgG level (114 U/mL vs. 105 U/mL, p &lt; 0.05). The percentage of recent CMV infections in the MDA5+ DM group was much higher than it was in the MDA5− IIM group (19.1% vs. 7.0%, p = 0.009). MDA5+ DM patients with CMV DNA-emia had poorer 1 year survival than the CMV-DNA− group (33.3% vs. 86.3%, p = 0.010). CMV-IgM-positive (CMV-IgM+) MDA5+ DM patients had lower CD4+ T cell counts (245.7 cells/μL vs. 420.5 cells/μL, p &lt; 0.05) and CD19+ B cell counts (97.3 cells/μL vs. 240.6 cells/μL, p &lt; 0.05).Conclusion: The number of CMV infections was significantly higher in IIM patients, particularly in MDA5+ DM patients. Lower CD4+ T cells and CD19+ B cells were observed in CMV-IgM+ MDA5+ DM patients. CMV infection may have an important role in the pathogenesis and prognosis of MDA5+ DM by disrupting immunity.
Prognostic Significance of Ultrasound Findings of Acute Acalculous Cholecystitis for Elderly Long-Term Bedridden Patients
Authors: Lin Qian , Shen Lei , Chen Cheng , Yang Zhen , Que Yifan , Liu Yani , Yin Ming , Xu Guogang , Li Junlai 
Published: October 2021

Background: Acute acalculous cholecystitis (AAC) is characterized by the development of cholecystitis in the gallbladder without gallstones or with small gallstones unrelated to inflammatory diseases. This disease is not rare in the elderly bedridden patients with co-morbidities and prone to develop life-threatening gangrene or perforation of gallbladder. Early imaging is essential for detecting and effectively treating AAC. This study aimed to evaluate the use of ultrasound diagnostic criteria for the diagnosis and prognosis of elderly long-term bedridden patients with suspected AAC.Methods: We retrospectively studied 374 elderly bedridden patients with clinical manifestations of AC at the acute stage of the disease. Gallbladder anomalies were found in 92 patients by ultrasound examination, which correlated with the duration time of clinical manifestations, complications, as well as therapeutic prognosis. The major and minor ultrasound criteria of AAC were made according to the Tokyo Guidelines 2018. Ultrasound results were thought to be AAC positive when they met two major criteria or one major and two minor criteria.Results: Forty-three (46.7%) of the 92 patients presented with AAC (+) test results based on the ultrasound criteria, with a higher incidence of complications (27.9%) than AAC (–) patients (0%; P &lt; 0.001). The median length of symptoms (8 vs. 4 days, P &lt; 0.001) and duration of antibiotic therapy (13 vs. 5 days, P &lt; 0.001) were longer in the AAC (+) group.Conclusions: The ultrasound-based AAC (+) group often had a worse prognosis than the AAC (–) group. Therefore, patients from the AAC (+) group should receive a follow-up ultrasound examination to detect disease progression early.
Combining CRISPR-Cas12a-Based Technology and Metagenomics Next Generation Sequencing: A New Paradigm for Rapid and Full-Scale Detection of Microbes in Infectious Diabetic Foot Samples
Authors: Chen Yixin , Shi Ya , Zhu Weifen , You Jiaxing , Yang Jie , Xie Yaping , Zhao Hanxin , Li Hongye , Fan Shunwu , Li Lin , Liu Chao 
Published: October 2021

Introduction: Diabetic foot infections (DFIs) pose a huge challenge for clinicians. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), is one of the most significant pathogens of DFI. Early pathogen identification will greatly benefit the diagnosis and treatment of the disease. However, existing diagnostic methods are not effective in early detection.Methods: We developed an assay that coupled loop-mediated isothermal amplification (LAMP) and clustered regularly interspaced short palindromic repeats (CRISPR) techniques to enable quick and specific detection of Staphylococcus aureus and differentiate MRSA in samples from patients with DFI. Furthermore, the results were compared using a reference culture, quantitative real-time polymerase chain reaction (qRT-PCR), and metagenomics next generation sequencing (mNGS).Results: The CRISPR-LAMP assay targeting nuc and mecA successfully detected S. aureus strains and differentiated MRSA. The limit of detection (LoD) of the real-time LAMP for nuc and mecA was 20 copies per microliter reaction in comparison to two copies per μL reaction for the qRT-PCR assay. The specificity of the LAMP-CRISPR assay for nuc was 100%, without cross-reactions with non-S. aureus strains. Evaluating assay performance with 18 samples from DFI patients showed that the assay had 94.4% agreement (17/18 samples) with clinical culture results. The results of mNGS for 8/18 samples were consistent with those of the reference culture and LAMP-CRISPR assay.Conclusion: The findings suggest that the LAMP-CRISPR assay could be promising for the point-of-care detection of S. aureus and the differentiation of MRSA in clinical samples. Furthermore, combining the LAMP-CRISPR assay and mNGS provides an advanced platform for molecular pathogen diagnosis of DFI.
Weighted Gene Co-expression Network Analysis Identifies a Cancer-Associated Fibroblast Signature for Predicting Prognosis and Therapeutic Responses in Gastric Cancer
Authors: Zheng Hang , Liu Heshu , Li Huayu , Dou Weidong , Wang Xin 
Published: October 2021

Background: Cancer-associated fibroblasts (CAFs) are the most prominent cellular components in gastric cancer (GC) stroma that contribute to GC progression, treatment resistance, and immunosuppression. This study aimed at exploring stromal CAF-related factors and developing a CAF-related classifier for predicting prognosis and therapeutic effects in GC.Methods: We downloaded mRNA expression and clinical information of 431 GC samples from Gene Expression Omnibus (GEO) and 330 GC samples from The Cancer Genome Atlas (TCGA) databases. CAF infiltrations were quantified by the estimate the proportion of immune and cancer cells (EPIC) method, and stromal scores were calculated via the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Stromal CAF-related genes were identified by weighted gene co-expression network analysis (WGCNA). A CAF risk signature was then developed using the univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. We applied the Spearman test to determine the correlation among CAF risk score, CAF markers, and CAF infiltrations (estimated via EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms). The TIDE algorithm was further used to assess immunotherapy response. Gene set enrichment analysis (GSEA) was applied to clarify the molecular mechanisms.Results: The 4-gene (COL8A1, SPOCK1, AEBP1, and TIMP2) prognostic CAF model was constructed. GC patients were classified into high– and low–CAF-risk groups in accordance with their median CAF risk score, and patients in the high–CAF-risk group had significant worse prognosis. Spearman correlation analyses revealed the CAF risk score was strongly and positively correlated with stromal and CAF infiltrations, and the four model genes also exhibited positive correlations with CAF markers. Furthermore, TIDE analysis revealed high–CAF-risk patients were less likely to respond to immunotherapy. GSEA revealed that epithelial–mesenchymal transition (EMT), TGF-β signaling, hypoxia, and angiogenesis gene sets were significantly enriched in high–CAF-risk group patients.Conclusion: The present four-gene prognostic CAF signature was not only reliable for predicting prognosis but also competent to estimate clinical immunotherapy response for GC patients, which might provide significant clinical implications for guiding tailored anti-CAF therapy in combination with immunotherapy for GC patients.
Vitamin C and Metabolic Syndrome: A Meta-Analysis of Observational Studies
Authors: Guo Hongbin , Ding Jun , Liu Qi , Li Yusheng , Liang Jieyu , Zhang Yi 
Published: October 2021

Background: The association between vitamin C and metabolic syndrome (MetS) has been evaluated in several epidemiological studies with conflicting results. This meta-analysis was therefore employed to further investigate the above issue.Methods: The observational studies on the associations of dietary and circulating (serum and plasma) vitamin C levels with MetS were searched in the PubMed, Web of Science, and Embase database up to April 2021. The pooled relative risk (RR) of MetS for the highest vs. lowest dietary and circulating vitamin C levels and the standard mean difference (SMD) of dietary and circulating vitamin C levels for MetS vs. control subjects were calculated, respectively.Results: A total of 28 observational studies were identified in this meta-analysis. Specifically, 23 studies were related to the dietary vitamin C level. The overall multivariable-adjusted RR demonstrated that the dietary vitamin C level was inversely associated with MetS (RR = 0.93, 95% CI: 0.88–0.97; P = 0.003). Moreover, the overall combined SMD showed that the dietary vitamin C level in MetS was lower than that in control subjects (SMD = −0.04, 95% CI: −0.08 to −0.01; P = 0.024). With regard to the circulating vitamin C level, 11 studies were included. The overall multivariable-adjusted RR demonstrated that the circulating vitamin C level was inversely associated with MetS (RR = 0.60, 95% CI: 0.49–0.74; P &lt; 0.001). In addition, the overall combined SMD showed that the circulating vitamin C level in MetS was lower than that in control subjects (SMD=-0.82, 95%CI: −1.24 to −0.40; P &lt; 0.001).Conclusions: Current evidence suggests that both dietary and circulating vitamin C level is inversely associated with MetS. However, due to the limitation of the available evidence, more well-designed prospective studies are still needed.
A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs
Authors: Xu Guoqiang , Yang Mei , Wang Qiaoli , Zhao Liufang , Zhu Sijin , Zhu Lixiu , Xu Tianrui , Cao Ruixue , Li Cheng , Liu Qiuyan , Xiong Wei , Su Yan , Dong Jian 
Published: October 2021

IntroductionColorectal cancer (CRC) is the most common gastrointestinal cancer and has a low overall survival rate. Tumor–node–metastasis staging alone is insufficient to predict patient prognosis. Autophagy and long noncoding RNAs play important roles in regulating the biological behavior of CRC. Therefore, establishing an autophagy-related lncRNA (ARlncRNA)-based bioinformatics model is important for predicting survival and facilitating clinical treatment.MethodsCRC data were retrieved from The Cancer Genome Atlas. The database was randomly divided into train set and validation set; then, univariate and multivariate Cox regression analyses were performed to screen prognosis-related ARlncRNAs for prediction model construction. Interactive network and Sankey diagrams of ARlncRNAs and messenger RNAs were plotted. We analyzed the survival rate of high- and low-risk patients and plotted survival curves and determined whether the risk score was an independent predictor of CRC. Receiver operating characteristic curves were used to evaluate model sensitivity and specificity. Then, the expression level of lncRNA was detected by quantitative real-time polymerase chain reaction, and the location of lncRNA was observed by fluorescence in situ hybridization. Additionally, the protein expression was detected by Western blot.ResultsA prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p &lt; 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC. LINC00174 and NKILA were expressed in the nucleus and cytoplasm of normal colonic epithelial cell line NCM460 and colorectal cancer cell lines HT29. Additionally, LINC00174 and NKILA were overexpressed in HT29 compared with NCM460. After autophagy activation, LINCC00174 expression was significantly downregulated both in NCM460 and HT29, while NKILA expression was significantly increased.ConclusionThe new ARlncRNA-based model predicts CRC patient prognosis and provides new research ideas regarding potential mechanisms regulating the biological behavior of CRC. ARlncRNAs may play important roles in personalized cancer treatment.
Blood Supply of Cranial Nerves Passing Through the Cavernous Sinus: An Anatomical Study and Its Implications for Microsurgical and Endoscopic Cavernous Sinus Surgery
Authors: Najera Edinson , Ibrahim Bilal , Muhsen Baha’eddin A. , Ali Assad , Sanchez Clariza , Obrzut Michal , Borghei-Razavi Hamid , Adada Badih 
Published: October 2021

BackgroundDespite improvements in surgical techniques, cranial nerve (CN) deficits remain the most frequent cause of disability following cavernous sinus (CS) surgery. The most common tumor affecting the CS is meningioma. They originate from lateral wall and have their blood supply from meningohypophyseal trunk (MHT) and inferolateral trunk (ILT). Pituitary adenomas commonly invade the CS through its medial wall and receive blood supply form medial branches of the internal carotid artery (ICA) (superior and inferior hypophyseal arteries). Some tumors may grow within the CS (e.g. trigeminal schwannomas, hemangiomas). These tumors are fed by all the intracavernous ICA branches. Tumors involving the CS may also displace the neurovascular structures, therefore, a better understanding of intracavernous neurovascular anatomy may reduce the postoperative morbidity associated with approaching CS tumors. In this anatomical study, the anatomic variations and their clinical implications of the intracavernous CNs’ blood supply were evaluated through transcranial and endonasal routes.MethodsTwenty sides of ten adult cadaveric formalin-fixed, latex-injected specimens were dissected in stepwise fashion under microscopic and endoscopic magnification. The origin and course of the intracavernous ICA branches supplying the intracavernous CNs are studied.ResultsThe proximal segment of the oculomotor nerve receives blood supply from the ILT in 85%, and the tentorial artery of the MHT in 15% of specimens. The distal segment is exclusively supplied by the ILT. The proximal trochlear nerve receives blood supply from the ILT (75%) and the tentorial artery (25%); the distal segment is exclusively supplied by the superior orbital branch. The proximal third of the abducens nerve receives its vascularity exclusively from the dorsal meningeal artery, and its middle and distal thirds from the ILT. The ophthalmic and proximal maxillary segments of the trigeminal nerve also receive blood supply from the ILT. The distal maxillary segment is supplied by the artery of the foramen rotundum. All ILT branches terminate on the inferomedial aspects of the intra-cavernous CNs. Extensive anastomoses are found between ILT branches and the branches arising from external carotid artery.ConclusionUnderstanding the anatomy of the intracavernous ICA’s branches is important to improving surgical outcomes with tumors involving the CS.
Association Between Serum Carcinoembryonic Antigen Levels at Different Perioperative Time Points and Colorectal Cancer Outcomes
Authors: Li Zhenhui , Zhang Dafu , Pang Xiaolin , Yan Shan , Lei Ming , Cheng Xianshuo , Song Qian , Cai Le , Wang Zhuozhong , You Dingyun 
Published: October 2021

BackgroundWhether elevated postoperative serum carcinoembryonic antigen (CEA) levels are prognostic in patients with stage II colorectal cancer (CRC) remains controversial.Patients and MethodsPrimary and sensitivity analysis populations were obtained from a retrospective, multicenter longitudinal cohort including consecutive patients without neoadjuvant treatment undergoing curative resection for stage I–III CRC. Serum CEA levels before (CEApre-m1) and within 1 (CEApost-m1), 2–3 (CEApost-m2–3), and 4–6 months (CEApost-m4–6) after surgery were obtained, and their associations with recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox regression. Sensitivity and subgroup analyses were performed.ResultsPrimary and sensitivity analysis populations included 710 [415 men; age, 54.8 (11.6) years] and 1556 patients [941 men; age, 56.2 (11.8) years], respectively. Recurrence hazard ratios (HRs) in the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups were 1.30 (95% CI: 0.91–1.85), 1.53 (95% CI: 0.89–2.62), 1.88 (95% CI: 1.08–3.28), and 1.15 (95% CI: 0.91–1.85), respectively. The HRs of the elevated CEApre-m1, CEApost-m1, CEApost-m2–3, and CEApost-m4–6 groups for OS were 1.09 (95% CI: 0.60–1.97), 2.78 (95% CI: 1.34–5.79), 2.81 (95% CI: 1.25–6.30), and 3.30 (95% CI: 1.67–.536), respectively. Adjusted multivariate analyses showed that both in the primary and sensitivity analysis populations, elevated CEApost-m2–3, rather than CEApre-m1, CEApost-m1, and CEApost-m4–6, was an independent risk factor for recurrence, but not for OS. The RFS in the elevated and normal CEApost-m2–3 groups differed significantly among patients with stage II disease [n = 266; HR, 2.89; 95% CI, 1.02–8.24 (primary analysis); n = 612; HR, 2.69; 95% CI, 1.34–5.38 (sensitivity analysis)].ConclusionsElevated postoperative CEA levels are prognostic in patients with stage II CRC, with 2–3 months after surgery being the optimal timing for CEA measurement.