bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of the Function, Immune Profiles, and Clinical Implication of m1A Regulators in Lung Adenocarcinoma
Authors: Bao Guangyao , Li Tian , Guan Xiaojiao , Yao Yao , Liang Jie , Xiang Yifang , Zhong Xinwen 
Published: June 2022

BackgroundPrevious studies have demonstrated that transcriptional RNA methyladenosine modification significantly affects tumor initiation and progression. However, clinical implications of N1-methyladenosine (m1A) regulators and their effect on tumor immunity in lung adenocarcinoma (LUAD) are still poorly elucidated.MethodsHerein, the characteristics of somatic mutation, copy number variation (CNV), DNA methylation, and expression levels of m1A regulators were thoroughly analyzed. We classified 955 lung adenocarcinoma patients into different m1A modification patterns based on an unsupervised consensus clustering algorithm. We then calculated the differences in gene expression, prognosis outcomes, and immune profiles among different m1A clusters. Subsequently, we screened differently expressed genes (DEGs) related to prognosis among different m1A clusters. We identified m1A related gene clusters according to the prognosis-related different expressed genes. We further constructed a scoring standard named the m1A score and comprehensively analyzed the survival outcomes, clinical-pathological features, immune microenvironment, treatment responses of immunotherapy, and drug susceptibility in different m1A score groups.ResultsIn total, three different m1A modification patterns were identified, which contained cluster A, B, and C. Among them, cluster A processed the poorest clinical outcomes, the lowest immune cell infiltration rate, and the highest tumor purity score. Then, three m1A gene clusters (gene cluster A, B, C) were speculated. Subsequently, we combined m1A modification patterns and m1A gene cluster to classify lung adenocarcinoma patients into high and low m1A score groups. The low m1A score group was accompanied by higher mortality, higher tumor mutation burden (TMB) and genome mutation frequency, and lower programmed cell death-Ligand 1 (PD-L1) expression and tumor immune dysfunction and exclusion (TIDE) expression. Moreover, the m1A score exhibited positive correlation with almost all immune cells. Finally, common chemotherapeutic and targeted therapy agents exhibited obvious differences in drug susceptibility in different m1A score groups.ConclusionsCollectively, we explored the potential value of m1A regulators in the prognosis and treatment of lung adenocarcinoma in multiple dimensions and provided some preliminary basis for the follow-up study of m1A regulators in lung adenocarcinoma.
Combining Clinicopathology, IVIM-DWI and Texture Parameters for a Nomogram to Predict Treatment Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer Patients
Authors: Su Rixin , Wu Shusheng , Shen Hao , Chen Yaolin , Zhu Jingya , Zhang Yu , Jia Haodong , Li Mengge , Chen Wenju , He Yifu , Gao Fei 
Published: June 2022

ObjectivesThis study aimed to create a nomogram for the risk prediction of neoadjuvant chemoradiotherapy (nCRT) resistance in locally advanced rectal cancer (LARC).MethodsClinical data in this retrospective study were collected from a total of 135 LARC patients admitted to our hospital from June 2016 to December 2020. After screening by inclusion and exclusion criteria, 62 patients were included in the study. Texture analysis (TA) was performed on T2WI and DWI images. Patients were divided into response group (CR+PR) and no-response group (SD+PD) according to efficacy assessment. Multivariate analysis was performed on clinicopathology, IVIM-DWI and texture parameters for screening of independent predictors. A nomogram was created and model fit and clinical net benefit were assessed.ResultsMultivariate analysis of clinicopathology parameters showed that the differentiation and T stage were independent predictors (OR values were 14.516 and 11.589, resp.; P&lt;0.05). Multivariate analysis of IVIM-DWI and texture parameters showed that f value and Rads-score were independent predictors (OR values were 0.855, 2.790, resp.; P&lt;0.05). In this study, clinicopathology together with IVIM-DWI and texture parameters showed the best predictive efficacy (AUC=0.979). The nomogram showed good predictive performance and stability in identifying high-risk LARC patients who are resistant to nCRT (C-index=0.979). Decision curve analyses showed that the nomogram had the best clinical net benefit. Ten-fold cross-validation results showed that the average AUC value was 0.967, and the average C-index was 0.966.ConclusionsThe nomogram combining the differentiation, T stage, f value and Rads-score can effectively estimate the risk of nCRT resistance in patients with LARC.
Colorectal Cancer Screening With High Risk-Factor Questionnaire and Fecal Immunochemical Tests Among 5, 947, 986 Asymptomatic Population: A Population-Based Study
Authors: Zhang Mingqing , Zhao Lizhong , Zhang Yongdan , Jing Haoren , Wei Lianbo , Li Zhixuan , Zhang Haixiang , Zhang Yong , Zhu Siwei , Zhang Shiwu , Zhang Xipeng 
Published: June 2022

BackgroundThe recent uptrend in colorectal cancer (CRC) incidence in China is causing an increasingly overwhelming social burden. And its occurrence can be effectively reduced by sensitizing CRC screening for early diagnosis and treatment. However, a large number of people in China do not undergo screening due to multiple factors. To address this issue, since 2012, a CRC screening program has been initiated in Tianjin.MethodsResidents aged 40-74 years were eligible for CRC screening. The first was to complete the high-risk factor questionnaire (HRFQ) and undergo fecal immunochemical test (FIT). Then those with a positive result in any of the two screening methods were recommended for a free colonoscopy.ResultsThe detection rate of intestinal diseases increased with age, had a male predominance, and was higher in residents from central urban areas and those with primary school above education level. The sensitivity of predicting CRC after colonoscopy in the high-risk group was 76.02%; the specificity was 25.33%.A significant decrease in the detection rate of intestinal disease, CRC and advanced adenoma was observed from positive FIT, the high-risk group and positive HRFQ, 47.13%, 44.79%, 42.30%; 3.15%, 2.44%, 1.76%; 7.72%, 6.42%, 5.08%, in that order, while no inter-group difference was found for the detection of polyps. In addition, the different combinations of HRFQ and FIT can enroll more high-risk population than FIT or (and) HRFQ only, and thus detect more intestinal diseases (include CRC/AA/Polyp).ConclusionThe superimposition of different screening method for HRFQ and FIT is an effective strategy for the detection of CRC, AA, and Polyp, compared to HRFQ or FIT alone. However, further improvements in screening and interventions are needed to promote colonoscopy compliance.
Application of a Novel 68Ga-HER2 Affibody PET/CT Imaging in Breast Cancer Patients
Authors: Miao Haitao , Sun Yuyun , Jin Yizi , Hu Xichun , Song Shaoli , Zhang Jian 
Published: June 2022

BackgroundBreast cancer is a heterogeneous disease, and the human epidermal growth factor receptor 2 (HER2) expression may vary considerably between primary and metastatic lesions, or even within a single lesion. Repeated biopsies cannot always be performed. In this feasibility trial, we assessed whether a novel 68Ga-NOTA-MAL-MZHER2 (68Ga-HER2) affibody PET/CT could determine the HER2 status of each lesion if there was a clinical need for it.Methods68Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status remained unclear after standard examinations (including bone scan, 18F-FDG PET/CT, CT, and feasible biopsy). All available images for each patient were evaluated through an independent review of two committee-certified radiologists with nuclear medicine expertise. In case of discrepancy, adjudication by a third radiologist was performed as needed. All radiologists were blinded to the clinical information.ResultsTwenty-four patients were enrolled. 68Ga-HER2 affibody PET/CT was requested by physicians due to the following reasons: 6 with multiple primary cancers, 13 with metastases not amenable to biopsy or repeated biopsy, 6 with inconsistent HER2 status between primary and metastatic lesions, and 4 with different HER2 status within different metastases. The final PET report revealed that the 68Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. The heterogeneity of 68Ga-HER2 affibody uptake was observed, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference between patients. 68Ga-HER2 affibody PET/CT demonstrated a high diagnostic accuracy in differentiating HER2-enriched breast cancer, with a sensitivity of 91.7% and a specificity of 84.6%, regardless of prior lines of anti-HER2 therapies.Conclusion68Ga-HER2 affibody PET/CT imaging could provide valuable information on HER2 expression of each tumor in the body of patients, which may help in personalized clinical decision-making. Its value is now under systemic assessment.
Current Trends and Research Hotspots in Pancreatic Stellate Cells: A Bibliometric Study
Authors: Yang Zhaoming , Xie Zhiqin , Wan Jian , Yi Bo , Xu Tao , Shu Xiaorong , Zhao Zhijian , Tang Caixi 
Published: June 2022

BackgroundPancreatic stellate cells (PSCs) play crucial roles in acute/chronic pancreatitis and pancreatic cancer. In this study, bibliometric analysis was used to quantitatively and qualitatively analyze the literature related to PSCs from 1998-2021 to summarize the current trends and research topics in this field.MethodsRelevant literature data were downloaded from the Science Citation Index Expanded Web of Science Core Collection (WoSCC) on April 07, 2021, using Clarivate Analytics. Biblioshiny R packages, VOSviewer, Citespace, BICOMB, gCLUTO, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com) were used to analyze the manually selected data.ResultsA total of 958 relevant studies published in 48 countries or regions were identified. The United States of America (USA) had the highest number of publications, followed by the People’s Republic of China, Germany, and Japan. Tohoku University (Japan), the University of New South Wales (Australia), the University of Texas MD Anderson Cancer Center (USA), Technical University of Munich (Germany), and University of Rostock (Germany) were the top five institutions with most publications. Nine major clusters were generated using reference co-citation analysis. Keyword burst detection revealed that progression (2016-2021), microenvironment (2016-2021), and tumor microenvironment (2017-2021) were the current frontier keywords. Biclustering analysis identified five research hotspots in the field of PSCs during 1998-2021.ConclusionIn this study, a scientometric analysis of 958 original documents related to PSCs showed that the research topics of these studies are likely in the transition from acute/chronic pancreatitis to pancreatic cancer. The current research trends regarding PSCs are related to pancreatic cancer, such as tumor microenvironment. This study summarizes five research hotspots in the field of PSCs between 1998 and 2021 and thus may provide insights for future research.
Clinical Features, Management, and Prognostic Factors of Intracranial Solitary Fibrous Tumor
Authors: Liu Jingdian , Wu Sisi , Zhao Kai , Wang Junwen , Shu Kai , Lei Ting 
Published: June 2022

BackgroundBecause of the low incidence and the constantly changing diagnostic and classification criteria, the clinical features, management, and prognostic factors of intracranial solitary fibrous tumor (ISFT) remain unclear and were thus analyzed in this study.MethodA total of 38 patients with ISFTs who were diagnosed in our institution were enrolled in this study. Patient data including age, gender, clinical presentation, histopathological features, immunohistochemistry staining, tumor location, tumor size, treatment methods, and prognosis were extracted and retrospectively analyzed.ResultsThe median age at diagnosis was 45.5 years (range 28–66 years) and the male-to-female ratio was 1:1.53 in our series. The 3-, 5-, and 10-year progression-free survival (PFS) rate was 82.2%, 62.8%, and 21.4%, respectively; and the 3-, 5-, and 10-year overall survival rate was 97.1%, 86.9%, and 64.2%, respectively. Patients with high WHO grade (grade 3) ISFTs experienced impaired PFS (p &lt; 0.05) and OS (p &lt; 0.01). Subtotal resection (STR) was associated with worse PFS and OS (p &lt; 0.001, respectively). Postoperative radiotherapy (PORT) improved PFS, especially local control rate, in patients with WHO grade 3 ISFTs (P = 0.025) or STR (p = 0.027). Moreover, CD34-negative immunostaining and a high Ki-67 index (&gt;10%) were associated with impaired PFS in ISFTs.ConclusionOur study provides evidence that high tumor grade, subtotal tumor resection, CD34 negative immunostaining, and high Ki-67 index (&gt;10%) were independent predictors for the poor prognosis of ISFTs. PORT can improve local control rate, and should be recommended for patients with high-grade ISFTs or STR.
Identification and Validation of lncRNA-SNHG17 in Lung Adenocarcinoma: A Novel Prognostic and Diagnostic Indicator
Authors: Li Xinyan , Yuan Yixiao , Pal Mintu , Jiang Xiulin 
Published: June 2022

BackgroundLung cancer has the highest death rate among cancers globally. Accumulating evidence has indicated that cancer-related inflammation plays an important role in the initiation and progression of lung cancer. However, the prognosis, immunological role, and associated regulation axis of inflammatory response-related gene (IRRGs) in non-small-cell lung cancer (NSCLC) remains unclear.MethodsIn this study, we perform comprehensive bioinformatics analysis and constructed a prognostic inflammatory response-related gene (IRRGs) and related competing endogenous RNA (ceRNA) network. We also utilized the Pearson’s correlation analysis to determine the correlation between IRRGs expression and tumor mutational burden (TMB), microsatellite instability (MSI), tumor-immune infiltration, and the drug sensitivity in NSCLC. Growth curve and Transwell assay used to verify the function of SNHG17 on NSCLC progression.ResultsFirst, we found that IRRGs were significantly upregulated in lung cancer, and its high expression was correlated with poor prognosis; high expression of IRRGs was significantly correlated with the tumor stage and poor prognosis in lung cancer patients. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment indicated that these IRRGs are mainly involved in the inflammatory and immune response-related signaling pathway in the progression of NSCLC. We utilized 10 prognostic-related genes to construct a prognostic IRRGs model that could predict the overall survival of lung adenocarcinoma (LUAD) patients possessing high specificity and accuracy. Our evidence demonstrated that IRRGs expression was significantly correlated with the TMB, MSI, immune-cell infiltration, and diverse cancer-related drug sensitivity. Finally, we identified the upstream regulatory axis of IRRGs in NSCLC, namely, lncRNA MIR503HG/SNHG17/miR-330-3p/regulatory axis. Finally, knockdown of SNHG17 expression inhibited lung adenocarcinoma (LUAD) cell proliferation and migration. Our findings confirmed that SNHG17 is a novel oncogenic lncRNA and may be a biomarker for the prognosis and diagnosis of LUAD.ConclusionDNA hypomethylation/lncRNA MIR503HG/SNHG17/microRNA-330-3p/regulatory axis may be a valuable biomarker for prognosis and is significantly correlated with immune cell infiltration in lung cancer.
Serum Vitamin D Insufficiency in Hospitalized Full-Term Neonates at a Tertiary Hospital in Eastern China
Authors: Wang Huawei , Du Yiming , Wu Zhixin , Geng Haifeng , Zhu Xueping , Zhu Xiaoli 
Published: June 2022

ObjectiveThis study explored the status of serum vitamin D in hospitalized full-term neonates at a tertiary hospital in eastern China.MethodsA prospective study was conducted among 471 hospitalized full-term neonates at the Children's Hospital of Soochow University between January 1 and June 20, 2020. Perinatal clinical data, serum 25-hydroxyvitamin D (25(OH)D3), laboratory examinations, serum calcium levels, and immune function were obtained and analyzed. We explored and analyzed the risk factors for vitamin D insufficiency or deficiency, and we also attempted to determine correlations between vitamin D and its influence on immunity.ResultsThe mean serum 25(OH)D3 was 33.65±6.07ng/ml.The prevalence of vitamin D insufficiency was 28.24%,vitamin D sufficiency was 71.76%, there was no vitamin D deficiency. The serum 25-(OH)D3 in singleton neonate was higher than twins or multiple infants (t = −10.918, P = 0.000). The serum 25-(OH)D3 were higher in neonates who born in spring and summer than in winter (H = 13.443, P = 0.001). The serum 25-(OH)D3 in appropriate for gestational age (AGA) and large for gestational age (LGA) neonates were higher than small for gestational age (SGA) (H = 7.686, P = 0.021). The serum 25-(OH)D3 were higher in neonates whose mothers had no underlying diseases than those with certain immunological and infectious diseases (F = 12.417, P = 0.000). The serum 25-(OH)D3 in neonates whose mothers had none or one perinatal complication were higher than those with two or more (F = 13.299, P = 0.000). The neonates with eosinophils ≤5% or normal platelet counts or serum Ca++ ≥0.9 mmol/L have higher serum 25-(OH)D3. Neonates born in winter were at risk for vitamin D insufficiency, and the incidence of infectious pneumonia, sepsis, cytomegalovirus infection, and hypocalcemia in the vitamin D insufficiency group were higher than sufficiency group (P &lt; 0.05). The serum CD3+, CD3+CD4+, and IgA levels in vitamin D sufficiency neonates were significantly higher than those in insufficiency group (P &lt; 0.05).ConclusionThe prevalence of vitamin D insufficiency was 28.24%, and birth in winter was a risk factor for vitamin D insufficiency in hospitalized full-term neonates in Suzhou area. Neonates with infectious pneumonia, sepsis, cytomegalovirus infection, and hypocalcemia exhibited a high risk of vitamin D insufficiency. The serum CD3+, CD3+CD4+, and IgA levels in neonates with vitamin D insufficiency were lower.
Evidence on Indications and Techniques to Increase the Future Liver Remnant in Children Undergoing Extended Hepatectomy: A Systematic Review and Meta-Analysis of Individual Patient Data
Authors: Fuchs Juri , Murtha-Lemekhova Anastasia , Rabaux-Eygasier Lucas , Kessler Markus , Ruping Fabian , Günther Patrick , Hoffmann Katrin 
Published: June 2022

BackgroundTechniques to increase the future liver remnant (FLR) have fundamentally changed the indications and criteria of resectability in adult liver surgery. In pediatric patients however, these procedures have rarely been applied and the potential benefit or harm as well as suited indications are unclear.MethodsA systematic literature search of MEDLINE, Web of Science, and CENTRAL was conducted. Based on a PRISMA-compliant, predefined methodology, all studies reporting pediatric patients (&lt; 18y) undergoing liver resection with either associating liver partition and portal vein ligation for stages hepatectomy (ALPPS) or preoperative portal vein embolization or ligation (PVE/PVL) were included. Baseline data, periinterventional morbidity, increase of FLR and outcomes were analyzed.Results15 studies reporting on 21 pediatric patients with a mean age of 4 years and 7 months (range 1.8 months – 17 years) were included. 12 ALPPS procedures, 8 PVE and 1 PVL were performed. The applied criteria for performing ALPPS or PVE were heterogenous and thresholds for minimally acceptable FLR varied. Mean FLR [% of total liver volume] before the intervention was 23.6% (range 15.0 – 39.3%) in the ALPPS group and 31.4% (range 21.5 – 56.0%) in the PVE group. Mean increase of FLR before stage 2 resection was 69.4% (range 19.0 – 103.8%) for ALPPS and 62.8% (range 25.0 – 108.0%) after PVE. No postoperative death occurred, one early intrahepatic recurrence after an ALPPS procedure was reported. Overall postoperative morbidity was 23.8%.ConclusionValidated criteria for minimal FLR in pediatric liver resection are lacking and so are clear indications for ALPPS or PVE. In special cases, ALPPS and PVE can be valuable techniques to achieve complete resection of pediatric liver tumors. However, more data are needed, and future studies should focus on a definition and validation of posthepatectomy liver failure as well as the minimally needed FLR in pediatric patients undergoing extended hepatectomy.Systematic Review Registration[www.clinicaltrials.gov], identifier [PROSPERO 2021 CRD42021274848].
In vitro Inhibition of HIV-1 by Cyclotide-Enriched Extracts of Viola tricolor
Authors: Conzelmann Carina , Muratspahić Edin , Tomašević Nataša , Münch Jan , Gruber Christian W. 
Published: June 2022

Since viral infectious diseases continue to be a global health threat, new antiviral drugs are urgently needed. A unique class of therapeutic compounds are antimicrobial peptides (AMPs). They can be found in humans, bacteria and plants. Plants express a wide variety of such defense peptides as part of their innate immune system to protect from invading pathogens. Cyclotides are non-classical AMPs that share a similar structure. Their unique topology consists of a circular peptide backbone and disulfide bonds. In previous studies they have been attributed to a wide range of biological activities. To identify novel cyclotides with antiviral activity, we established a library of plant extracts largely consisting of cyclotide-rich species and screened them as inhibitors of HIV-1 infection. Subsequent extraction and fractionation revealed four cyclotide-containing subfractions from Viola tricolor with antiviral activity. These subfractions inhibited HIV-1 infection with IC50 values between 0.6 and 11.2 μg/ml, and selectivity indices of up to 8.1. The identification and characterization of antiviral cyclotides and the determination of the antiviral mechanisms may allow to develop novel agents to combat viral infections. Therefore, cyclotides represent a natural source of bioactive molecules with prospects for development as therapeutics.