bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic Tumor Stiffness Measured by Shear Wave Elastography Is Prognostic for HCC Progression Following Treatment With Anti-PD-1 Antibodies Plus Lenvatinib: A Retrospective Analysis of Two Independent Cohorts
Authors: Yuan Guosheng , Xie Fuli , Song Yangda , Li Qi , Li Rong , Hu Xiaoyun , Zang Mengya , Cheng Xiao , Lu Guanting , Huang Jing , Fan Wenzhe , Rong Xiaoxiang , Sun Jian , Chen Jinzhang 
Published: June 2022

BackgroundThe clinical significance of liver stiffness (LS) measured by shear wave elastography (SWE) in programmed cell death protein-1 (PD-1) inhibitors treated advanced hepatocellular carcinoma (HCC) patients remains unknown. This study aimed to explore the prognostic value of baseline LS by SWE prior to PD-1 inhibitor treatment in combination with lenvatinib.MethodsWe retrospectively evaluated patients (n=133) with HCC who received anti-PD-1 antibodies plus lenvatinib at two high-volume medical centres, between January 2020 and June 2021. Univariate and multivariate logistic regression analysis were used to develop a novel nomogram. RNA sequencing and immunohistochemical staining were used to assess the heterogeneity of biological and immune characteristics associated with tumor stiffness.ResultsThe objective response rate (ORR) and disease control rate (DCR) of the whole population were 23.4% and 72.2%, respectively. A LS value of the baseline tumorous foci of 19.53 kPa had the maximum sum of sensitivity and specificity, making it the optimal cut-off value for predicting PD-1 inhibitor efficacy. The nomogram comprised baseline tumor LS and albumin-bilirubin grade (ALBI), which provided favorable calibration and discrimination in the training dataset with an AUC of 0.840 (95%CI: 0.750-0.931) and a C-index of 0.828. Further, it showed acceptable discrimination in the validation cohort, with an AUC of 0.827 (95%CI: 0.673-0.980) and C-index of 0.803. The differentially expressed genes enriched in high stiffness tumors were predominantly associated with metabolic pathways, while those enriched in low stiffness tumors were related to DNA damage repair. Furthermore, patients with high stiffness tumors had a relatively lower infiltration of immune cells and histone deacetylase pathway inhibitors were identified as candidate drugs to promote the efficacy of immunotherapy.ConclusionsBaseline LS value of tumorous foci by SWE—that is, before administration of a PD-1 inhibitor in combination with lenvatinib—is a convenient predictor of PD-1 inhibitor efficacy in patients with advanced HCC, which has potential to be used for pretreatment stratification to optimize treatment of advanced HCC.
Maternal Lineage and Habitat Use Patterns Explain Variation in the Fecundity of a Critically Endangered Baleen Whale
Authors: Bishop Ana L. , Crowe Leah M. , Hamilton Philip K. , Meyer-Gutbrod Erin L. 
Published: June 2022

The critically endangered North Atlantic right whale population (Eubalaena glacialis) has experienced multiple periods of decreased reproduction within its observable history, which have played a role in the overall decline of the species. In addition to this synchronized variation in reproduction across the population, there exists considerable individual variation in fecundity. To determine the impacts of family history and habitat use behavior on these individual variations in fecundity, photo identification data collected during four decades of visual monitoring were used to create a calving index for sexually mature females that could be used to evaluate matrilineal influence on fecundity. Reproductive life histories were analyzed to assess fecundity variation within matrilines over time. Individual variations in fecundity were also assessed with respect to a recent climate-driven habitat distribution shift by a loyal cohort of right whales that use the Gulf of St. Lawrence during the summer and autumn seasons. Lifetime fecundity in the oldest known living reproductive female, or matriarch, in a matriline was positively associated with the fecundity of her female progeny. Sexually mature females that have used the Gulf of St. Lawrence since 2015 were significantly more likely to give birth over this time period compared to individuals who did not use that habitat. Individuals of both sexes were significantly more likely to use the Gulf of St. Lawrence if their mothers did as well; however, this association declined as offspring aged. These results provide insight on the environmental, behavioral, and genetic factors that contribute to individual variation in fecundity. Low calving rates and increased dangers posed by habitat use shifts in the past decade have played a major role in the species’ decline, and these new insights into the mechanistic drivers of right whale reproduction and habitat use show that lineage guides progeny behavior and reproductive success. As anthropogenic climate change continues to disrupt right whale seasonal distributions through changing ocean circulation patterns, understanding the demographic consequences of novel habitat use patterns will be essential to updating protective policies.
Changes in HIV Testing Utilization Among Chinese Men Who Have Sex With Men During the COVID-19 Pandemic in Shenzhen, China: An Observational Prospective Cohort Study
Authors: Zhang Kechun , Chen Siyu , Chan Paul Shing-fong , Fang Yuan , Cao He , Chen Hongbiao , Hu Tian , Chen Yaqi , Zhou Xiaofeng , Wang Zixin 
Published: June 2022

BackgroundThe Coronavirus Diseases 2019 (COVID-19) directly affects HIV prevention and sexual health services utilization among men who have sex with men (MSM). This study investigated changes in human immunodeficiency virus (HIV) testing utilization among MSM before and after the COVID-19 pandemic received initial control in Shenzhen, China.MethodsThis study was a sub-analysis of a prospective observational cohort study conducted among MSM in Shenzhen, China between August 2020 and May 2021. Participants were recruited through outreaching in gay venues, online recruitment, and peer referral. Participants completed a baseline online survey between August and September 2020 and a follow-up online survey between April and May 2021. This study was based on 412 MSM who reported to be HIV-negative/unknown sero-status at baseline, 297 (72.1%) of them completed the follow-up online survey. Multilevel logistic regression models (level 1: sources of recruitment; level 2: individual participants) were fitted.ResultsWhen comparing follow-up data with baseline data, a significant increase was observed in the uptake of any type of HIV testing (77.9% at Month 6 vs. 59.2% at baseline, p &lt; 0.001). After adjusting for age group, education level, current employment status and monthly personal income, two predisposing factors were associated with higher uptake of HIV testing during the follow-up period. They were: (1) condomless anal intercourse with male non-regular male sex partners at follow-up only (AOR: 5.29, 95%CI: 1.27, 22.01) and (2) sanitizing before and after sex at baseline (AOR: 1.26, 95%CI: 1.02, 1.47). Regarding enabling factors, utilization of HIV testing (AOR: 3.90, 95%CI: 2.27, 6.69) and STI testing (AOR: 2.43, 95%CI: 1.20, 4.93) 6 months prior to the baseline survey was associated with higher uptake of HIV testing during the follow-up period. Having the experience that HIV testing service providers reduced service hours during the follow-up period was also positively associated with the dependent variable (AOR: 3.45, 95%CI: 1.26, 9.41).ConclusionsHIV testing utilization among MSM might rebound to the level before the COVID-19 outbreak after the pandemic received initial control in China. This study offered a comprehensive overview to identify potential reasons that can influence the uptake of HIV testing among Chinese MSM.
A Novel YTHDF3-Based Model to Predict Prognosis and Therapeutic Response in Breast Cancer
Authors: Liu Jie , Zhu Jing , Wang Xin , Zhou Zhisheng , Liu Haiyan , Zhu Dajiang 
Published: June 2022

Background: Due to high tumor heterogeneity, breast cancer (BC) patients still suffer poor survival outcomes. YTHDF3 plays a critical role in the prognosis of BC patients. Hence, we aimed to construct a YTHDF3-based model for the prediction of the overall survival (OS) and the sensitivity of therapeutic agents in BC patients.Methods: Based on The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) database, we obtained BC patients’ data (n = 999) with YTHDF3 expression profiles. The association between YTHDF3 expression and 5-year OS was determined via Cox proportional hazards regression (CPHR) analysis. By integrating the variables, we established a prognostic nomogram. The model was estimated via discrimination, calibration ability, and decision curve analysis (DCA). The performance of the model was compared with the TNM stage system through receiver operating characteristic (ROC) curves and DCA. By means of the Genomics of Drug Sensitivity in Cancer (GDSC) database (https://www.cancerrxgene.org/), the therapeutic agents’ response was estimated. Gene set enrichment analysis (GSEA) demonstrated possible biological mechanisms related to YTHDF3. TIMER and CIBERSORTx were employed to analyze the association between YTHDF3 and tumor-infiltrating immune cells.Results: The high YTHDF3 expression was significantly correlated with poor 5-year OS in BC patients. Through multivariate CPHR, four independent prognostic variables (age, TNM stage, YTHDF3 expression, and molecular subtype) were determined. On the basis of the four factors, a YTHDF3-based nomogram was built. The area under the curve (AUC) of the ROC curve for the model surpassed that of the TNM stage system (0.72 vs. 0.63, p = 0.00028). The model predictions showed close consistency with the actual observations via the calibration plot. Therapeutic response prediction was conducted in high- and low-risk groups and compared with each other. The BC patients with higher risk scores showed more therapeutic resistance than those with a lower risk score.Conclusion: YTHDF3 was verified as a prognostic biomarker of BC, and a novel YTHDF3-based model was constructed to predict the 5-year OS of BC patients. Our model could be applied to effectively predict the therapeutic response of commonly used agents for BC patients.
Novel Brain-Stiffness-Mimicking Matrix Gel Enables Comprehensive Invasion Analysis of 3D Cultured GBM Cells
Authors: Wang Shuowen , Wang Yiqi , Xiong Jin , Bao Wendai , Li Yaqi , Qin Jun , Han Guang , Hu Sheng , Lei Junrong , Yang Zehao , Qian Yu , Dong Shuang , Dong Zhiqiang 
Published: June 2022

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults, which is fast growing and tends to invade surrounding normal brain tissues. Uncovering the molecular and cellular mechanisms of GBM high invasion potential is of great importance for the treatment and prognostic prediction. However, the commonly used two-dimensional (2D) cell culture and analysis system suffers from lack of the heterogeneity and in vivo property of brain tissues. Here, we established a three-dimensional (3D) cell culture-based analysis system that could better recapitulate the heterogeneity of GBM and mimic the in vivo conditions in the brain. The GBM cell lines, DBTRG and U251, were cultured by hanging drop culture into the GBM multicellular spheroids, which were embedded in the optimized 3D brain-stiffness-mimicking matrix gel (0.5 mg/ml Collagen Ⅰ + 3 mg/ml Matrigel+ 3.3 mg/ml Hyaluronic Acid (HA)). The biochemical composition of the optimized matrix gel is similar to that of the brain microenvironment, and the elastic modulus is close to that of the brain tissue. The dynamics of the GBM spheroids was examined using high-content imaging for 60 h, and four metrics including invasion distance, invasion area, single-cell invasion velocity, and directionality were employed to quantify the invasion capacity. The result showed that DBTRG cells possess higher invasion capacity than U251 cells, which was consistent with the results of the classic transwell test. Transcriptome analysis of both cell lines was performed to explore the underlying molecular mechanisms. Our novel brain-stiffness-mimicking matrix gel enables comprehensive invasion analysis of the 3D cultured GBM cells and provides a model basis for in-depth exploration of the mechanisms regulating GBM invasion including the interaction between GBM cells and brain stroma.
A Prospective, Multicenter, Single-Group Target-Value Clinical Trial to Evaluate the Safety and Efficacy of a Large Bore Aspiration Catheter System for the Endovascular Treatment of Acute Ischemic Stroke
Authors: Chen Fei , Bai Xuesong , Hu Wei , Guo Fuqiang , Chen Jian , Zhou Zhiming , Chen Yanfei , Gao Peng , Liu Yongchang , Yang Qingwu , Liu Xinfeng , Xu Yun , Chen Huisheng , Wang Yabing , Yang Bin , Dmytriw Adam A. , Patel Aman B. , Ma Qingfeng , Jiao Liqun 
Published: June 2022

ObjectiveThis study was conducted to determine the safety and efficacy of the Esperance® Distal Access Catheter (0.071”), a novel large bore aspiration catheter in treating acute ischemic stroke (AIS) with large vessel occlusion (LVO).MethodsA prospective multicenter clinical trial involving 15 stroke centers was performed. Baseline characteristics, procedural data, and angiographic and clinical outcomes of all acute stroke procedures (from May 2020 to March 2021) using the novel large bore aspiration catheter were analyzed.ResultsDuring the study period, 160 consecutive patients were recruited. The mean age and median baseline NIHSS were 65.4 years and 16, respectively. Successful reperfusion was achieved in 147 (91.9%) cases [at least modified Thrombolysis in Cerebral Infarction (mTICI) 2b] with aspiration alone, with complete reperfusion (mTICI 3) in 94 (58.8%) cases. Successful/complete first pass reperfusion was achieved in 104 (64.60%) cases, including mTICI 2b in 34 (21.1%) cases and mTICI 3 in 70 (43.5%) cases. The time from groin puncture to successful reperfusion was 44 (33, 62) min. There were 16 (9.9%) cases requiring rescue therapy using stent-retriever. Procedure-related complications included 2 (1.3%) cases of arterial perforation, 2 (1.3%) cases of arterial dissection, 12 (7.5%) cases of distal embolization, and 1(0.6%) case of puncture site infection. The rate of symptomatic intracranial hemorrhage (sICH) was 3.8% and mortality rate was 13.8%. A total of 99 (62.3%) cases had a favorable outcome (mRS 0–2) at 90 days.ConclusionsIn current practice, the first-line aspiration approach with the Esperance® Distal Access Catheter is safe and efficacious. This device may achieve high reperfusion rates with lower instances of rescue stent retriever therapy.
Laser Navigation Combined With XperCT Technology Assisted Puncture of Brainstem Hemorrhage
Authors: Wang Qingbo , Guo Wei , Zhang Tao , Wang Shuangquan , Li Chenglong , Yuan Zhengbo , Wei Qi , Geng Xin , Li Zefu 
Published: June 2022

BackgroundBrainstem hemorrhage has a rapid onset with high mortality and disability rates. In recent years, an increasing number of studies have reported on the surgical treatment of brainstem hemorrhage. The introduction of stereotaxic instruments and navigation systems has improved the accuracy of surgical treatment; however, the popularity of these devices in the primary hospitals is not high. In this study, we introduce laser navigation combined with the XperCT technology to assist in the puncture and drainage of brainstem hemorrhage, aiming to improve surgical accuracy and facilitate the drainage of brainstem hemorrhage in primary hospitals.Material and MethodsA total of five patients (four men and one woman), aged 34–70 years, who underwent hematoma puncture drainage with the assistance of laser navigation combined with XperCT technology at the Binzhou Medical University Hospital, China, between June 2020 and Aug 2021 were included in the study. The brainstem hemorrhages had volumes of 7–18 ml. Statistical analyses of the postoperative puncture deviation distance (distance between the actual puncture end and simulated puncture end) and postoperative improvement were also performed.ResultsThe operations were successfully completed in all five patients. The puncture deviation distance was &lt;6 mm in all five patients and &lt;2 mm in two patients. The postoperative hematoma clearance rate was about 70%−90%. Among four patients with respiratory failure, three had improved breathing and resumed spontaneous breathing. Out of three patients with high fever, one showed a substantial decrease in body temperature. There were no cases of postoperative infection. Of the five patients, two recovered consciousness, one died, and two voluntarily gave up further treatment and were discharged.ConclusionsLaser navigation combined with the XperCT technology could improve the accuracy of surgical puncture. The technique might be convenient for widespread clinical application because of its low trauma, high precision, short operation time, and low operation cost.
Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome
Authors: Wang Hongkai , Wei Yu , Hu Xiaoxin , Pan Jian , Wu Junlong , Wang Beihe , Zhang Hailiang , Shi Guohai , Liu Xiaohang , Zhao Jinou , Zhu Yao , Ye Dingwei 
Published: June 2022

PurposeThe computed tomography fat attenuation index (FAI) is an ideal quantifiable imaging factor to identify the inflammation degree of peri-tumor adipose tissue. We aimed to verify whether FAI could reflect peri-tumor adipose inflammation, predict the survival outcome of renal cell carcinoma (RCC), and discover transcriptomic features of tumor tissues and adjacent adipocytes.Materials and MethodsTwo clinical cohorts (Fudan University Shanghai Cancer Center [FUSCC] cohort [n=129] and TCGA cohort [n=218]) were used to explore the association between FAI and clinical outcome. A prospective cohort (n = 19) was used to discover the molecular phenotyping of peri-tumor adipose tissue and tumor tissue according to their FAI value. A clinical cohort (n = 32) in which patients received cyto-reductive surgery was used to reveal the dynamic change of FAI.ResultsA high peri-tumor FAI was significantly associated with a worse outcome in both the FUSCC (HR = 2.28, p = 0.01) and the TCGA cohort (HR = 2.24, p &lt;0.001). The analysis of the RNA expression of paired RCC tissue and peri-tumor fat tissue showed synchronized alterations in pathways such as cytokine–cytokine receptor interaction and complement and coagulation cascades. RCC tissues showed significant alterations in the neuroactive ligand–receptor interaction pathway. Immune deconvolution analysis showed enhanced infiltration of macrophages in high FAI tumor tissues with a lower angiogenesis level. We also observed synchronous dynamic changes in FAI and tumor size after targeted therapy.ConclusionIn summary, FAI could be used in RCC to reflect the biological characteristics and tumor immune micro-environment of both the tumor and the peri-tumor adipose. High peri-tumor FAI had the potential to predict a worse survival outcome in various cohorts. This study demonstrates that the crosstalk exists between a tumor and its micro-environment and could be reflected easily by imaging procedures, which could facilitate clinical decision making.
Roles of Cadherin2 in Thyroid Cancer
Authors: Chen Yun , Hong Chaojin , Zhou Qihao , Qin Zhiquan 
Published: June 2022

BackgroundThe majority of drug-resistant cells in Thyroid cancer (THCA) tend to exhibit an Epithelial mesenchymal transition (EMT) phenotype, and abnormal expression of the cell adhesion molecule Cadherin2 (CDH2) is a hallmark of EMT. However, the roles of CDH2 in THCA and its underlying mechanisms are unknown.MethodsWe analyzed the CDH2 expression in The Cancer Genome Atlas (TCGA) database and screened for genes positively associated with CDH2. Small interfering RNA and cell transfection were used for knocking down CDH2 in THCA cells, cell counting kit-8 (CCK-8) assay and immunofluorescence to detect cell proliferation. Binding miRNAs of CDH2 and CDH2-associated genes were predicted using the Encyclopedia of RNA Interactomes (ENCORI) database. The expression of genes in clinical THCA tissues was investigated from the Human Protein Atlas (HPA) database and validated by qRT-PCR. We conducted the cell functions pathways of CDH2 and CDH2-associated gene FRMD3 by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also showed the correlation between CDH2 and FRMD3 expression and tumor immune infiltration.ResultsThe expression of CDH2 was significantly higher in THCA tumor tissues compared to normal tissues. Moreover, there were strongly associations of CDH2 expression with the stages T and N. Cellular function assays showed that CDH2 exerted its growth-promoting activity of THCA. To better understand how CDH2 was regulated in THCA, we sought genes associated with CDH2. Correlation analysis revealed that there were negative correlations between genes (CDH2, FRMD3) and miRNAs (hsa-miR-410-3p, hsa-miR-411-5p, hsa-miR-299-5p). Moreover, CDH2 and FRMD3 expression were significantly higher in tumor tissues than in normal tissues, while hsa-miR-410-3p, hsa-miR-411-5p and hsa-miR-299-5p were significantly decreased in tumor tissues compared with normal tissues in THCA. GO and KEEG results showed that CDH2 and FRMD3 were strongly associated with immune-related functions. High expression of CDH2 and FRMD3 was linked to the suppression of immune cells. There were strong negativity correlations between CDH2, FRMD3 and T-cell exhaustion factors.ConclusionOur data indicated that CDH2 and CDH2-related gene FRMD3 might have the critical effects on altering tumors becoming ‘cold tumors’ eventually leading to immune checkpoint inhibitor resistance.
Primary Osteosarcoma of the Breast: A Rare Case Report and Literature Review
Authors: Li Shike , Xue Qingfeng , Shi Wenyu 
Published: June 2022

BackgroundPrimary osteosarcoma of the breast (POB) is an extremely aggressive and heterogeneous neoplasm that originates from nonepithelial elements of the mammary gland and accounts for fewer than 1% of breast cancers and fewer than 5% of all sarcomas.Case PresentationAn 83-year-old Chinese woman went to our hospital because of a palpable mass she had had for 8 months in the left breast accompanied by persistent dull pain for 10 days. This mass was initially misdiagnosed as a degenerating fibroadenoma and was graded as probably benign (BI-RADS category 3) by ultrasonography (US) and computed tomography (CT) plain scan and contrast enhancement of chest. Eight months later, it was presumed to be highly malignant and graded as BI-RADS category 4C because of its rapid growth and more calcifications by US and CT. 99mTc-MDP whole-body bone imaging showed that there was a mass-like abnormal radioactive concentration of Tc-99m outside the bone of the left chest. The lumpectomy of the left breast was indicated, and the pathological findings were POB. She succumbed to respiratory failure caused by multiple lung metastases 4 months after the operation.ConclusionPOB is rare, and US and CT cannot reliably distinguish the causes of calcified breast masses between benign and malignant tumors. It can be diagnosed by pathology when metaplastic carcinoma, malignant phyllodes tumor, or carcinosarcoma containing osteoid and bone is excluded. This case could help clinicians to improve the prognosis and treatment of this disease.