bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA Circ_0000098 Elevates ALX4 Expression via Adsorbing miR-1204 to Inhibit the Progression of Hepatocellular Carcinoma
Authors: Li Ming , Yue Wenjing , Li Qiankun , Yu Wenyu , Li Yao , Cao Xiaoling 
Published: December 2021

BackgroundCircular RNAs (CircRNAs) feature prominently in the progression of various cancers. However, the biological functions of many circRNAs in hepatocellular carcinoma (HCC) are far from fully clarified. This work is performed to decipher the function of circ_0000098 (circSLC30A7) in modulating the progression of HCC and its molecular mechanism.MethodsMicroarray data (GSE97332) were available from the Gene Expression Omnibus (GEO) database, and circRNA differentially expressed in HCC tissues was screened out by GEO2R tool. Circ_0000098, microRNA-1204 (miR-1204), and aristaless-like homeobox-4 (ALX4) mRNA expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8), scratch wound healing, and Transwell assays were adopted to determine proliferation, migration, and invasion of HCC cells. ALX4 protein, E-cadherin, N-cadherin, and Vimentin expressions were evaluated by Western blot. In addition, the targeting relationship between miR-1204 and circ_0000098 or ALX4 was studied with dual-luciferase reporter assay and RIP assay.ResultsCirc_0000098 expression level was markedly declined in HCC tissues and cells, and its underexpression was associated with larger tumor size of HCC patients. Knocking down circ_0000098 observably promoted the multiplication, migration, invasion, and epithelial-mesenchymal transition (EMT) of Huh7 and SMMC-7721 cells. Additionally, circ_0000098 was mainly distributed in the cytoplasm of HCC cells, and up-regulated ALX4 expression through competitively decoying miR-1204.ConclusionCirc_0000098, as a competitive endogenous RNA (ceRNA) of miR-1204, upregulates ALX4 expression and suppresses the growth, migration, invasion, and EMT of HCC cells.
Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model
Authors: Yue Xiaofei , Dong Xiangjun , Huang Mengting , Yang Hongli , Qian Kun , Yi Changhong , Alwalid Osamah , Ren Yanqiao , Han Ping , Li Qian 
Published: December 2021

ObjectivesTo discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard.MethodsTwenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI).ResultsA total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P &lt; 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes.ConclusionsThe TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment.
Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer
Authors: Gu Meijia , He Ti , Yuan Yuncong , Duan Suling , Li Xin , Shen Chao 
Published: December 2021

BackgroundCervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy resistance are not well studied. This study aimed to comprehensively analyze cells from pretreated and chemoresistant cervical cancer tissues to generate a molecular census of cell populations.MethodsBiopsy tissues collected from patients with cervical squamous cell carcinoma, cervical adenocarcinoma, and chronic cervicitis were subjected to single-cell RNA sequencing using the 10× Genomics platform. Unsupervised clustering analysis of cells was performed to identify the main cell types, and important cell clusters were reclustered into subpopulations. Gene expression profiles and functional enrichment analysis were used to explore gene expression and functional differences between cell subpopulations in cervicitis and cervical cancer samples and between chemoresistant and chemosensitive samples.ResultsA total of 24,371 cells were clustered into nine separate cell types, including immune and non-immune cells. Differentially expressed genes between chemoresistant and chemosensitive patients enriched in the phosphoinositide 3-kinase (PI3K)/AKT pathway were involved in tumor development, progression, and apoptosis, which might lead to chemotherapy resistance.ConclusionsOur study provides a comprehensive overview of the cancer microenvironment landscape and characterizes its gene expression and functional difference in chemotherapy resistance. Consequently, our study deepens the insights into cervical cancer biology through the identification of gene markers for diagnosis, prognosis, and therapy.
Second Primary Renal Cell Carcinoma With Nonrenal Malignancies: An Analysis of 118 Cases and a Review of Literature
Authors: Chen Jinchao , Qi Nienie , Wang Hua , Wang Zongping , He Yedie , Zhu Shaoxing 
Published: December 2021

ObjectivesTo evaluate the nature, diagnosis, treatment and prognosis of second primary renal cell carcinoma (SPRCC).Materials and MethodsWe retrospectively collected data from 118 patients with SPRCC. Clinical characteristics, imaging features and treatments were analyzed and comparisons between SPRCC and renal metastases (RM) were made.ResultsSPRCC accounts for 11.4% of all RCC. The most common types of extrarenal malignancies included lung, colorectal, breast and gynecological cancers. The median age was 58.5 years old, and 61.0% (72/118) of the patients were male. About 5.1% of the patients presented with symptoms. The average tumor diameter was 4.4 cm (1-8.4 cm). The diagnostic specificity of enhanced computed tomography (CT) was 80.1%. When comparing with RM, more patients with stage I–II extrarenal malignancy and less patients with bilateral, multiple, and endogenic renal masses on computed tomography were found in the SPRCC group. A total of 110 SPRCC patients underwent surgery, including 48 radical nephrectomies and 62 partial nephrectomies. The median overall survival time was 117 months. Female, asymptomatic status, no distant metastasis, and surgical treatment predicted a better survival.ConclusionsSPRCC are not uncommon, and it should be considered during the follow-up of patients with nonrenal malignancy. The differential diagnosis between SPRCC and RM was mainly based on imaging and puncture biopsy.
Cryotherapy for Prevention of Taxane-Induced Peripheral Neuropathy: A Meta-Analysis
Authors: Jia Junting , Guo Yimeng , Sundar Raghav , Bandla Aishwarya , Hao Zhiying 
Published: December 2021

PurposeTaxanes are widely used in gynecological cancer therapy, however, taxane-induced peripheral neuropathy (TIPN) limits chemotherapy dose and reduces patients’ quality of life. As a safe and convenient intervention, cryotherapy has been recommended as a promising intervention in the recent clinical guidelines for the prevention of TIPN. Although there are a considerable number of studies which explored the use of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN), there is insufficient large-scale clinical evidence. We performed a meta-analysis on the current available evidence to examine whether cryotherapy can prevent TIPN in cancer patients receiving taxanes.MethodsWe searched databases including PubMed, Embase, and Cochrane from inception to August 3, 2021 for eligible trials. Clinical trials that examined the efficacy of cryotherapy for prevention of TIPN were included. The primary outcome was the incidence of TIPN, and secondary outcomes were incidence of taxane dose reduction and changes in nerve conduction studies. The meta-analysis software (RevMan 5.3) was used to analyze the data.ResultsWe analyzed 2250 patients from 9 trials. Assessments using the Common Terminology Criteria for Adverse Events (CTCAE) score showed that cryotherapy could significantly reduce the incidence of motor and sensory neuropathy of grade≥2 (sensory: RR 0.65, 95%CI 0.56 to 0.75, p&lt;0.00001; motor: RR 0.18, 95% CI [0.03, 0.94], p=0.04). When evaluated using the Patient Neuropathy Questionnaire (PNQ), cryotherapy demonstrated significant reduction in the incidence of sensory neuropathy (RR 0.11, 95% CI 0.04 to 0.31], p&lt;0.0001), but did not show significant reduction in the incidence of motor neuropathy (RR 0.46, 95% CI 0.11 to 1.88, p=0.28). Cryotherapy was associated with reduced incidences of taxane dose reduction due to TIPN (RR 0.48, 95% CI [0.24, 0.95], p=0.04) and had potential to preserve motor nerves.ConclusionsCryotherapy is likely to prevent TIPN in patients receiving taxanes. High quality and sufficient amount of evidence is warranted.
Multi-Institutional Study Validates Safety of Intraoperative Cesium-131 Brachytherapy for Treatment of Recurrent Head and Neck Cancer
Authors: Luginbuhl Adam , Calder Alyssa , Kutler David , Zender Chad , Wise-Draper Trisha , Patel Jena , Cheng Michael , Karivedu Vidhya , Zhan Tingting , Parashar Bhupesh , Gulati Shuchi , Yao Min , Lavertu Pierre , Takiar Vinita , Tang Alice , Johnson Jennifer , Keane William , Curry Joseph , Cognetti David , Bar-Ad Voichita 
Published: December 2021

IntroductionSurgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection.Methods and MaterialsFindings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts—surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)—were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated.ResultsForty-nine patients were enrolled in the surgery + Cs-131 prospective study. Grade 1 to 3 adverse events (AEs) occurred in 18 patients (37%), and grade 4 AEs occurred in 2 patients. Postoperative percutaneous endoscopic gastrostomy (PEG) tubes were needed in 10 surgery + Cs-131 patients (20%), and wound and vascular complications were observed in 12 patients (24%). No cases of osteoradionecrosis were reported in the surgery + Cs-131 cohort. We found a 49% 2-year disease-free survival at the site of treatment with a substantial number of patients (31%) developing metastatic disease, which led to a 31% overall survival at 5 years.ConclusionsAmong patients with local/regional recurrent HNSCC status-post radiation, surgery + Cs-131 demonstrated acceptable safety with compelling oncologic outcomes, as compared to historic control cohorts.Clinical Trial RegistrationClinicalTrials.gov, identifiers NCT02794675 and NCT02467738.
Effect of a Low-Dose/High-Frequency Training in Introducing a Nurse-Led Neonatal Advanced Life Support Service in a Referral Hospital in Ethiopia
Authors: Tadesse Misrak , Hally Suzanne , Rent Sharla , Platt Phillip L. , Eusterbrock Thomas , Gezahegn Wendmagegn , Kifle Tsinat , Kukora Stephanie , Pollack Louis D. 
Published: December 2021

Background and Objective: In Ethiopia, birth asphyxia causes ~30% of all neonatal deaths and 11–31% of deaths among neonates delivered in healthcare facilities that have breathing difficulty at birth. This study aimed to examine the impact of low-dose, high-frequency (LDHF) training for introducing a nurse-led neonatal advanced life support (NALS) service in a tertiary care hospital in Ethiopia.Methods: Through a retrospective cohort study, a total of 12,001 neonates born post-implementation of the NALS service (between June 2017 and March 2019) were compared to 2,066 neonates born before its implementation (between June 2016 and September 2016). Based on when the neonates were born, they were divided into six groups (groups A to F). All deliveries occurred in the inpatient Labor and Delivery Unit (LDU) at St. Paul's Hospital Millennium Medical College. The number of neonatal deaths in the LDU, neonatal intensive care unit (NICU) admission rate, and proportion of neonates with normal axillary temperature (36.5–37.5°C) within the first hour of life were evaluated. Data were analyzed using the χ2 test, and p-values &lt; 0.05 were considered statistically significant. Following the implementation of the NALS service, semi-structured interviews with key stakeholders were conducted to evaluate their perception of the service; the interviews were recorded, transcribed, and coded for thematic analysis.Results: There was a decrease in the proportion of neonates who died in the LDU (from 3.5 to 1%) during the immediate post-implementation period, followed by a sustained decrease over the study period (p &lt; 0.001). The change in the NICU admission rate (from 22.8 to 21.2%) was insignificant (p = 0.6) during this initial period. However, this was followed by a significant sustained decrease (7.8% in group E and 9.8% in group F, p &lt; 0.001). The proportion of newborns with normal axillary temperature improved from 46.2% during the initial post-implementation period to 87.8% (p &lt; 0.01); this proportion further increased to 99.8%. The program was perceived positively by NALS team members, NICU care providers, and hospital administrators.Conclusion: In resource-limited settings, LDHF training for neonatal resuscitation improves the neonatal resuscitation skills and management of delivery room attendants.
Deprescribing Antipsychotics Based on Real-World Evidence to Inform Clinical Practice: Safety Considerations in Managing Older Adults with Dementia
Authors: Hsieh Stephanie , Yuan Jing , Lu Z. Kevin , Li Minghui 
Published: December 2021

Background: Antipsychotics are commonly used in dementia patients but have potential risks that often outweigh clinical benefits. Limited studies have assessed the healthcare utilization and medical costs associated with antipsychotic use, especially those focused on cumulative days of use.Objectives: To examine clinical and economic burdens associated with different cumulative days of antipsychotic use in older adults with dementia in the United States.Methods: This study used Medicare Current Beneficiary Survey (2015–2017). Older (≥65 years) Medicare beneficiaries with dementia, without concurrent schizophrenia, bipolar disorder, Huntingon’s disease, or Tourette’s syndrome were included. Antipsychotic use was measured using Medicare Part D prescription events. Healthcare utilization was measured as inpatient services, outpatient services, and emergency room (ER) visits. Total medical costs were classified as Medicare and out-of-pocket costs. The logistic regression, negative binomial regression, and generalized linear model with a log link and gamma distribution were used to examine factors, healthcare utilization, and medical costs. Survey sampling weights were applied to generate national estimates.Results: Among older adults with dementia, 13.18% used antipsychotics. Factors associated with antipsychotic use were being Hispanic (OR: 2.90; 95% CI: 1.45, 5.78), widowed (OR: 3.52; 95% CI: 1.46, 8.48), and single (OR: 3.25; 95% CI: 1.53, 6.87). Compared to non-users, antipsychotic use was associated with higher inpatient visits (IRR: 2.11; 95% CI 1.53, 2.90), ER visits (IRR: 1.61; 95% CI: 1.21, 2.13), total costs (β: 0.53; 95% CI: 0.36, 0.71), Medicare costs (β: 0.49; 95% CI 0.26, 0.72), and out-of-pocket costs (β: 0.66; 95% CI: 0.35, 0.97). With the increase in cumulative days of antipsychotic use, the magnitude of clinical and economic burdens was decreased.Conclusion: The significant clinical and economic burdens associated with antipsychotic use, especially with short-term use, provide real-world evidence to inform clinical practice on deprescribing antipsychotics among community-dwelling geriatric dementia patients.
Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells
Authors: Li Gaopan , Zhong Yuhuan , Wang Wenyi , Jia Xiaokang , Zhu Huaichang , Jiang Wenwen , Song Yu , Xu Wen , Wu Shuisheng 
Published: December 2021

The potential antitumor effects of sempervirine (SPV), an alkaloid compound derived from the traditional Chinese medicine Gelsemium elegans Benth., on different malignant tumors were described in detail. The impact of SPV on glioma cells and the basic atomic components remain uncertain. This study aimed to investigate the activity of SPV in vitro and in vivo. The effect of SPV on the growth of human glioma cells was determined to explore three aspects, namely, cell cycle, cell apoptosis, and autophagy. In this study, glioma cells, U251 and U87 cells, and one animal model were used. Cells were treated with SPV (0, 1, 4, and 8 μM) for 48 h. The cell viability, cell cycle, apoptosis rate and autophagic flux were examined. Cell cycle, apoptotic, autophagy, and Akt/mTOR signal pathway-related proteins, such as CDK1, Cyclin B1, Beclin-1, p62, LC3, AKT, and mTOR were investigated by Western blot approach. As a result, cells induced by SPV led to G2/M phase arrest and apoptosis. SPV also promoted the effect of autophagic flux and accumulation of LC3B. SPV reduced the expression of p62 protein and induced the autophagic death of glioma cells. Furthermore, SPV downregulated the expressions of AKT and mTOR phosphorylated proteins in the mTOR signaling pathway, thereby affecting the onset of apoptosis and autophagy in U251 cells. In conclusion, SPV induced cellular G2/M phase arrest and blockade of the Akt/mTOR signaling pathway, thereby triggering apoptosis and cellular autophagy. The in vivo and in vitro studies confirmed that SPV inhibits the growth of glioma cancer.
Effectiveness of Medicinal Plants for Glycaemic Control in Type 2 Diabetes: An Overview of Meta-Analyses of Clinical Trials
Authors: Willcox Merlin L. , Elugbaju Christina , Al-Anbaki Marwah , Lown Mark , Graz Bertrand 
Published: December 2021

Aims: To rank the effectiveness of medicinal plants for glycaemic control in Type 2 Diabetes (T2DM).Methods: MEDLINE, EMBASE, CINAHL and Cochrane Central were searched in October 2020. We included meta-analyses of randomised controlled clinical trials measuring the effectiveness of medicinal plants on HbA1c and/or Fasting Plasma Glucose (FPG) in patients with T2DM.Results: Twenty five meta-analyses reported the effects of 18 plant-based remedies. Aloe vera leaf gel, Psyllium fibre and Fenugreek seeds had the largest effects on HbA1c: mean difference –0.99% [95% CI−1.75, −0.23], −0.97% [95% CI −1.94, −0.01] and −0.85% [95% CI −1.49, −0.22] respectively. Four other remedies reduced HbA1c by at least 0.5%: Nigellasativa, Astragalus membranaceus, and the traditional Chinese formulae Jinqi Jiangtang and Gegen Qinlian. No serious adverse effects were reported. Several other herbal medicines significantly reduced FPG. Tea and tea extracts (Camellia sinensis) were ineffective. However, in some trials duration of follow-up was insufficient to measure the full effect on HbA1c (&lt;8 weeks). Many herbal remedies had not been evaluated in a meta-analysis.Conclusion: Several medicinal plants appear to be as effective as conventional antidiabetic treatments for reducing HbA1c. Rigorous trials with at least 3 months’ follow-up are needed to ascertain the effects of promising plant-based preparations on diabetes.
Pterostilbene Alleviates Cholestasis by Promoting SIRT1 Activity in Hepatocytes and Macrophages
Authors: Ma Chuanrui , Xiang Jiaqing , Huang Guixiao , Zhao Yaxi , Wang Xinyu , Wu Han , Jiang Kewei , Liang Zhen , Kang Lin , Yang Guangyan , Yang Shu 
Published: December 2021

Background and purpose: FXR is a promising target for the treatment of human cholestatic liver disease (CLD). SIRT1 is a deacetylase which promotes FXR activity through deacetylating FXR. Pterostilbene (PTE) is an activator of SIRT1. However, the role of PTE in cholestasis has so far not been investigated. We examined whether PTE treatment alleviate liver injury in DDC or ANIT-induced experimental cholestasis, and explored the underlying mechanisms.Experimental approach: Mice with DDC- or ANIT-induced cholestasis were treated with different dose of PTE. Primary hepatocytes and bone marrow derived macrophages were used in vitro to assess the molecular mechanism by which PTE may improve CLD. Identical doses of UDCA or PTE were administered to DDC- or ANIT-induced cholestasis mice.Key results: PTE intervention attenuated DDC or ANIT-induced cholestasis. PTE inhibited macrophage infiltration and activation in mouse liver through the SIRT1-p53 signaling pathway, and it improved hepatic bile metabolism through the SIRT1-FXR signaling pathway. Compare with UDCA, the same doses of PTE was more effective in improving cholestatic liver injury caused by DDC or ANIT.Conclusion and implications: SIRT1 activation in macrophages may be an effective CLD treatment avenue. Using CLD models, we thus identified PTE as a novel clinical candidate compound for the treatment of CLD.