bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Preoperative Thoracic Paravertebral Blocks on Emergence Agitation During Tracheal Extubation: A Randomized Controlled Trial
Authors: Liu Wei , Luo Taijun , Wang Fei , Zhang Ding , Liu Tao , Huang Jiapeng , Xu Shaofa 
Published: June 2022

ObjectiveThis study aims to compare the effects of preoperative thoracic paravertebral blocks (TPVB) with intercoastal nerve blocks (ICNB) on emergence agitation (EA) during tracheal extubation in patients who underwent thoracoscopic lobectomy.Design, Setting, and ParticipantsA randomized clinical trial was conducted in patients undergoing thoracoscopic lobectomy at Beijing Chest Hospital between June 2019 and December 2020.InterventionsPatients were randomly assigned 1:1 to receive either ultrasound-guided preoperative TPVB or ICNB.Main Outcomes and MeasuresThe primary outcome was the occurrence of emergency agitation, which was evaluated by Aono’s four-point scale (AFPS). Secondary outcomes included hemodynamics [mean arterial pressure (MAP) and heart rate (HR)]; and post-operative pain intensity [visual analog scale (VAS), Ramsay sedation score (RSS), and patient-controlled analgesia (PCA) demand times].ResultsAmong the 100 patients aged 55–75 years old, 50 were randomized to each group; 97 patients completed the trial. Compared to the ICNB group, the occurrence of EA in the TPVB group was significantly lower [31.3% (15/48) vs. 12.2% (6/49), relative risk = 1.276, 95% CI: 1.02–1.60, P = 0.028]. For patients in the TPVB group, the MAP and HR at 5, 10, and 30 min after extubation were significantly lower; the intraoperative details including emergence time, extubation time, and consumption of sufentanil were significantly shorter than that in the ICNB group. Additionally, patients in the TPVB group showed significantly lower VAS at rest or coughing and significantly lower RSS at 60 and 240 min after extubation than patients in the ICNB group (all P &lt; 0.05).ConclusionPreoperative TPVB was associated with less EA during tracheal extubation when compared with ICNB in patients undergoing thoracoscopic lobectomy.Clinical Trial Registration[http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1900023852].
Serum Pregenomic RNA Combined With Hepatitis B Core-Related Antigen Helps Predict the Risk of Virological Relapse After Discontinuation of Nucleos(t)ide Analogs in Patients With Chronic Hepatitis B
Authors: Wang Fa-Da , Zhou Jing , Li Lan-Qing , Wang Meng-Lan , Tao Ya-Cao , Wang Yong-Hong , Zhang Dong-Mei , Chen En-Qiang 
Published: June 2022

Background and AimCessation of nucleos(t)ide analogs (NAs) therapy in patients with chronic hepatitis B (CHB) is uncommon. Although criteria for discontinuation appear in some guidelines, the indicators for assessing discontinuation of NAs are limited, whether NAs can be safely ceased remains a difficult clinical issue. Our study aimed to investigate the role of serum pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) at the end of treatment (EOT) in guiding the safe discontinuation of NAs in CHB patients.MethodsThis is a retrospective study, clinical data of all CHB patients who discontinued NAs treatment at West China Hospital between June 2020 and January 2021 were collected, including EOT pgRNA, HBcrAg, hepatitis B surface antigen (HBsAg), etc. All patients should meet the Asian-Pacific guideline for discontinuation. Observing virological relapse (VR) rates during 1 year of NAs discontinuation and analyzing the relationship between EOT pgRNA, HBcrAg, and VR.ResultsA total of 64 patients were enrolled in this study and 33 (51.5%) patients experienced VR in 1 year. EOT pgRNA positivity (OR = 14.59, p = 0.026) and EOT higher HBcrAg levels (OR = 14.14, p = 0.001) were independent risk factors for VR. The area under the receiver-operating characteristic (AUROC) value of EOT HBcrAg for VR was 0.817 (p &lt; 0.001), optimal cut-off value was 3.3 log10 U/mL. Patients with EOT pgRNA positivity and EOT HBcrAg &gt;3.3 log10 U/mL were more likely to experience VR after discontinuation of NAs (88.9 vs. 45.5%, p = 0.027).ConclusionAccording to current guidelines, a higher VR rate occurs after cessation of NAs. EOT pgRNA positivity and higher HBcrAg level carries a higher risk of VR. Combining these novel markers can better help us assess whether patients can safely cease NAs treatment.
A Clinical-Radiomics Nomogram Based on Magnetic Resonance Imaging for Predicting Progression-Free Survival After Induction Chemotherapy in Nasopharyngeal Carcinoma
Authors: Liu Lu , Pei Wei , Liao Hai , Wang Qiang , Gu Donglian , Liu Lijuan , Su Danke , Jin Guanqiao 
Published: June 2022

PurposeThis paper aimed to establish and verify a radiomics model based on magnetic resonance imaging (MRI) for predicting the progression-free survival of nasopharyngeal carcinoma (NPC) after induction chemotherapy (IC).Materials and MethodsThis cohort consists of 288 patients with clinical pathologically confirmed NPC, which was collected from January 2015 to December 2018. All NPC patients were randomly divided into two cohorts: training (n=202) and validation (n=86). Radiomics features from the MRI images of NPC patients were extracted and selected before IC. The patients were classified into high- and low-risk groups according to the median of Radscores. The significant imaging features and clinical variables in the univariate analysis were constructed for progression-free survival (PFS) using the multivariate Cox regression model. A survival analysis was performed using Kaplan–Meier with log-rank test and then each model’s stratification ability was evaluated.ResultsEpstein–Barr virus (EBV) DNA before treatment was an independent predictor for PFS (p &lt; 0.05). Based on the pyradiomic platform, we extracted 1,316 texture parameters in total. Finally, 16 texture features were used to build the model. The clinical radiomics-based model had good prediction capability for PFS, with a C-index of 0.827. The survival curve revealed that the PFS of the high-risk group was poorer than that of the low-risk group.ConclusionThis research presents a nomogram that merges the radiomics signature and the clinical feature of the plasma EBV DNA load, which may improve the ability of preoperative prediction of progression-free survival and facilitate individualization of treatment in NPC patients before IC.
The Evaluation of Zoomed Echo-Planar Diffusion-Weighted Magnetic Resonance Imaging With Two-dimensional Spatial-Selective Radiofrequency Excitation Pulses in Patients With Hilar Cholangiocarcinoma
Authors: Liu Jingjing , Huang Mengyue , Ren Yanan , Xu Man , Li Yinhua , Cheng Jingliang , Zhu Jinxia 
Published: June 2022

BackgroundWe aimed to investigate the feasibility and application of using the zoomed diffusion-weighted echo-planar imaging (z-EPI DWI) sequences for hilar cholangiocarcinoma assessment compared with conventional single-shot EPI diffusion-weighted imaging (c-EPI DWI).MethodsBoth c-EPI DWI and z-EPI DWI were preoperatively performed in 16 patients with histopathologically-confirmed hilar cholangiocarcinoma. A two-dimensional spatial-selective radiofrequency (RF) pulse was applied to the z-EPI DWI using an echo-planar transmit trajectory. Anatomic structural visualization, lesion conspicuity, artifact presence and overall image quality were evaluated and compared between the two sequence images. The ratio of differences regarding hilar cholangiocarcinoma lesion sizes measured on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) were compared from both EPI techniques. The DW images for tumor involvement of the bile duct were reviewed based on histopathological examination of the surgical intraoperative evaluation. ADC measurements of DWIs in the hilar cholangiocarcinoma lesions were conducted.ResultsThe hepatic hilar region was better delineated by visualization of anatomical structures, lesion conspicuity and overall image quality using the z-EPI DWI and these analyses were compared with the c-EPI DWI method (all p&lt;0.05). Better lesion delineation of bile duct walls and lumens was noted in four patients with z-EPI DWI compared with those of c-EPI DWI. No significant differences were noted between the two image datasets for artifacts (p=0.876). The ratio of differences regarding hilar cholangiocarcinoma lesion sizes was significantly lower (p= 0.018) on T2WI and DWI, as determined by the z-EPI DWI than that determined by the c-EPI method. The use of z-EPI DWI resulted in the accurate diagnosis of the Bismuth-Corlette classification of 15 tumors (15/16, 93.75%), whereas the use of c-EPI DWI resulted in correct diagnosis of 12 tumors (12/16, 75.00%). There were no significant differences between c-EPI DWI and z-EPI DWI in the ADC values of hilar cholangiocarcinoma lesions (p= 0.48).Conclusionz-EPI DWI resulted in remarkable image quality improvements for hilar cholangiocarcinoma. The ability to detect and delineate lesions using z-EPI DWI was superior to that of c-EPI DWI.
Contrast-Enhanced Computed Tomography–Based Radiogenomics Analysis for Predicting Prognosis in Gastric Cancer
Authors: Liu Han , Wang Yiyun , Liu Yingqiao , Lin Dingyi , Zhang Cangui , Zhao Yuyun , Chen Li , Li Yi , Yuan Jianyu , Chen Zhao , Yu Jiang , Kong Wentao , Chen Tao 
Published: June 2022

ObjectiveThe aim of this study is to identify prognostic imaging biomarkers and create a radiogenomics nomogram to predict overall survival (OS) in gastric cancer (GC).MaterialRNA sequencing data from 407 patients with GC and contrast-enhanced computed tomography (CECT) imaging data from 46 patients obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA) were utilized to identify radiogenomics biomarkers. A total of 392 patients with CECT images from the Nanfang Hospital database were obtained to create and validate a radiogenomics nomogram based on the biomarkers.MethodsThe prognostic imaging features that correlated with the prognostic gene modules (selected by weighted gene coexpression network analysis) were identified as imaging biomarkers. A nomogram that integrated the radiomics score and clinicopathological factors was created and validated in the Nanfang Hospital database. Nomogram discrimination, calibration, and clinical usefulness were evaluated.ResultsThree prognostic imaging biomarkers were identified and had a strong correlation with four prognostic gene modules (P &lt; 0.05, FDR &lt; 0.05). The radiogenomics nomogram (AUC = 0.838) resulted in better performance of the survival prediction than that of the TNM staging system (AUC = 0.765, P = 0.011; Delong et al.). In addition, the radiogenomics nomogram exhibited good discrimination, calibration, and clinical usefulness in both the training and validation cohorts.ConclusionsThe novel prognostic radiogenomics nomogram that was constructed achieved excellent correlation with prognosis in both the training and validation cohort of Nanfang Hospital patients with GC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.
High Levels of DEAH-Box Helicases Relate to Poor Prognosis and Reduction of DHX9 Improves Radiosensitivity of Hepatocellular Carcinoma
Authors: Chen Xi , Lin Letao , Chen Guanyu , Yan Huzheng , Li Zhenyu , Xiao Meigui , He Xu , Zhang Fujun , Zhang Yanling 
Published: June 2022

BackgroundLiver hepatocellular carcinoma (LIHC), one of the most common primary malignancies, exhibits high levels of molecular and clinical heterogeneity. Increasing evidence has confirmed the important roles of some RNA helicase families in tumor development, but the function of the DEAH-box RNA helicase family in LIHC therapeutic strategies has not yet been clarified.MethodsThe LIHC dataset was downloaded from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to group the patients. Least absolute shrinkage and selection operator Cox regression and univariate and multivariate Cox regression were used to develop and validate a prognostic risk model. The Tumor Immune Estimation Resource and Tumor Immune Single Cell Hub databases were used to explore the role of DEAH-box RNA helicases in LIHC immunotherapy. In vitro experiments were performed to investigate the role of DHX9 in LIHC radiosensitivity.ResultsTwelve survival-related DEAH-box RNA helicases were identified. High helicase expression levels were associated with a poor prognosis and clinical features. A prognostic model comprising six DEAH-box RNA helicases (DHX8, DHX9, DHX34, DHX35, DHX38, and DHX57) was constructed. The risk score of this model was found to be an independent prognostic indicator, and LIHC patients with different prognosis were distinguished by the model in the training and test cohorts. DNA damage repair pathways were also enriched in patients with high-risk scores. The six DEAH-box RNA helicases in the risk model were substantially related to innate immune cell infiltration and immune inhibitors. In vitro experiments showed that DHX9 knockdown improved radiosensitivity by increasing DNA damage.ConclusionThe DEAH-box RNA helicase signature can be used as a reliable prognostic biomarker for LIHC. In addition, DHX9 may be a definitive indicator and therapeutic target in radiotherapy and immunotherapy for LIHC.
Comprehensive Analysis of Role of Cyclin-Dependent Kinases Family Members in Colorectal Cancer
Authors: Guan Liping , Tang Yuanyuan , Li Guanghua , Qin Zhao , Li Shaoshan 
Published: June 2022

BackgroundCyclin-dependent kinases (CDKs) are cell cycle regulators, and abnormal activation can accelerate tumor cell proliferation. However, The relation between CDKs dysregulation to colorectal cancer incidence and progression have not been examined in detail. Methods:Differences in CDKs expression between colorectal cancer and normal tissues, associations between expression and clinical prognosis, incidence and frequencies of CDKs gene mutations, and the influences of CDKs on tumor infiltration by immune cells were examined by analyses of Oncomine, Gene Expression Profiling Interactive Analysis, Kaplan-Meier plotter, cBioPortal, GeneMANIA, and TIMER databases.ResultsColorectal cancer tissues showed enhanced expression levels of CDKs 1/2/4/5/6/8/12/13/19 but reduced CDK3 expression. CDK7 was highly expressed in some colorectal cancer tissues but downregulated in others. Expression levels of CDK1/3/4/7/8/10/11b/13/18/19/20 were correlated with clinical stage, and CDK 5/10/12/16 expression levels predicted prognosis and survival. Differential CDKs expression correlated with cell cycle progression, amino acid polypeptide modifications, and activation of other protein kinases. Expression levels of all CDKs except CDK16 were correlated with infiltration of CD4+T, CD8+T, B and Tregs cells.ConclusionsCDK 1 and 4 could be used as diagnostic biomarkers for CRC. CDK 5/10/12/16 can be utilized as prognostic biomarkers.
Time Free From Hospitalization in Children and Adolescents With Cystic Fibrosis: Findings From FEV1, Lung Clearance Index and Peak Work Rate
Authors: Gambazza Simone , Mariani Alessandra , Brivio Anna , Carta Federica , Blardone Chiara , Lisiero Saba , Russo Maria , Colombo Carla 
Published: June 2022

BackgroundAn exercise test combined with a multiple breath washout nitrogen test (MBWN2) may offer a comprehensive clinical evaluation of cystic fibrosis (CF) disease in children with normal spirometry. The purpose of the present study is to explore whether information derived from spirometry, MBWN2, and exercise tests can help the CF multidisciplinary team to characterize time free from hospitalization due to pulmonary exacerbation (PE) in a cohort of pediatric patients with CF.MethodsThis prospective observational study was carried out at the Lombardia Region Reference Center for Cystic Fibrosis in Milano, Italy. In 2015, we consecutively enrolled children and adolescents aged &lt;18 years with spirometry, MBWN2, and Godfrey exercise test performed during an outpatient visit.ResultsOver a median follow-up time of 2.2 years (interquartile range [IQR], 2.01; 3.18), 28 patients aged between 13.0 and 17.4 years were included. When lung functions were outside the normal range, 50% of patients were hospitalized 4 months after the outpatient visit, and their response to exercise was abnormal (100%). Half of the individuals with normal forced expiratory volume in the first second (FEV1) and abnormal lung clearance index (LCI) experienced the first hospital admission 9 months after the clinic visit, and 84.2% presented an abnormal response to exercise. Conversely, 15.8% had abnormal exercise responses when lung functions were considered normal, with half of the adolescents hospitalized at 11 months.ConclusionMaintaining ventilation homogeneity, along with a normal ability to sustain intense work, may have a positive impact on the burden of CF disease, here conceived as time free from hospitalization due to PE.
Therapeutic Drug Monitoring of Ceftazidime-Avibactam Concentrations in Carbapenem-Resistant K. pneumoniae-Infected Patients With Different Kidney Statuses
Authors: Teng Xin-Qi , Qu Qiang , Luo Yue , Long Wen-Ming , Zhuang Hai-Hui , Xu Jiao-Hua , Wen Yu-Xin , Zhang Hui-Lin , Qu Jian 
Published: June 2022

Aims: Carbapenem-resistant K. pneumoniae (CRKP) is the most common carbapenem-resistant Enterobacteriaceae with high mortality. Ceftazidime-avibactam (CAZ-AVI) has exhibited excellent in vitro activity in vivo against CRKP. However, the efficacy of CAZ-AVI in KPC-producing CRKP-infected patients with different kidney statuses varies, such as renal insufficiency, normal renal function, and augmented renal clearance (ARC). We explored the use of therapeutic drug monitoring (TDM) to evaluate the concentration and efficacy of CAZ-AVI in CRKP-infected patients with different kidney statuses.Methods: Serum concentrations for CAZ and AVI were determined by the high-performance liquid chromatography method. Bacterial identification, routine susceptibility testing, renal function index, and others were performed in standard protocols in the hospital’s clinical laboratories.Results: In the two patients with ARC, in case 1, CAZ-AVI 2.5g q6h was used with good efficacy, and the concentrations were up to the pharmacokinetics/pharmacodynamics targets. In Case 2, 2.5 g q8h was used with invalid effectiveness, and AVI Cmin was only 0.797 mg/l, which is lower than the PK/PD target. Case 3 was renal insufficiency using CAZ-AVI 1.25 q8h, and case 4 was normal renal function using 2.5 g q8h. Their concentrations were both up to the PK/PD targets.Conclusion: TDM results demonstrated that CAZ-AVI steady-state plasma concentration varies among patients with different kidney statuses, providing evidence for the utility of TDM of CAZ-AVI in individualized drug dose adjustment. ARC patients may need more CAZ-AVI daily doses than the standard dose.
A Mechanistic Exploratory Study on the Therapeutic Efficacy of Astragaloside IV Against Diabetic Retinopathy Revealed by Network Pharmacology
Authors: Zhao Zhi-Hao , Xu Min , Fu Cong , Huang Ying , Wang Ting-Hua , Zuo Zhong-Fu , Liu Xue-Zheng 
Published: June 2022

Purpose: Diabetic retinopathy (DR) is a serious complication of diabetes mellitus, which nearly happens to all the diabetic sufferers. This study aims to identify the preliminary molecular regulation involved in the therapeutic efficacy of astragaloside IV (AS- IV) for DR.Methods: Diabetic rat models were established and treated with AS-IV. Optical coherence tomography (OCT) and Hematoxylin-eosin (HE) staining was employed to demonstrate the histopathological changes. The main targets of AS-IV were identified by searching from public databases of traditional Chinese medicine (GeneCards, PharmMapper and Swiss Target Prediction). Besides, disease targets of DR were also obtained by integrated data from GEO datasets and predicted from public databases. Protein-protein interaction (PPI) network was constructed by Cytoscape with overlapping genes and 10 core targets were selected, on which Gene Ontology (GO) along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. The interaction between AS-IV and these crucial genes were analyzed using molecular docking. RT-qPCR and western blot were used to verify the expression variation of core targets.Results: OCT imaging and HE staining demonstrated that AS-IV administration significantly increased retinal thickness in diabetic rats, obviously alleviating DR induced histopathological changes as well as elevated blood glucose levels. 107 common targets of AS-IV and DR were determined after intersection. PPI network analysis filtered 10 hub genes potentially targeted by AS-IV, including VEGFA, CASP3, HIF1α, STAT3, CTNNB1, SRC, AKT1, EGFR, IL1β and IL6. Enrichment analysis indicated that these genes were mainly enriched in biological processes like T cell activation, epithelial cell proliferation and protein kinase B signaling, and involved in oxidative stress, apoptosis and inflammation-related pathways. The molecular docking prediction suggested that AS-IV exhibited stable binding to these core targets. In addition, mRNA levels of core targets in diabetic rats were differentially expressed before and after AS-IV treatment. Western blot further revealed that AS-IV treatment elevated DR-depressed protein levels of PI3K and AKT.Conclusion: Our study elucidated the effect of AS-IV in attenuating retinopathy induced by diabetes in rats and preliminarily unveiled the therapeutic efficacy of AS-IV in the treatment of DR might be attributed to activation of PI3K-AKT signaling pathway.
On-Line Solid Phase Extraction High Performance Liquid Chromatography Method Coupled With Tandem Mass Spectrometry for the Therapeutic Monitoring of Cannabidiol and 7-Hydroxy-cannabidiol in Human Serum and Saliva
Authors: Franco Valentina , Palmisani Michela , Marchiselli Roberto , Crema Francesca , Fattore Cinzia , De Giorgis Valentina , Varesio Costanza , Rota Paola , Dibari Vincenza Flora , Perucca Emilio 
Published: June 2022

Cannabidiol is a novel antiseizure medication approved in Europe and the US for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis complex. We describe in this article a new and simple liquid chromatography-mass spectrometry method (LC-MS/MS) for the determination of cannabidiol and its active metabolite 7-hydroxy-cannabidiol in microvolumes of serum and saliva (50 μl), to be used as a tool for therapeutic drug monitoring (TDM) and pharmacokinetic studies. After on-line solid phase extraction cannabidiol, 7-hydroxy-cannabidiol and the internal standard cannabidiol-d3 are separated on a monolithic C18 column under gradient conditions. Calibration curves are linear within the validated concentration range (10–1,000 ng/ml for cannabidiol and 5–500 ng/ml for 7-hydroxy-cannabidiol). The method is accurate (intraday and interday accuracy within 94–112% for cannabidiol, 91–109% for 7-hydroxy-cannabidiol), precise (intraday and interday precision &lt;11.6% for cannabidiol and &lt;11.7% for 7- hydroxy-cannabidiol) and sensitive, with a LOQ of 2.5 ng/ml for cannabidiol and 5 ng/ml for 7-hydroxy-cannabidiol. The stability of the analytes was confirmed under different storage conditions. Extraction recoveries were in the range of 81–129% for cannabidiol and 100–113% for 7-hydroxy-cannabidiol. The applicability of the method to TDM was demonstrated by analysis of human serum and saliva samples obtained from patients with epilepsy treated with cannabidiol.