bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between dietary inflammatory index and oral cancer risk: A systematic review and dose–response meta-analysis
Authors: Luo Zhicheng , Zhu Xidi , Hu Yingyun , Yan Shipeng , Chen Lizhang 
Published: September 2022

BackgroundDietary inflammatory index (DII) has been suggested to be associated with oral cancer risk. However, a quantitative comprehensive assessment of the dose–response relationship has not been reported. We performed a meta-analysis to clarify the risk of oral cancer with DII.MethodsWe searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to 1 March 2022. Fixed- or random-effects models were utilized to estimate the pooled odds ratio (OR) of oral cancer with DII, as appropriate. Restricted cubic splines were used to model the dose–response relationship.ResultsWe included five case–control studies involving 1,278 cases and 5,137 controls in the meta-analysis. Risk of oral cancer was increased by 135% with the highest versus lowest DII level [OR: 2.35, 95% confidence interval (CI): 1.88–2.94], and 79% with higher versus lower DII level (OR: 1.79, 95% CI: 1.49–2.15). We found no evidence of a nonlinear dose–response association of DII with oral cancer (pnon-linearity = 0.752), and the risk was increased by 17% (OR: 1.17, 95% CI: 1.05–1.30) with 1 unit increment in DII score.ConclusionThis meta-analysis suggested that a higher DII score was associated with increased risk of oral cancer. Therefore, reducing pro-inflammatory components and promoting anti-inflammatory components of diet may be effective in the prevention of oral cancer.
Occult neck metastases risk factors and the role of elective neck dissection in cT3-4N0 adenoid cystic carcinoma of the parotid gland
Authors: Yuan Junhui , Meng Fan , Xu Chunmiao , Li Wenlu , Wu Shuang , Li Hailiang 
Published: September 2022

ObjectivesTo determine the predictor for occult neck metastases and the role of elective neck dissection (END) in cT3-4N0 parotid adenoid cystic carcinoma (ACC).MethodsPatients with surgically treated parotid ACC were retrospectively enrolled. Predictors of occult neck metastases and the effect of END on disease specific survival (DSS), overall survival (OS), locoregional control survival (LRC), and distant metastasis free survival (DMS) were analyzed.ResultsOccult neck metastases occurred in 35 (19.7%) of the 178 patients undergoing an END. The tumor stage [p=0.011, 4.215 (1.387–10.435)] and intra-parotid lymph node metastasis [p=0.032, 3.671 (1.693–8.775)] were related to the possibility of occult neck metastases independently. The END group had better 10-year LRC than the observation group (56% vs. 43%, p=0.002) and also better 10-year DMS than the observation group (43% vs. 32%, p&lt;0.001). The two groups had similar 10-year DSS (40% vs. 33%, p=0.230) and OS (31% vs. 23%, p=0.094) rates. Furthermore, the Cox model confirmed that END was independently associated with better LRC rate [p=0.022, 2.576 (1.338–6.476)] and better DMS [p=0.011, 2.343 (1.274–7.462)].ConclusionsOccult neck metastases in cT3-4N0 parotid ACC was not common. A T4 tumor with intra-parotid lymph node metastasis had the highest possibility of occult neck metastases. END had no effect on DSS or OS but significantly decreased the risk of locoregional recurrence and distant metastasis.
Surgical techniques and function outcome for cingulate gyrus glioma, how we do it
Authors: Gong Fangyuan , Jin Lei , Song Qiuwei , Yang Zhong , Chen Hong , Wu Jinsong 
Published: September 2022

ObjectiveCingulate cortex and cingulum both play crucial roles in limbic system. The aim of study is to observe and analyze surgical outcomes of cingulate gyrus glioma through extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome.MethodThe authors retrospectively studied 95 consecutive adult cases of primary cingulate gliomas that all underwent craniotomies and tumor resection. The patients were classified into unitary sub-region based on the four-division model. The information of clinical symptoms, pathology, EOR, postoperative neurological outcome and survival were analyzed through group comparison.ResultLow-grade gliomas (LGGs) were more prevalent (69.47%) for cingulate gyrus. Diffuse astrocytoma (40.00%) was most common histopathological diagnosis in total. Regarding sub-regions tumor involved in, midcingulate cortex (MCC) glioma was most prevalent (54.74%) followed by anterior cingulate cortex (ACC) glioma. Among all patients, 83 patients (87.37%) received EOR ≥ 90%. In LGG group, 58 patients (87.88%) received EOR ≥ 90%. The achievement of EOR significantly correlated with survival (P = 0.006). MCC cases were significantly associated with short-term morbidity in either language or motor function (P = 0.02). Majority of ACC cases (80.65%) escaped from any short-term deficits and nearly 90% free for permanent morbidity. Tumors in the dominant hemisphere were significantly associated with language dysfunction or cognition dysfunction, either short-term (P=0.0006) or long-term morbidity (P=0.0111). Age was the only postoperative susceptible predictor for all types of transient (P=0.021) and permanent (P=0.02) neurological deficit.ConclusionRegarding cingulate gyrus glioma, the management of surgical plans could be carried out into four sub-region level. In spite of short-term neurological dysfunction caused by surgical procedure, majority of transient dysfunction could be relieved or recovered in long-term. The necessary effort to prolong overall survival is still to achieve advisable EOR.
Establishment and validation of a clinicopathological prognosis model of gastroenteropancreatic neuroendocrine carcinomas
Authors: Chen Jing , Liu Yibing , Xu Ke , Ren Fei , Li Bowen , Sun Hong 
Published: September 2022

BackgroundGastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are a rare, highly malignant subset of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, how to predict the prognosis of GEP-NECs by clinical features is still under study. This study aims to establish and validate a nomogram model of overall survival (OS) in patients with GEP-NECs for predicting their prognosis.MethodsWe selected patients diagnosed with GEP-NECs from the Surveillance, Epidemiology, and End Results (SEER) database and two Chinese hospitals. After randomization, we divided the data in the SEER database into the train cohort and the test cohort at a ratio of 7:3 and used the Chinese cohort as the validation cohort. The Cox univariate and multivariate analyses were performed to incorporate statistically significant variables into the nomogram model. We then established a nomogram and validated it by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, the area under the curve (AUC), and the decision curve analysis (DCA) curve.ResultsWe calculated the nomogram C-index as 0.797 with a 95% confidence interval (95% CI) of 0.783–0.815 in the train cohort, 0.816 (95% CI: 0.794–0.833) in the test cohort and 0.801 (95% CI: 0.784–0.827) in the validation cohort. Then, we plotted the calibration curves and ROC curves, and AUCs were obtained to verify the specificity and sensitivity of the model, with 1-, 3- and 5-year AUCs of 0.776, 0.768, and 0.770, respectively, in the train cohort; 0.794, 0.808, and 0.799 in the test cohort; 0.922, 0.925, and 0.947 in the validation cohort. The calibration curve and DCA curves also indicated that this nomogram model had good clinical benefits.ConclusionsWe established the OS nomogram model of GEP-NEC patients, including variables of age, race, sex, tumor site, tumor grade, and TNM stage. This model has good fitting, high sensitivity and specificity, and good clinical benefits.
Population pharmacokinetic model of vancomycin in postoperative neurosurgical patients
Authors: Wei Shifeng , Zhang Dongjie , Zhao Zhigang , Mei Shenghui 
Published: September 2022

Objective: Vancomycin is commonly used in postoperative neurosurgical patients for empirical anti-infective treatment due to the low success rate of bacterial culture in cerebrospinal fluid (about 20%) and the high mortality of intracranial infection. At conventional doses, the rate of target achievement for vancomycin trough concentration is low and the pharmacokinetics of vancomycin varies greatly in these patients, which often leads to treatment failure. The objective of this study was to establish a population pharmacokinetic (PPK) model of vancomycin in postoperative neurosurgical patients for precision medicine.Method: A total of 895 vancomycin plasma concentrations from 560 patients (497 postoperative neurosurgical patients) were retrospectively collected. The model was analyzed by nonlinear mixed effects modeling method. One-compartment model and mixed residual model was employed. The influence of covariates on model parameters was tested by forward addition and backward elimination. Goodness-of-fit, bootstrap and visual predictive check were used for model evaluation. Monte Carlo simulations were employed for dosing strategies with AUC24 targets 400–600.Result: Estimated glomerular filtration rate (eGFR), body weight (BW) and mannitol had significant influence on vancomycin clearance (CL). eGFR(mL/min)=144×(Scr/a)b×0.993age, for female, a = 0.7, Scr ≤ 0.7 mg/dl, b = −0.329, Scr > 0.7 mg/dl, b = −1.209; for male, a = 0.9, Scr ≤ 0.9 mg/dl, b = −0.411, Scr > 0.9 mg/dl, b = −1.210. Vancomycin clearance was accelerated when co-medicated with mannitol and increased with eGFR and BW. In the final model, the population typical value is 7.98 L/h for CL and 60.2 L for apparent distribution volume, CL (L/h)=7.98×(eGFR/115.2)0.8×(BW/70)0.3×eA, where A = 0.13 when co-medicated with mannitol, otherwise A = 0. The model is stable and effective, with good predictability.Conclusion: In postoperative neurosurgical patients, a higher dose of vancomycin may be required due to the augmented renal function and the commonly used mannitol, especially in those with high body weight. Our vancomycin PPK model could be used for individualized treatment in postoperative neurosurgical patients.
Fuzheng Huayu Recipe and its active compounds inhibited HBeAg production by promoting TOMM34 gene expression in HBV-infected hepatocytes
Authors: Xing Lu , Zeng Rui , Huang Kai , Xue Jingbo , Liu Hongliang , Zhao Zhimin , Peng Yuan , Hu Xudong , Liu Chenghai 
Published: September 2022

Background and aim: Fuzheng Huayu Recipe (FZHY) is a Chinese patent medicine (approval No. Z20020074) included in the national medical insurance catalogue, which is mainly used for anti-hepatic fibrosis treatment of hepatitis B virus (HBV) induced liver fibrosis and liver cirrhosis. In clinical practice, we discovered that FZHY might also have a direct anti-HBV effect on inhibiting HBeAg production, but the mechanism underlying was unclear. This study aimed to clarify the molecular mechanism of the inhibition effect of FZHY on HBeAg production.Methods: The decrease degree of serum HBeAg titer in FZHY + entecavir (ETV) group patients were analyzed through clinical data. C57BL/6N-Tg (1.28HBV)/Vst HBV transgenic mice were used for in vivo experiments. HepG2. 2.15 cells (wild-type HBV replication cells) were used for in vitro experiments.Results: The clinical study results showed that the decrease degree of serum HBeAg titer in FZHY+ETV group was significantly higher than that in ETV group after 48 weeks treatment. In vivo experiments results showed that FZHY could significantly reduce the serum HBeAg titer in HBV transgenic mice, and promote HBeAg seroconversion. In vitro experiments results showed that FZHY could reduce HBeAg titer dependently, but it did not significantly inhibit the expression of HBsAg and HBV-DNA. Further cell experiments in vitro discovered that TOMM34 might be the key target for FZHY to inhibit HBeAg production. The subsequent pharmacological screening experiment of 20 active compounds in FZHY showed that quercetin, baicalin and cordycepin could promote the expression of TOMM34 gene and reduce the production of HBeAg.Conclusion: In conclusion, FZHY and its active compounds quercetin, baicalin and cordycepin could inhibit HBeAg production by promoting the expression of TOMM34 gene in HBV-infected hepatocytes.
Development of a novel cell-based, In-Cell Western/ERK assay system for the high-throughput screening of agonists acting on the delta-opioid receptor
Authors: Asghar Junaid , Latif Liaque , Alexander Stephen P. H. , Kendall David A. 
Published: September 2022

Background: Extracellular signal-regulated kinases (ERKs) are important signaling mediators in mammalian cells and, as a result, one of the major areas of research focus. The detection and quantification of ERK phosphorylation as an index of activation is normally conducted using immunoblotting, which does not allow high-throughput drug screening. Plate-based immunocytochemical assays provide a cheaper and relatively high-throughput alternative method for quantifying ERK phosphorylation. Here, we present optimization steps aimed to increase assay sensitivity and reduce variance and cost using the LI-COR In-Cell Western (I-CW) system in a recombinant CHO-K1 cell line, over-expressing the human delta-opioid receptor (hDOPr) as a model.Methods: Cells cultured in 96-well microassay plates were stimulated with three standard/selective DOPr agonists (SNC80, ADL5859, and DADLE) and a novel selective DOPr agonist (PN6047) to elicit a phospho-ERK response as an index of activation. A number of experimental conditions were investigated during the assay development.Key results: Preliminary experiments revealed a clearly visible edge-effect which significantly increased assay variance across the plate and which was reduced by pre-incubation for 30 min at room temperature. ERK phosphorylation was detectable as early as 1 min after agonist addition, with a distinct peak at 3–5 min. Optimization of the cell seeding densities showed that 25,000 cells per well have the lowest basal phospho-ERK response and an optimal agonist ERK1/2 signal. Pre-incubation with apyrase (an ATPase) did not reduce the basal or agonist responses. All agonists produced concentration-dependent increases in phospho-ERK activation, and pertussis toxin was able to attenuate these ERK responses. Naltrindole, which is a selective DOPr antagonist, was able to antagonize the DOPr-mediated ERK activation of the ligands.Conclusion: We have developed an optimization protocol and highlighted a number of considerations when performing this high-throughput fluorescence immunocytochemical (ICC) assay measuring ERK phosphorylation in the human DOPr. The optimized protocol was found to be a more conducive option for the screening of delta agonists. This provides a basis for additional assay development to investigate opioid pharmacology. This protocol should be widely applicable for measuring ERK phosphorylation in any cell line and investigating other protein targets in GPCR drug discovery.
Population pharmacokinetics of voriconazole and initial dosage optimization in patients with talaromycosis
Authors: Jiang Zhiwen , Wei Yinyi , Huang Weie , Li Bingkun , Zhou Siru , Liao Liuwei , Li Tiantian , Liang Tianwei , Yu Xiaoshu , Li Xiuying , Zhou Changjing , Cao Cunwei , Liu TaoTao 
Published: September 2022

The high variability and unpredictability of the plasma concentration of voriconazole (VRC) pose a major challenge for clinical administration. The aim of this study was to develop a population pharmacokinetics (PPK) model of VRC and identify the factors influencing VRC PPK in patients with talaromycosis. Medical records and VRC medication history of patients with talaromycosis who were treated with VRC as initial therapy were collected. A total of 233 blood samples from 69 patients were included in the study. A PPK model was developed using the nonlinear mixed-effects models (NONMEM). Monte Carlo simulation was applied to optimize the initial dosage regimens with a therapeutic range of 1.0–5.5 mg/L as the target plasma trough concentration. A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.34 L/h, the volume of distribution was 97.4 L, the absorption rate constant was set at 1.1 h-1, and the bioavailability was 95.1%. Clearance was found to be significantly associated with C-reactive protein (CRP). CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. ‏Monte Carlo simulation based on CRP levels showed that a loading dose of 250 mg/12 h and a maintenance dose of 100 mg/12 h are recommended for patients with CRP ≤ 96 mg/L, whereas a loading dose of 200 mg/12 h and a maintenance dose of 75 mg/12 h are recommended for patients with CRP &gt; 96 mg/L. The average probability of target attainment of the optimal dosage regimen in CRP ≤ 96 mg/L and CRP &gt; 96 mg/L groups were 61.3% and 13.6% higher than with empirical medication, and the proportion of Cmin &gt; 5.5 mg/L decreased by 28.9%. In conclusion, the VRC PPK model for talaromycosis patients shows good robustness and predictive performance, which can provide a reference for the clinical individualization of VRC. Adjusting initial dosage regimens based on CRP may promote the rational use of VRC.
Drug-induced kidney injury in Chinese critically ill pediatric patients
Authors: Hu Biwen , Ye Ling , Li Tong , Feng Zeying , Huang Longjian , Guo Chengjun , He Li , Tan Wei , Yang Guoping , Li Zhiling , Guo Chengxian 
Published: September 2022

Background: Drug-induced acute kidney injury (DIKI) is a common adverse drug reaction event but is less known in pediatric patients. The study explored the DIKI in Chinese pediatric patients using the Pediatric Intensive Care database (PIC).Method: We screened pediatric patients with acute kidney injury (AKI) using the KDIGO criteria from the PIC and then assessed the relationship between their drugs and DIKI using the Naranjo scale. For the fifteen frequently used DIKI-suspected drugs, we divided patients into drug-exposed and non-exposed groups, using the outcome of whether DIKI was presented or not. Propensity score matching (PSM) was used to control for the effects of four confounders, age, gender, length of hospital stay, and major diagnosis. Unconditional logistic regression was used to identify statistically significant differences between the two groups.Results: A total of 238 drugs were used 1,863 times by the 81 patients with DIKI during their hospital stay. After screening the Naranjo scale to identify the top 15 suspected DIKI drugs with a high frequency of use, we found that furosemide injection (p = 0.001), midazolam injection (p = 0.001), 20% albumin prepared from human plasma injection (p = 0.004), fentanyl citrate injection (p = 0.001), compound glycyrrhizin injection (p = 0.026), vancomycin hydrochloride for intravenous (p = 0.010), and milrinone lactate injection (p = 0.009) were associated with DIKI.Conclusion: In critically ill pediatric patients, DIKI is more likely to occur after using furosemide injection, midazolam injection, 20% albumin prepared from human plasma injection, fentanyl citrate injection, compound glycyrrhizin injection, vancomycin hydrochloride for intravenous, milrinone lactate injection.
Systematic evaluation of tumor microenvironment and construction of a machine learning model to predict prognosis and immunotherapy efficacy in triple-negative breast cancer based on data mining and sequencing validation
Authors: Gou Qiheng , Liu Zijian , Xie Yuxin , Deng Yulan , Ma Ji , Li Jiangping , Zheng Hong 
Published: September 2022

Background: The role of the tumor microenvironment (TME) in predicting prognosis and therapeutic efficacy has been demonstrated. Nonetheless, no systematic studies have focused on TME patterns or their function in the effectiveness of immunotherapy in triple-negative breast cancer.Methods: We comprehensively estimated the TME infiltration patterns of 491 TNBC patients from four independent cohorts, and three cohorts that received immunotherapy were used for validation. The TME subtypes were comprehensively evaluated based on immune cell infiltration levels in TNBC, and the TRG score was identified and systematically correlated with representative tumor characteristics. We sequenced 80 TNBC samples as an external validation cohort to make our conclusions more convincing.Results: Two TME subtypes were identified and were highly correlated with immune cell infiltration levels and immune-related pathways. More representative TME-related gene (TRG) scores calculated by machine learning could reflect the fundamental characteristics of TME subtypes and predict the efficacy of immunotherapy and the prognosis of TNBC patients. A low TRG score, characterized by activation of immunity and ferroptosis, indicated an activated TME phenotype and better prognosis. A low TRG score showed a better response to immunotherapy in TNBC by TIDE (Tumor Immune Dysfunction and Exclusion) analysis and sensitivity to multiple drugs in GDSC (Genomics of Drug Sensitivity in Cancer) analysis and a significant therapeutic advantage in patients in the three immunotherapy cohorts.Conclusion: TME subtypes played an essential role in assessing the diversity and complexity of the TME in TNBC. The TRG score could be used to evaluate the TME of an individual tumor to enhance our understanding of the TME and guide more effective immunotherapy strategies.
Modeling the expenditure and reconstitution of distance above critical speed during two swimming interval training sessions
Authors: Raimundo João Antônio Gesser , De Aguiar Rafael Alves , Lisbôa Felipe Domingos , Ribeiro Guilherme , Caputo Fabrizio 
Published: September 2022

In swimming, the speed-time relationship provides the critical speed (CS) and the maximum distance that can be performed above CS (D′). During intermittent severe intensity exercise, a complete D′ depletion coincides with task failure, while a sub-CS intensity is required for D′ reconstitution. Therefore, determining the balance D′ remaining at any time during intermittent exercise (D'BAL) could improve training prescription. This study aimed to 1) test the D'BAL model for swimming; 2) determine an equation to estimate the time constant of the reconstitution of D' (τD′); and 3) verify if τD′ is constant during two interval training sessions with the same work intensity and duration and recovery intensity, but different recovery duration. Thirteen swimmers determined CS and D′ and performed two high-intensity interval sessions at a constant speed, with repetitions fixed at 50 m. The duration of passive recovery was based on the work/relief ratio of 2:1 (T2:1) and 4:1 (T4:1). There was a high variability between sessions for τD' (coefficient of variation of 306%). When τD′ determined for T2:1 was applied in T4:1 and vice versa, the D'BAL model was inconsistent to predict the time to exhaustion (coefficient of variation of 29 and 28%). No linear or nonlinear relationships were found between τD′ and CS, possibly due to the high within-subject variability of τD'. These findings suggest that τD′ is not constant during two high-intensity interval sessions with the same recovery intensity. Therefore, the current D'BAL model was inconsistent to track D′ responses for swimming sessions tested herein.