bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Prognostic Value of CD133 in Predicting the Relapse and Recurrence Pattern of High-Grade Gliomas on MRI: A Meta-Analysis
Authors: Abdoli Shadbad Mahdi , Hosseinkhani Negar , Asadzadeh Zahra , Brunetti Oronzo , Silvestris Nicola , Baradaran Behzad 
Published: September 2021

BackgroundCancer stem cells have been implicated in tumor relapse, tumor invasion, and cancer therapy resistance in high-grade gliomas; thus, characterizing cancer stem cell-related markers can help determine the prognosis of affected patients. Preclinical studies have reported that CD133 is implicated in tumor recurrence and cancer therapy resistance in high-grade gliomas; however, clinical studies have reported inconclusive results regarding its prognostic value in patients with high-grade gliomas.MethodsWe systematically searched the PubMed, Scopus, Web of Science, and Embase databases to obtain peer-reviewed studies published before March 10, 2021. Then, we conducted the current systematic review and meta-analysis based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. By applying the random-effect model, the effect size of studies investigating the progression-free survival (PFS), time to local recurrence (TTL), and time to distant recurrence (TTD) were calculated using RevMan version 5.4. The heterogeneity between the included studies was studied by the I2 index and Cochran’s Q test. Egger test was performed on funnel plots to investigate the potential asymmetry and publication bias among the included studies using CMA version 2.ResultsWith the 10% cut-off, CD133 protein overexpression is associated with the inferior PFS of patients with high-grade gliomas. Increased CD133 protein expression is associated with sooner distant tumor recurrence on MRI in glioblastoma patients and patients with high-grade gliomas and improved TTL on MRI in glioblastoma patients.ConclusionBased on the current evidence from 1086 patients with high-grade gliomas, CD133 overexpression is a valuable marker to predict tumor relapse and tumor recurrence patterns in patients with high-grade gliomas.
Low-Dose Apatinib Combined With S-1 in Refractory Metastatic Colorectal Cancer: A Phase 2, Multicenter, Single-Arm, Prospective Study
Authors: Li Ning , Deng Wenying , Zhang Guifang , Du Yali , Guo Yanwei , Ma Yijie , Wei Chen , Bie Liangyu , Zhang Chi , Song Tao , Luo Suxia , Fang Baijun 
Published: September 2021

PurposeApatinib is an approved third-line treatment for metastatic gastric cancer in China and demonstrates good safety, tolerability, and efficacy in other advanced solid tumors. The aim of this prospective, single-arm, multicenter, phase 2 study was to assess the efficacy and safety of low-dose apatinib combined with S-1 in the treatment of refractory mCRC.Patients and MethodsPatients with refractory mCRC were enrolled and administered apatinib combined with S-1 until disease progression, patient decision to withdraw, or unacceptable toxic effects. The primary endpoint was investigator-evaluated progression-free survival (PFS) and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR).ResultsFrom December 2017 to December 2018, 30 patients were enrolled and 29 patients were eligible for the evaluation of efficacy and safety. The median PFS (mPFS) and OS (mOS) were 7.9 and 12.9 months, respectively. Exploratory analysis revealed that patients administered S-1 ≥ 70 days achieved longer mPFS and mOS. Four patients achieved a partial response, 22 achieved stable disease, and three had progressive disease, attributing to an ORR of 13.79% and a DCR of 89.66%. Ten grade 3 adverse events were reported and the frequency of each grade 3 adverse event was less than 5%. No grade 4 side events were observed.ConclusionsThese results indicated that apatinib combined with S-1 showed promising efficacy and manageable toxicity in patients with progressive mCRC after at least 2 prior lines of therapy, making it a promising therapeutic option for mCRC treatment.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT03397199, identifier NCT03397199.
Development and Validation of a Clinical Prognostic Nomogram for Esophageal Adenocarcinoma Patients
Authors: Shao Chen-ye , Yu Yue , Li Qi-fan , Liu Xiao-long , Song Hai-zhu , Shen Yi , Yi Jun 
Published: September 2021

BackgroundClinical staging is essential for clinical decisions but remains imprecise. We purposed to construct a novel survival prediction model for improving clinical staging system (cTNM) for patients with esophageal adenocarcioma (EAC).MethodsA total of 4180 patients diagnosed with EAC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and included as the training cohort. Significant prognostic variables were identified for nomogram model development using multivariable Cox regression. The model was validated internally by bootstrap resampling, and then subjected to external validation with a separate cohort of 886 patients from 2 institutions in China. The prognostic performance was measured by concordance index (C-index), Akaike information criterion (AIC) and calibration plots. Different risk groups were stratified by the nomogram scores.ResultsA total of six variables were determined related with survival and entered into the nomogram construction. The calibration curves showed satisfied agreement between nomogram-predicted survival and actual observed survival for 1-, 3-, and 5-year overall survival. By calculating the AIC and C-index values, our nomogram presented superior discriminative and risk-stratifying ability than current TNM staging system. Significant distinctions in survival curves were observed between different risk subgroups stratified by nomogram scores.ConclusionThe established and validated nomogram presented better risk-stratifying ability than current clinical staging system, and could provide a convenient and reliable tool for individual survival prediction and treatment strategy making.
Adherence to the Porto Criteria Based on the Hungarian Nationwide Pediatric Inflammatory Bowel Disease Registry (HUPIR)
Authors: Müller Katalin E. , Dezsőfi Antal , Cseh Áron , Szűcs Dániel , Vass Noémi , Nemes Éva , Kadenczki Orsolya , Tárnok András , Szakos Erzsébet , Guthy Ildikó , Kovács Márta , Karoliny Anna , Czelecz Judit , Tokodi István , Tomsits Erika , Veres Gábor 
Published: September 2021

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort.Methods: Newly diagnosed pIBD cases (ages 0–18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016.Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% (p &lt; 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 (p &lt; 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%).Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%.
Changes of Infant- and Family-Centered Care Practices Administered to Extremely Preterm Infants During Implementation of the NIDCAP Program
Authors: Klein Valérie , Zores-Koenig Claire , Dillenseger Laurence , Langlet Claire , Escande Benoît , Astruc Dominique , Le Ray Isabelle , Kuhn Pierre ,   Strasbourg NIDCAP Study group
Published: September 2021

Introduction:Many studies have evaluated the Neonatal Individualized Developmental Care and Assessment Program (NIDCAP), but few studies have assessed changes in infant- and family-centered developmental care (IFCDC) practices during its implementation.Objectives:The primary objective of this single center study was to investigate the impact of the implementation of the NIDCAP program on IFCDC practices used for management of extremely preterm infants (EPIs). The secondary objective was to determine during implementation the impact of this program on the short-term medical outcomes of all EPIs hospitalized at our center.Methods:All EPIs (&lt;28 weeks gestational age) who were hospitalized at Strasbourg University Hospital from 2007 to 2014 were initially included. Outborn infants were excluded. The data of EPIs were compared for three time periods: 2007 to 2008 (pre-NIDCAP), 2010 to 2011, and 2013 to 2014 (during-NIDCAP implementation) using appropriate statistical tests. The clinical and caring procedures used during the first 14 days of life were analyzed, with a focus on components of individualized developmental care (NIDCAP observations), infant pain management (number of painful procedures, clinical pain assessment), skin-to-skin contact (SSC; frequency, day of initiation, and duration), and family access and involvement in the care of their children (duration of parental presence, parental participation in care). The short-term mortality and morbidity at discharge were evaluated.Results:We examined 228 EPIs who received care during the three time periods. Over time, painful procedures decreased, but pain evaluations, parental involvement in care, individualized observations, and SSC increased (allp&lt; 0.01). In addition, the first SSC was performed earlier (p= 0.03) and lasted longer (p&lt; 0.01). There were no differences in mortality and morbidity, but there were reductions in the duration of mechanical ventilation (p= 0.02) and the time from birth to first extubation (p= 0.02), and an increase of weight gain at discharge (p= 0.02).Conclusion:NIDCAP implementation was accompanied by progressive, measurable, and significant changes in IFCDC strategies. There were, concomitantly, moderate but statistically significant improvements in multiple important outcome measures of all hospitalized EPI.
Whey Protein Lipid Concentrate High in Milk Fat Globule Membrane Components Inhibit Porcine and Human Rotavirus in vitro
Authors: Monaco Marcia H. , Gross Gabriele , Donovan Sharon M. 
Published: September 2021

Background: The milk fat globule membrane (MFMG) is a complex milk component that has been shown to inhibit rotavirus (RV) binding to cell membranes in vitro. Herein, a whey protein lipid concentrate high in MFGM components (WPLC) and whey protein concentrate (WPC; control) were screened for anti-infective activity against porcine OSU and human Wa strains of RV in both the African Green Monkey kidney (MA104) and the human colorectal adenocarcinoma (Caco-2) cell lines.Materials and Methods: Confluent cells were exposed to OSU or Wa RV in the presence of WPLC or WPC (control) at 0, 0.1, 0.5, 1.0, 2.5, or 5 mg/ml. Infectivity was detected by immunohistochemistry and expressed as % inhibition relative to 0 mg/ml. WPLC efficacy over WPC was expressed as fold-change. One-way ANOVA analyzed data for the independent and interactive effects of concentration, test material, and RV strain.Results: Both WPLC and WPC exhibited concentration-dependent inhibition of human Wa and porcine OSU RV infectivity in MA104 and Caco-2 cells (p &lt; 0.0001). WPLC was 1.5–4.8-fold more effective in reducing infectivity than WPC. WPLC efficacy was independent of RV strains, but varied between cell lines. WPLC and WPC at concentrations ≥0.5 mg/mL were most effective in reducing human Wa RV infectivity in MA104 cells (p &lt; 0.0001).Conclusions: WPLC decreased infectivity of two strains for RV which differ in their dependency on sialic acid for binding to cells. Inhibition was observed in the most commonly used cell type for RV infectivity assays (MA104) and an intestinal cell line (Caco-2). An effect on virus infectivity might be a potential mechanisms of action contributing to beneficial effects of supplementation of infant formula with MGFM reducing the risk of infections and consequently diarrhea incidence in infants.
Is Curcumin at the Threshold of Therapeutic Effectiveness on Patients with Colon Cancer?—A Systematic Review
Authors: Shafei Laila Khaled Ismael Abdelgawad , Mohamed Ibrahim Mohamed Izham , Billa Nashiru 
Published: September 2021

Curcumin, obtained from curcuma longa, has been the subject of decades of scientific investigation on its therapeutic usefulness. It is reported to possess several therapeutic properties, of which anti-colon cancer is of interest in this review. Clinically however, curcumin has yet to firm up its place among established anti-colon cancer therapeutic contenders. We aimed to systematically review prevailing clinical evidence on the role of curcumin in colon cancer treatment. The review drawing from literature on clinical studies indicates fairly long term tolerability. No regression of tumor was reported when curcumin was the sole intervention. Increase in p53 level expression was reported in a placebo controlled study but no reduction in PGE2 or 5HETE. Pharmacokinetic data on healthy humans indicate that formulated curcumin delivery systems present significantly higher systemic bioavailability. It appears therefore that the clinical use of curcumin can potentially be realized only through appropriate formulation interventions.Systematic Review Registration: [website], identifier [registration number]
Lcz696 Alleviates Myocardial Fibrosis After Myocardial Infarction Through the sFRP-1/Wnt/β-Catenin Signaling Pathway
Authors: Liu Jing , Zheng Xuehui , Zhang Chen , Zhang Chunmei , Bu Peili 
Published: September 2021

Background: Lcz696 (ARNI, angiotensin receptor–neprilysin inhibitor; sacubitril/valsartan) shows an inhibitory effect on fibrosis after myocardial infarction (MI). However, the underlying signaling mechanisms are poorly understood. The Wnt/β-catenin signaling pathway is activated after MI and participates in the process of myocardial fibrosis. Here, we aimed to assess the efficacy of ARNI for alleviating myocardial fibrosis after MI and hypothesized that ARNI alleviates myocardial fibrosis by inhibiting the Wnt/β-catenin signaling pathway and overexpressing sFRP-1, an inhibitor of the Wnt/β-catenin signaling pathway.Methods: Mice randomized at 1 week post-MI were administered lcz696 (60 mg/kg, n = 21), valsartan (30 mg/kg, n = 19), or corn oil (n = 13) orally for 4 weeks, while the sham-operated group received vehicle (corn oil, n = 19). Cardiac function and extent of myocardial fibrosis were measured. Western blotting and quantitative real-time polymerase chain reaction were used to detect the expression of Wnt/β-catenin pathway-related proteins. Furthermore, primary myocardial fibroblasts were stimulated with angiotensin II (Ang II) and cultured with lcz696 and the sFRP-1 inhibitor way316606 to detect the expression of Wnt/β-catenin pathway proteins.Results: Both lcz696 and valsartan alleviated myocardial fibrosis and improved cardiac function, but lcz696 had superior efficiency compared to valsartan. Furthermore, β-catenin expression was inhibited and sFRP-1 was overexpressed after drug treatment, which could be significantly improved by lcz696 in mice. In addition, lcz696 inhibited β-catenin expression in AngII-stimulated myocardial fibroblasts, and β-catenin expression increased after the inhibition of sFRP-1.Conclusion: ARNI alleviated cardiac fibrosis and cardiac remodeling by inhibiting the Wnt/β-catenin signaling pathway. In addition, ARNI can lead to overexpression of sFRP-1, which is an inhibitor of the Wnt/β-catenin signaling pathway. These results indicate a new therapeutic target of ARNI to improve myocardial fibrosis and prevent myocardial remodeling.
Population Pharmacokinetics of Rituximab in Pediatric Patients With Frequent-Relapsing or Steroid-Dependent Nephrotic Syndrome
Authors: Chen Yewei , Shen Qian , Dong Min , Xiong Ye , Xu Hong , Li Zhiping 
Published: September 2021

Objectives: Rituximab is frequently used off-label for the treatment of frequent-relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS), but the relapse rate remained high and the dosing regimen varied widely. The objective of this study was to characterize rituximab pharmacokinetics (PK) in pediatric patients with FRNS/SDNS, and to investigate the differences in rituximab PK between patients with FRNS/SDNS and other disease populations.Methods: Fourteen pediatric patients received rituximab for FRNS/SDNS treatment were enrolled in a prospective, open-label, single-center PK study. A population PK model of rituximab was developed and validated, and PK parameters were derived for quantitative evaluation.Results: A two-compartment PK model best described the data. Body surface area was the most significant covariate for both central clearance (CL) and apparent central volume of distribution (V1). Patients with FRNS/SDNS exhibited a clinically relevant increase in rituximab CL compared to patient population with non-Hodgkin’s lymphoma (NHL).Conclusion: This pilot study indicated that higher doses or more frequent regimens of rituximab may be required for optimal therapeutic effects in patients with FRNS/SDNS. Further clinical studies with more patients are warranted to confirm this result.
Characterization of Atrial Propagation Patterns and Fibrotic Substrate With a Modified Omnipolar Electrogram Strategy in Multi-Electrode Arrays
Authors: Riccio Jennifer , Alcaine Alejandro , Rocher Sara , Martinez-Mateu Laura , Laranjo Sergio , Saiz Javier , Laguna Pablo , Martínez Juan Pablo 
Published: September 2021

Introduction: The omnipolar electrogram method was recently proposed to try to generate orientation-independent electrograms. It estimates the electric field from the bipolar electrograms of a clique, under the assumption of locally plane and homogeneous propagation. The local electric field evolution over time describes a loop trajectory from which omnipolar signals in the propagation direction, substrate and propagation features, are derived. In this work, we propose substrate and conduction velocity mapping modalities based on a modified version of the omnipolar electrogram method, which aims to reduce orientation-dependent residual components in the standard approach.Methods: A simulated electrical propagation in 2D, with a tissue including a circular patch of diffuse fibrosis, was used for validation. Unipolar electrograms were calculated in a multi-electrode array, also deriving bipolar electrograms along the two main directions of the grid. Simulated bipolar electrograms were also contaminated with real noise, to assess the robustness of the mapping strategies against noise. The performance of the maps in identifying fibrosis and in reproducing unipolar reference voltage maps was evaluated. Bipolar voltage maps were also considered for performance comparison.Results: Results show that the modified omnipolar mapping strategies are more accurate and robust against noise than bipolar and standard omnipolar maps in fibrosis detection (accuracies higher than 85 vs. 80% and 70%, respectively). They present better correlation with unipolar reference voltage maps than bipolar and original omnipolar maps (Pearson's correlations higher than 0.75 vs. 0.60 and 0.70, respectively).Conclusion: The modified omnipolar method improves fibrosis detection, characterization of substrate and propagation, also reducing the residual sensitivity to directionality over the standard approach and improving robustness against noise. Nevertheless, studies with real electrograms will elucidate its impact in catheter ablation interventions.
Detecting Pathogen Exposure During the Non-symptomatic Incubation Period Using Physiological Data: Proof of Concept in Non-human Primates
Authors: Davis Shakti , Milechin Lauren , Patel Tejash , Hernandez Mark , Ciccarelli Greg , Samsi Siddharth , Hensley Lisa , Goff Arthur , Trefry John , Johnston Sara , Purcell Bret , Cabrera Catherine , Fleischman Jack , Reuther Albert , Claypool Kajal , Rossi Franco , Honko Anna , Pratt William , Swiston Albert 
Published: September 2021

Background and Objectives: Early warning of bacterial and viral infection, prior to the development of overt clinical symptoms, allows not only for improved patient care and outcomes but also enables faster implementation of public health measures (patient isolation and contact tracing). Our primary objectives in this effort are 3-fold. First, we seek to determine the upper limits of early warning detection through physiological measurements. Second, we investigate whether the detected physiological response is specific to the pathogen. Third, we explore the feasibility of extending early warning detection with wearable devices.Research Methods: For the first objective, we developed a supervised random forest algorithm to detect pathogen exposure in the asymptomatic period prior to overt symptoms (fever). We used high-resolution physiological telemetry data (aortic blood pressure, intrathoracic pressure, electrocardiograms, and core temperature) from non-human primate animal models exposed to two viral pathogens: Ebola and Marburg (N = 20). Second, to determine reusability across different pathogens, we evaluated our algorithm against three independent physiological datasets from non-human primate models (N = 13) exposed to three different pathogens: Lassa and Nipah viruses and Y. pestis. For the third objective, we evaluated performance degradation when the algorithm was restricted to features derived from electrocardiogram (ECG) waveforms to emulate data from a non-invasive wearable device.Results: First, our cross-validated random forest classifier provides a mean early warning of 51 ± 12 h, with an area under the receiver-operating characteristic curve (AUC) of 0.93 ± 0.01. Second, our algorithm achieved comparable performance when applied to datasets from different pathogen exposures – a mean early warning of 51 ± 14 h and AUC of 0.95 ± 0.01. Last, with a degraded feature set derived solely from ECG, we observed minimal degradation – a mean early warning of 46 ± 14 h and AUC of 0.91 ± 0.001.Conclusion: Under controlled experimental conditions, physiological measurements can provide over 2 days of early warning with high AUC. Deviations in physiological signals following exposure to a pathogen are due to the underlying host’s immunological response and are not specific to the pathogen. Pre-symptomatic detection is strong even when features are limited to ECG-derivatives, suggesting that this approach may translate to non-invasive wearable devices.