bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipopolysaccharide regulates thymic stromal lymphopoietin expression via TLR4/MAPK/Akt/NF-κB signaling pathways in nasal fibroblasts: differential inhibitory effects of macrolide and corticosteroid
Authors: Kang Ju-Hyung , Yang Hyun-Woo , Park Joo-Hoo , Shin Jae-Min , Kim Tae-Hoon , Lee Seung Hoon , Lee Heung-Man , Park Il-Ho 
Published: January 2020

Abstract
BackgroundChronic rhinosinusitis (CRS) is inflammatory disease of sinonasal mucosa. Thymic stromal lymphopoietin (TSLP) is associated with Th-2 response and induced by pathogen, allergen, Toll-like receptor (TLR) ligands, and cytokines. Fibroblasts have known to modulators of wound healing, from inflammation to tissue remodeling. We examined effect of lipopolysaccharide (LPS) on TSLP production and underlying mechanisms. We aimed to determine whether effects of commonly used medications in CRS, corticosteroids and macrolides, are related to LPS-induced TSLP in nasal fibroblasts.ResultsFibroblasts were isolated from inferior turbinate tissues of CRS patients. TSLP and TLR4 expression was determined by RT-PCR, western blot, ELISA, and immunofluorescence staining. MAPK, Akt, and NF-κB phosphorylation was determined by western blot and/or luciferase assay. LPS increased TSLP expression in a dose- and time-dependent manner. LPS antagonist and corticosteroids inhibited TLR4 expression in LPS-stimulated fibroblasts. LPS-RS, macrolides, corticosteroids, and specific inhibitors suppressed LPS-induced alterations. Ex vivo culture showed similar results.ConclusionsLPS induces TSLP production via TLR4, MAPK, Akt, and NF-κB pathways. Effects of corticosteroids and macrolides are related to LPS-induced TSLP expression. We would explore new treatment modalities targeting LPS-induced TSLP production that could replace current usage of corticosteroid and macrolides in treatment of CRS.
A Population-Based Survey to Assess Cannabis on Quality of Life among Colorectal Cancer Survivors
Authors: Calcaterra Susan , Burnett-Hartman Andrea N. , Powers J. David , Corley Douglas A , McMullen Carmit M , Pawloski Pamala A. , Feigelson Heather Spencer 
Published: January 2020

Abstract
Background: As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. Methods: A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network’s (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥ 18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. Results: Of the 1,784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% CI 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤ 4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of -6.14, 95% CI -8.07 to -4.20). Conclusion: Among CRC survivors, cannabis use was common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.
Surgical intra- and extra-articular anterior cruciate ligament reconstruction: a meta-analysis
Authors: Cheng Xiangyun , Liu Fanxiao , Zhou Dongsheng , Paulus Alexander C. 
Published: January 2020

Abstract
Background: It is still controversial whether the combination of anterior cruciate ligament (ACL) reconstruction and extra-articular reconstruction (EAR) have good clinical efficacy. This meta-analysis aims to compare the clinical effectiveness of ACL reconstruction and combined reconstruction. Methods: Electronic databases, including Medline/PubMed, Embase and the Cochrane Library, were systematically searched to identify targeted studies. A meta-analysis aims to pool the outcome estimates of interest, such as the Lysholm, International Knee Documentation Committee (IKDC) and Tegner scores and the results from the KT-1000/2000 arthrometer test, the Lachman test and the pivot shift test. Results : Twelve studies involving 1146 knees were identified. Compared with single ACL reconstruction, combined reconstruction had better results for a pivot shift of grade 1 (relative ratio [RR] = 0.88, 95% CI: 0.83-0.94) and grade 2 (RR = 0.95, 95% CI: 0.91-0.99) rather than grade 3 (RR = 0.98, 95% CI: 0.90-1.06) and no statistically significant difference for both Lachman grade 1 (RR = 0.96, 95% CI: 0.89-1.05) and grade 2 (RR = 0.96, 95% CI: 0.90-1.03). Combined reconstruction resulted in significant improvements on the instrumented joint laxity test when considering a failure standard of more than 5 mm (a side-to-side arthrometric difference) (RR = 0.94, 95% CI: 0.89-0.98) rather than 3 mm (RR = 0.94, 95% CI: 0.86-1.03). Moreover, combined reconstruction increased the IKDC score at the 12-month (weighted mean difference [WMD] = -6.38, 95% CI: -9.66 to -3.10), 24-month (WMD = -5.60, 95% CI: -8.54 to -2.66) and 36-month follow-ups (WMD = -4.71, 95% CI: -7.59 to -1.83) and the Tegner score at the 36-month follow-up (WMD = -0.53, 95% CI: -0.97 to -0.09), but it did not increase the Lysholm score at the 36-month follow-up (WMD = -0.84, 95% CI: -2.02 to 0.34). Conclusion : With the advances in reconstruction techniques, combined reconstructions were found to be effective in improving rotational stability and to lead to good functional scores. However, obviously, the combined reconstruction technique is more time-consuming and requires an additional incision, which is not suitable for all ACL-deficient patients. Therefore, programs should be personalized and customized for the specific situation of each patient.
Change in Serum Markers Failed to Predict Persistent Infection after Two-stage Exchange ArthroplastyChange in Serum Markers Failed to Predict Persistent Infection after Two-stage Exchange Arthroplasty
Authors: Jiang Qiao , Yang Xue , Xu Chi , Chai Wei , Zhou Yong-gang , Chen Jiying 
Published: January 2020

Abstract
BackgroundTwo-stage exchange arthroplasty is a viable choice for prosthetic joint infection (PJI). After removing the infected prosthesis and implanting an antibiotic-loaded spacer in first stage, the proper timing of reimplantation is crucial for successful treatment. So far, there is no gold reference to determine the eradication of PJI before reimplantation. The combination of serum indicators, synovial white cell count (WBC), culture results, intraoperative histology, and clinical symptoms is used extensively to guide the timing of reimplantation. However, the proper timing of reimplantation was ill defined.PurposeWe wonder: (1) the utility of serum indicators, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen, when predicted failure of reimplantation; (2) correlation between primary culture results and serum markers’ change.MethodA retrospective review of 226 patients treated with a two-stage exchange arthroplasty from 2014 to 2017 was conducted. PJI was diagnosed by using the Musculoskeletal Infection Society (MSIS) criteria. Serum biomarkers and organisms results at the set of PJI diagnosis and reimplantation were reviewed. Treatment success was defined according to the Delphi consensus criteria with a minimum follow-up of 2 year; receiver operator characteristic (ROC) depicted the utility of change in four serum markers when predicted failure.ResultsThe ROC area under the curves (AUC) was 0.543 in CRP, 0.572 in IL-6, 0.621 in ESR, 0.463 in fibrinogen and the combination of them was 0.709 when predicted persistent PJI using value change. The AUC of ROC was 0.521 in CRP, 0.472 in IL-6, 0.413 in ESR, 0.552 in fibrinogen and the combination was 0.630 when determine reimplantation by percent change. No significant association was found between culture results and change in serum markers.ConclusionNeither percent change nor value change in serum makers was proved to be poor markers when predicted persistent PJI, and initial causative organism didn’t influence the normalize of serum markers. Persistent PJI after TJA was still tough to diagnose. The combination of clinical symptom, pathology results, synovial fluid analysis and serum markers may improve the utility.
FBXL6 governs c-MYC to promote hepatocellular carcinoma through ubiquitination and stabilization of HSP90AA1
Authors: Shi Weidong , Feng Lanyun , Dong Shu , Ning Zhouyu , Hua Yongqiang , Liu Luming , Chen Zhen , Meng Zhiqiang 
Published: January 2020

Abstract
BackgroundHeat shot protein 90 (HSP90) AA1 functions as an onco-protein to regulate the assembly, manipulation, folding and degradation of its client proteins, including c-MYC. However, the mechanisms underlying the regulation of HSP90AA1 are poorly understood.MethodsTranscriptome RNA-sequencing data of Liver hepatocellular carcinoma (LIHC) samples were used to detect the mRNA expression of FBXL6. Immunoprecipitation/Mass Spectrum (IP/MS) method was used to identify the interacting proteins of FBXL6. The co-immunoprecipitation assay was used to determine the interaction between FBXL6 and HSP90AA1. The in vivo ubiquitination assay was performed to determine the regulation of HSP90AA1 by FBXL6. Luciferase reporter and chromatin immunoprecipitation assays were used to determine the transcriptional regulation of FBXL6 by c-MYC. Cell counting and colony formation assays were implemented to detect the biological effects of FBXL6 on the growth of HCC cells in vitro. The effect of FBXL6 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. ResultsHere, we identified the orphan F-box protein FBXL6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin ligase for HSP90AA1. FBXL6 promoted K63-dependent ubiquitination of HSP90AA1 to stabilize it. Through analysis of multiple public liver cancer GEO data, we found that FBXL6 was significantly increased in liver cancer tissues and positively correlated with c-MYC pathway. FBXL6 accumulation in liver cancers causes the stabilization and activation of c-MYC by preventing HSP90AA1 degradation. Activated c-MYC, which in turn directly binds to the promoter region of FBXL6 to induce its mRNA expression.ConclusionCollectively, our data revealed an unknown axis of FBXL6-HSP90AA1-c-MYC which might contribute to the oncogenesis of liver cancer, and we propose that inhibition of FBXL6 might represent an effective therapeutic strategy for liver cancer treatment.
Cultural Adaptation of Health Literacy Measures: Translation Validation of the Newest Vital Sign in Arabic-speaking Parents of Children with Type 1 Diabetes in Kuwait.
Authors: Al-Abdulrazzaq Dalia , Al-Taiar Abdullah , Al-Haddad Muneera , Al-Tararwa Abeer , Al-Zanati Nabeela , Al-Yousef Amna , Davidsson Lena , Al-Kandari Hessa 
Published: January 2020

Abstract
Background Low level of health literacy (HL) has been linked to several adverse health outcomes independently from education, ethnicity and socio-economic status. There is a dire need for a reliable tool to assess HL of patients and general public in Arab countries. This study aimed to assess the feasibility of use and reliability of the Arabic version of the Newest Vital Sign (NVS) in parents of children with type 1 diabetes (T1D).Methods Translation and cross-cultural adaptation of the Arabic version of the NVS (NVS-Ar) was conducted according to established guidelines. In order to investigate the functionality of NVS, the final version of NVS-Ar was administered to 175 adult caregivers of children with T1D, who are native Arabic speakers. We assessed the association between NVS-Ar score for the parents and HbA1C for their children. The internal consistency was evaluated by Cronbach’s Alpha (CA) and reliability was assessed by test retest method.Results The median (interquartile rang IQR) score was 4.0 (3-5). The internal consistency of the NVS-Ar was moderate (CA= 0.58). While the intraclass correlation coefficient (ICC) was 0.61. There was no correlation between NVS-Ar score and HbA1C (Spearman's rho = 0.055; p=0.62). Furthermore, there was significant inverse association between adequate HL and optimal glycemic control among children, which remained evident even after adjusting for the duration of T1D, age or education of the parents/child guardian. However, it lost statistical significance when we adjust for treatment regimen.Conclusion Our findings demonstrate that NVS is unlikely to be a predictive tool for functional HL in Arabic settings and that there is a need to properly translate and validate other tools such as TOFLA or alternatively develop a reliable tool de novo.
Endoscopic Thulium Laser Ablation of Upper Tract Urothelial Carcinoma: a Retrospective Study with Subgroup Analyses
Authors: Hsieh Yu Che , Huang Steven K. , Su Chia-Cheng , Wang Jhih-Cheng , Shen Kun-Hung , Feng I-Jung , Chiu Allen W. , Liu Chien-Liang 
Published: January 2020

Abstract
Introduction The gold standard treatment for upper tract urothelial carcinomas (UTUC) is radical nephroureterectomy with bladder-cuff excision. However, the role of combination of ureterorenoscopy and laser ablation has recently become more essential. This study aimed to investigate the efficacy of Thulium laser ablation of UTUC and estimate clinical outcomes with subgroup analyses. Methods After obtaining informed consent, we retrospectively reviewed all patients who had undergone endoscopic Thulium laser ablation of UTUC as their primary treatment from Jun 2012, to Nov 2018. Sixty-eight patient were enrolled, and thirty-four patients were analyzed after selection by exclusion criteria. Comparisons with bivariate analyses between patients with and without recurrence were examined. Multivariable cox regression model were further applied. Further, Kaplan-Meier survival estimate were presented with comparison of the survival curves, we also combined two of three tumor characteristics (stage, size, and grade of tumor) for subgroup analyses. Results Fifteen patients (44%) had local tumor recurrence. Seven patients (21%) had recurrence at the urinary bladder. Two patients (6%) had lymph node or distal metastasis. A total of 4 patients (12%) had cancer-specific death. In bivariate analyses, statistical significance is noted for age, tumor grade and tumor size with p-values of 0.018, 0.047 and 0.014, respectively. In the multivariable analysis, statistical significance is noted for age and tumor size with p-values of 0.017, and 0.042, respectively. In Kaplan–Meier estimate for subgroup analysis, statistical significance is only noted in the tumor size + tumor grade group but almost achieved in the tumor size + biopsy stage group with p-value of 0.0275 and 0.0518, respectively. Conclusion In our experience, tumor size and tumor grade are influential recurrence factors. However, biopsy stage does not achieve statistical significance in both the recurrence analysis and survival estimate. In the subgroup analyses, tumor size is a more influential factor than tumor grade in the prognosis of local recurrence.
Expression of serotonin 1A and 2A receptors in molecular- and projection-defined neurons of the mouse insular cortex
Authors: Ju Anes , Fernandez-Arroyo Beatriz , Wu Yifan , Jacky Débora , Beyeler Anna 
Published: January 2020

Abstract
The serotonin (5-HT) system is the target of multiple anxiolytics, including Buspirone, which is a partial agonist of the serotonin 1A receptor (5‑HT1A). Similarly, ligands of the serotonin 2A receptor (5-HT2A) were shown to alter anxiety level. The 5-HT1A and 2A receptors are widely expressed across the brain, but the target region(s) underlying the influence of those receptors on anxiety remain unknown. Interestingly, recent studies in human and non-human primates have shown that the 5-HT1A and 5-HT2A binding potential within the insular cortex (insula) are correlated to anxiety. As an initial step to define the function of 5‑HT transmission in the insula, we quantified the proportion of specific neuronal populations of the insula expressing 5‑HT1A or 5‑HT2A. We analyzed six neural populations, including two defined by their fast amino acid transmitter (excitatory or inhibitory), and four defined by their projections to different downstream targets. First, we found that more than 70% of glutamatergic neurons, and only 30% of GABAergic neurons express the 5‑HT1A. Second, 5-HT1A is highly expressed (~80%) in the insular populations projecting to two sub-nuclei of the amygdala (central and basolateral), as well as in the populations projecting to the rostral and caudal sections of the lateral hypothalamus (LH). Similarly, 70% of insular glutamatergic neurons and only 20% of insular GABAergic neurons contain 5-HT2A. Finally, the 5-HT2A is present in most of insula-amygdala and insula-LH projection neurons (>60%). These observations suggest that a majority of glutamatergic neurons can respond to 5-HT through 5-HT1A or 5‑HT2A in the insula, and that 5-HT directly affects a limited number of GABAergic neurons. This study defines a molecular and neuroanatomical map of the 5-HT system within the insular cortex, providing ground knowledge to identify the potential role of serotonergic modulation of selective insular populations in anxiety.
Serum IgG-indcued microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma
Authors: Ding Xu , Yang Wei , Ren Qinghua , Hu Jiajian , Yang Shen , Han Wei , Wang Jing , Wang Xu , Wang Huanmin 
Published: January 2020

Abstract
BackgroundOpsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis via several signaling pathways. However, mechanisms underlying OMS remain unclear. Here we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS.MethodsThe activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated.ResultsIncubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells. Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB, which was relieved by the inhibitors of NO signaling. By contrast, neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. Neuronal cytolysis was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG.Conclusions﻿Serum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate.
Widespread occurrence of Candidatus Phytoplasma ulmi infecting elm species in Germany
Authors: Schneider Bernd , Kätzel Ralf , Kube Michael 
Published: January 2020

Abstract
Background: Candidatus Phytoplasma ulmi is the causative agent of elm yellows and has been categorised in the European Union as a quarantine pathogen in the past. For central and northern European countries, information on the occurrence and distribution of the pathogen and its impact on elms is scarce, so a survey of native elm trees has been conducted in Germany. Results: About 6,500 samples in total, from Ulmus minor , Ulmus laevis and Ulmus glabra , were collected nationwide. Phytoplasma detection was performed by applying a universal 16Sr DNA-based real-time PCR assay and a novel Ca . P. ulmi species-specific real-time PCR assay targeting the 16S-23S spacer region. Both assays revealed that 28% of the samples were infected by Ca . P. ulmi, but infection rates of the elm species and regional incidences differed. The infection of trees is not correlated to disease-specific symptoms. The survey identified a regional disparity of infection which was high in east, south and central Germany, whereas only a few infected sites were found in the western and northern parts of the country. No correlation was apparent between altitude level and the prevalence of infection. First insights into the monitoring of the seasonal titre of Ca . P. ulmi in an infected tree by real-time PCR revealed high colonisation in all parts of the tree throughout the year. Conclusions: Ca . P. ulmi-infection is widely present in elms in Germany. The rare occurrence of symptoms indicates either a high degree of tolerance in elm populations or a low virulence of pathogen strains enabling high infection rates in a long-living host.
Fenofibrate decreased microalbuminuria in the type 2 diabetes patients with hypertriglyceridemia
Authors: Sun Xiaomeng , Liu Jia , Wang Guang 
Published: January 2020

Abstract
Background: This study was to research the efficacy of fenofibrate in the treatment of microalbuminuria in the patients with type 2 diabetes mellitus (T2DM) and hypertriglyceridemia.Methods: Type 2 diabetic patients (56) with microalbuminuria and hypertriglyceridemia aged 30 to 75 were randomly divided into the fenofibrate treatment group(n=28) and the control group (n=28) for 180 days. Urinary microalbumin /creatinine ratio (UACR) and other metabolic parameters were compared at baseline, during treatment and after treatment.Results: After 180 days, the reduction of levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in two groups were no differences. In treatment group, uric acid (UA) (296.42 ± 56.41 vs 372.46 ± 72.78), triglyceride (TG) [1.51(1.17, 2.06) vs 3.04(2.21, 3.29)], and UACR [36.45 (15.78,102.41) vs 129.00 (53.00, 226.25)] were significantly decreased compared with the baseline. The high-density lipoprotein cholesterol (HDL-C) levels were significantly increased (1.22 ± 0.26 vs 1.09 ± 0.24) compared with the baseline. The decrease in UACR [-44.05(-179.47, -12.16) vs -8.15(-59.69, 41.94)]in treatment group was significantly higher compared with the control group. The decrease in UACR was positively associated with the decreases in TG ( r = 0.447, P = 0.042) and UA ( r = 0.478, P = 0.024) after fenofibrate treatment.Conclusion: In the patients with hypertriglyceridemia and type 2 diabetes mellitus, fenofibrate can improve microalbuminuria and do not increase the deterioration of glomerular filtration rate