bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt8b Regulates Myofibroblast Differentiation of Lung-Resident Mesenchymal Stem Cells via the Activation of Wnt/β-catenin Signaling in Pulmonary Fibrogenesis
Authors: Shi Chaowen , Chen Xiang , Yin Wenna , Hou Jiwei , Sun Zhaorui , Han Xiaodong 
Published: May 2021

Abstract
BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Lung resident mesenchymal stem cells (LR-MSCs) are important regulators of pathophysiological processes including tissue repair and inflammation, and evidence suggests that this cell population also plays an essential role in fibrosis. Our previous study demonstrated that Wnt/β-catenin signaling is aberrantly activated in the lungs of bleomycin-treated mice and induces myofibroblast differentiation of LR-MSCs. However, the underlying correlation between LR-MSCs and the Wnt/β-catenin signaling remains poorly understood. MethodsWe used mRNA microarray, immunohistochemistry assay, qRT-PCR, and western blotting to measure the expression of Wnt8b in myofibroblast differentiation of LR-MSCs and BLM-induced mouse fibrotic lungs. Immunofluorescence staining and western blotting were performed to analyze myofibroblast differentiation of LR-MSCs after overexpressing or silence Wnt8b. Moreover, we analyzed the effects of Wnt8b inhibition on BLM-induced pulmonary fibrosis by Sirius Red Staining and immunohistochemical staining.ResultsWe found that Wnt8b was highly expressed by LR-MSCs undergoing myofibroblast differentiation. In vitro, Wnt8b promoted LR-MSCs differentiate into myofibroblasts via activating Wnt/β-catenin signaling. Moreover, siRNA-mediated inhibition of Wnt8b prevented Transforming growth factor (TGF)-β1-induced myofibroblast differentiation of LR-MSCs in vitro and ameliorated pulmonary fibrotic lesions. Conclusions﻿Our study identified Wnt proteins and Wnt/β-catenin signaling in pulmonary fibrosis in vitro and in vivo, and highlighted Wnt8b as a potential therapeutic target in pulmonary fibrosis. Moreover, these finding might provide a new perspective in the development of treatment strategies for IPF.
Characteristics of immune cell infiltration landscape in colorectal cancer to Aid in Immunotherapy
Authors: Kuang Fei , Luo De , Zhou Mengjia , Du Juan , Liu Yuee , Li Yuehua 
Published: May 2021

Abstract
The tumor microenvironment (TME) is a complex environment composed of a variety of stromal cells and immune cells that infiltrate the tumor space. Recent clinical work has clearly shown such intratumoral immune cell infiltration (ICI) to be closely related to colorectal cancer (CRC) patient survival, yet the specific landscape of infiltrating immune cells associated with this cancer type remains to be clarified. We utilized two computational algorithms to evaluate the ICI status of 712 CRC patients, stratifying these patients into two ICI status-based patterns and assigning ICI scores through the use of principal component analyses. We found that the overall survival (OS) of patients with higher ICI scores was significantly longer than that of patients with low ICI scores. When ICI scores were combined with the results of tumor mutational burden (TMB) analyses, we determined that CRC patients with both high ICI scores and low TMB exhibited the best survival outcomes. High expression of MARCO in those patients with low ICI scores was correlated with reduced natural killer (NK) and effector T cell infiltration and with increased regulatory T cell infiltration, suggesting that these factors may be linked to poor patient prognosis. These results suggest ICI scores to be a valuable biomarker for the prognostic evaluation of CRC patients. Future efforts to analyze the ICI patterns of larger patient sample cohorts will help to extend these analyses, offering new insights into the role of the TME in cancer progression while highlighting novel immunotherapeutic approaches to treating this cancer type.
Performance of Rapid Rk39 Tests for the Diagnosis of Visceral Leishmaniasis in Ethiopia: A Systematic Review and Meta Analysis
Authors: Hagos Dawit Gebreegziabiher , Schallig Henk D.F.H. , Kebede Kebede , Abdulkadir Mahmud , Wolday Dawit 
Published: May 2021

Abstract
Background
Visceral Leishmaniasis (VL) is a severely neglected disease affecting millions of people with high mortality if left untreated. In Ethiopia, the primary laboratory diagnosis of VL is by using rK39-based rapid diagnostic tests (RDT). Different RDT brands are available with very variable performance and studies from Ethiopia showed a very wide range of sensitivity and specificity. Therefore, the objective of this systematic review and meta-analysis was to determine the pooled sensitivity and specificity of rk39 RDT in Ethiopia.
Method:
PUBMED, EMBASE, and google scholar were searched using predefined search terms to systematically retrieve all relevant articles. Eligibility screening was independently performed by two members and disparities were solved by other reviewers in the team. Methodological quality was also checked using the quality assessment of diagnostic accuracy studies (QUADAS-2) checklists.
Results
A total of 664 articles were retrieved from the PUBMED, EMBASE and google scholar online database searches. After removal of duplicates and initial, and final selection steps, 12 articles were included in the study. The overall pooled sensitivity and specificity of all rk39-based RDTs reported to diagnose VL in Ethiopia were 88.0 % ( 95%CI: 86.0–89.0%) and 84.0 % ( 95% CI: 82.0–86.0%), respectively. The sensitivity and specificity of the two rk39-based commercial test kits were for DiaMed RDT: 86.9% (95% CI: 84.3–89.1%) and 82.2 % ( 95% CI: 79.3–85.0%), and for InBios RDT: 80.0% (95% CI: 77.0–82.8%) and 97.4% (95% CI: 95.0–98.8%), respectively.
Conclusion
The sensitivity and specificity of rk39-based RDTs for the diagnosis of VL in Ethiopia were found to be lower compared to other parts of the world. However, the sensitivity of rk39-based RDTs was higher than in other east African countries. On the other hand, the specificity was lower than the east Africa studies (91.1%). The sensitivity and specificity of the rk39-based RDTs were in northern Ethiopia notably lower than in the other parts of Ethiopia.
Ictal Focal Hyperperfusion Demonstrated by Arterial Spin Labeling in Child With Refractory Frontal Lobe Epilepsy: A Case Report
Authors: Zhang Jia , Li Yang , Yuan Meng , Zhang Jinxiu , Luo Huan , Yao Zeshan , Gan Jing 
Published: May 2021

Abstract
BackgroundEpilepsy is one of the most common chronic neurological diseases, despite the great variety and prevalence of antiepileptic drug treatments, one-third of epilepsies remain drug-resistant. To our best knowledge, the patient reported in this case report is the first case of children with frontal lobe epilepsy achieving rapid and non-invasive surgical localization by arterial spin labeling (ASL) with EEG.Case presentationA 4-year-old previously healthy girl with repeated panic attacks and generalized tonic-clonic seizures. Levetiracetam, clonazepam, oxcarbazepine, and lacosamide were successively administrated with poor outcome. Seizure control was not obtained from any of these treatments. Using the quantitative analysis system of CBF, the imaging on PLD1025ms presented a mean CBF value of 17.81ml/100g/min for the lesion, 36% of the average value of the entire right hemisphere, thus presenting abnormally significant hypoperfusion. The patient became seizure free after lesionectomy of the frontal lobe by ASL combined with electroencephalogram (EEG) rapid localization. And the histopathological diagnosis was focal cortical dysplasia (FCD) type IIa. And there was no recurrence of the seizure was observed for 6 months after the operation.Conclusions﻿The positive outcome suggests that the combined use of ASL with EEG could be a beneficial option for presurgical evaluation of pediatric epilepsy.
Bendamustine Plus Rituximab Versus R-Minichop as First-Line Treatment in Unfit Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Study in China
Authors: Zhang Dongdong , Liu Tao , Kaweme Natasha Mupeta , Dong Youhong , Zhang Liling 
Published: May 2021

Abstract
Objective: To evaluate the efficacy and safety of bendamustine plus rituximab (BR) and low-does CHOP chemotherapy regimen-rituximab combination (R-miniCHOP) in elderly patients with diffuse large-B cell lymphoma, unfit for full dose immunochemotherapy.Method: Patients over 70 years with diffuse larger B-cell lymphoma or follicular lymphoma grade 3B, defined as unfit according to Comprehensive Geriatric Assessment (CGA), were included in our study. BR or R-miniCHOP was individualized according to the patients’ performance status and the presence of comorbidities. All the patients were received 4-6 cycles of immunochemotherapy at three-week intervals. Objective remission rate and adverse reaction were evaluated between the two groups.Result: This study included thirty-two patients enrolled between January 2020 and November 2020. The median age was 74 years (range 70-82). Twelve patients received BR, whereas twenty patients were treated with R-miniCHOP. The objective remission rate in the BR group was a slightly higher than the R-miniCHOP group (83.3% vs 75%), but with no statistical significance (P = 0.581). Furthermore, the objective remission rate was influenced by a serum beta 2 microglobulin concentration of 3 mg/L or less. The BR group showed a lower incidence of leukopenia than the R-miniCHOP group (P = 0.029), but had a higher incidence of fever (P = 0.036). Conclusion: BR showed equivalent efficacy but more improved safety in unfit patients with diffuse large-B cell lymphoma compared to R-miniCHOP. BR should be considered as an alternative treatment in this subgroup of patients.
Assessment of Life Factors Affecting the Occurrence of Depressive Episodes in Adolescents: a Secondary Analysis Using the Korea Youth Risk Behavior Survey
Authors: Lee Jongha , Han Changsu , Ko Young-Hoon , Lee Moon-Soo , Yoon Ho-Kyoung 
Published: May 2021

Abstract
Background Adolescence is a period that witnesses many changes in lifestyle, such as in social activity and school life, and it is vulnerable to the depressive disorder. Therefore, we intended to evaluate the factors affecting the onset of depressive episodes. Methods We conducted a secondary analysis using the 2019 Korean Youth Risk Behavior Web-based survey data, including a total of 57,303 subjects from the first year of middle school to the third year of high school and selected among 400 schools. Factors including dietary habits, physical activity, study time, internet use time and other health risk behaviors were included in the analysis. Logistic regression analysis was performed to evaluate the risk of occurrence of depressive episodes. Results Physical activity, internet use for more than three hours on weekdays, and a study time of more than two hours on weekends were assessed as risk factors of depressive episodes. On the other hand, internet use on weekends and having breakfast regularly were suggested as a protective way to reduce risk in Korean students. Conclusion We identified the factors influencing the depressive episode of adolescents. We suggest that activities appropriate to the culture and lifestyle of adolescents should be recommended in order to reduce the occurrence of depressive episodes.
MiR-214 promotes carcinogenesis in triple-negative breast cancer by inhibiting FRK expression
Authors: Lee Jieun , Oh Sooeun , Kim Dong-Min , Kang Jun , Lee Ahwon 
Published: May 2021

Abstract
Background Triple-negative breast cancer (TNBC) is known to have a poor prognosis with limited treatment options. In-house data revealed that miR-214 was up-regulated in breast cancer tissue, but there have been conflicting results about the role of miR-214 in oncogenesis in breast cancer. In this study, we aimed to investigate the potential role of miR-214 and its target in carcinogenesis.Methods We used three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and control breast epithelial cell line (MCF-10A) to evaluate miR-214 expression and function. Target genes were predicted based on pre-formed miRNA databases. miR-214 was transfected into cell lines, and cell proliferation, invasion and migration assays, and RT-PCR analysis were performed. Results MiR-214 was significantly overexpressed in MDA-MB-231 line, which represents TNBC. Fyn-related kinase (FRK) was selected as a potential target of miR-214. Endogenous FRK levels were down-regulated in MDA-MB-231 cells. miR-214 transfected MDA-MB-231 cell line resulted in increased cell proliferation, and silencing FRK using si-FRK also induced cell proliferation in MDA-MB-231 cells. When MDA-MB-231 cells were transfected with miR-214, cell invasion and migration were enhanced. Furthermore, si-FRK-transfected MDA-MB-231 cells showed increased cell invasion and migration compared to the control cells. Conclusions Our results suggest that miR-214 might play a role in tumor proliferation and invasion to promote breast cancer oncogenesis by suppressing FRK activity, leading to cancer progression.
Thyroid Hormone Replacement Therapy Is Associated With Longer Overall Survival in Patients With Resectable Gastroesophageal Cancer - a Retrospective Single Center Analysis
Authors: Puhr Hannah Christina , Reiter Thorsten J , El-Mahrouk Mohamed , Saliternig Lena , Wolf Peter , Mair Maximilian J , Steindl Ariane , Paireder Matthias , Asari Reza , Schoppmann Sebastian F , Berghoff Anna S , Preusser Matthias , Ilhan-Mutlu Ayseguel 
Published: May 2021

Abstract

Purpose: As thyroid hormones modulate proliferative pathways, it is surmised that they can be associated with cancer development. Since the potential association of gastroesophageal cancer and thyroid disorders has not been addressed so far, the aim of this study was to investigate the association of thyroid hormone parameters with the outcome of these patients, so novel prognostic and even potentially therapeutic markers can be defined. Methods: Clinical and endocrinological parameters of patients with resectable gastroesophageal cancer treated between 1990 and 2018 at the Vienna General Hospital, Austria including history of endocrinological disorders and laboratory analyses of thyroid hormones at first cancer diagnosis were investigated and correlated with the overall survival (OS).Results: In a total of 865 patients, a tendency towards prolonged OS in hypothyroid patients (euthyroid, n=647: median OS 29.7 months; hyperthyroid, n=50: 23.1 months; hypothyroid, n=70: 47.9 months; p=0.069) as well as a significant positive correlation of thyroid hormone replacement therapy with the OS was observed (without, n=53: median OS 30.6 months; with, n=67: 51.3 months; p=0.017). Furthermore, triiodothyronine (T3) levels were also associated with the OS (median OS within limit of normal: 23.4, above: 32.4, below: 9.6 months; p=0.045).Conclusion: Thyroid disorders and their therapeutic interventions might be associated with the OS in patients with resectable gastroesophageal cancer. As data on the correlation of these parameters is scarce, this study proposes an important impulse for further analyses concerning the association of thyroid hormones with the outcome in patients with gastroesophageal tumors.
In-Silico Investigation towards the Non-Invasive Optical Detection of Blood Lactate
Authors: Chatterjee Subhasri , Budidha Karthik , Qassem Meha , Kyriacou Panicos A. 
Published: May 2021

Abstract
This paper uses Monte Carlo simulations to investigate the interaction of shortwave infrared (SWIR) light with vascular tissue as a step toward the development of a non-invasive optical sensor for measuring blood lactate in humans. The primary focus of this work was to determine the optimal source-detector separation, penetration depth of light at SWIR wavelengths in tissue, and the optimal light power required for reliable detection of lactate. The investigation also focused on determining the non-linear variations in absorbance of lactate at a few select SWIR wavelengths. SWIR photons only penetrated 1.3 mm and did not travel beyond the hypodermal fat layer. The maximum output power was only 2.51% of the input power, demonstrating the need for a highly sensitive detection system. Simulations optimized a source-detector separation of 1 mm at 1684 nm for accurate measurement of lactate in blood.
FDA-Approved Antitussive Dextromethorphan Enhances Antifibrotic Effectiveness of Pirfenidone In Bleomycin-Induced Mice and Patients With Idiopathic Pulmonary Fibrosis
Authors: Liu Nana , Wang Yubao , Huang Jie , Du Yunze , Wei Luqing , Li Dongsheng , Hong Jau-Shyong , Ning Wen , Feng Jing 
Published: May 2021

Abstract
Background: We aimed to investigate whether dextromethorphan (DM), an antitussive, can improve the antifibrotic efficacy of pirfenidone in treating idiopathic pulmonary fibrosis, a fatal interstitial lung disease characterized by progressive and irreversible respiratory failure. Methods: A bleomycin-induced mice pulmonary fibrosis study and an open label randomized clinical trial were performed to evaluate the effectiveness of pirfenidone combined with DM.Results: In the animal study, pirfenidone combined with DM protected mice against bleomycin-induced pulmonary fibrosis with better capabilities than pirfenidone alone or DM alone indicated by lung histologic analysis and hydroxyproline levels. In the clinical study, pirfenidone plus DM markedly mitigated pulmonary functions (FEV1 and FVC) decline and ameliorated chest HRCT imaging scores (ground glass opacities and reticulation) of patients with IPF than pirfenidone alone at one year after administration. There were no significant differences in adverse reactions between pirfenidone-DM group and pirfenidone group.Conclusions: DM significantly potentiates antifibrotic effectiveness of pirfenidone in a mouse IPF model and patients with IPF and does not increase side effects of pirfenidone.
NF-kB-Dependent Activation of STAT3 by H. Pylori is Suppressed by TFF1
Authors: Soutto Mohammed , Bhat Nadeem , Khalafi Shayan , Zhu Shoumin , Poveda Julio , Garcia-Buitrago Monica , Zaika Alexander , El-Rifai Wael 
Published: May 2021

Abstract
Background: H. pylori infection is the main risk factor for gastric cancer. In this study, we investigated H. pylori-mediated activation of STAT3 and NF-κB in gastric cancer, using in vitro and in vivo models.Methods: To investigate the activation of NF-κB and STAT3 by H. pylori strains we used In vitro and in vivo mouse models, western blots, immunofluorescence, ChIP Assay, luciferase and quantitative real-time PCR assays.Results: Following infection with H. pylori in vitro, we found an earlier phosphorylation of NF-kB-p65 (S536), followed by STAT3 (Y705). Immunofluorescence, using in vitro and in vivo models, demonstrated nuclear localization of NF-kB and STAT3, following H. pylori infection. NF-kB and STAT3 luciferase reporter assays confirmed earlier activation of NF-kB followed by STAT3. In vitro and in vivo models demonstrated induction of mRNA expression of IL-6 (p<0.001), VEGF-α (p<0.05), IL-17 (p<0.001), and IL-23 (p<0.001). Using ChIP, we confirmed co-binding of both NF-kB-p65 and STAT3 on the IL6 promoter. The reconstitution of Trefoil Factor 1 (TFF1) suppressed activation of NF-kB with reduction in IL6 levels and STAT3 activity, in response to H. pylori infection. Using pharmacologic (BAY11-7082) and genetic (IκB super repressor (IκBSR)) inhibitors of NF-kB-p65, we confirmed the requirement of NF-kB-p65 for activation of STAT3, as measured by phosphorylation, transcription activity, and nuclear localization of STAT3 in in vitro and in vivo models. Conclusion: Our findings suggest the presence of an early autocrine NF-kB-dependent activation of STAT3 in response to H. pylori infection. TFF1 acts as an anti-inflammatory guard against H. pylori mediated activation of pro-inflammatory networks.
Diagnostic Value Comparison of CellDetect, Fluorescent In Situ Hybridization (FISH) and Cytology in Urothelial Carcinoma
Authors: Shang Donghao , Xu Xiuhong , Liu Yuting , Chen Zhenghao , Wang Daye 
Published: May 2021

Abstract
Background To evaluate clinical effectiveness of a novel CellDetect method, when compared with Fluorescent In Situ Hybridization (FISH), and urine cytology, in the diagnosis of urothelial carcinoma (UC). Methods A total of 264 patients with suspicious UC were enrolled in this study, all tissue specimens were collected by biopsy or surgery. Urine was obtained for examinations prior to the surgical procedure, CellDetect staining was carried out with CellDetect kit and FISH was performed with UroVysion detection kit according to the manufacturer's instructions. All urine cytology specimens were centrifuged and obtained by cytospin method, the slides were stained by standard Papanicolaou method.Results There were 128 cases of UC and 136 cases of non-UC in this study, with no significant difference in gender and age between the two groups. Our results indicated that the sensitivity of CellDetect, FISH, and urine cytology was 82.8%, 83.6%, and 39.8%, respectively. In addition, the specificity of the three examinations was 88.2%, 90.4%, and 86.0%, respectively. The sensitivity of CellDetect and FISH are significantly superior compared to conventional urine cytology, however, there was no significant difference in specificity among three staining techniques. In addition, the sensitivity of CellDetect in lower urinary tract UC, upper urinary tract UC, NMIBC, and MIBC was 83.3%, 81.8%, 83.5%, and 72.0%, respectively, the screening ability of CellDetect has no correlation with tumor location and stage. Sensitivity of CellDetect in low grade and high grade UC was 51.6% and 92.8%, screening ability of CellDetect in high grade UC is significantly superior compared to that in low grade UC.Conclusions CellDetect and FISH show equal value in diagnosing UC, both are superior to that of conventional urine cytology. Compared to FISH, CellDetect is cost-effective and easier to operate, it has extensive clinical application value in monitoring recurrence of UC and screening of indetectable UC.