bluuebunny/crossref_metadata_2025_split huggingface dataset:
SLAMF7 Regulates Inflammatory Response In Macrophage During Polymicrobial Sepsis
Authors: Wu Yongjian , Lao Juanfeng , Li Miao , Wu Minhao , Ming Siqi , Liu Lei , Gong Sitang , Zhou Haibo , Huang Xi 
Published: February 2021

Abstract
Uncontrolled microbe-triggered inflammation results in multiple organ injury and shock in sepsis. However, the regulatory mechanisms that restrict cytokine storm are still elusive. Using gene screening, we identified an immunoglobulin-like receptor called Signaling Lymphocyte Activation Molecular Family-7 (SLAMF7), as a key regulator of inflammation during sepsis. We found that the expression of SLAMF7 on monocytes and macrophages was significantly elevated in sepsis subjects and septic mice. SLAMF7 attenuated TLR dependent MAPKs and NF-κB signaling activation by co-operating with Src homology 2-containing inositol‑5'‑phosphatase1 (SHIP1). Furthermore, SLAMF7 interacted with SHIP1 and TNF receptor associated factor 6 (TRAF6) to inhibite K63 ubiquitination of TRAF6. In addition, we found that intracellular domain tyrosine phosphorylation sites of SLAMF7 and phosphatase domain of SHIP1 were indispensable for the interaction of SLAMF7/SHIP1/TRAF6 and the modulation of cytokines production. Finally, recombinant murine SLAMF7 peptide agonist or genetic knockout of SLAMF7 in mice demonstrated that SLAMF7 confered protection against lethal sepsis and endotoxemia by suppressing inflammatory cytokines. Taken together, our findings reveal a critical negative regulatory role of SLAMF7 on cytokine storm in macrophages during polymicrobial sepsis, and therefore provide new sights into a novel diagnostic marker and therapeutic target for sepsis.
Exercise Training Ameliorates Cognitive Dysfunction in Amyloid Beta-injected Rat Model: Possible Mechanisms of Angiostatin/VEGF Signaling
Authors: Zarezadehmehrizi ALIASGHAR , Hong Junyoung , Lee Jong-hae , Rajabi Hamid , Gharakhanlou Reza , Naghdi Naser , Azimi Mohammad , Park Yoonjung 
Published: February 2021

Abstract
Vascular endothelial growth factor (VEGF) regulates angio/neurogenesis and also tightly links to the pathogenesis of Alzheimer’s disease (AD). Although exercise has a beneficial effect on neurovascular function and cognitive function, the direct effect of exercise on VEGF-related signaling and cognitive deficit in AD are incompletely understood. Therefore, the purpose of this study was to investigate the protective effect of exercise on angiostatin/VEGF cascade and cognitive function in AD model rats. Wistar male rats were randomly divided into five groups: control (CON), injection of DMSO (Sham-CON), CON-exercise (sham-EX), intrahippocampal injection of Aβ (AD), and AD-exercise (AD-EX). Rats in EX groups underwent treadmill exercise for 4 weeks, then the cognitive function was measured by the Morris Water Maze (MWM) test. mRNA levels of HIF-1, VEGF, VEGFR2, and angiostatin were determined by RT-PCR. We found that cognitive function was impaired in AD rats, but exercise training improved it. Moreover, exercise training increased the reduced mRNA expression level of VEGF signaling, including HIF1α, VEGF, and VEGFR2 in the hippocampus from AD rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from AD rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in AD, possibly through enhancing VEGF signaling and reducing angiostatin.
Machine Learning Model and Strategy for Fast and Accurate Detection of Leaks in Water Supply Network
Authors: Fan Xudong , Zhang Xijin , Yu Xiong (Bill) 
Published: February 2021

Abstract
The water supply network (WSN) is subjected to leaks that compromise its service to the communities, which, however, is challenging to identify with conventional approaches before the consequences surface. This study developed Machine Learning (ML) models to detect leaks in the WDN. Water pressure data under leaking versus non-leaking conditions were generated with holistic WSN simulation code EPANET considering factors such as the fluctuating user demands, data noise, and the extent of leaks, etc. The results indicate that Artificial Neural Network (ANN), a supervised ML model, can accurately classify leaking versus non-leaking conditions; it, however, requires balanced dataset under both leaking and non-leaking conditions, which is difficult for a real WSN that mostly operate under normal service condition. Autoencoder neural network (AE), an unsupervised ML model, is further developed to detect leak with unbalanced data. The results show AE ML model achieved high accuracy when leaks occur in pipes inside the sensor monitoring area, while the accuracy is compromised otherwise. This observation will provide guidelines to deploy monitoring sensors to cover the desired monitoring area. A novel strategy is proposed based on multiple independent detection attempts to further increase the reliability of leak detection by the AE and is found to significantly reduce the probability of false alarm. The trained AE model and leak detection strategy is further tested on a testbed WSN and achieved promising results. The ML model and leak detection strategy can be readily deployed for in-service WSNs using data obtained with internet-of-things (IoTs) technologies such as smart meters.
Appraisal of Pollution and Source Apportionment of Potentially Toxic Elements in Different Soils Collected around the Industrial Area
Authors: Verma Falwinder , Dhaliwal Salwinder Singh , Kumar Vinod , Kumar Rakesh , Singh Jaswinder , Parkash Chander , Singh Sharanpreet 
Published: February 2021

Abstract
It is imperative to understand the pollution of potentially toxic elements (PTEs) in different soils in order to determine the sustainable management approaches for soils. Potentially toxic elements (Fe, Mn, As, Pb, Zn, Ni, Cu, Cn, Co and Cd), and pH and organic carbon were determined in agricultural, non-agricultural and industrial soils of Indian, Punjab. The findings of PTEs indicated that industrial soils recorded highest concentration of PTEs followed by non-agricultural and agricultural soils. The percentage change recorded from agricultural to non-agricultural soils for PTEs were 3.19% for Fe, 25.3% for Mn, 63.8% for Cu, 13.5% for Cn, 49.8% for Pb, 79.6% for Ni, 35.8% for Co and 32% for Cd. From non-agricultural to industrial soils the percentage change observed for PTEs were 89% for Zn, 2.03% for Fe, 21.9% for Mn, 68.2% Cu, 9.2% for Cn, 35.8% for Pb, 18.4% for Co, 30.4% for Cd and 43.4% for As. The results of contamination factor, enrichment factor, geoaccumulation index, pollution and modified pollution indices indicated that Cd and As showed severe contamination in all studied soil types. Ecological risk assessment results revealed that Cd exhibited very risk in different soil types. The outcomes of this study will aid in forming approaches to decline the perils allied with PTEs in soils, and produce guidelines to save the environs from long term accrual of PTEs.
Metabolomic Profiling of Brain Protective Effect of Edaravine on Cerebral Ischemia-reperfusion Injury in Mice
Authors: Ma Hui-fen , Su Lin-jie , Zhang Da-wei , Gong Shuai-shuai , Liu Yi-ning , Zhang Yuan-yuan , Li Fang , Kou Junping 
Published: February 2021

Abstract
Edaravine (EDA) injection has seen extensively applied in clinic for treating stroke. Nevertheless, the metabolite signatures and underlying mechanisms associated with EDA remains unclear, which deserves further elucidation for improving the accuracy of EDA usage. Ischemia stroke was simulated by intraluminal occlusion of the right middle cerebral artery for 1 h followed by reperfusion for 24 h in mice. Brain infarct size, neurogical deficits and lactate dehydrogenase (LDH) level were improved by EDA. Significantly differential metabolites were screened with untargeted metabolomics by cross-comparisons with pre- and post-treatment of EDA under cerebral ischemia/reperfusion (I/R) injury. The possibly involved pathways, such as valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, taurine and hypotaurine metabolism, were enriched with differential metabolites and relatively regulatory enzymes, respectively. The network of differential metabolites was constructed for integral exhibition of metabolic characteristics. Targeted analysis of taurine, an important metabolic marker, was performed for further validating. The decreased level of taurine was confirmed in MCAO/R mice and increased by EDA. The inhibition of EDA on cerebral endothelial cell apoptosis was confirmed by TdT-mediated dUTP nick-end labeling (TUNEL) stain. Cysteine sulfinic acid decarboxylase (CSAD), the rate-limiting enzyme of taurine generation, significantly increased along with inhibiting endothelial cells apoptosis after treatment of EDA. Thus, CSAD, as the possible new therapeutic target of EDA was selected and validated by western blotting and immunofluorescence. Together, this study provided the metabolite signatures and identified CSAD as an unrecognized therapeutic intervention for EDA in treatment of ischaemic stroke via inhibiting brain endothelial cells apoptosis.
A Spatial Analysis of Negative Health Outcomes for Newborns Among Undocumented Immigrant Populations in the United States
Authors: Boyer Brittnee , Shaw Jenna , Tovar Ida , Read Rebekah , Sloan Chantel 
Published: February 2021

Abstract
Background Undocumented immigrants constitute a highly vulnerable population that may experience increased risk of negative health outcomes for newborn children. The spatial relationship between the proportion of undocumented immigrants residing in an area and negative birth outcomes has not been studied on a national scale, although real and perceived access to healthcare are unlikely to be geographically consistent. Methods We compiled estimates of the percent of undocumented immigrants, negative newborn health outcomes, and socioeconomic data for 173 counties in the United States, drawn and calculated from publicly-available databases. We used a negative binomial regression model to determine the relationship between undocumented immigrants and three negative birth outcomes: NICU admission, low birth weight, and infant mortality. Incidence rate ratios are reported as the primary analytical metric. Results A higher proportion of undocumented immigrants in a county was not a significant predictor of higher rates of negative health outcomes for newborns. However, counties with a higher Hispanic/Latino population, higher African American population, and higher percentages of persons with bachelor’s degrees were all associated with poorer outcomes. NICU admission rates were higher in counties with a high Hispanic/Latino population (IRR: 1.31) and counties with a high African American population (IRR: 1.29). Low birth weight had a similar trend (High Hispanic/Latino population IRR: 1.39; High African American population IRR: 1.32), along with infant mortality (High Hispanic/Latino population IRR: 1.37; High African American population IRR: 1.30). Those with high proportions of Republican voters were less likely to have negative birth outcomes; the incidence rate ratio for negative birth outcomes among a high level of Republican voters was 0.74 for admission into the NICU and 0.72 for low birth weight. Conclusion We did not find a statistical association between counties with high rates of undocumented immigrants and negative health outcomes for newborns. This could be the result of the healthy immigrant effect, incomplete data on undocumented immigrants, or there may be an association not statistically detectable at such a large spatial scale.
Integrative Bioinformatics and Experimental Investigation Introduces OBI1-AS1 as a Key LncRNA in the Progression of Low-grade Glioma to Glioblastoma
Authors: Mamivand Ali , Bayat Shiva , Maghrouni Abolfazl , Shabani Sasan , Khoshnevisan Alireza , Raouf Mohammad-Taghi , Saffar Hiva , Tabrizi Mina 
Published: February 2021

Abstract
Background:Long non-coding RNAs (LncRNAs) are widely known for their multiple functions in the context of cancer from tumor initiation to tumor progression and metastasis. Gliomas are the most prevalent primary forms of brain tumor, classed from grades I to IV according to their malignant histological features with grade IV also known as Glioblastoma Multiforme (GBM) displaying the highest level of malignancy. This fact intensifies the importance of searching for Differentially Expressed LncRNAs (DELncRNAs) between GBM and Low-Grade Glioma in the hope of finding new targets for diagnostic and therapeutic measures. Methods: In the current study, we performed bioinformatics analysis to obtain a list of DELncRNAs and further chose the unprecedentedly studied OBI1-AS1 for further investigations. We also carried out Real-Time PCR to validate our bioinformatics findings.Results:Both analyses were in concordance and pinpointed downregulated expression of OBI1-AS1 in GBM compared to LGG samples. Additional supplementary bioinformatics studies exhibited OBI1-AS1 role in synaptic signal transduction and neural differentiation in addition to its role in pluripotency and maintenance of stemness. Conclusion:All the aforementioned findings introduce OBI1-AS1 as a new attractive lncRNA to be further studied for a better clarification of its roles in glioma progression and a deeper understanding of malignant transformation of LGG to GBM.
Intraperitoneal Injection of Lithium Chloride Induces Lateralized Activation of the Insular Cortex in Adult Mice
Authors: Qian Kai , Liu Jiaqi , Cao Yiqing , Yang Jing , Qiu Shuang 
Published: February 2021

Abstract
Insular cortex is a critical brain region that participates in the interoceptive sensations. Here, we combined the iDISCO+ method and Fos immunostaining to confirm that the middle part of the right-side, but not the left-side, insular cortex in adult male mice is activated by intraperitoneal injection of lithium chloride. Lateralized activation of the insular cortex is also observed in adult female mice, but not in young or aged male mice. Furthermore, asymmetrical activation of the insular cortex was completely blocked when both sides of the vagal nerve are transected, whereas intravenous injection of lithium chloride has no effect on the insular activation. Combined together, these results indicate that the insular cortex unilaterally responds to aversive visceral stimuli in an age-dependent way and this process depends on the vagal afferent pathways.
Risk Factors for Radiation Pneumonitis in Lung Cancer Patients with Subclinical Interstitial Lung Disease after Thoracic Radiation Therapy
Authors: Li Fangjuan , Liu Hui , Wu Hongyu , Liang Shixiong , Xu Yaping 
Published: February 2021

Abstract
Background: Previous studies have found that patients with subclinical interstitial lung disease (ILD) are more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. The present study aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy (IMRT) in lung cancer patients with subclinical ILD.Methods: We retrospectively analyzed lung cancer patients with subclinical ILD who were treated with thoracic IMRT with a prescribed dose of ≥50 Gy in our institutions between January 2016 and December 2017.Results: A total of 87 consecutive lung cancer patients with subclinical ILD were selected for the study. The cumulative incidence of grades ≥2 and ≥3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, the mean lung dose (MLD) ≥12Gy was a significant risk factor for grade ≥2 RP (p = 0.049). Chemotherapy with gemcitabine in the past，V5≥50%，and subclinical ILD involving ≥25% of lung volume were significantly associated with grade ≥3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively).Conclusion: MLD is a significant risk factor for grade ≥2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5, and those with subclinical ILD involving ≥25% of lung volume have an increased risk of grade ≥3 RP in lung cancer patients with subclinical ILD.
Evidence that methylphenidate Treatment Evokes Anxiety-Like Behavior Through Glucose Hypometabolism and Disruption of the Orbitofrontal Cortex Metabolic Networks
Authors: Schmitz Felipe , Silveira Josiane Silva , Venturin Gianina T , Greggio Samuel , Peixoto Guilherme , Zimmer Eduardo , Costa Jaderson , Wyse Angela 
Published: February 2021

Abstract
Methylphenidate (MPH) has been widely misused by children and adolescents who do not meet all diagnostic criteria for attention-deficit/hyperactivity disorder without a consensus about the consequences. Here, we evaluate the effect of MPH treatment on glucose metabolism and metabolic network in the rat brain, as well as on performance in behavioral tests. Wistar male rats received intraperitoneal injections of MPH (2.0 mg/kg) or an equivalent volume of 0.9% saline solution (controls), once a day, from the 15th to the 44th day of age. Fluorodeoxyglucose-18 was used to investigate the cerebral metabolism, and a cross-correlation matrix was used to examine the brain metabolic network in MPH-treated rats using micro-positron emission tomography imaging. Performance in the light-dark transition box, eating-related depression, and sucrose preference tests were also evaluated. While MPH provoked glucose hypermetabolism in the auditory, parietal, retrosplenial, somatosensory, and visual cortices; hypometabolism was identified in the left orbitofrontal cortex. MPH-treated rats show a brain metabolic network more efficient and connected, but careful analyzes reveal that the MPH interrupts the connection of the orbitofrontal cortex with other brain areas. Anxiety-like behavior was also observed in MPH-treated rats. This study shows that glucose metabolism evaluated by microPET in the brain can be affected by MPH in different ways according to the region of the brain studied. It may be related, at least in part, to a rewiring in brain the metabolic network and behavioral changes observed, representing an important step in exploring the mechanisms and consequences of MPH treatment.
Comparison of the Efficiency of Mammography, Contrast-Enhanced Spectral Mammography and Magnetic Resonance Imaging in Female Patients with Multifocal and Multicentral Breast Cancer
Authors: Steinhof-Radwańska Katarzyna , Lorek Andrzej , Holecki Michał , Barczyk-Gutkowska Anna , Grażyńska Anna , Szczudło-Chraścina Joanna , Kajor Maciej , Lorek Joanna , Bożek Oskar , Gisterek Iwona 
Published: February 2021

Abstract
Background. The multifocality and multicentrality of breast cancer are the decisive factors influencing surgeon’s choice between breast conserving therapy (BCT) and mastectomy.Methods. The analysis included 71 breast cancer subjects out of 727 patients initially operated on due to breast cancer from January 2013 to April 2019. MG, CESM and MRI were compared with one another in terms of the presence of multifocal/multicentral breast cancers (MFMCC), and assessed for compliance with the postoperative histopathological examination (HP), by calculating the sensitivity and specificity for each of the methods. The aim was to examine which histopathological types of breast cancer were characterised by a more frequent occurrence of MFMCC in relation to the general number of cancers identified in HP. It was also analysed if MRI and CESM changed the planned scope of surgery. Results. The sensitivity of MG in detecting MFMCC was 42.1% (26.31 – 59.18), its specificity, positive (PPV) and negative predictive value (NPV) were 93.9% (79.77 – 99.26), 88.8% and 58.5%, respectively. For CESM, the sensitivity was 84.2% (68.75 – 93.98), its specificity, PVV and NPV were 90.9% (75.67 – 98.08), 91.4%, and 83.3%, respectively. For MRI, all above mentioned parameters were higher, as follow: level of sensitivity 94.7% (82.25 – 99.36), specificity – 93.9% (79.77 – 99.26), PPV – 94.7%, and NPV – 93.9%. In 38 out of 71 patients (53.5%), histopathological examination (HP) confirmed the multifocal and multicentral nature of the breast cancer. Conclusion1. In patients with multifocal/multicentral breast cancer both CESM and MRI are highly sensitive in detection of additional cancer foci. 2. Both CESM and MRI change the extent of surgical intervention in every fourth patient. Trial registration: retrospectively registered
3D-Hepatocellular Carcinoma (3D-HCC) Models of Diffused and Aggregated Spheroids using a 96-Pillar/Well Plate
Authors: Lee Sangyun , Teng Yvonne , Son Miseol , Ku Bosung , Whang Hyun Ju , Tergaonkar Vinay , Chow Pierce Kah-Hoe , Lee Dong Woo , Nam Do-Hyun 
Published: February 2021

Abstract
Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related mortality worldwide. The genetic and physiological complexity of HCC is a major barrier to the study of tumorigenesis and identification of therapeutic targets. The three-dimensional (3D) culture of cancer cells within an extracellular matrix (ECM) provides an in vitro tumor model that best recapitulates in vivo tumor pathophysiology.Methods: In the current study, we cultured cells and made spheroids by aggregating cells or diffusing cells in Matrigel attached on the tip of the 96-pillar plate. According to the initial cell position in Matrigel, two 3D-HCC cancer in-vitro models (diffused spheroid model and aggregated spheroid model) were established. These two models were applied to drug sensitivity assays to identify drug sensitivity changes. The protein expression and cytokine activation related to the drug resistance and maintenance of the physiological properties of HCC cells were analyzed in both models. This 3D culture method not only maintained the phenotype of the tumor but allowed easy high-throughput screening (HTS) due to its 96-array plate configuration.Results: The Aggregated Spheroid Model (ASM) showed higher expression of cancer markers associated with proliferation, tight junctions formation and epithelial cell identity in HCC cells, as well as cytokine factors associated with immune cell recruitment/activation, ECM regulation, cancer interaction, and angiogenesis regulation.Conclusions: Overall, the proposed ASM better recapitulates the tumor microenvironment, demonstrating the involvement of the ECM/tight junctions in the cell-to-cell signaling processes. This provides more instructive data for in vitro screening of tumor cells.