bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of pseudoephedrine and emodin ameliorates LPS-induced acute lung injury by regulating macrophage M1/M2 polarization through the VIP/cAMP/PKA pathway
Authors: Wang Wen-Ba , Li Jing-Tao , Hui Yi , Shi Jie , Wang Xu-Yan , Yan Shu-Guang 
Published: February 2022

Abstract
Background
Acute lung injury (ALI) is an acute multifactorial infectious disease induced by trauma, pneumonia, shock, and sepsis. This study aimed to investigate the protective effects of pseudoephedrine and emodin combined treatment in experimental ALI, as well as the mechanisms underlying the regulation of inflammation and pulmonary edema via the VIP/cAMP/PKA pathway.

Methods
The wistar rats were randomly divided into fifteen groups (n = 5). Rats in each group were given intragastric administration 1 h before LPS injection. Those in the control and LPS groups were given intragastric administrations of physiological saline, rats in other groups were given intragastrically administered of differential dose therapeutic agents. The rats in the LPS and treatment groups were then injected intraperitoneally with LPS (7.5 mg/kg) to induce ALI. After being treated with pseudoephedrine and emodin for 12 h, all animals were sacrifice. Anal temperatures were taken on an hourly basis for 8 h after LPS injection. Pathological examination of lung specimen was performed by H&E staining. Cytokines (IL-1β, TNF-α, IL-6, iNOS, IL-10, Arg-1, CD86, CD206, F4/80, VIP) in lung tissue were assayed by ELISA and immunofluorescence. The expression of VIP, CAMP, AQP-1, AQP-5, p-PKA, PKA, p-IκBα, IκBα, p-p65, p65, p-P38, P38, p-ERK1/2, ERK1/2, p-JNK1/2, JNK1/2 protein in lung was determined by western blotting.

Results
After rats being treated with pseudoephedrine + emodin, reduced of fever symptoms. The contents of inflammatory cytokines (IL-1β, TNF-α, IL-6, iNOS) were decreased and anti-inflammatory cytokines (IL-10, Arg-1) were significantly increased in serum. Pseudoephedrine + emodin treatment effectively promoted VIP cAMP and p-PKA protein expression in lung tissues, and significantly inhibited NF-κB, MAPK phosphorylation, Pseudoephedrine + emodin treatment can inhibit M1 polarization and promoted M2 polarization via the VIP/cAMP/PKA signaling pathway.

Conclusions
The combination of Pseudoephedrine and emodin was effective in ameliorating LPS-induced ALI in rats by inducing VIP/cAMP/PKA signaling. Inhibiting the NF-κB, MAPK inflammatory pathway, relief of pulmonary edema suppressing macrophage M1 polarization, and promoting macrophage M2 polarization.
Toddalolactone protects against osteoarthritis by ameliorating chondrocyte inflammation and suppressing osteoclastogenesis
Authors: Xu Yiming , Xue Song , Zhang Tian , Jin Xinmeng , Wang Cong , Lu Haiming , Zhong Yiming , Chen Hongjie , Zhu Libo , Ma Jinzhong , Sang Weilin 
Published: February 2022

Abstract
Background
Osteoarthritis (OA) is widely recognized as the most common chronic joint disease accompanied by progressive cartilage and subchondral bone damage. Toddalolactone (TOD), a natural compound extracted from Toddalia asiatica (L.) Lam., has been widely used in the treatment of stroke, rheumatoid arthritis, and oedema. Nevertheless, what TOD acts as in the pathogenesis and progression of OA hasn’t been reported. In this investigation, we have aimed to determine how TOD affects OA in vitro and in vivo.

Methods
LPS (10 µg/ml) and IL-1β (10 ng/ml) were employed to induce chondrocyte inflammation or RANKL to induce osteoclast differentiation in bone marrow derived macrophages (BMMs). The effects of TOD on chondrocyte inflammation and osteoclast differentiation were evaluated. Anterior cruciate ligament transection (ACLT) was performed to develop an OA animal model and study the effects of TOD.

Results
We found that TOD inhibited the expression of inflammatory and catabolic mediators (IL-6, IL-8, TNF-α, MMP2, MMP9, and MMP13) in inflammatory chondrocytes in vitro. Furthermore, TOD was proven to inhibit RANKL-induced-osteoclastogenesis and inhibit the expression of osteoclast marker genes. Our data also confirmed that TOD suppressed the destruction of articular cartilage and osteoclastogenesis via inhibiting the activation of NF-κB and MAPK signalling pathways. In the ACLT mouse model, we found that TOD attenuated cartilage erosion and inhibited bone resorption.

Conclusions
These results showed that TOD can be adopted as a potential therapeutic agent for OA.
Sociodemographic and clinical characteristics of paediatric patients admitted to a neuropsychiatric care hospital in the COVID-19 era
Authors: Gatta Michela , Raffagnato Alessia , Mason Federica , Fasolato Rachele , Traverso Annalisa , Zanato Silvia , Miscioscia Marina 
Published: February 2022

Abstract
Background
Since the first months of 2020, Italy and the world have been facing the COVID-19 pandemic. In addition to the dangerous and potentially deadly effects on physical health, it has caused a radical change in the lifestyle of the population and a potential danger for mental health too. These events were inserted into the context of a growing epidemiological trend regarding children’s psychiatric disorders in the past decade.

Aim
To study the population of patients admitted to a Neuropsychiatric Hospital Unit of North Italy in the first COVID-19 year, comparing them with the population of patients hospitalised during the year immediately before, according to sociodemographic and clinical variables.

Methodology
The study is an observational retrospective cohort. In total, 198 patients hospitalised due to neuropsychiatric problems from February 2019 to March 2021 were recruited. Data were analysed through mean and standard deviation, t-test, percentages, chi square test, and the Fischer exact test.

Results
Risk factors associated with mental health disorders were similar between the two years. The hospitalisation modality showed a decrease in scheduled hospitalisations compared to urgent ones, and among the reasons that led patients to hospitalisation there was a conspicuous increase in eating disorders. More suicidal and self-harming behaviours occurred in the COVID-19 group too, compared to the previous year. The methods used to attempt suicide were changed considerably, with a prevalence of that attempted within the home. Changes in pharmacological therapies also occurred, necessary for more than 80% of inpatients during the COVID year, with a greater use of neuroleptics. There were alarming data about hospitalisation relapses, which increased from 12.2% in the pre-COVID year to 35.0% in the COVID year.

Conclusion
Data shed light on clinical and policy issues in mental health care during the developmental age. Since the COVID-19 health emergency is not yet over, and its effects, especially on mental health, will be long-term, it is necessary to implement services and activities dedicated to both primary and secondary prevention of neuropsychiatric diseases especially during adolescent ages.
PRACT: a pragmatic randomized adaptive clinical trial protocol to investigate a culturally adapted brief negotiational intervention for alcohol use in the emergency department in Tanzania
Authors: Staton Catherine A. , Zadey Siddhesh , O’Leary Paige , Phillips Ashley , Minja Linda , Swahn Monica H. , Hirshon Jon Mark , Boshe Judith , Sakita Francis , Vissoci Joao Ricardo Nickenig , Mmbaga Blandina T. 
Published: February 2022

Abstract
Background
Alcohol use in resource-limited settings results in significant morbidity and mortality. These settings lack the necessary specialty-trained personnel and infrastructure. Therefore, implementing evidence-based interventions from high-income settings, like a brief negotiational intervention (BNI) for alcohol, will require rapid production of evidence of effectiveness to guide implementation priorities. Thus, this study describes a clinical trial protocol to rapidly optimize and evaluate the impact of a culturally adapted BNI to reduce alcohol-related harms and alcohol consumption among injury patients.

Methods
Our pragmatic, adaptive, randomized controlled trial (PRACT) is designed to determine the most effective intervention approach to reduce hazardous alcohol use among adult (≥18 years old) in acute (< 24 h) injury patients. Our culturally adapted, nurse-delivered, intervention (PPKAY) has been augmented with evidence-based, culturally appropriate standards and will be evaluated as follows. Stage 1 of the trial will determine if PPKAY, either with a standard short-message-service (SMS) booster or with a personalized SMS booster is more effective than usual care (UC). While optimizing statistical efficiency, Stage 2 drops the UC arm to compare the PPKAY with a standard SMS booster to PPKAY with a personalized SMS booster. Finally, in Stage 3, the more effective arm in Stage 2 is compared to PPKAY without an SMS booster. The study population is acute injury patients who present to Kilimanjaro Christian Medical Centre, Tanzania, who (1) test alcohol positive by breathalyzer upon arrival; (2) have an Alcohol Use Disorder Identification Test of 8 or above; and/or (3) have reported drinking alcohol prior to their injury. Outcome measures will be evaluated for all arms at 3, 6, 9, 12, and 24 months. The primary outcome for the study is the reduction of the number of binge drinking days in the 4 weeks prior to follow-up. Secondary outcomes include alcohol-related consequences, measured by the Drinker Inventory of Consequences.

Discussion
The findings from this study will be critically important to identify alcohol harm reduction strategies where alcohol research and interventions are scarce. Our innovative and adaptive trial design can transform behavior change research and identify the most effective nurse-driven intervention to be targeted for integration into standard care.

Trial registration
ClinicalTrials.govNCT04535011. Registered on September 1, 2020.
Upregulated galectin-1 in Angiostrongylus cantonensis L5 reduces body fat and increases oxidative stress tolerance
Authors: Sun Wei-Wei , Yan Xiu-Mei , Qiao Ai-Jun , Zhang Yuan-Jiao , Yang Ling , Huang Hui-Cong , Shi Hong-Fei , Yan Bao-Long 
Published: February 2022

Abstract
Background
Angiostrongylus cantonensis L5, parasitizing human cerebrospinal fluid, causes eosinophilic meningitis, which is attributed to tissue inflammatory responses caused primarily by the high percentage of eosinophils. Eosinophils are also involved in killing helminths, using the peroxidative oxidation and hydrogen peroxide (H2O2) generated by dismutation of superoxide produced during respiratory burst. In contrast, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival. In previous study, we demonstrated the extracellular function of Acan-Gal-1 in inducing the apoptosis of macrophages. Here, the intracellular functions of Acan-Gal-1 were investigated, aiming to further reveal the mechanism involved in A. cantonensis L5 worms surviving inflammatory responses in the human central nervous system.

Methods
In this study, a model organism, Caenorhabditis elegans, was used as a surrogate to investigate the intracellular functions of Acan-Gal-1 in protecting the worm from its host’s immune attacks. First, structural characterization of Acan-Gal-1 was analyzed using bioinformatics; second, qRT-PCR was used to monitor the stage specificity of Acan-gal-1 expression in A. cantonensis. Microinjections were performed to detect the tissue specificity of lec-1 expression, the homolog of Acan-gal-1 in C. elegans. Third, microinjection was performed to develop Acan-gal-1::rfp transgenic worms. Then, oxidative stress assay and Oil Red O fat staining were used to determine the functions of Acan-Gal-1 in C. elegans.

Results
The results of detecting the stage specificity of Acan-gal-1 expression showed that Acan-Gal-1 was upregulated in both L5 and adult worms. Detection of the tissue specificity showed that the homolog of Acan-gal-1 in C. elegans, lec-1 was expressed ubiquitously and mainly localized in cuticle. Investigating the intracellular functions of Acan-Gal-1 in the surrogate C. elegans showed that N2 worms expressing pCe-lec-1::Acan-gal-1::rfp, with lipid deposition reduced, were significantly resistant to oxidative stress; lec-1 mutant worms, where lipid deposition increased, showed susceptible to oxidative stress, and this phenotype could be rescued by expressing pCe-lec-1::Acan-gal-1::rfp. Expressing pCe-lec-1::Acan-gal-1::rfp or lec-1 RNAi in fat-6;fat-7 double-mutant worms, where fat stores were reduced, had no significant effect on the oxidative stress tolerance.

Conclusion
In C. elegans worms, upregulated Acan-Gal-1 plays a defensive role against damage due to oxidative stress for worm survival by reducing fat deposition. This might indicate the mechanism by which A. cantonensis L5 worms, with upregulated Acan-Gal-1, survive the immune attack of eosinophils in the human central nervous system.

Graphical Abstract
Double burden of COVID-19 knowledge deficit: low health literacy and high information avoidance
Authors: Chen Xuewei , Li Ming , Kreps Gary L. 
Published: February 2022

Abstract
Objective
People with lower levels of health literacy are likely to report engaging in information avoidance. However, health information avoidance has been overlooked in previous research on responses to viral outbreaks. The purpose of this cross-sectional survey study was to assess the relationship between health literacy and COVID-19 information avoidance. Students (n = 561) at a university in the south central region of the U.S. completed our online survey conducted from April to June 2020 using simple random sampling. We measured information avoidance and the degree to which people opt not to learn about COVID-19 when given the choice. We assessed participants’ health literacy level using the Newest Vital Sign (NVS), eHealth Literacy Scale (eHEALS), and All Aspect of Health Literacy Scale (AAHLS).

Results
Those with lower health literacy were more likely to avoid information about COVID-19. This negative association between health literacy and information avoidance was consistent across all types of health literacy measures: NVS scores (b = − 0.47, p = 0.033), eHEALS scores (b = − 0.12, p = 0.003), functional health literacy (b = − 0.66, p = 0.001), communicative health literacy (b = − 0.94, p < 0.001), information appraisal (b = − 0.36, p = 0.004), and empowerment (b = − 0.62, p = 0.027). The double burden of low health literacy and high information avoidance is likely to lead to a lack of knowledge about COVID-19.
Altered central and blood glutathione in Alzheimer’s disease and mild cognitive impairment: a meta-analysis
Authors: Chen Jinghan Jenny , Thiyagarajah Mathura , Song Jianmeng , Chen Clara , Herrmann Nathan , Gallagher Damien , Rapoport Mark J. , Black Sandra E. , Ramirez Joel , Andreazza Ana C. , Oh Paul , Marzolini Susan , Graham Simon J. , Lanctôt Krista L. 
Published: February 2022

Abstract
Background
Increasing evidence implicates oxidative stress (OS) in Alzheimer disease (AD) and mild cognitive impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of the brain and blood GSH may shed light on GSH changes earlier in the disease.

Aim
To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses.

Method
Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using MEDLINE, PsychInfo, and Embase (1947–June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS) and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively.

Results
For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] −1.45 [−1.83, −1.06], p<0.001) and MCI (−1.15 [−1.71, −0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (−0.87 [−1. 30, −0.44], z=3.96, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (−0.66 [−1.11, −0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.

Conclusion
Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.
A review on advances in 18F-FDG PET/CT radiomics standardisation and application in lung disease management
Authors: Anan Noushin , Zainon Rafidah , Tamal Mahbubunnabi 
Published: February 2022

AbstractRadiomics analysis quantifies the interpolation of multiple and invisible molecular features present in diagnostic and therapeutic images. Implementation of 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomics captures various disorders in non-invasive and high-throughput manner.18F-FDG PET/CT accurately identifies the metabolic and anatomical changes during cancer progression. Therefore, the application of18F-FDG PET/CT in the field of oncology is well established. Clinical application of18F-FDG PET/CT radiomics in lung infection and inflammation is also an emerging field. Combination of bioinformatics approaches or textual analysis allows radiomics to extract additional information to predict cell biology at the micro-level. However, radiomics texture analysis is affected by several factors associated with image acquisition and processing. At present, researchers are working on mitigating these interrupters and developing standardised workflow for texture biomarker establishment. This review article focuses on the application of18F-FDG PET/CT in detecting lung diseases specifically on cancer, infection and inflammation. An overview of different approaches and challenges encountered on standardisation of18F-FDG PET/CT technique has also been highlighted. The review article provides insights about radiomics standardisation and application of18F-FDG PET/CT in lung disease management.
Ricolinostat promotes the generation of megakaryocyte progenitors from human hematopoietic stem and progenitor cells
Authors: Jiang Jianan , Qin Jinhua , Li Jisheng , Lin Xiaosong , Zhang Bowen , Fan Zeng , He Lijuan , Zeng Quan , Yue Wen , Zheng Min , Pei Xuetao , Li Yanhua 
Published: February 2022

AbstractBackgroundEx vivo production of induced megakaryocytes (MKs) and platelets from stem cells is an alternative approach for supplying transfusible platelets. However, it is difficult to generate large numbers of MKs and platelets from hematopoietic stem cells and progenitor cells (HSPCs).MethodsTo optimize the differentiation efficiency of megakaryocytic cells from HSPCs, we first employed a platelet factor 4 (PF4)-promoter reporter and high-throughput screening strategy to screen for small molecules. We also investigated the effects and possible mechanisms of candidate small molecules on megakaryocytic differentiation of human HSPCs.ResultsThe small molecule Ricolinostat remarkably promoted the expression of PF4-promoter reporter in the megakaryocytic cell line. Notably, Ricolinostat significantly enhanced the cell fate commitment of MK progenitors (MkPs) from cord blood HSPCs and promoted the proliferation of MkPs based on cell surface marker detection, colony-forming unit-MK assay, and quantitative real-time PCR analyses. MkPs generated from Ricolinostat-induced HSPCs differentiated into mature MKs and platelets. Mechanistically, we found that Ricolinostat enhanced MkP fate mainly by inhibiting the secretion of IL-8 and decreasing the expression of the IL-8 receptor CXCR2.ConclusionThe addition of Ricolinostat to the culture medium promoted MkP differentiation from HSPCs and enhanced the proliferation of MkPs mainly by suppressing the IL-8/CXCR2 pathway. Our results can help the development of manufacturing protocols for the efficient generation of MKs and platelets from stem cells in vitro.
Single-cell analysis of mouse uterus at the invasion phase of embryo implantation
Authors: He Jia-Peng , Tian Qing , Zhu Qiu-Yang , Liu Ji-Long 
Published: February 2022

AbstractBackgroundEmbryo implantation into the uterus is a crucial step for human reproduction. A hypothesis has been proposed that the molecular circuit invented by trophoblasts for invasive embryo implantation during evolution might be misused by cancer cells to promote malignancy. Unfortunately, our current understanding of the molecular mechanism underlying embryo implantation is far from complete.ResultsHere we used the mouse as an animal model and generated a single-cell transcriptomic atlas of the embryo implantation site of mouse uterus at the invasion phase of embryo implantation on gestational day 6. We revealed 23 distinct cell clusters, including 5 stromal cell clusters, 2 epithelial cell clusters, 1 smooth muscle cell cluster, 2 pericyte clusters, 4 endothelial cell clusters, and 9 immune cell clusters. Through data analysis, we identified differentially expression changes in all uterine cell types upon embryo implantation. By integrated with single-cell RNA-seq data from E5.5 embryos, we predicted cell–cell crosstalk between trophoblasts and uterine cell types.ConclusionsOur study provides a valuable resource for understanding of the molecular mechanism of embryo implantation.
RPCA-DRNN technique for monaural singing voice separation
Authors: Lai Wen-Hsing , Wang Siou-Lin 
Published: February 2022

AbstractIn this study, we propose a methodology for separating a singing voice from musical accompaniment in a monaural musical mixture. The proposed method uses robust principal component analysis (RPCA), followed by postprocessing, including median filter, morphology, and high-pass filter, to decompose the mixture. Subsequently, a deep recurrent neural network comprising two jointly optimized parallel-stacked recurrent neural networks (sRNNs) with mask layers and trained on limited data and computation is applied to the decomposed components to optimize the final estimated separated singing voice and background music to further correct misclassified or residual singing and background music in the initial separation. The experimental results of MIR-1K, ccMixter, and MUSDB18 datasets and the comparison with ten existing techniques indicate that the proposed method achieves competitive performance in monaural singing voice separation. On MUSDB18, the proposed method reaches the comparable separation quality in less training data and lower computational cost compared to the other state-of-the-art technique.