bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune defects in patients with pulmonaryMycobacterium abscessusdisease without cystic fibrosis
Authors: Schuurbiers Milou M.F. , Bruno Mariolina , Zweijpfenning Sanne M.H. , Magis-Escurra Cecile , Boeree Martin , Netea Mihai G. , van Ingen Jakko , van de Veerdonk Frank , Hoefsloot Wouter 
Published: February 2021

The prevalence ofMycobacterium abscessusinfections in non-cystic fibrosis (CF) patients has increased in recent years. In this study, we investigate whether immune defects explain the apparent susceptibility to this opportunistic infection in non-CF patients.We performed stimulations of peripheral blood mononuclear cells and whole blood from 13 patients withM. abscessuspulmonary disease and 13 healthy controls to investigate their cytokine production after 24 h and 7 days.Patients were predominantly women (54%) with a mean age of 59 years; 62% had nodular bronchiectatic disease. Many patients had predisposing pulmonary diseases, such as COPD (46%), and asthma (23%). Patients with COPD showed an impaired interleukin (IL)-6 response toM. abscessusand a reduced IL-17 response toCandida, together with aM. abscessus-specific enhanced IL-22 production. Patients without COPD showed higher levels of interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory molecule. Within the non-COPD patients, those with bronchiectasis showed defective interferon (IFN)-γ production in response toCandida albicans.In conclusion, susceptibility toM. abscessusis likely determined by a combination of immunological defects and predisposing pulmonary disease. The main defect in the innate immune response was a shift of the ratio of IL-1β to IL-1Ra, which decreased the bioactivity of this pathway in the adaptive immune response. In the adaptive immune response there was defective IL-17 and IFN-γ production. Patients with COPD and bronchiectasis showed different cytokine defects. It is therefore crucial to interpret the immunological results within the clinical background of the patients tested.
The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial
Authors: Raeissadat Seyed Ahmad , Ghazi Hosseini Parsa , Bahrami Mohammad Hasan , Salman Roghani Reza , Fathi Mohammad , Gharooee Ahangar Azadeh , Darvish Mahtab 
Published: February 2021

Abstract
Background
Our study compare the short and long-term efficacy of the intra articular injections (IAIs) of hyaluronic acid (HA), platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), and ozone in patients with knee osteoarthritis (OA).

Methods
In this randomized clinical trial, 238 patients with mild to moderate knee OA were randomized into 4 groups of IAIs: HA (3 doses weekly), PRP (2 doses with 3 weeks interval), PRGF (2 doses with 3 weeks interval), and Ozone (3 doses weekly). Our outcome measures were the mean changes from baseline (immediately from the first injections) until 2,6, and 12 months post intervention in scores of visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index.

Results
A total of 200 patients enrolled in the final analysis. The mean age of patients was 56.9 ± 6.3 years, and 69.5% were women. In 2 months follow up, significant improvement of pain, stiffness, and function were seen in all groups compared to the baseline, but the ozone group had the best results (P < 0.05). In 6 month follow up HA, PRP, and PRGF groups demonstrated better therapeutic effects in all scores in comparison with ozone (P < 0.05). At the end of the 12th month, only PRGF and PRP groups had better results versus HA and ozone groups in all scores (P < 0.05). Despite the fact that ozone showed better early results, its effects begin to wear off earlier than other products and ultimately disappear in 12 months.

Conclusions
Ozone injection had rapid effects and better short-term results after 2 months, but its therapeutic effects did not persist after 6 months and at the 6-month follow up, PRP,PRGF and HA were superior to ozone. Only patients in PRP and PRGF groups improved symptoms persisted for 12 months. Therefore, these products could be the preferable choices for long-term management.

Trial registration
Registered in the Iranian Center of Clinical Trials (www.irct.ir) in 11/11/2017 with the following code: IRCT2017082013442N17.
Discovery and validation of methylation signatures in blood-based circulating tumor cell-free DNA in early detection of colorectal carcinoma: a case–control study
Authors: Sui Jinke , Wu Xianrui , Wang Chenyang , Wang Guoqiang , Li Chengcheng , Zhao Jing , Zhang Yuzi , Xiang Jianxing , Xu Yu , Nian Weiqi , Cao Fuao , Yu Guanyu , Lou Zheng , Hao Liqiang , Liu Lianjie , Li Bingsi , Zhang Zhihong , Cai Shangli , Liu Hao , Lan Ping , Zhang Wei 
Published: February 2021

Abstract
Background
Early detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients’ compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC.

Results
In total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2–93.7%) and the sensitivity was 88.6% (82.4–93.2%). In terms of different stages, the sensitivities were 79.4% (62.1–91.2%) in patients with stage I, 88.9% (77.3–95.8%) in patients with stage II, 91.4% (76.9–98.2%) in patients with stage III and 96.2% (80.3–99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1–97.0%) and sensitivity of 83.6% (72.5–91.6%). Sensitivities for stage I-III were 87.0% (79.7–92.4%) in the training set and 82.5% (70.2–91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2–11.2%) in healthy control, 30.8% (19.9–43.5%) in benign colorectal disease and 58.3% (27.5–84.7%) in advanced adenoma, while the sensitivities of stage I–IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8–91.2%] versus 41.2% [34.6–48.1%], P < 0.001) under comparable specificity (90.1% [85.4–93.7%] versus 90.6% [86.0–94.1%]).

Conclusions
Together our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies.
microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1
Authors: Zhou Jing , Lin Yang , Kang Xiuhua , Liu Zhicheng , Zhang Wei , Xu Fei 
Published: February 2021

Abstract
Background
Previous reports have identified that human bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) with their cargo microRNAs (miRNAs) are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis (IPF). Therefore, we explored whether delivery of microRNA-186 (miR-186), a downregulated miRNA in IPF, by BMSC EVs could interfere with the progression of IPF in a murine model.

Methods
In a co-culture system, we assessed whether BMSC-EVs modulated the activation of fibroblasts. We established a mouse model of PF to evaluate the in vivo therapeutic effects of BMSC-EVs and determined miR-186 expression in BMSC-EVs by polymerase chain reaction. Using a loss-of-function approach, we examined how miR-186 delivered by BMSC-EVs affected fibroblasts. The putative relationship between miR-186 and SRY-related HMG box transcription factor 4 (SOX4) was tested using luciferase assay. Next, we investigated whether EV-miR-186 affected fibroblast activation and PF by targeting SOX4 and its downstream gene, Dickkopf-1 (DKK1).

Results
BMSC-EVs suppressed lung fibroblast activation and delayed IPF progression in mice. miR-186 was downregulated in IPF but enriched in the BMSC-EVs. miR-186 delivered by BMSC-EVs could suppress fibroblast activation. Furthermore, miR-186 reduced the expression of SOX4, a target gene of miR-186, and hence suppressed the expression of DKK1. Finally, EV-delivered miR-186 impaired fibroblast activation and alleviated PF via downregulation of SOX4 and DKK1.

Conclusion
In conclusion, miR-186 delivered by BMSC-EVs suppressed SOX4 and DKK1 expression, thereby blocking fibroblast activation and ameliorating IPF, thus presenting a novel therapeutic target for IPF.
Dynamic proteomic profiling of human periodontal ligament stem cells during osteogenic differentiation
Authors: Li Jianjia , Wang Zhifa , Huang Xiangyu , Wang Zhaodan , Chen Zehao , Wang Runting , Chen Zhao , Liu Wei , Wu Buling , Fang Fuchun , Qiu Wei 
Published: February 2021

Abstract
Background
Human periodontal ligament stem cells (hPDLSCs) are ideal seed cells for periodontal regeneration. A greater understanding of the dynamic protein profiles during osteogenic differentiation contributed to the improvement of periodontal regeneration tissue engineering.

Methods
Tandem Mass Tag quantitative proteomics was utilized to reveal the temporal protein expression pattern during osteogenic differentiation of hPDLSCs on days 0, 3, 7 and 14. Differentially expressed proteins (DEPs) were clustered and functional annotated by Gene Ontology (GO) terms. Pathway enrichment analysis was performed based on the Kyoto Encyclopedia of Genes and Genomes database, followed by the predicted activation using Ingenuity Pathway Analysis software. Interaction networks of redox-sensitive signalling pathways and oxidative phosphorylation (OXPHOS) were conducted and the hub protein SOD2 was validated with western blotting.

Results
A total of 1024 DEPs were identified and clustered in 5 distinctive clusters representing dynamic tendencies. The GO enrichment results indicated that proteins with different tendencies show different functions. Pathway enrichment analysis found that OXPHOS was significantly involved, which further predicted continuous activation. Redox-sensitive signalling pathways with dynamic activation status showed associations with OXPHOS to various degrees, especially the sirtuin signalling pathway. SOD2, an important component of the sirtuin pathway, displays a persistent increase during osteogenesis. Data are available via ProteomeXchange with identifier PXD020908.

Conclusion
This is the first in-depth dynamic proteomic analysis of osteogenic differentiation of hPDLSCs. It demonstrated a dynamic regulatory mechanism of hPDLSC osteogenesis and might provide a new perspective for research on periodontal regeneration.

Graphical abstract
The effect of endothelial progenitor cell transplantation on neointimal hyperplasia and reendothelialisation after balloon catheter injury in rat carotid arteries
Authors: Wang Wei , Zhang Yingqian , Hui Hui , Tong Wei , Wei Zechen , Li Zhongxuan , Zhang Suhui , Yang Xin , Tian Jie , Chen Yundai 
Published: February 2021

Abstract
Background
Reendothelialisation is the natural pathway that inhibits neointimal hyperplasia and in-stent restenosis. Circulating endothelial progenitor cells (EPCs) derived from bone marrow (BM) might contribute to endothelial repair. However, the temporal and spatial distributions of reendothelialisation and neointimal hyperplasia after EPC transplantation in injured arteries are currently unclear.

Methods
A carotid balloon injury (BI) model was established in Sprague-Dawley rats, and PKH26-labelled BM-derived EPCs were transplanted after BI. The carotid arteries were harvested on the first, fourth, seventh, and 14th day post-injury and analysed via light-sheet fluorescence microscopy and pathological staining (n = 3). EPC and human umbilical vein endothelial cell culture supernatants were collected, and blood samples were collected before and after transplantation. The paracrine effects of VEGF, IGF-1, and TGF-β1 in cell culture supernatants and serum were analysed by enzyme-linked immunosorbent assay (n = 4).

Results
Transplanted EPCs labelled with PKH26 were attached to the injured luminal surface the first day after BI. In the sham operation group, the transplanted EPCs did not adhere to the luminal surface. From the fourth day after BI, the mean fluorescence intensity of PKH26 decreased significantly. However, reendothelialisation and inhibition of neointimal hyperplasia were significantly promoted by transplanted EPCs. The degree of reendothelialisation of the EPC7d and EPC14d groups was higher than that of the BI7d and BI14d groups, and the difference in neointimal hyperplasia was observed between the EPC14d and BI14d groups. The number of endothelial cells on the luminal surface of the EPC14d group was higher than that of the BI14d group. The number of infiltrated macrophages in the injured artery decreased in the EPC transplanted groups.

Conclusions
Transplanted EPCs had chemotactic enrichment and attached to the injured arterial luminal surface. Although decreasing significantly after the fourth day at the site of injury after transplantation, transplanted EPCs could still promote reendothelialisation and inhibit neointimal hyperplasia. The underlying mechanism is through paracrine cytokines and not differentiation into mature endothelial cells.
Neuregulin 1/ErbB4 signaling contributes to the anti-epileptic effects of the ketogenic diet
Authors: Wang Jin , Huang Jie , Li Yuan-Quan , Yao Shan , Wu Cui-Hong , Wang Ying , Gao Feng , Xu Min-Dong , Huang Guo-Bin , Zhao Chang-Qin , Wu Jia-Hui , Zhang Yun-Long , Jiao Renjie , Deng Zi-Hao , Jie Wei , Li Hui-Bin , Xuan Aiguo , Sun Xiang-Dong 
Published: February 2021

Abstract
Background
The ketogenic diet (KD) has been recognized as a potentially effective therapy to treat neuropsychiatric diseases, including epilepsy. Previous studies have indicated that KD treatment elevates γ-Amino butyric acid (GABA) levels in both human and murine brains, which presumably contributes to the KD’s anti-seizure effects. However, this has not been systematically investigated at the synaptic level, and the underlying molecular mechanisms remain to be elucidated.

Methods
Kainic acid (KA)-induced acute and chronic seizure models were utilized to examine the effects of KD treatment on seizure threshold and epileptogenesis. Synaptic activities in the hippocampus were recorded with the technique of electrophysiology. The effects of the KD on Neuregulin 1 (Nrg1) expression were assessed via RNA sequencing, real-time PCR and Western blotting. The obligatory role of Nrg1 in KD’s effects on seizures was evaluated through disruption of Nrg1 signaling in mice by genetically deleting its receptor-ErbB4.

Results
We found that KD treatment suppressed seizures in both acute and chronic seizure models and enhanced presynaptic GABA release probability in the hippocampus. By screening molecular targets linked to GABAergic activity with transcriptome analysis, we identified that KD treatment dramatically increased the Nrg1 gene expression in the hippocampus. Disruption of Nrg1 signaling by genetically deleting its receptor-ErbB4 abolished KD’s effects on GABAergic activity and seizures.

Conclusion
Our findings suggest a critical role of Nrg1/ErbB4 signaling in mediating KD’s effects on GABAergic activity and seizures, shedding light on developing new therapeutic interventions to seizure control.
Impact of electron beam irradiation on the chlorophyll degradation and antioxidant capacity of mango fruit
Authors: Nguyen Truc Trung , Uthairatanakij Apiradee , Srilaong Varit , Laohakunjit Natta , Kato Masaya , Jitareerat Pongphen 
Published: February 2021

AbstractAt the present, the mechanism of chlorophyll degradation in response to ionizing irradiation in harvested fruits have not been examined. To understand the effect of electron beam (E-beam) irradiation on the chlorophyll degrading pathway in relation to chlorophyll degrading enzymes activity, reactive oxygen species (ROS) and antioxidant capacities of harvested mangoes stored at 13 °C for 16 days were studied. E-beam-treated fruit significantly suppressed the activities of chlorophyll degrading enzymes especially pheophytinase (PPH) and chlorophyll degrading peroxidase (Chl-POX) in the late stage of storage. This resulted in the chlorophyll content being maintained. However, E-beam irradiation did not affect the activities of chlorophyllase (Chlase) and magnesium de-chelatase (MD). The respiration rate, ethylene production, ROS accumulation (hydrogen peroxide [H2O2] and superoxide radical [O−.2]) immediately increased after E-beam treatment, following which they significantly decreased in comparison to the control. E-beam treatment enhanced the fruit’s antioxidant capacity by activating the activities of catalase (CAT) and ascorbate peroxidase (APX) and glutathione (GSH) content, and inactivated the activity of superoxide dismutase (SOD). Further, it did not affect the activity of glutathione reductase (GR) and glutathione disulfide (GSSG), vitamin C content, or total phenolic content. These results imply that E-beam treatment has the potential to delay chlorophyll degradation by suppressing the Chl-POX and PPH activities as well as reduce ROS production via CAT, APX, and SOD activities and GSH content.
Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data
Authors: Hu Jianchang , Li Cai , Wang Shiying , Li Ting , Zhang Heping 
Published: February 2021

Abstract
Background
The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors.

Methods
In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations.

Results
We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2.

Conclusions
Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.
Childhood maltreatment is associated with distrust and negatively biased emotion processing
Authors: Hepp Johanna , Schmitz Sara E. , Urbild Jana , Zauner Kathrin , Niedtfeld Inga 
Published: February 2021

Abstract
Background
Cognitive models of post-traumatic stress disorder (PTSD) propose that trauma entails cognitive alterations of increased distrust and perceived threat from others. We tested whether these predictions also hold in individuals with varying levels of childhood maltreatment (CM), which is much more prevalent than traumatic events as required for a PTSD diagnosis. We hypothesized that higher levels of CM would entail greater distrust and perceived threat, and that distrust would be more change-resistant in participants with more CM.

Methods
The study was pre-registered; the pre-registration protocol, data, and code are available at https://osf.io/pufy2/. We recruited 549 participants (M age = 29.2, 74.5% women) for an online study via websites related to CM, Borderline Personality Disorder, and via snowball method on social media. Participants self-reported their level of CM on the childhood trauma questionnaire (CTQ). Next, they played two rounds of a hypothetical distrust game, indicating the perceived trustworthiness of avatars by way of estimating expected monetary deductions from them (i.e. higher amounts indicating greater distrust). After the first round, we provided participants with the feedback that very little money was taken from them. We expected those with more CM to be less responsive to the positive feedback and to adapt their estimates less in the subsequent round. Following the distrust game, participants completed an emotion rating task in which they rated the emotional expressions of 60 faces on a scale from ‘very negative’ to ‘very positive’. We included angry, fearful, and happy facial expressions, and expected individuals with higher CM levels to provide more negative ratings. We conducted linear mixed effects models with random intercepts for raters and stimuli (crossed), and modelled random slopes for all within-person predictors.

Results
As hypothesized, higher levels of CM were associated with higher levels of distrust and a weaker decrease in distrust following positive feedback. Further supporting our hypotheses, individuals with higher levels of CM showed more negatively shifted emotion ratings.

Conclusions
Increased distrust and perceived interpersonal threat following trauma, as proposed in cognitive models of PTSD, likely also apply to individuals with CM, following a dose-response relationship. We discuss clinical implications of considering any level of CM as a potentially relevant treatment-factor, even when a trauma-related disorder is not the main diagnosis, and propose future research avenues.