bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR
Authors: He Mingyu , Yan Gege , Wang Yang , Gong Rui , Lei Hong , Yu Shuting , He Xiaoqi , Li Guanghui , Du Weijie , Ma Tianshuai , Gao Manqi , Yu Meixi , Liu Shenzhen , Xu Zihang , Idiiatullina Elina , Zagidullin Naufal , Pavlov Valentin , Cai Benzhi , Yuan Ye , Yang Lei 
Published: May 2021

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light‐emitting diodes (LED)‐based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation‐induced autophagy characterized by alterations in autophagy protein markers including Beclin‐1, LC3‐II/LC3‐I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti‐tumour activities of blue LED irradiation. Next, ROS scavenger N‐acetyl‐L‐cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED‐induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin‐1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin‐1 and EGFR‐immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin‐1 upon blue LED irradiation in OS cells. In addition, Beclin‐1 down‐regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti‐tumour effects on OS by triggering ROS and EGFR/Beclin‐1‐mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
Fructose‐1,6‐bisphosphatase aggravates oxidative stress‐induced apoptosis in asthma by suppressing the Nrf2 pathway
Authors: Hu Jiapeng , Wang Jia , Li Chunlu , Shang Yunxiao 
Published: May 2021

AbstractAsthma is a chronic airway disease that causes excessive inflammation, oxidative stress, mucus production and bronchial epithelial cell apoptosis. Fructose‐1,6‐bisphosphatase (Fbp1) is one of the rate‐limiting enzymes in gluconeogenesis and plays a critical role in several cancers. However, its role in inflammatory diseases, such as asthma, is unclear. Here, we examined the expression, function and mechanism of action of Fbp1 in asthma. Gene Expression Omnibus (GEO) data sets revealed that Fbp1 was overexpressed in a murine model of asthma and in interleukin (IL)‐4‐ or IL‐13‐stimulated bronchial epithelial cells. We confirmed the findings in an animal model as well as Beas‐2B and 16HBE cells. In vitro investigations revealed that silencing of Fbp1 reduced apoptosis and the proportion of cells in the G2/M phase, whereas overexpression led to increases. Fbp1 knock‐down inhibited oxidative stress by activating the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway, whereas Fbp1 overexpression aggravated oxidative stress by suppressingthe Nrf2 pathway. Moreover, the Nrf2 pathway inhibitor ML385 reversed the changes caused by Fbp1 inhibition in Beas‐2B and 16HBE cells. Collectively, our data indicate that Fbp1 aggravates oxidative stress‐induced apoptosis by suppressing Nrf2 signalling, substantiating its potential as a novel therapeutic target in asthma.
Integrated microenvironment‐associated genomic profiles identify LRRC15 mediating recurrent glioblastoma‐associated macrophages infiltration
Authors: Tang Haichao , Liu Wensi , Xu Zhaoxu , Zhao Jianhang , Wang Weitao , Yu Zhaojin , Wei Minjie 
Published: May 2021

AbstractGlioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. In our study, we aimed to identify potential tumour target correlated with rGBM microenvironment based on the gene expression profiles and clinical information of rGBM patients from The Cancer Genome Atlas (TCGA) database. LRRC15 gene with prognostic value was screened by univariate and multivariate analysis, and the correlation between macrophages and LRRC15 was identified as well. Furthermore, the prognosis correlation and immune characteristics of LRRC15 were validated using the Chinese Glioma Genome Atlas (CGGA) database and our clinical tissues by immunochemistry assay. Additionally, we utilized the transwell assay and carboxy fluorescein succinimidyl ester (CFSE) tracking to further confirm the effects of LRRC15 on attracting microglia/macrophages and tumour cell proliferation in the TME. Gene profiles‐based rGBM microenvironment identified that LRRC15 could act in collusion with microglia/macrophages in the rGBM microenvironment to promote the poor prognosis, especially in mesenchymal subtype, indicating the strategies of targeting LRRC15 to improve macrophages‐based immunosuppressive effects could be promising for rGBM treatments.
Uraemic extracellular vesicles augment osteogenic transdifferentiation of vascular smooth muscle cells via enhanced AKT signalling and PiT‐1 expression
Authors: Freise Christian , Querfeld Uwe , Ludwig Antje , Hamm Bernd , Schnorr Jörg , Taupitz Matthias 
Published: May 2021

AbstractExtracellular vesicles (EV) function as messengers between endothelial cells (EC) and vascular smooth muscle cells (VSMC). Since chronic kidney disease (CKD) increases the risk for vascular calcifications, we investigated whether EV derived from uraemic milieu‐stimulated EC and derived from uraemic rats impact the osteogenic transdifferentiation/calcification of VSMC. For that purpose, human EC were treated with urea and indoxyl sulphate or left untreated. Experimental uraemia in rats was induced by adenine feeding. ‘Uraemic’ and control EV (EVUR; EVCTRL) were isolated from supernatants and plasma by using an exosome isolation reagent. Rat VSMC were treated with a pro‐calcifying medium (CM) with or without EV supplementation. Gene expressions, miRNA contents and protein expressions were determined by qPCR and Western blots, respectively. Calcifications were determined by colorimetric assays. Delivery of miRNA inhibitors/mimics to EV and siRNA to VSMC was achieved via transfection. EVCTRL and EVUR differed in size and miRNA contents. Contrary to EVCTRL, EC‐ and plasma‐derived EVUR significantly increased the pro‐calcifying effects of CM, including altered gene expressions of osterix, runx2, osteocalcin and SM22α. Further, EVUR enhanced the protein expression of the phosphate transporter PiT‐1 in VSMC and induced a phosphorylation of AKT and ERK. Knock down of PiT‐1 and individual inhibition of AKT and ERK signalling in VSMC blocked the pro‐calcifying effects of EVUR. Similar effects were achieved by inhibition of miR‐221/‐222 and mimicking of miR‐143/‐145 in EVUR. In conclusion, EVUR might represent an additional puzzle piece of the complex pathophysiology of vascular calcifications in CKD.
Construction of circRNA‐miRNA‐mRNA network in the pathogenesis of recurrent implantation failure using integrated bioinformatics study
Authors: Ahmadi Mohsen , Pashangzadeh Salar , Moraghebi Mahta , Sabetian Soudabeh , Shekari Mohammad , Eini Fatemeh , Salehi Ensieh , Mousavi Pegah 
Published: May 2021

AbstractThis research attempted to elucidate the molecular components are involved in the pathogenesis of recurrent implantation failure (RIF). We initially identified that 386 mRNAs, 144 miRNAs and 2548 circRNAs were differentially expressed (DE) in RIF and then investigated the genetic cause of the observed abnormal expression by constructing a circRNA‐miRNA‐mRNA network considering the competing endogenous RNA theory. We further analysed the upstream transcription factors and related kinases of DEmRNAs (DEMs) and demonstrated that SUZ12, AR, TP63, NANOG, and TCF3 were the top five TFs binding to these DEMs. Besides, protein‐protein interaction analysis disclosed that ACTB, CXCL10, PTGS2, CXCL12, GNG4, AGT, CXCL11, SST, PENK, and FOXM1 were the top 10 hub genes in the acquired network. Finally, we performed the functional enrichment analysis and found that arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), pathways in cancer, TNF signalling pathway and steroid hormone biosynthesis were the potentially disrupted pathways in RIF patients. Optimistically, our findings may deepen our apprehensions about the underlying molecular and biological causes of RIF and provide vital clues for future laboratory and clinical experiments that will ultimately bring a better outcome for patients with RIF.
Scabies itch: an update on neuroimmune interactions and novel targets
Authors: Kim H.S. , Hashimoto T. , Fischer K. , Bernigaud C. , Chosidow O. , Yosipovitch G. 
Published: May 2021

AbstractFrequently described as ‘the worst itch’ one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. The aim of this review is to provide an overview of the scope of itch in scabies and highlight candidate mechanisms underlying this itch. We herein discuss scabies itch, with a focus on the nature, candidate underlying mechanisms and treatment options. We also synthesize this information with current understanding of the mechanisms contributing to non‐histaminergic itch in other conditions. Itch is a major problem in scabies and can lead to grave consequences. We provide the latest insights on host–mite interaction, secondary microbial infection and neural sensitization with special emphasis on keratinocytes and mast cells to better understand the mechanism of itch in scabies. Also, the most relevant current modalities remaining under investigation that possess promising perspectives for scabies itch (i.e. protease‐activated receptor‐2 (PAR‐2) inhibitor, Mas‐related G protein‐coupled receptor X2 (MRGPRX2) antagonist) are discussed. Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to control itch in individuals with scabies.
Plantar involvement correlates with obesity, pain and impaired mobility in epidermolysis bullosa simplex: a retrospective cohort study
Authors: Reimer‐Taschenbrecker A. , Hess M. , Hotz A. , Fischer J. , Bruckner‐Tuderman L. , Has C. 
Published: May 2021

AbstractBackgroundEpidermolysis bullosa simplex (EBS) is the most common type of EB, a group of rare genodermatoses. Affected individuals suffer from skin blistering and report a high disease burden. In some EBS subtypes, plantar keratoderma (PK) has been described.ObjectivesThis study investigated the presence and correlation of PK with body mass index, pain and mobility in EBS.MethodsIndividuals (n = 157) with genetically characterized EBS were included in this retrospective cohort study, and clinical data were collected over 16 years (referral patients to the largest German EB centre). Descriptive statistics and mixed linear models were used to assess correlations.ResultsPK was found in 75.8% of patients beginning at a mean age of 4.3 years. Both focal and diffuse PK were observed, and 60% of adults with localized and severe EBS were preobese or obese, with ˜30% of patients reporting severely reduced mobility. The presence of PK, especially diffuse PK, correlated significantly with local infections, obesity, pain and requirement of a wheelchair.ConclusionAlong with treating skin fragility and blistering, PK should be considered a potential marker of increased morbidity and may represent a target of EBS therapy development.
Sharing a written medical summary with patients on the post‐admission ward round: A qualitative study of clinician and patient experience
Authors: Crucefix Anna L. , Fleming Aaron P. L. , Lebus Caroline S. , Slowther Anne‐Marie , Fritz Zoë 
Published: May 2021

AbstractRationale, Aims and ObjectivesSharing aspects of the traditional medical record with patients has been successful in primary and antenatal care, but has not been investigated in the UK inpatient setting. Our aim was to evaluate the impact on patient and clinician experience of providing patients with a written lay summary of their care‐plan in the acute care setting.MethodWe carried out a qualitative interview study on two acute medicine wards in an NHS University Teaching Hospital for a 4‐week period in 2019. A summary record, designed in response to suggestions from doctors and patients from a previous study, was distributed to patients on the first ward round after admission. Eligible participants included all doctors and nurses working on and all patients and their families attending the acute medical units; patients were excluded if they lacked capacity to consent or were under 18. We interviewed 20 patients, 10 relatives, 10 doctors and 7 nurses.ResultsPatients felt that the summary improved their ability to remember details about their care so they could more accurately and easily update their relatives. They did not feel that the summary induced anxiety. Patient‐doctor communication was improved: patients felt empowered to ask more questions and doctors felt that it solidified their plan and encouraged them to avoid medical jargon. Most patients felt the summary included the ‘right’ amount of information. Healthcare professionals were more concerned about the risk of breaching confidentiality than patients. Doctors felt that providing summaries was time‐consuming; there were differing opinions about whether this was a worthwhile investment of time. Clinicians recognized that the traditional medical record has many roles.ConclusionsA summary record could empower patients and improve patient‐doctor communication but would require additional clinician and administrative time.
Exploring the acceptance of COVID‐19 vaccine among healthcare workers and general population using health belief model
Authors: Al‐Metwali Basma Zuheir , Al‐Jumaili Ali Azeez , Al‐Alag Zahraa Adel , Sorofman Bernard 
Published: May 2021

AbstractRationale, aims and objectivesLittle is known about hesitancy to receive the COVID‐19 vaccines. The objectives of this study were (1) to assess the perceptions of healthcare workers (HCWs) and the general population regarding the COVID‐19 vaccines, (2) to evaluate factors influencing the acceptance of vaccination using the health belief model (HBM), and (3) to qualitatively explore the suggested intervention strategies to promote the vaccination.MethodsThis was a cross‐sectional study based on electronic survey data that was collected in Iraq during December first‐19th, 2020. The electronic survey was designed using Qualtrics. HBM was followed to develop the survey items. A regression analysis was used to identify factors influencing people accepting vaccination. Thematic analysis for participant comments to an open‐ended question.ResultsA total of 1680 completed surveys were received. The mean age of 31.2 ± 9.9 years, 53.0% were female and 47.0% were male. The largest group was HCWs (45.7%), followed by general population (37.5%) and health college students (16.8%). Our findings expressed some hesitancy to receive the COVID‐19 vaccine with the acceptance rate of 61.7%. The HCWs perceived significantly higher susceptibility and severity of the COVID‐19 infection compared to the general population. The HCWs were significantly more likely than the general population to receive COVID‐19 vaccine. Concerns with proper storage was the biggest barrier to vaccine receipt. The regression analysis indicated eight factors that were significantly associated with the willingness to receive COVID‐19 vaccine: Preventive measures, perceived benefit, perceived barriers, cue to action, subjective norm, supportive of vaccination in general and having received a flu vaccine before.ConclusionsAwareness campaign can focus on enhancing the vaccine perceived benefit, debunking misconceptions, and increasing the disease perceived severity. Additionally, the public health leaders need to minimize the perceived barriers by providing the vaccines and appeasing people concerns about their storage, effectiveness, and adverse events.
Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan
Authors: Shiroma Sho , Hatta Waku , Tsuji Yosuke , Yoshio Toshiyuki , Yabuuchi Yohei , Hoteya Shu , Tsuji Shigetsugu , Nagami Yasuaki , Hikichi Takuto , Kobayashi Masakuni , Morita Yoshinori , Sumiyoshi Tetsuya , Iguchi Mikitaka , Tomida Hideomi , Inoue Takuya , Mikami Tatsuya , Hasatani Kenkei , Nishikawa Jun , Matsumura Tomoaki , Nebiki Hiroko , Nakamatsu Dai , Ohnita Ken , Suzuki Haruhisa , Ueyama Hiroya , Hayashi Yoshito , Sugimoto Mitsushige , Yamaguchi Shinjiro , Michida Tomoki , Yada Tomoyuki , Asahina Yoshiro , Narasaka Toshiaki , Kuribayashi Shiko , Kiyotoki Shu , Mabe Katsuhiro , Fujishiro Mitsuhiro , Masamune Atsushi , Fujisaki Junko 
Published: May 2021

AbstractBackground and AimThis study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).MethodsWe retrospectively reviewed 10,320 patients who underwent ESD for EGC during November 2013–October 2016. We evaluated overall bleeding rates and their inter‐group differences. Factors associated with early/late (cut‐off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated.ResultsOverall, the post‐ESD bleeding rate was 4.7% (489/10 320); the median time to post‐ESD bleeding was 4 days. The post‐ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1).ConclusionWe revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.
A domesticated Harbinger transposase forms a complex with HDA6 and promotes histone H3 deacetylation at genes but not TEs in Arabidopsis
Authors: Zhou Xishi , He Junna , Velanis Christos N. , Zhu Yiwang , He Yuhan , Tang Kai , Zhu Mingku , Graser Lisa , de Leau Erica , Wang Xingang , Zhang Lingrui , Andy Tao W. , Goodrich Justin , Zhu Jian‐Kang , Zhang Cui‐Jun 
Published: May 2021

ABSTRACTIn eukaryotes, histone acetylation is a major modification on histone N‐terminal tails that is tightly connected to transcriptional activation. HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements (TEs) in Arabidopsis thaliana. HDA6 has been shown to participate in several complexes in plants, including a conserved SIN3 complex. Here, we uncover a novel protein complex containing HDA6, several Harbinger transposon‐derived proteins (HHP1, SANT1, SANT2, SANT3, and SANT4), and MBD domain‐containing proteins (MBD1, MBD2, and MBD4). We show that mutations of all four SANT genes in the sant‐null mutant cause increased expression of the flowering repressors FLC, MAF4, and MAF5, resulting in a late flowering phenotype. Transcriptome deep sequencing reveals that while the SANT proteins and HDA6 regulate the expression of largely overlapping sets of genes, TE silencing is unaffected in sant‐null mutants. Our global histone H3 acetylation profiling shows that SANT proteins and HDA6 modulate gene expression through deacetylation. Collectively, our findings suggest that Harbinger transposon‐derived SANT domain‐containing proteins are required for histone deacetylation and flowering time control in plants.
Does It Matter Where You Search? Twitter versus Traditional News Media
Authors: MILAS COSTAS , PANAGIOTIDIS THEODORE , DERGIADES THEOLOGOS 
Published: May 2021

AbstractWe compare news in Twitter with traditional news outlets and emphasize their differential impact on Eurozone's sovereign bond market. We reveal a two‐way information flow between Twitter's “Grexit” tweets and “Grexit” mentions in traditional news which suggests not only that both types of news serve as important empirical predictors for the sovereign bond market but also that the “old” (traditional news) and the “new” (Twitter) media are connected; however, the influence of Twitter on traditional news is stronger. Grexit tweets raise the Greek spread more than Grexit mentions in traditional news. Weak contagion effects are reported for Portugal and Ireland.
Role of central kisspeptin and RFRP‐3 in energy metabolism in the male Wistar rat
Authors: Cázarez‐Márquez Fernando , Eliveld Jitske , Ritsema Wayne I. G. R. , Foppen Ewout , Bossenbroek Yvonne , Pelizzari Simone , Simonneaux Valérie , Kalsbeek Andries 
Published: May 2021

AbstractKisspeptin (Kp) and (Arg)(Phe) related peptide 3 (RFRP‐3) are two RF‐amides acting in the hypothalamus to control reproduction. In the past 10 years, it has become clear that, apart from their role in reproductive physiology, both neuropeptides are also involved in the control of food intake, as well as glucose and energy metabolism. To investigate further the neural mechanisms responsible for these metabolic actions, we assessed the effect of acute i.c.v. administration of Kp or RFRP‐3 in ad lib. fed male Wistar rats on feeding behaviour, glucose and energy metabolism, circulating hormones (luteinising hormone, testosterone, insulin and corticosterone) and hypothalamic neuronal activity. Kp increased plasma testosterone levels, had an anorexigenic effect and increased lipid catabolism, as attested by a decreased respiratory exchange ratio (RER). RFRP‐3 also increased plasma testosterone levels but did not modify food intake or energy metabolism. Both RF‐amides increased endogenous glucose production, yet with no change in plasma glucose levels, suggesting that these peptides provoke not only a release of hepatic glucose, but also a change in glucose utilisation. Finally, plasma insulin and corticosterone levels did not change after the RF‐amide treatment. The Kp effects were associated with an increased c‐Fos expression in the median preoptic area and a reduction in pro‐opiomelanocortin immunostaining in the arcuate nucleus. No effects on neuronal activation were found for RFRP‐3. Our results provide further evidence that Kp is not only a very potent hypothalamic activator of reproduction, but also part of the hypothalamic circuit controlling energy metabolism.