bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid Reprogramming Induced by TFEB-ERRα Axis Enhanced Membrane Fluidity to Promote EC Progression
Authors: Mao Xiaodan , Lei Huifang , Yi Tianjin , Su Pingping , Tang Shuting , Tong Yao , Dong Binhua , Ruan Guanyu , Mustea Alexander , Sehouli Jalid , Sun Pengming 
Published: September 2021

Abstract
Background: Endometrial cancer (EC) is one of the most common tumors in women. Estrogen-related receptor α (ERRα) has been reported to play a critical role in EC progression. However, the underlying mechanism of ERRα-mediated lipid reprogramming in EC remains elusive. Here, we show that transcription factor EB (TFEB)-ERRα axis promote lipid reprogramming to enhance invasion and metastasis of EC.Methods: TFEB and ERRα were analyzed and validated by RNA-sequencing data of EC tissues from the Cancer Genome Atlas (TCGA). TFEB-ERRα axis were assessed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The mechanism of TFEB-ERRα was investigated using loss-of-function and gain-of-function assays in vitro. Lipidomics and proteomics were performed to identify the ERRα-related lipid metabolism pathway. Furthermore, immunohistochemistry and lipidomics were performed in the tissues to verify the ERRα-related lipids.Results: Both TFEB and ERRα were highly expression in EC patients and related to EC progression. ERRα was the directly target of TFEB to mediate EC lipid metabolism. Lipidomics assays demonstrated that ERRα mainly effects on glycerophospholipids (GPs) and phosphatidylcholine (PC) and significantly elevates the ratio of PC/sphingomyelin (SM) in EC cells, which indicated the enhanced membrane fluidity. Specifically, ERRα induced unsaturated fatty acid (UFA)-containing PCs, phosphatidylglycerol (PGs), SMs etc. Combined proteomics analysis revealed the increase of UFA-containing GPs mainly related to mitochondrial function. Then, the levels of maximum oxygen consumption rates (OCRs), adenosine triphosphate (ATP) and lipid metabolism-related genes acc, fasn, acadm were found to be positively correlated with TFEB/ERRα expression. Mechanistically, our functional assays indicate that TFEB promoted EC cell migration in a ERRα-dependent manner by epithelial-mesenchymal transformation (EMT) signaling. Consistent with in vitro, higher PC(18:1/18:2)+HCOO were found in EC patients and those who with higher expression of TFEB/ERRα had a deeper myometrial invasion and lower serum high-density lipoprotein (HDL). Moreover, PC(18:1/18:2)+HCOO was an independent risk factor of the patients with lymph node metastasis and positively related to ERRα. Conclusion: Lipid reprogramming induced by TFEB-ERRα axis increases UFA- containing PC, PG and SM, which enhanced membrane fluidity via EMT signaling to promote EC progression. Of note, PC(18:1/18:2)+HCOO was the ERRα-associated potential predictor of EC metastasis.
Immunohistochemical Analysis Revealed the Expression of Bone Morphogenetic Proteins-4, 6, 7, and 9 in Human Induced Membrane Samples Treated With the Masquelet Technique
Authors: Niikura Takahiro , Oda Takahiro , Jimbo Naoe , Komatsu Masato , Oe Keisuke , Fukui Tomoaki , Matsumoto Tomoyuki , Hayashi Shinya , Matsushita Takehiko , Itoh Tomoo , Kuroda Ryosuke 
Published: September 2021

Abstract
BackgroundInduced membrane (IM) is the key component of Masquelet reconstruction surgery for the treatment of bone defects. It is formed around the cement spacer and is known to secrete growth factors and osteoinductive factors. However, information on the presence of osteoinductive factors in IM is not enough in the literature. The purpose of this study was to investigate the existence of bone morphogenetic proteins (BMPs) in the IM harvested from patients during the treatment of bone defects using the Masquelet technique.MethodsWe included six patients whose bone defects were treated using the Masquelet technique. The affected bone was the femur in three patients and the tibia in three patients. During the second-stage surgery, 1-cm2 pieces of IM were harvested. Histological sections of IM were immunostained with anti-BMP-4, 6, 7, and 9 antibodies. Human bone tissue served as the positive control.ResultsThe existence of BMP-4, 6, 7, and 9 was observed in all IM samples. Further, immunolocalization of BMP-4, 6, 7, and 9 was observed in blood vessels and fibroblasts of all IM samples. Immunolocalization of BMP-4, 6, 7, and 9 was also observed in bone tissue within the IM in one sample, in which osteogenesis inside the IM was observed.ConclusionsThis study revealed that osteoinductive factors BMP-4, 6, 7, and 9 were present in the IM harvested from patients. This helps explain how the Masquelet technique effectively contributes to the healing of large bone defects. It may thus be possible for surgeons to omit the addition of BMPs to bone grafts give the endogenous secretion of BMPs from the IM.Trial registrationNot applicable.
DMTHB Ameliorates Memory Impairment in Alzheimer's Disease Mice Through Inhibition of IL-16 Signaling
Authors: Zhang Yuanqiang , Liu Dongqing , Yao Xutao , Zhang Yubin 
Published: September 2021

Abstract
Aim: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Growing evidence suggested that AD is associated with neuroinflammation, characterized with the chronic activation of microglial cells and astrocytes along with the subsequent excessive generation of the proinflammatory molecule. This study aimed to investigate the effect and molecular mechanism of IL-16 and Demethylenetetrahydroberberine (DMTHB) on Alzheimer’s disease (AD).Methods: AD mice model were made by intracranial injection of Aβ25–35. Morris water maze (MWM) was applied to evaluate the capacity of learning and memory of mice. Moreover, concentrations of IL-6, IL‐1β, and TNF-α in the brain tissue were measured by western blot. DMTHB-binding proteins were identified by mass spectrometry analysis. Pathological change and neuronal death were detected by HE staining and Nissl staining. The expressions of tau and Aβ in the brain tissue were measured by immunohistochemistry and Western blot.Results: Our results showed that the cognition of AD mice was significantly improved after DMTHB administration. In addition, the content of p-Tau, Aβ and inflammatory cytokine (TNF-α， IL‐1β and IL-6) in the brains of AD mice were reduced by DMTHB treatment. The biotin-avidin system-based assay displayed that DMTHB can target and bind to inflammatory cytokine IL-16. Then, siRNA knockdown experiments demonstrated that interfering IL-16 expression can remarkably improve the cognitive ability and neuroinflammation in AD mice. Conclusion: These results indicated that IL-16 is a potential therapeutic target for treatment of AD, and DMTHB has shown a potential natural medicine against AD through regulation of IL-16 signaling, including PI3K/Akt/GSK-3β/Tau pathway.
Long Non-coding RNA CRNDE Exacerbates NPC Advancement Mediated by the miR-545-5p/CCND2 Axis
Authors: Ge Sichen , Jiang Chengyi , Li Min , Cheng Zhongqiang , Feng Xiaojia 
Published: September 2021

Abstract
Background: Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, together with all associated regulatory networks, on nasopharyngeal carcinoma (NPC) and its treatment possibilities.Methods：Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed CRNDE, miR-545-5p and CCND2 expression within NPCs and representative cell lineages. CCK-8 cell counting-, EdU-, wound-healing- / transwell-assays analyzed cellular proliferation, migrative, together with invasive properties. Apoptosis / cell cycle progression were scrutinized through flow cytometry. Dual-luciferase reporter assays validated CRNDE / miR-545-5p / CCND2 interplay. Proteomic expression of apoptosis-related protein, EMT-related protein and CCND2 protein were evaluated through Western blotting. In addition, Ki67 expression was evaluated through immunohistochemical staining. The effect of CRNDE in vivo was assessed by nude murine xenograft model studies.Results: This study demonstrated up-regulated expression of CRNDE and CCND2 within NPC tissues /cell lines. Meanwhile, miR-545-5p was downregulated. CRNDE knockdown or miR-545-5p over-expression drastically reduced NPC proliferative, migrative and invasive properties, promoted apoptosis / altered cell cycle, and inhibited the expression of CCND2. However, miR-545-5p downregulation had opposing effects. All inhibiting functions generated by CRNDE downregulation upon NPC progression could be counterbalanced or synergistically exacerbated, depending on miR-545-5p downregulation or upregulation, respectively. Multiple-level investigations revealed CRNDE to serve as a sponge for miR-545-5p and can target CCND2 within NPCs.Conclusions：CRNDE increases CCND2 expression by competitive binding with miR-545-5p, thus accelerating the development of NPC. This provides potential therapeutic targets and prognostic markers against NPC.
Increased Risk of Graves´ophthalmopathy in Patients With Increasing TRAb After Radioiodine Treatment and the Impact of CTLA4 on TRAb Titres
Authors: Shahida Bushra , Tsoumani Kleoniki , Planck Tereza , Modhukur Vijayachitra , Asp Pernilla , Sundlov Anna , Tennvall Jan , Åsman Peter , Lindgren Ola , Lantz Mikael 
Published: September 2021

Abstract
Introduction. Treatment of Graves´ disease (GD) with radioiodine increases the risk of developing Graves´ ophthalmopathy (GO) but the link between thyroid and orbital tissue remains undefined.The aim was to investigate the relationship between GO and TRAb after treatment with radioiodine and to define the impact of risk genes.Methods. GD patients without ophthalmopathy or previous treatment with radioiodine were prospectively included at treatment with radioiodine for hyperthyroidism. A follow-up was performed one year later for registration of GO development. The study was performed at a University Hospital Clinic; referral center of all patients treated with radioiodine in the south of Sweden. The main outcome measures were development of TRAb, anti-TPO, anti-TG after three months and GO after 12 months and relationship to the genetic background (HLA, CTLA-4, CYR61).Results. Three months of radioiodine TRAb increased in two thirds of patients (p<0.0005) but not in the other third. Anti-TPO was associated with TRAb (R=0.362, p <0.0001) but not anti-TG. At follow-up one year later (n=204) 32 patients developed GO with a proportion of 70% in the group increasing in TRAb and 30 % in the group with unchanged or lower TRAb (p-value <0.0005). Patients with GO had higher levels of TRAb than patients without GO. CTLA-4 (rs231775 SNP) was significantly (p<0.005) associated with TRAb levels above the median three months after radioiodine.Conclusions. The increase in TRAb after treatment with radioiodine is associated with GO and a genetic variation in CTLA-4 is associated with higher levels of TRAb.
An Alternative to Increase Accumulation of Phenolic Compound in Grapevine Callus Cultures: Chemical Mutagen Applications
Authors: CETİN Emine Sema , DALER Selda 
Published: September 2021

Abstract
This research was carried out to investigate the effects of chemical mutagen applications on producing phenolic compounds in calli obtained from leaf petiole explants of the Royal grape variety.Petioles were cultured in B5 medium containing 0.5 mg/L benzyl amino purine and 0.5 mg/L indole acetic acid to obtain callus. Calli obtained during the period following planting were subcultured in the same culture conditions three times at one month intervals. In the fourth subculture, the calli were transferred to nutrient mediums with the same composition containing ethyl methanesulfonate, sodium azide, azacitidine and acridine orange in three different doses, 0.5 mM, 1.0 mM, and 2.0 mM, and cultured in these mediums for 60, 120 and 180 minutes. Then, they were cultured again for four weeks in mutagen-free nutrient mediums with the same content as their previous mediums. At the end of this period, calli were taken from their nutrient medium, and total phenolic compound, total flavanol, total flavonol and anthocyanin analyzes were performed.As a result of the research, it has been determined that all mutagens applied are effective in increasing the production of phenolic compounds depending on the dose and time.
Weather Forecasting Based on Data-Driven and Physics Informed Reservoir Computing Models
Authors: Mammedov Yslam D. , Olugu Ezutah Udoncy , Farah Guleid A. 
Published: September 2021

Abstract
In response to the growing demand for the global energy supply chain, wind power has become an important research subject among studies in the advancement of renewable energy sources. The major concern is the stochastic volatility of weather conditions that hinder the development of wind power forecasting approaches. To address this issue, the current study proposes a weather prediction method divided into two models for wind speed and atmospheric system forecasting. First, the data-based model incorporated with wavelet transform and recurrent neural networks is employed to predict the wind speed. Second, the physics-informed echo state network was used to learn the chaotic behaviour of the atmospheric system. The findings were validated with a case study conducted on wind speed data from Turkmenistan. The results suggest the out-performance of physics-informed model for accurate and reliable forecasting analysis, which indicates the potential for implementation in wind energy analysis.
A Case-Control Study of the Causes of Acute Respiratory Infection among Hospitalized Patients in Northeastern Laos
Authors: Phommasone Koukeo , Xaiyaphet Xaipasong , Garcia-Rivera Jose A. , Hontz Robert D. , Pathavongsa Viengmone , Keomoukda Patsalin , Vongsouvath Malavanh , Mayxay Mayfong , Vongsouvath Manivanh , Newton Paul N , Ashley Elizabeth A. , Dubot-Pérès Audrey 
Published: September 2021

Abstract
Background
With the advent of highly sensitive real-time PCR, multiple pathogens have been identified from nasopharyngeal swabs of patients with acute respiratory infections (ARIs). However, the detection of microorganisms in the upper respiratory tract does not necessarily indicate disease causation. We conducted a matched case-control study, nested within a broader fever aetiology project, to facilitate determination of the aetiology of ARIs in hospitalised patients in Northeastern Laos.
Methods
Consenting febrile patients of any age admitted to Xiengkhuang Provincial Hospital were included if they met the inclusion criteria for ARI presentation (at least one of the following: cough, rhinorrhoea, nasal congestion, sore throat, difficulty breathing, and/or abnormal chest auscultation). One healthy control for each patient, matched by sex, age, and village of residence, was recruited for the study. Nasopharyngeal swabs were collected from participants and tested for 33 pathogens by probe-based multiplex real-time RT-PCR (FastTrack Diagnostics Respiratory pathogen 33 kit). Attributable fraction of illness for a given microorganism was calculated by comparing results between patients and controls (= 100 *[OR-1]/OR)(OR = Odds Ratio).
Results
Between 24th June 2019 and 24th June 2020, 205 consenting ARI patients and 205 matching controls were recruited. After excluding eight pairs due to age mismatch, 197 pairs were included in the analysis. Males were predominant with sex ratio 1.2:1 and children < 5 years old accounted for 59% of participants. At least one potential pathogen was detected in 172 (87%) patients and 175 (89%) controls. ARI in admitted patients were attributed to influenza B virus, influenza A virus, human metapneumovirus (HMPV), and respiratory syncytial virus (RSV) in 17.8%, 17.2%, 7.5%, and 6.5% of participants, respectively. SARS-CoV-2 was not detected in any cases or controls.
Conclusion
Determining ARI aetiology in individual patients remains challenging. Among hospitalised patients with ARI symptoms presenting to a provincial hospital in Northeastern Laos, half were determined to be caused by one of several respiratory viruses, in particular influenza A virus, influenza B virus, HMPV, and RSV.
Record of New Genotypes of Enterocytozoon Bieneusi in Wild Populations of Rhesus Macaque (Macaca Mulatta) in China
Authors: Yu Mengshi , Liu Xue , Karim Fazal , Xie Meng , Wu Jiayun , Li Diyan , Ni Qingyong , Zhang Mingwang , Xu Huailiang , Yao Yongfang 
Published: September 2021

Abstract
Background: Enterocytozoon bieneusi is a zoonotic pathogen with a wide range of animal host. In China, there are only a few reports of E. bieneusi infection in wild populations of Rhesus macaque. Here, we determined the prevalence of E. bieneusi in 9 populations of Rhesus macaque and assessed their zoonotic potential.Methods: A total of 324 fecal samples of Rhesus macaque were collected from 9 populations in 5 provinces (Sichuan, Chongqing, Qinghai, Tibet and Hainan) in China, and performed genotype of ITS gene to analyze the zoonotic potential.Results: 38 of the 324 (11.72%) specimens from wild Rhesus macaques were infected with E. bieneusi. 11 genotypes were identified including 3 known genotypes: D (n= 24), EbpC (n= 4) and SCC-2 (n= 1); 8 novel genotypes named Mul6 (n= 1), Mul7 (n= 1), Mul8 (n= 1), Mul9 (n= 1), Mul10 (n= 2), Mul11 (n= 1), Mul12 (n= 1) and Mul13 (n= 1). According to the phylogenetic analysis, Mul6, Mul7, Mul8, Mul9, Mul11 Mul12 and Mul13 were clustered into Group 1, while Mul10 were clustered into Group 5.Conclusions: To the best of our knowledge, this is the first study reporting the prevalence and genotypes of E. bieneusi in several wild populations of Rhesus macaque in China. It is concluded that, population of Rhesus Macaques is likely to prone of E. bieneusi transmission in many regions of China, which found the zoonotic genotypes D and EbpC and the novel genotypes with zoonotic potential, it should be paid more attention to prevent.
Prevalence and Factors Associated with Bullying Phenomenon Among Pre-Adolescents Attending First-Grade Secondary Schools of Palermo, Italy, and a Comparative Systematic Literature Review.
Authors: Costantino Claudio , Mazzucco Walter , Scarpitta Francesco , Ventura Gianmarco , Marotta Claudia , Bono Stefania Enza , Arcidiacono Evelina , Gentile Maurizio , Sannasardo Pierfrancesco , Gambino Carlo Roberto , Sannasardo Claudia Emilia , Vella Carlotta , Vitale Francesco , Casuccio Alessandra , Restivo Vincenzo 
Published: September 2021

Abstract
Background: Bullying is recognized as one of the most significant social and health problems in the school environment for children and adolescents. In Italy, bullying involved 2 in 10 kids between 11-17 years that referred to have been bullied two or more times in a month. In Sicily, the estimated prevalence of children aged 11 to 15 that suffered at least one act of bullying in the last two months was 14% in 2011.Methods: A questionnaire consisting of 30 items investigating physical, verbal and indirect bullying, observers of bullying, resiliency, and prosociality was administered to preadolescents of ten first-grade secondary schools within the Palermo Province in order to analyze prevalence and factors associated with bullying phenomenon. Also, a systematic literature review (SLR) analyzing manuscripts that reported prevalence of the bullying phenomenon worldwide was conducted. Results: Survey: a total of 867 students, belonging to 35 second and 31 third classes of ten different schools in Palermo, Italy, were recruited in the survey. The values of physical bullying are included between the 4% of the single question method and the almost forty percent detected by the score of 7 method. Verbal bullying oscillates between 15.9% and 66.3%. Observers average values varies from 15.8% to 47.5%. SLR: the estimated prevalence showed a considerable fluctuation. The occurrence of the bullying phenomenon was low in some Northern European countries, while in Anglo-Saxon countries it affected over a quarter of the middle school student population (28% in Maryland, USA and 21% in the UK). Conclusions The prevalence of the bullying phenomenon recorded by this survey with the three different methods used is similar to observations in international literature. In the Sicilian context, a higher prevalence of bullying phenomena was observed in pre-adolescents attending major classes and in schools with lower socio-economic index. Though it remains difficult to obtain univocal data that clarifies the prevalence of different type of bullying, the continuous investigation of prevalence and factors associated with the phenomenon is a necessary starting point to introduce interventions and preventive measures in Public Health programs.
On the Analysis of Data Augmentation Methods for Spectral Imaged Based Heart Sound Classification Using Convolutional Neural Networks
Authors: Zhou George , Chen Yunchan , Chien Candace 
Published: September 2021

Abstract
Background: The application of machine learning to cardiac auscultation has the potential to improve the accuracy and efficiency of both routine and point-of-care screenings. The use of Convolutional Neural Networks (CNN) on heart sound spectrograms in particular has defined state-of-the-art performance. However, the relative paucity of patient data remains a significant barrier to creating models that can adapt to the wide range of between-subject variability. To that end, we examined a CNN model’s performance on automated heart sound classification, before and after various forms of data augmentation, and aimed to identify the most optimal augmentation methods for cardiac spectrogram analysis.Results: We built a standard CNN model to classify cardiac sound recordings as either normal or abnormal. The baseline control model achieved an ROC AUC of 0.945±0.016. Among the data augmentation techniques explored, horizontal flipping of the spectrogram image improved the model performance the most, with an ROC AUC of 0.957±0.009. Principal component analysis color augmentation (PCA) and perturbations of saturation-value (SV) of the hue-saturation-value (HSV) color scale achieved an ROC AUC of 0.949±0.014 and 0.946±0.019, respectively. Time and frequency masking resulted in an ROC AUC of 0.948±0.012. Pitch shifting, time stretching and compressing, noise injection, vertical flipping, and applying random color filters all negatively impacted model performance.Conclusion: Data augmentation can improve classification accuracy by expanding and diversifying the dataset, which protects against overfitting to random variance. However, data augmentation is necessarily domain specific. For example, methods like noise injection have found success in other areas of automated sound classification, but in the context of cardiac sound analysis, noise injection can mimic the presence of murmurs and worsen model performance. Thus, care should be taken to ensure clinically appropriate forms of data augmentation to avoid negatively impacting model performance.