bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative statistical analyses of multiple liquid biopsy analytes in metastatic breast cancer
Authors: Keup Corinna , Suryaprakash Vinay , Hauch Siegfried , Storbeck Markus , Hahn Peter , Sprenger-Haussels Markus , Kolberg Hans-Christian , Tewes Mitra , Hoffmann Oliver , Kimmig Rainer , Kasimir-Bauer Sabine
Published: May 2021

Background

Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA).

Methods

Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients. CTC mRNA and EV mRNA were analyzed using a multi-marker qPCR. Plasma from CTC-depleted blood was utilized for cfDNA isolation. gDNA from CTCs was isolated from mRNA-depleted CTC lysates. CTC gDNA and cfDNA were analyzed by targeted sequencing. Hierarchical clustering was performed within each analyte, and its results were combined into a score termed Evaluation of multiple Liquid biopsy analytes In Metastatic breast cancer patients All from one blood sample (ELIMA.score), which calculates the contribution of each analyte to the overall survival prediction. Singular value decomposition (SVD), mutual information calculation, k-means clustering, and graph-theoretic analysis were conducted to elucidate the dependence between individual analytes.

Results

A combination of two/three/four LBAs increased the prevalence of patients with actionable signals. Aggregating the results of hierarchical clustering of individual LBAs into the ELIMA.score resulted in a highly significant correlation with overall survival, thereby bolstering evidence for the additive value of using multiple LBAs. Computation of mutual information indicated that none of the LBAs is independent of the others, but the ability of a single LBA to describe the others is rather limited—only CTC gDNA could partially describe the other three LBAs. SVD revealed that the strongest singular vectors originate from all four LBAs, but a majority originated from CTC gDNA. After k-means clustering of patients based on parameters of all four LBAs, the graph-theoretic analysis revealed CTC ERBB2 variants only in patients belonging to one particular cluster.

Conclusions

The additional benefits of using all four LBAs were objectively demonstrated in this pilot study, which also indicated a relative dominance of CTC gDNA over the other LBAs. Consequently, a multi-parametric liquid biopsy approach deconvolutes the genomic and transcriptomic complexity and should be considered in clinical practice.
Prevalence of IGFBP3, NOS3 and TCF7L2 polymorphisms and their association with hypertension: a population-based study with Brazilian women of African descent
Authors: Neto Abel Barbosa Lira , Vasconcelos Nancy Borges Rodrigues , dos Santos Tamara Rodrigues , Duarte Luisa Elvira Cavazzani , Assunção Monica Lopes , de Sales-Marques Carolinne , Ferreira Haroldo da Silva
Published: May 2021

Objective

African ancestry seems to be a risk factor for hypertension; however, few genetic studies have addressed this issue. This study aimed to investigate the prevalence of polymorphisms NOS3; rs1799983, IGFBP3; rs11977526 and TCF7L2; rs7903146 in Brazilian women of African descent and their association with hypertension.

Results

The prevalences of the less frequent genotypes were 26.5% TT genotype of NOS3; rs1799983, 16.7% AA genotype of IGFBP3; rs11977526, and 18.3% TT genotype of TCF7L2; rs7903146. For these conditions, the prevalence of hypertension and PR (adjusted) relatively to the ancestral genotype were, respectively: 52.0% vs 24.5% (PR = 1.54; p < 0.001), 62.0% vs 24.1% (PR = 1.59; p < 0.001), and 38.9% vs 27.9% (PR = 0.86; p = 0.166). Associations with hypertension were statistically significant, except for the TCF7L2; rs7903146 polymorphism, after adjusted analysis. Brazilian Afro-descendant women with the TT genotype for the NOS3 gene and the AA genotype for the IGFBP3 gene are more susceptible to hypertension. The understanding of underlying mechanisms involving the pathogenesis of hypertension can motivate research for the development of new therapeutic targets related to nitric oxide metabolism and the management of oxidative stress.
Amaranth leaf extract protects against hydrogen peroxide induced oxidative stress in Drosophila melanogaster
Authors: Johnmark Ndinawe , Kinyi Hellen W.
Published: May 2021

Objective

Amaranths leaves are rich in ascorbic acid and polyphenol compounds which have antioxidant activity. The aim of this study was to evaluate their in vivo antioxidant activity. The effect of consumption of Amaranth leaf extract on in vivo antioxidant activity, catalase enzyme activity and H2O2 induced oxidative stress in Drosophila melanogaster flies was assessed.

Results

Consumption of Amaranth leaf extract was associated with increased survival on exposure to H2o2 in a dose dependent manner in Drosophila melanogaster flies. The study concludes that the ethanolic extract of Amaranth leaves offer protection against hydrogen peroxide-induced oxidative stress.
Blood and skeletal muscle ageing determined by epigenetic clocks and their associations with physical activity and functioning
Authors: Sillanpää Elina , Heikkinen Aino , Kankaanpää Anna , Paavilainen Aini , Kujala Urho M. , Tammelin Tuija H. , Kovanen Vuokko , Sipilä Sarianna , Pietiläinen Kirsi H. , Kaprio Jaakko , Ollikainen Miina , Laakkonen Eija K.
Published: May 2021

The aim of this study was to investigate the correspondence of different biological ageing estimates (i.e. epigenetic age) in blood and muscle tissue and their associations with physical activity (PA), physical function and body composition. Two independent cohorts (N = 139 andN = 47) were included, whose age span covered adulthood (23–69 years). Whole blood and m. vastus lateralis samples were collected, and DNA methylation was analysed. Four different DNA methylation age (DNAmAge) estimates were calculated using genome-wide methylation data and publicly available online tools. A novel muscle-specific methylation age was estimated using the R-package ‘MEAT’. PA was measured with questionnaires and accelerometers. Several tests were conducted to estimate cardiorespiratory fitness and muscle strength. Body composition was estimated by dual-energy X-ray absorptiometry. DNAmAge estimates from blood and muscle were highly correlated with chronological age, but different age acceleration estimates were weakly associated with each other. The monozygotic twin within-pair similarity of ageing pace was higher in blood (r = 0.617–0.824) than in muscle (r = 0.523–0.585). Associations of age acceleration estimates with PA, physical function and body composition were weak in both tissues and mostly explained by smoking and sex. The muscle-specific epigenetic clock MEAT was developed to predict chronological age, which may explain why it did not associate with functional phenotypes. The Horvath’s clock and GrimAge were weakly associated with PA and related phenotypes, suggesting that higher PA would be linked to accelerated biological ageing in muscle. This may, however, be more reflective of the low capacity of epigenetic clock algorithms to measure functional muscle ageing than of actual age acceleration. Based on our results, the investigated epigenetic clocks have rather low value in estimating muscle ageing with respect to the physiological adaptations that typically occur due to ageing or PA. Thus, further development of methods is needed to gain insight into muscle tissue-specific ageing and the underlying biological pathways.
Methylated circulating tumor DNA as a biomarker for colorectal cancer diagnosis, prognosis, and prediction
Authors: Nassar Farah J. , Msheik Zahraa S. , Nasr Rihab R. , Temraz Sally N.
Published: May 2021

Worldwide, colorectal cancer (CRC) is a deadly disease whose death rate ranks second among cancers though its incidence ranks third. Early CRC detection is key and is associated with improved survival outcomes. However, existing tests for CRC diagnosis have several weaknesses thus rendering them inefficient. Moreover, reliable prognostic tests that can predict the overall cancer outcome and recurrence of the disease as well as predictive markers that can assess effectiveness of therapy are still lacking. Thus, shifting to noninvasive liquid biopsy or blood-based biomarkers is vital to improving CRC diagnosis, prognosis, and prediction. Methylated circulating tumor DNA (ctDNA) has gained increased attention as a type of liquid biopsy that is tumor-derived fragmented DNA with epigenetic alterations. Methylated ctDNA are more consistently present in blood of cancer patients as compared to mutated ctDNA. Hence, methylated ctDNA serves as a potential biomarker for CRC that is worth investigating. In this review, we explore what has been reported about methylated ctDNA as a biomarker for CRC diagnosis that can distinguish between CRC patients or those having adenoma and healthy controls as validated specifically through ROC curves. We also examine methylated ctDNA as a biomarker for CRC prognosis and prediction as confirmed through robust statistical analyses. Finally, we discuss the major technical challenges that limits the use of methylated ctDNA for clinical application and suggest possible recommendations to enhance its usage.
NEFM DNA methylation correlates with immune infiltration and survival in breast cancer
Authors: Li Dandan , Zhao Wenhao , Zhang Xinyu , Lv Hanning , Li Chunhong , Sun Lichun
Published: May 2021

Background

This study aims to determine whether NEFM (neurofilament medium) DNA methylation correlates with immune infiltration and prognosis in breast cancer (BRCA) and to explore NEFM-connected immune gene signature.

Methods

NEFM transcriptional expression was analyzed in BRCA and normal breast tissues using Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The relationship between NEFM DNA methylation and NEFM transcriptional expression was investigated in TCGA. Potential influence of NEFM DNA methylation/expression on clinical outcome was evaluated using TCGA BRCA, The Human Protein Atlas and Kaplan–Meier plotter databases. Association of NEFM transcriptional expression/DNA methylation with cancer immune infiltration was investigated using TIMER and TISIDB databases.

Results

High expression of NEFM correlated with better overall survival (OS) and recurrence-free survival (RFS) in TCGA BRCA and Kaplan–Meier plotter, whereas NEFM DNA methylation with worse OS in TCGA BRCA. NEFM transcriptional expression negatively correlated with DNA methylation. NEFM DNA methylation significantly negatively correlated with infiltrating levels of B, CD8+ T/CD4+ T cells, macrophages, neutrophils and dendritic cells in TIMER and TISIDB. NEFM expression positively correlated with macrophage infiltration in TIMER and TISIDB. After adjusted with tumor purity, NEFM expression weekly negatively correlated with infiltration level of B cells, whereas positively correlated with CD8+ T cell infiltration in TIMER gene modules. NEFM expression/DNA methylation correlated with diverse immune markers in TCGA and TISIDB.

Conclusions

NEFM low-expression/DNA methylation correlates with poor prognosis. NEFM expression positively correlates with macrophage infiltration. NEFM DNA methylation strongly negatively correlates with immune infiltration in BRCA. Our study highlights novel potential functions of NEFM expression/DNA methylation in regulation of tumor immune microenvironment.
Increased PARylation impacts the DNA methylation process in type 2 diabetes mellitus
Authors: Zampieri Michele , Bacalini Maria Giulia , Barchetta Ilaria , Scalea Stefania , Cimini Flavia Agata , Bertoccini Laura , Tagliatesta Stefano , De Matteis Giovanna , Zardo Giuseppe , Cavallo Maria Gisella , Reale Anna
Published: May 2021

Background

Epigenetic modifications, such as DNA methylation, can influence the genetic susceptibility to type 2 diabetes mellitus (T2DM) and the progression of the disease. Our previous studies demonstrated that the regulation of the DNA methylation pattern involves the poly(ADP-ribosyl)ation (PARylation) process, a post-translational modification of proteins catalysed by the poly(ADP-ribose) polymerase (PARP) enzymes. Experimental data showed that the hyperactivation of PARylation is associated with impaired glucose metabolism and the development of T2DM. Aims of this case–control study were to investigate the association between PARylation and global and site-specific DNA methylation in T2DM and to evaluate metabolic correlates.

Results

Data were collected from 61 subjects affected by T2DM and 48 healthy individuals, recruited as controls. Global levels of poly(ADP-ribose) (PAR, a surrogate of PARP activity), cytosine methylation (5-methylcytosine, 5mC) and de-methylation intermediates 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) were determined in peripheral blood cells by ELISA-based methodologies. Site-specific DNA methylation profiling of SOCS3, SREBF1 and TXNIP candidate genes was performed by mass spectrometry-based bisulfite sequencing, methyl-sensitive endonucleases digestion and by DNA immuno-precipitation. T2DM subjects presented higher PAR levels than controls. In T2DM individuals, increased PAR levels were significantly associated with higher HbA1c levels and the accumulation of the de-methylation intermediates 5hmC and 5fC in the genome. In addition, T2DM patients with higher PAR levels showed reduced methylation with increased 5hmC and 5fC levels in specific SOCS3 sites, up-regulated SOCS3 expression compared to both T2DM subjects with low PAR levels and controls.

Conclusions

This study demonstrates the activation of PARylation processes in patients with T2DM, particularly in those with poor glycaemic control. PARylation is linked to dysregulation of DNA methylation pattern via activation of the DNA de-methylation cascade and may be at the basis of the differential gene expression observed in presence of diabetes.
CD157 in bone marrow mesenchymal stem cells mediates mitochondrial production and transfer to improve neuronal apoptosis and functional recovery after spinal cord injury
Authors: Li Jing , Li Heyangzi , Cai Simin , Bai Shi , Cai Huabo , Zhang Xiaoming
Published: May 2021

Background

Recent studies demonstrated that autologous mitochondria derived from bone marrow mesenchymal stem cells (BMSCs) might be valuable in the treatment of spinal cord injury (SCI). However, the mechanisms of mitochondrial transfer from BMSCs to injured neurons are not fully understood.

Methods

We modified BMSCs by CD157, a cell surface molecule as a potential regulator mitochondria transfer, then transplanted to SCI rats and co-cultured with OGD injured VSC4.1 motor neuron. We detected extracellular mitochondrial particles derived from BMSCs by transmission electron microscope and measured the CD157/cyclic ADP-ribose signaling pathway-related protein expression by immunohistochemistry and Western blotting assay. The CD157 ADPR-cyclase activity and Fluo-4 AM was used to detect the Ca2+ signal. All data were expressed as mean ± SEM. Statistical analysis was analyzed by GraphPad Prism 6 software. Unpaired t-test was used for the analysis of two groups. Multiple comparisons were evaluated by one-way ANOVA or two-way ANOVA.

Results

CD157 on BMSCs was upregulated when co-cultured with injured VSC4.1 motor neurons. Upregulation of CD157 on BMSCs could raise the transfer extracellular mitochondria particles to VSC4.1 motor neurons, gradually regenerate the axon of VSC4.1 motor neuron and reduce the cell apoptosis. Transplantation of CD157-modified BMSCs at the injured sites could significantly improve the functional recovery, axon regeneration, and neuron apoptosis in SCI rats. The level of Ca2+ in CD157-modified BMSCs dramatically increased when objected to high concentration cADPR, ATP content, and MMP of BMSCs also increased.

Conclusion

The present results suggested that CD157 can regulate the production and transfer of BMSC-derived extracellular mitochondrial particles, enriching the mechanism of the extracellular mitochondrial transfer in BMSCs transplantation and providing a novel strategy to improve the stem cell treatment on SCI.
Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages
Authors: Lv Haijin , Yuan Xiaofeng , Zhang Jiebin , Lu Tongyu , Yao Jia , Zheng Jun , Cai Jianye , Xiao Jiaqi , Chen Haitian , Xie Shujuan , Ruan Ying , An Yuling , Sui Xin , Yi Huimin
Published: May 2021

Objectives

Acute lung injury (ALI) remains a common cause of morbidity and mortality worldwide, and to date, there is no effective treatment for ALI. Previous studies have revealed that topical administration of mesenchymal stem cells (MSCs) can attenuate the pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance the survival and function of cells. The present study aimed to assess whether HS-pretreated MSCs could enhance immunomodulation and recovery from ALI.

Materials and methods

HS pretreatment was performed at 42 °C for 1 h, and changes in biological characteristics and secretion functions were detected. In an in vivo mouse model of ALI, we intranasally administered pretreated umbilical cord-derived MSCs (UC-MSCs), confirmed their therapeutic effects, and detected the phenotypes of the macrophages in bronchoalveolar lavage fluid (BALF). To elucidate the underlying mechanisms, we cocultured pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in the macrophages were assessed.

Results

The data showed that UC-MSCs did not exhibit significant changes in viability or biological characteristics after HS pretreatment. The administration of HS-pretreated UC-MSCs to the ALI model improved the pathological changes and lung damage-related indexes, reduced the proinflammatory cytokine levels, and modulated the M1/M2 macrophage balance. Mechanistically, both the in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs, which negatively modulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in alveolar macrophages. These effects were partially reversed by knocking down HSP70 expression.

Conclusion

HS pretreatment can enhance the beneficial effects of UC-MSCs in inhibiting NLRP3 inflammasome activation in macrophages during ALI. The mechanism may be related to the upregulated expression of HSP70.

Graphical abstract
The role of Serpina3n in the reversal effect of ATRA on dexamethasone-inhibited osteogenic differentiation in mesenchymal stem cells
Authors: Jiang Hai-Tao , Deng Rui , Deng Yan , Nie Mao , Deng Yi-Xuan , Luo Hong-Hong , Yang Yuan-Yuan , Ni Na , Ran Cheng-Cheng , Deng Zhong-Liang
Published: May 2021

Background

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis. Patients with GIOP are susceptible to fractures and the subsequent delayed bone union or nonunion. Thus, effective drugs and targets need to be explored. In this regard, the present study aims to reveal the possible mechanism of the anti-GIOP effect of all-trans retinoic acid (ATRA).

Methods

Bone morphogenetic protein 9 (BMP9)-transfected mesenchymal stem cells (MSCs) were used as an in vitro osteogenic model to deduce the relationship between ATRA and dexamethasone (DEX). The osteogenic markers runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin were detected using real-time quantitative polymerase chain reaction, Western blot, and immunofluorescent staining assay. ALP activities and matrix mineralization were evaluated using ALP staining and Alizarin Red S staining assay, respectively. The novel genes associated with ATRA and DEX were detected using RNA sequencing (RNA-seq). The binding of the protein–DNA complex was validated using chromatin immunoprecipitation (ChIP) assay. Rat GIOP models were constructed using intraperitoneal injection of dexamethasone at a dose of 1 mg/kg, while ATRA intragastric administration was applied to prevent and treat GIOP. These effects were evaluated based on the serum detection of the osteogenic markers osteocalcin and tartrate-resistant acid phosphatase 5b, histological staining, and micro-computed tomography analysis.

Results

ATRA enhanced BMP9-induced ALP, RUNX2 expressions, ALP activities, and matrix mineralization in mouse embryonic fibroblasts as well as C3H10T1/2 and C2C12 cells, while a high concentration of DEX attenuated these markers. When DEX was combined with ATRA, the latter reversed DEX-inhibited ALP activities and osteogenic markers. In vivo analysis showed that ATRA reversed DEX-inhibited bone volume, bone trabecular number, and thickness. During the reversal process of ATRA, the expression of retinoic acid receptor beta (RARβ) was elevated. RARβ inhibitor Le135 partly blocked the reversal effect of ATRA. Meanwhile, RNA-seq demonstrated that serine protease inhibitor, clade A, member 3N (Serpina3n) was remarkably upregulated by DEX but downregulated when combined with ATRA. Overexpression of Serpina3n attenuated ATRA-promoted osteogenic differentiation, whereas knockdown of Serpina3n blocked DEX-inhibited osteogenic differentiation. Furthermore, ChIP assay revealed that RARβ can regulate the expression of Serpina3n.

Conclusion

ATRA can reverse DEX-inhibited osteogenic differentiation both in vitro and in vivo, which may be closely related to the downregulation of DEX-promoted Serpina3n. Hence, ATRA may be viewed as a novel therapeutic agent, and Serpina3n may act as a new target for GIOP.
Sex differences in vancomycin-resistant enterococci bloodstream infections—a systematic review and meta-analysis
Authors: Correa-Martínez Carlos L. , Schuler Franziska , Kampmeier Stefanie
Published: May 2021

Background

Vancomycin-resistant enterococci (VRE) have emerged in the healthcare setting worldwide. Infections with these pathogens, i.e., bloodstream infections (BSI), are accompanied with an impaired patient outcome. Diverse factors comprising patient characteristics, therapeutic strategies, and infection control measures are positively or negatively associated with VRE BSI occurrence. However, whether sex-specific differences influence the frequency of VRE BSI is yet unknown.

The aim of this systematic review was to comprehensively summarize and analyze sex prevalence in VRE BSI patients.

Main text

A systematic search for relevant articles was conducted in PubMed and Web of Science. After screening for eligibility, data extraction from included articles and risk of bias assessment were processed. The prevalence of male/female sex in VRE BSI patients and 95% CI were calculated for each study and summarized as pooled estimated effect.

In total, nine articles met the inclusion criteria. Risk of bias assessment resulted in low (six studies) to moderate bias (three studies). The pooled prevalence of male patients suffering from VRE BSI was 59% resulting in a 1.4 male/female prevalence ratio.

Conclusions

Current literature suggests sex differences with male preference (59%) in the distribution of VRE BSI cases. Further primary studies should address the question of male-specific factors favoring the enhanced frequency of VRE BSI.
Learning adaptive representations for entity recognition in the biomedical domain
Authors: Lauriola Ivano , Aiolli Fabio , Lavelli Alberto , Rinaldi Fabio
Published: May 2021

Background

Named Entity Recognition is a common task in Natural Language Processing applications, whose purpose is to recognize named entities in textual documents. Several systems exist to solve this task in the biomedical domain, based on Natural Language Processing techniques and Machine Learning algorithms. A crucial step of these applications is the choice of the representation which describes data. Several representations have been proposed in the literature, some of which are based on a strong knowledge of the domain, and they consist of features manually defined by domain experts. Usually, these representations describe the problem well, but they require a lot of human effort and annotated data. On the other hand, general-purpose representations like word-embeddings do not require human domain knowledge, but they could be too general for a specific task.

Results

This paper investigates methods to learn the best representation from data directly, by combining several knowledge-based representations and word embeddings. Two mechanisms have been considered to perform the combination, which are neural networks and Multiple Kernel Learning. To this end, we use a hybrid architecture for biomedical entity recognition which integrates dictionary look-up (also known as gazetteers) with machine learning techniques. Results on the CRAFT corpus clearly show the benefits of the proposed algorithm in terms ofF1score.

Conclusions

Our experiments show that the principled combination of general, domain specific, word-, and character-level representations improves the performance of entity recognition. We also discussed the contribution of each representation in the final solution.
Single cell RNA-seq analysis of the flexor digitorum brevis mouse myofibers
Authors: Verma Rohan X. , Kannan Suraj , Lin Brian L. , Fomchenko Katherine M. , Nieuwenhuis Tim O. , Patil Arun H. , Lukban Clarisse , Yang Xiaoping , Fox-Talbot Karen , McCall Matthew N. , Kwon Chulan , Kass David A. , Rosenberg Avi Z. , Halushka Marc K.
Published: May 2021

Background

Skeletal muscle myofibers can be separated into functionally distinct cell types that differ in gene and protein expression. Current single cell expression data is generally based upon single nucleus RNA, rather than whole myofiber material. We examined if a whole-cell flow sorting approach could be applied to perform single cell RNA-seq (scRNA-seq) in a single muscle type.

Methods

We performed deep, whole cell, scRNA-seq on intact and fragmented skeletal myofibers from the mouse fast-twitch flexor digitorum brevis muscle utilizing a flow-gated method of large cell isolation. We performed deep sequencing of 763 intact and fragmented myofibers.

Results

Quality control metrics across the different gates indicated only 171 of these cells were optimal, with a median read count of 239,252 and an average of 12,098 transcripts per cell. scRNA-seq identified three clusters of myofibers (a slow/fast 2A cluster and two fast 2X clusters). Comparison to a public skeletal nuclear RNA-seq dataset demonstrated a diversity in transcript abundance by method. RISH validated multiple genes across fast and slow twitch skeletal muscle types.

Conclusion

This study introduces and validates a method to isolate intact skeletal muscle myofibers to generate deep expression patterns and expands the known repertoire of fiber-type-specific genes.
Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway
Authors: Cheng Ji-wen , Duan Li-xia , Yu Yang , Wang Pu , Feng Jia-le , Feng Guan-zheng , Liu Yan
Published: May 2021

Background

Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell–cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms.

Methods

First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments.

Results

We established that MSCs promoted the stemness of PCa cells by cell–cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo.

Conclusions

Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.
Synonymous point mutation of gtfB gene caused by therapeutic X-rays exposure reduced the biofilm formation and cariogenic abilities of Streptococcus mutans
Authors: Wang Zheng , Zhou Yujie , Han Qi , Ye Xingchen , Chen Yanyan , Sun Yan , Liu Yaqi , Zou Jing , Qi Guohai , Zhou Xuedong , Cheng Lei , Ren Biao
Published: May 2021

Background

The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays.

Results

X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The “silent mutation” of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes’ expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB2043 T>C, similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type.

Conclusion

The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency.
Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults
Authors: Van Regenmortel Niels , Moers Lynn , Langer Thomas , Roelant Ella , De Weerdt Tim , Caironi Pietro , Malbrain Manu L. N. G. , Elbers Paul , Van den Wyngaert Tim , Jorens Philippe G.
Published: May 2021

Purpose

Iatrogenic fluid overload is a potential side effect of intravenous fluid therapy in the hospital. Little attention has been paid to sodium administration as a separate cause of harm. With this narrative review, we aim to substantiate the hypothesis that a considerable amount of fluid-induced harm is caused not only by fluid volume, but also by the sodium that is administered to hospitalized patients.

Methods

We show how a regular dietary sodium intake is easily surpassed by the substantial amounts of sodium that are administered during typical hospital stays. The most significant sodium burdens are caused by isotonic maintenance fluid therapy and by fluid creep, defined as the large volume unintentionally administered to patients in the form of dissolved medication. In a section on physiology, we elaborate on the limited renal handling of an acute sodium load. We demonstrate how the subsequent retention of water is an energy-demanding, catabolic process and how free water is needed to excrete large burdens of sodium. We quantify the effect size of sodium-induced fluid retention and discuss its potential clinical impact. Finally, we propose preventive measures, discuss the benefits and risks of low-sodium maintenance fluid therapy, and explore options for reducing the amount of sodium caused by fluid creep.

Conclusion

The sodium burdens caused by isotonic maintenance fluids and fluid creep are responsible for an additional and avoidable derailment of fluid balance, with presumed clinical consequences. Moreover, the handling of sodium overload is characterized by increased catabolism. Easy and effective measures for reducing sodium load and fluid retention include choosing a hypotonic rather than isotonic maintenance fluid strategy (or avoiding these fluids when enough free water is provided through other sources) and dissolving as many medications as possible in glucose 5%.
Resuscitative endovascular balloon occlusion of the aorta vs epinephrine in the treatment of non-traumatic cardiac arrest in swine
Authors: Hutin Alice , Levy Yaël , Lidouren Fanny , Kohlhauer Matthias , Carli Pierre , Ghaleh Bijan , Lamhaut Lionel , Tissier Renaud
Published: May 2021

Background

The administration of epinephrine in the management of non-traumatic cardiac arrest remains recommended despite controversial effects on neurologic outcome. The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) could be an interesting alternative. The aim of this study was to compare the effects of these 2 strategies on return of spontaneous circulation (ROSC) and cerebral hemodynamics during cardiopulmonary resuscitation (CPR) in a swine model of non-traumatic cardiac arrest.

Results

Anesthetized pigs were instrumented and submitted to ventricular fibrillation. After 4 min of no-flow and 18 min of basic life support (BLS) using a mechanical CPR device, animals were randomly submitted to either REBOA or epinephrine administration before defibrillation attempts. Six animals were included in each experimental group (Epinephrine or REBOA). Hemodynamic parameters were similar in both groups during BLS, i.e., before randomization. After epinephrine administration or REBOA, mean arterial pressure, coronary and cerebral perfusion pressures similarly increased in both groups. However, carotid blood flow (CBF) and cerebral regional oxygenation saturation were significantly higher with REBOA as compared to epinephrine administration (+ 125% and + 40%, respectively). ROSC was obtained in 5 animals in both groups. After resuscitation, CBF remained lower in the epinephrine group as compared to REBOA, but it did not achieve statistical significance.

Conclusions

During CPR, REBOA is as efficient as epinephrine to facilitate ROSC. Unlike epinephrine, REBOA transitorily increases cerebral blood flow and could avoid its cerebral detrimental effects during CPR. These experimental findings suggest that the use of REBOA could be beneficial in the treatment of non-traumatic cardiac arrest.
RANSAC algorithm for instantaneous frequency estimation and reconstruction of frequency-modulated undersampled signals
Authors: Djurović Igor
Published: May 2021

Frequency modulated (FM) signals sampled below the Nyquist rate or with missing samples (nowadays part of wider compressive sensing (CS) framework) are considered. Recently proposed matching pursuit and greedy techniques are inefficient for signals with several phase parameters since they require a search over multidimensional space. An alternative is proposed here based on the random samples consensus algorithm (RANSAC) applied to the instantaneous frequency (IF) estimates obtained from the time-frequency (TF) representation of recordings (undersampled or signal with missing samples). The O’Shea refinement strategy is employed to refine results. The proposed technique is tested against third- and fifth-order polynomial phase signals (PPS) and also for signals corrupted by noise.
Single base station positioning based on multipath parameter clustering in NLOS environment
Authors: Wang Yong , Wu Qihong , Zhou Mu , Yang Xiaolong , Nie Wei , Xie Liangbo
Published: May 2021

This paper proposes a scattering area model for processing multipath parameters achieve single base station positioning. First of all, we construct a scattering area model based on the spatial layout of obstacles near the base station and then collect the multipath signals needed for positioning and extract parameters. Second, we use the joint clustering algorithm improved by k-means clustering and mean shift clustering algorithm to process the parameters and extract useful information. Third, the processed information is combined with the spatial layout information of the scattering area model to construct equations, and then the solving problem of equations is converted into a least-squares optimization problem. Finally, the Levenberg-Marquardt (LM) algorithm is used to solve the optimal solution and estimate the mobile target position. The simulation results show that the positioning algorithm in this paper can be used by a single base station to locate the target in an outdoor non-line-of-sight (NLOS) environment, and the accuracy is improved compared with the traditional positioning algorithm.
A robot vision navigation method using deep learning in edge computing environment
Authors: Li Jing , Yin Jialin , Deng Lin
Published: May 2021

In the development of modern agriculture, the intelligent use of mechanical equipment is one of the main signs for agricultural modernization. Navigation technology is the key technology for agricultural machinery to control autonomously in the operating environment, and it is a hotspot in the field of intelligent research on agricultural machinery. Facing the accuracy requirements of autonomous navigation for intelligent agricultural robots, this paper proposes a visual navigation algorithm for agricultural robots based on deep learning image understanding. The method first uses a cascaded deep convolutional network and hybrid dilated convolution fusion method to process images collected by a vision system. Then, it extracts the route of processed images based on the improved Hough transform algorithm. At the same time, the posture of agricultural robots is adjusted to realize autonomous navigation. Finally, our proposed method is verified by using non-interference experimental scenes and noisy experimental scenes. Experimental results show that the method can perform autonomous navigation in complex and noisy environments and has good practicability and applicability.
Location-sharing protocol for privacy protection in mobile online social networks
Authors: Ruan Ou , Zhang Lixiao , Zhang Yuanyuan
Published: May 2021

Location-based services are becoming more and more popular in mobile online social networks (mOSNs) for smart cities, but users’ privacy also has aroused widespread concern, such as locations, friend sets and other private information. At present, many protocols have been proposed, but these protocols are inefficient and ignore some security risks. In the paper, we present a new location-sharing protocol, which solves two issues by using symmetric/asymmetric encryption properly. We adopt the following methods to reduce the communication and computation costs: only setting up one location server; connecting social network server and location server directly instead of through cellular towers; avoiding broadcast encryption. We introduce dummy identities to protect users’ identity privacy, and prevent location server from inferring users’ activity tracks by updating dummy identities in time. The details of security and performance analysis with related protocols show that our protocol enjoys two advantages: (1) it’s more efficient than related protocols, which greatly reduces the computation and communication costs; (2) it satisfies all security goals; however, most previous protocols only meet some security goals.
Single image super resolution based on multi-scale structure and non-local smoothing
Authors: Wang Wenyi , Hu Jun , Liu Xiaohong , Zhao Jiying , Chen Jianwen
Published: May 2021

In this paper, we propose a hybrid super-resolution method by combining global and local dictionary training in the sparse domain. In order to present and differentiate the feature mapping in different scales, a global dictionary set is trained in multiple structure scales, and a non-linear function is used to choose the appropriate dictionary to initially reconstruct the HR image. In addition, we introduce the Gaussian blur to the LR images to eliminate a widely used but inappropriate assumption that the low resolution (LR) images are generated by bicubic interpolation from high-resolution (HR) images. In order to deal with Gaussian blur, a local dictionary is generated and iteratively updated by K-means principal component analysis (K-PCA) and gradient decent (GD) to model the blur effect during the down-sampling. Compared with the state-of-the-art SR algorithms, the experimental results reveal that the proposed method can produce sharper boundaries and suppress undesired artifacts with the present of Gaussian blur. It implies that our method could be more effect in real applications and that the HR-LR mapping relation is more complicated than bicubic interpolation.
OSDDY: embedded system-based object surveillance detection system with small drone using deep YOLO
Authors: Madasamy Kaliappan , Shanmuganathan Vimal , Kandasamy Vijayalakshmi , Lee Mi Young , Thangadurai Manikandan
Published: May 2021

Computer vision is an interdisciplinary domain for object detection. Object detection relay is a vital part in assisting surveillance, vehicle detection and pose estimation. In this work, we proposed a novel deep you only look once (deep YOLO V3) approach to detect the multi-object. This approach looks at the entire frame during the training and test phase. It followed a regression-based technique that used a probabilistic model to locate objects. In this, we construct 106 convolution layers followed by 2 fully connected layers and 812 × 812 × 3 input size to detect the drones with small size. We pre-train the convolution layers for classification at half the resolution and then double the resolution for detection. The number of filters of each layer will be set to 16. The number of filters of the last scale layer is more than 16 to improve the small object detection. This construction uses up-sampling techniques to improve undesired spectral images into the existing signal and rescaling the features in specific locations. It clearly reveals that the up-sampling detects small objects. It actually improves the sampling rate. This YOLO architecture is preferred because it considers less memory resource and computation cost rather than more number of filters. The proposed system is designed and trained to perform a single type of class called drone and the object detection and tracking is performed with the embedded system-based deep YOLO. The proposed YOLO approach predicts the multiple bounding boxes per grid cell with better accuracy. The proposed model has been trained with a large number of small drones with different conditions like open field, and marine environment with complex background.
Development of a patient safety care activity scale for clinical nurses in Korea
Authors: Yang Ya Ki
Published: May 2021

Background

The aim of this study was to develop a scale to measure patient safety care activities for clinical nurses and to verify validity and reliability it.

Methods

Literature review and expert consultation were utilized to develop the scale of the Patient Safety Care Activities. The validity and reliability analyses were conducted with 428 nurses working at 5 general hospitals. Exploratory factor analysis of the scale was performed, and convergent and discriminant validity as well as internal consistency reliability were determined.

Results

Eight subcategories (security, patient identification, operation (invasive procedure), medication, blood transfusion, management of infection, management of falls & sores, management of firefighting) with 44 items were validated to measure patient safety care activities. Convergent and discriminant validity indicated the applicability of the eight-factor Patient Safety Care Activities scale. The reliability of the Patient Safety Care Activities Scale was acceptable, with Cronbach’s a = .88 ~ .95.

Conclusion

The developed scale showed content, construct validity, and reliability, as well as convergent validity for each item and discriminant validity between the factors. This makes it suitable for use in a diverse range of future studies on patient safety care activity.
STEM stereotypes predict students’ STEM career interest via self-efficacy and outcome expectations
Authors: Luo Tian , So Winnie Wing Mui , Wan Zhi Hong , Li Wai Chin
Published: May 2021

Background

Nurturing students’ interest in science, technology, engineering, and mathematics (STEM) careers is a major goal of STEM education. Although the relationship between students’ stereotypical beliefs regarding STEM careers and their career interest can be reasonably hypothesized, research investigating the extent to which and how students’ STEM career interest is directly or indirectly influenced by their stereotypical beliefs is lacking. This study investigated how upper primary students’ stereotypical beliefs regarding STEM careers predicted their STEM self-efficacy and STEM career-related outcome expectations and how these constructs predicted their STEM career interest. Structural equation modelling was used to analyse quantitative survey data of 824 fourth- to sixth-grade students and test the hypothesized models.

Results

Students’ stereotypical beliefs regarding STEM careers negatively predicted their self-efficacy in STEM activities and career-related outcome expectations. Additionally, the students’ self-efficacy in STEM activities and career-related outcome expectations in turn predicted their STEM career interest.

Conclusions

These results explain the potential indirect effect of STEM stereotypes on students’ career interest through self-efficacy and outcome expectations. The findings highlight the significant role of STEM stereotypes, self-efficacy in STEM activities, and career-related outcome expectations in students’ career development. The implications of this study for STEM education are also discussed.