bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatic removal of NUMT‐associated variants in mitotiling next‐generation sequencing data from whole blood samples
Authors: Ring Joseph David , Sturk‐Andreaggi Kimberly , Alyse Peck Michelle , Marshall Charla 
Published: August 2018

AbstractNuclear mitochondrial DNA segments (NUMTs) have arisen because of the transposition of segments of the mitochondrial DNA genome (mitogenome) into the nuclear genome. When using a “mitotiling” strategy, NUMTs may be more readily amplified when targeting the entire mitogenome compared to the control region, as hundreds of primers are required for complete sequencing coverage. In samples with a high percentage of nuclear DNA copies per cell, such as whole blood, NUMT coenrichment may be exacerbated. The present study examined bioinformatic approaches for removing NUMTs and NUMT‐associated variants (NAVs) from next‐generation sequence data generated using two mitotiling kits (Precision ID and QIAseq). Across 16 samples with low mtDNA copy number, NUMT coenrichment produced 890 NAVs with >5% variant frequency. The use of the consensus sequence to eliminate NUMT reads proved to be effective for QIAseq data, and resulted in >85% NAV removal in Precision ID data. This method was bolstered by NAV filtering in Precision ID analysis. Alternative high stringency mapping to the revised Cambridge Reference Sequence (rCRS) and the human genome reference GRCh38 for the QIAseq data caused a reduction in mitogenome coverage without complete NUMT removal. These bioinformatic solutions facilitate mitotiling sequence data analysis for low‐level variant detection.
What drove the health system reforms in the Kingdom of Saudi Arabia? An analysis
Authors: Rahman Redwanur , Alsharqi Omar Z. 
Published: August 2018

SummaryPurposeThe primary objective of this article is to present the key directions taken by the Saudi health care system, following the announcement of the Saudi Vision 2030. The changing international scenario, together with reduced oil revenues, high population growth, emerging lifestyle diseases, and demands for better quality of care, has impacted the development of the Saudi health system. The government is now ardently pursuing private sector development and has initiated privatization and marketization as a core strategy of reforms in its health system. This article posits that the current economic conditions of the KSA and local and global market dynamics are the primary drivers for these reforms.MethodsThis study is based on a scoping literature review.FindingsThe intended reforms will have very limited contribution to improving the population's health, and the study remains inconclusive.ConclusionThe Kingdom took a protective approach in reforming its health sector. The social values that undergird the government actions, especially, how much priority it gives to maintain status quo in the social and economic fabric vis‐à‐vis economic growth and development, have exerted a significant influence on whether the KSA chooses a pro‐government or a pro‐market approach; however, this could lead to a hybrid model of health care system.
Responsiveness of the urban primary health care delivery system in Bangladesh: A comparative analysis
Authors: Hamid Syed Abdul , Begum Afroza 
Published: August 2018

SummaryThis study analyses the responsiveness of outpatient care to assess the quality of urban primary health care among all 5 types of health care providers in Bangladesh, namely, the Urban Primary Health Care Services Delivery Project, the NGO Health Services Delivery Project (NHSDP), NGOs, private hospitals, and the Ministry of Health and Family Welfare (MOHFW). Other than some public‐private comparisons, there is an absolute knowledge gap regarding responsiveness in urban health systems, particularly in the context of Bangladesh, and this gap motivates this study. The study used primary data collected from 810 randomly selected outpatients. The survey used a structured questionnaire on all 7 domains of responsiveness of outpatient care suggested by the World Health Organization. The estimated mean responsiveness score reveals that overall, approximately 33% of the patients rated the responsiveness of the system as poor. In reported responsiveness, the NHSDP was ranked at the top and the MOHFW at the bottom. The latter is quite expected. Overall, prompt attention and autonomy were the worst‐performing domains, and choice of provider, dignity, and clear communication were the better‐performing ones. The results suggest the need to improve the degree of responsiveness of all domains, especially those that are more concerned with access to health care, namely, prompt attention, dignity, clear communication, and confidentiality. The Ministry of Health and Family Welfare facilities should give additional consideration to promote prompt attention, autonomy, and quality of basic amenities. Private facilities should also provide additional stress on improving prompt attention and autonomy. The nontherapeutic quality of health care needs to be emphasized in the medical education system. Further research based on household surveys could be worthwhile to measure responsiveness more comprehensively.
What is the supporting role of health care providers from the perspective of patients with renal allograft rejection? A qualitative study
Authors: Ebadzadeh Mohammad Reza , Nouhi Esmat , Farokhzadian Jamileh , Mangolian Shahrbabaki Parvin 
Published: August 2018

SummaryCoping with the new conditions for patients with renal allograft rejection is a complex phenomenon influenced by a number of factors. It appears that the supportive role of health care providers in many aspects is 1 of the most important factors in patient satisfaction, increased quality of life, and application of proper coping mechanisms. This study explored the perceptions of patients with renal allograft rejection about the supportive role of health care providers.This study was conducted with a qualitative research approach and content analysis. Participants were 19 patients with renal allograft rejection in teaching hospitals in southeastern Iran who were selected by purposive sampling. Data were collected through semistructured interviews and analyzed by qualitative content analysis.During content analysis, 2 categories emerged: empathy and emotional support and educational counseling. These themes reflect the nature of patient perceptions of the supportive role of health care providers.The findings suggest that the supportive role of health care providers plays an important role in the promoting a feeling of comfort, reliability, and security in patients with renal allograft rejection and improves their coping mechanisms. These findings give health care providers greater motivation to provide comprehensive care from knowledge of their supportive role.
Using Linked Text Sets to Promote Advocacy and Agency Through a Critical Lens
Authors: Batchelor Katherine E. 
Published: August 2018

AbstractThe author shares three preservice teachers’ linked text sets, including young adult literature and other media forms, and their critiques of the linked text sets, centering on a self‐selected social justice topic: racism and the importance of the Black Lives Matter movement, rape culture, and ending the stigma behind mental health. The author ends with discussion of how the preservice teachers felt advocacy and agency through creating and then critiquing their linked text sets and what recognizing their implicit biases means to their future students and teaching. The author hopes that by sharing what these three preservice teachers found in their critiques of their work, other educators may be able to not only use these text sets and suggested text additions and create new linked text sets for their students, but also think about their own curricular decisions through a critical lens.
miR‐383 promotes cholangiocarcinoma cell proliferation, migration, and invasion through targeting IRF1
Authors: Wan Peiqi , Chi Xiaojv , Du Qiang , Luo Jing , Cui Xiao , Dong Kun , Bing Yan , Heres Caroline , Geller David A. 
Published: August 2018

AbstractInterferon regulatory factor 1 (IRF1) has been found to serve as a tumor suppressor in cholangiocarcinoma, and enabled prediction of clinical progression and prognosis in our previous study. The objective of the current study is to screen and identify valuable microRNAs (miR), which target IRF1 to regulate cholangiocarcinoma cell proliferation, migration, and invasion. High expression of miR‐383 was observed in cholangiocarcinoma tissues and cells. Meanwhile, we found the predicted binding site of miR‐383 on the IRF1 3′‐untranslated region (3′‐UTR) according to the miR target database. The miR‐383 expression was negatively related to IRF1 messeneger RNA (mRNA) and protein expression in cholangiocarcinoma tissue samples, and miR‐383 negatively regulated IRF1 mRNA and protein expression in cholangiocarcinoma cells. Subsequently, we conducted a luciferase reporter assay to prove the predicted binding site miR‐383 on IRF1 3′‐UTR. Moreover, the results of the rescue study suggested that IRF1 was a functional target of miR‐383 involved in regulating cholangiocarcinoma cell proliferation, migration, and invasion. Finally, we evaluated the clinical and prognostic significance of miR‐383 in cholangiocarcinoma cases, and found that high expression of miR‐383 was correlated with advanced tumor stage, large tumor size, present vascular invasion, and metastasis, and acted as an unfavorable independent prognostic factor. In conclusion, miR‐383 serves as a tumor‐suppressive miR to regulate cholangiocarcinoma cell proliferation, migration, and invasion via directly targeting IRF1.
Retracted: Long noncoding RNA MALAT1 alleviates lipopolysaccharide‐induced inflammatory injury by upregulating microRNA‐19b in murine chondrogenic ATDC5 cells
Authors: Pan Lin , Liu Deheng , Zhao Lei , Wang Liqin , Xin Miaomiao , Li Xingfu 
Published: August 2018

AbstractOsteoarthritis is the most frequent chronic bone‐joint disease in middle‐aged and older people worldwide. This study investigated the effects of long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) on lipopolysaccharide (LPS)‐induced murine chondrogenic ATDC5 cell inflammatory injury. Cell viability and apoptosis were assessed using cell counting kit‐8 assay and annexin V‐phycoerythrin (PE) staining, respectively. The expression levels of interleukin‐1β (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor α (TNF‐α), MALAT1, and microRNA‐19b (miR)‐19b were measured using quantitative reverse‐transcription polymerase chain reaction. Enzyme‐linked immunosorbent assay was conducted to detect the concentrations of IL‐1β, IL‐6, IL‐8, and TNF‐α in culture supernatant of ATDC5 cells. Expressions of key factors involved in cell apoptosis, proinflammatory response, Wnt/β‐catenin, and nuclear factor κB (NF‐κB) pathways were analyzed using Western blot analysis. We found that LPS treatment remarkably induced ATDC5 cell apoptosis and inflammatory injury. MALAT1 was upregulated in LPS‐stimulated ATDC5 cells. Overexpression of MALAT1 significantly reversed the LPS‐induced ATDC5 cell inflammatory injury, while suppression of MALAT1 had opposite effects. Further results showed that MALAT1 positively regulated the expression of miR‐19b in ATDC5 cells. Knockdown of miR‐19b reversed the protective effect of MALAT1 on LPS‐induced ATDC5 cells. In addition, MALAT1 reduced LPS‐induced Wnt/β‐catenin and NF‐κB pathways activation in ATDC5 cells by upregulating miR‐19. To conclude, our research verified that MALAT1 alleviated LPS‐induced ATDC5 cell inflammatory injury by upregulating miR‐19b and inactivating Wnt/β‐catenin and NF‐κB pathways. This finding will be helpful for further understanding the critical roles of MALAT1 and miR‐19b in osteoarthritis and may provide possible targets for osteoarthritis diagnosis and treatment.
Impact of curcumin on sirtuins: A review
Authors: Zendedel Elham , Butler Alexandra E , Atkin Stephen L , Sahebkar Amirhossein 
Published: August 2018

AbstractCurcumin is a bioactive phytochemical that modulates several physiological and cellular processes leading to therapeutic effects against different diseases. Sirtuins are highly conserved nicotine adenine dinucleotide‐dependent proteins that regulate the activity of target enzymes and transcription factors by deacetylation. Curcumin possesses both antioxidant and anti‐inflammatory properties and has been shown to increase sirtuin‐1 (SIRT1) by activating small molecules. Upregulation of SIRT1 by curcumin has been reported to confer protective effects against a range of neurological disorders including glutamate excitotoxicity, β‐amyloid‐induced cell death in cortical neurons, cerebral ischemic damage, and stroke. Activation of AMPK and SIRT1 by curcumin has also been noted to mediate the protective effects of curcumin against ischemia/reperfusion injury, cardiac fibrosis, diabetes, and lipid metabolism abnormalities. These protective effects of SIRT1 activation are partly mediated by the deacetylation of p53 and reduction of apoptosis. In this review, we summarize the role of SIRT1 in mediating the pharmacological effects of curcumin in several diseases.
Piperlongumine inhibits angiotensin II‐induced extracellular matrix expression in cardiac fibroblasts
Authors: Wu Xianchuang , Liu Yuxin , An Jihong , Li Jiahuan , Lv Weiling , Geng Shengnan , Zhang Yongzhou 
Published: August 2018

AbstractPiperlongumine (PL), a single component isolated from Piper longum, has been reported to possess anti‐inflammatory, antibacterial, antiangiogenic, antioxidant, antitumor, and antidiabetic activities. However, its role in cardiac fibrosis remains to be clarified. Therefore, we determined the effects of PL on cardiac fibroblasts (CFs) proliferation, and extracellular matrix (ECM) production under angiotensin II (Ang II) conditions, and further investigated the underlying molecular mechanism. Our data revealed that PL inhibited the proliferation and migration of CFs induced by Ang II. In addition, PL blocked the transformation of CFs to myofibroblasts induced by Ang II, as well as decreased cellular reactive oxygen species (ROS) production and malondialdehyde level in Ang II‐stimulated CFs. Furthermore, PL significantly suppressed the Ang II‐increased phosphorylation of extracellular regulated protein kinase 1/2 (ERK1/2) in CFs. Taken together, the results of the current study demonstrated that PL inhibits Ang II‐induced cell proliferation, migration, and ECM expression in CFs through the inactivation of the ERR1/2 signaling pathway. These data strongly suggest that PL may be a promising therapeutic candidate for the treatment of cardiac fibrosis.
MiR‐27a‐5p regulates apoptosis of liver ischemia‐reperfusion injury in mice by targeting Bach1
Authors: Xing Yu , Li Jing , Li Shi‐peng , Xi Jiri , Ma Ning , Liu Lei , Wang Jin‐Shan , Cai Jin‐Zhen 
Published: August 2018

AbstractIschemia‐reperfusion (I/R) injury causes cellular dysfunction and a series of immune or apoptotic reactions. Bach1 is a mammalian transcription factor that represses Hmox1, which encodes heme oxygenase‐1 (HO‐1) that can degrade heme into free iron, carbon monoxide, and biliverdin, to play an important role in antioxidant, anti‐inflammatory, and antiapoptotic activities. MicroRNAs (miRNAs) can be found in a variety of eukaryotic cells and viruses, a class of noncoding small RNAs that are encoded by endogenous genes. The aims of this study were to determine whether miR‐27a‐5p targets Bach1 and regulates cellular death; the dual‐luciferase reporter assay was used to detect this and the results showed that miR‐27a‐5p significantly decreased the luciferase activity of the Bach1 3′‐untranslated region. MiR‐27a‐5p was increased in mice during hepatic I/R and Bach1 was decreased. By transfecting the AML12 cells with the mimic, inhibitor miR‐27a‐5p in hypoxia/reoxygenation (H/R) models showed that overexpression of miR‐27a‐5p decreased Bach1 messenger RNA, upregulated HO‐1 expression, and promoted antiapoptotic Bcl‐2 and downregulated proapoptotic caspase‐3 gene expression. In contrast, the miR‐27a‐5p inhibitor yielded the opposite results. Meanwhile, transfection with Bach1 small interference RNA obviously upregulated the protein levels of HO‐1 and resulted in an increase in Bcl‐2 and a decrease in caspase‐3 protein levels. Thus, we can conclude that miR‐27a‐5p is relevant to liver I/R injury and overexpression of miR‐27a‐5p may alleviate apoptosis in H/R injury by targeting Bach1 in vitro.
The effect of ICRT‐3 on Wnt signaling pathway in head and neck cancer
Authors: Sogutlu Fatma , Kayabasi Cagla , Ozmen Yelken Besra , Asik Aycan , Gasimli Roya , Dogan Fatma , Yilmaz Süslüer Sunde , Biray Avcı Cigir , Gunduz Cumhur 
Published: August 2018

AbstractThe effect of Wnt pathway in head and neck cancer could not be elucidated, even though the aberrant Wnt signaling plays a key role in the development of many types of cancer. The inhibitor of β‐catenin responsive transcription (ICRT‐3) blocks the Wnt signaling pathway by binding to β‐catenin, which is a coactivator of the Wnt signaling pathway and a promising agent for inhibiting aberrant signaling. In our study, we aimed to evaluate the effect of ICRT‐3 on the cytotoxicity, apoptosis, cell cycle progression, migration, and gene expressions in head and neck cancer stem cell (HNCSC) and hypopharynx cancer. The effect of this compound on cytotoxicity and cell viability in FaDu and HNCSC line was assessed by using the water‐soluble tetrazolium salt‐1 method. The effect of ICRT‐3 on apoptosis was detected by using Annexin V and caspase‐3, caspase‐9 kit, on cell cycle progression by cycle test plus DNA reagent kit, on gene expression by dual luciferase reporter assay, and on migration activity by wound healing assay in both cell lines. ICRT‐3 was determined to have cytotoxic and apoptotic effect in both cell lines. In addition, it was also found that the administration of ICRT‐3 caused cell cycle arrest and significant decrease in gene expression level and migration ability of the cells.
AZD9291 promotes autophagy and inhibits PI3K/Akt pathway in NSCLC cancer cells
Authors: Zhang Zhirui , Zhang Mengxiao , Liu Hao , Yin Wu 
Published: August 2018

AbstractAZD9291, a third‐generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI), is highly selective against EGFR T790M‐mutant non–small cell lung cancer (NSCLC). On investigating the growth inhibitory effects of AZD9291 on NSCLC and the underlying mechanism, we found that AZD9291 can trigger autophagy‐mediated cell death in both A549 and H1975 cells by increasing the expression of phosphatidylethanolamine‐modified microtubule‐associated protein light‐chain 3 (LC3) and decreasing the expression of p62. In the presence of the autophagy inhibitor chloroquine, the AZD9291‐induced increase in LC3 level was further augmented. AZD9291 decreased the levels of phosphoinositide‐3 kinase (PI3K), protein kinase B (Akt), and phosphorylated Akt. AZD9291‐induced cell death was enhanced by Akt knockdown, and the levels of both EGFR and phosphorylated EGFR were decreased by AZD9291. AZD9291 was also found to significantly suppress the tumor growth in H1975 xenograft nude mice. Thus, AZD9291 was found to induce autophagy, decrease in EGFR levels, and show a strong inhibitory effect on NSCLC both in vitro and in vivo. Furthermore, the PI3K/Akt signaling pathway was found to play a critical role in AZD9291‐induced cell death.
Rosmarinic acid inhibits nicotine‐induced C‐reactive protein generation by inhibiting NLRP3 inflammasome activation in smooth muscle cells
Authors: Yao Yang , Mao Junjun , Xu Shouzhu , Zhao Lei , Long Lihui , Chen Lin , Li Dongmin , Lu Shemin 
Published: August 2018

Atherosclerosis is widely known to be a chronic inflammatory disease. C‐reactive protein (CRP), an important inflammatory factor, plays an essential role in the pathogenesis of atherosclerosis. Nicotine, the main addictive component of cigarette, has been shown to induce the production of CRP. The aim of this study was to investigate the effect of rosmarinic acid (RA), a polyphenol with antiinflammatory activity, on nicotine‐induced elevation of CRP in vascular smooth muscle cells (VSMCs). We found that pretreatment of VSMCs with RA attenuated nicotine‐induced expression of CRP in a time‐ and dose‐dependant manner. In addition, RA also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and reactive oxygen species (ROS) production resulting from nicotine treatment in VSMCs. To confirm these findings in vivo, we constructed a nicotine‐induced atherosclerosis rat model. RA did not significantly reduce the serum nicotine level of the rats, whereas it significantly decreased the levels of serum lipids, including concentrations of cholesterol, triglycerides, and low‐density lipoprotein cholesterol, and the serum level of CRP. RA also led to diminished nicotine‐induced activation of NLRP3 inflammasome and elevation in the CRP level in the aortic tissue of the model rats. The results of this study suggested a protective role of RA in nicotine‐induced atherosclerosis by inhibiting the ROS–NLRP3 inflammasome–CRP axial, and RA therefore represented a potential effective therapeutic approach to atherosclerosis, in particular for those who smoke.
The landscape of DNA methylation in hepatocellular carcinoma
Authors: Zheng Yong‐Fa , Lu Xiaojie , Zhang Xiao‐Yu , Guan Bu‐Gao 
Published: August 2018

AbstractBetter understanding of the relationship between changes in the overall methylation status of hepatocellular carcinoma (HCC) and disease progression will help us find good strategies for the early detection and treatment of HCC patients. The purpose of the study was to study the relations between the methylation status changes in HCC patients and progression of the disease to enable early detection and treatment of HCC patients. First, the DNA methylation data of 50 HCC samples and the surrounding normal samples were extracted and the change pattern of methylation status in the DNA promoter region of HCC samples against that of normal samples was studied. Then, some DNA methylation genes that could accurately identify cancer and cancer‐adjacent tissues were identified using the k‐top scoring pair method. Also, a prognostic signature that could predict the survival of HCC patients was constructed based on the overall survival time and death information of the early HCC patients. Finally, the obtained prognostic signature was verified. In conclusion, this study described the changes in the methylation spectrum during the development of HCC and identified genes associated with HCC progression and prognosis, which may offer new opportunities for the diagnosis and treatment of HCC.