bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Nickel on the Structure and Functioning of a Freshwater Plankton Community Under High Dissolved Organic Carbon Conditions: A Microcosm Experiment
Authors: Nys Charlotte , Van Regenmortel Tina , De Schamphelaere Karel
Published: May 2019

In the present study, we aimed to test the protectiveness of the bioavailability-normalization procedure, with its associated hazardous concentrations for x% of the species (HCx), that is currently implemented to derive environmental threshold concentrations for nickel (Ni) in European environmental legislative frameworks. We exposed a natural plankton-dominated community to 3 constant Ni concentrations, that is, a control with no Ni added (background Ni of 1.2–4 µg/L) and the bioavailability-normalized HC5 and HC50 of 24 and 97 µg dissolved Ni/L, respectively, during a 56-d microcosm experiment under high dissolved organic carbon (DOC) conditions (DOC of 14 mg/L at test initiation). The effects of the bioavailability-normalized HC5 and HC50 values were evaluated at the levels of community structure (community composition and plankton group abundances), community functioning (measured as indirect physicochemical proxies for overnight respiration and carbon fluxes), and individual species abundances. The bioavailability-normalized HC50 treatment had clear effects (defined as effects occurring on at least 2 consecutive sampling days) on both the structure and functioning of the investigated aquatic community. Through its effect on community functioning (i.e., reduced pH and DOC), Ni also influenced its own bioavailability. Clear direct effects of Ni were observed for only 3 species (the Cyanobacteria Oscillatoria sp. 1 and the rotifers Asplanchna/Testidunela sp. and Trichocerca group similis). Most other effects occurring in the plankton community in the HC50 treatment were indirect and likely driven by the direct effect of Ni on the Cyanobacteria Oscillatoria sp. 1, which was the dominant phytoplankton species in the control microcosms. In contrast, the bioavailability-normalized HC5 did not induce clear effects on community structure and functioning endpoints: these were only affected on individual sampling days. Clear (direct) effects were observed for only 2 plankton species (the rotifer Trichocerca group similis and the Cyanobacteria Oscillatoria sp. 1), but their abundances recovered to control levels at the end of the study. In addition, a few species (1 phytoplankton and 3 zooplankton species) were affected in the HC5 treatment only on the last sampling day. It is uncertain whether these species would have shown clear effects over a longer exposure duration. Thus, our study shows that the bioavailability-normalized HC5 of Ni at high DOC induced clear effects on a few individual species. However, the overall conclusion is that the bioavailability-normalized HC5 of Ni as derived through the procedure that is currently implemented in European legislative frameworks protects against clear effects on community structure and function. Environ Toxicol Chem 2019;38:1923–1939. © 2019 SETAC.
Narrow‐wide‐row planting pattern increases the radiation use efficiency and seed yield of intercrop species in relay‐intercropping system
Authors: Raza Muhammad Ali , Feng Ling Yang , van der Werf Wopke , Cai Gao Ren , Khalid Muhammad Hayder Bin , Iqbal Nasir , Hassan Muhammad Jawad , Meraj Tehseen Ahmad , Naeem Muhammd , Khan Imran , Rehman Sana ur , Ansar Muhammad , Ahmed Mukhtar , Yang Feng , Yang Wenyu
Published: May 2019

Planting arrangements affect radiation use efficiency (RUE) and competitiveness of intercrop species in intercropping systems. Here, we reveal that narrow‐wide‐row planting arrangement in maize‐soybean relay‐intercropping system increases the dry matter and competitiveness of soybean, increased the RUE of maize and soybean, and compensates the yield loss of maize by substantially increasing the yield of soybean. In this field study, maize was planted with soybean in different planting arrangements (P1, 20:180, P2, 40:160; P3, 60:140, and P4, 80:120) of relay intercropping, all the relay‐intercropping treatments were compared with sole crops of maize (SM) and soybean (SS). Results showed that P1 improved the total RUE 3.26 g/MJ (maize RUE + soybean RUE) of maize and soybean in relay‐intercropping system. Compared to P4, treatment P1 increased the soybean competition ratio (CR) values (by 55%) but reduced the maize CR values (by 29%), which in turn significantly improved the yield of soybean by maintaining the maize yield. Generally, in P1, soybean produced 82% of SS yield, and maize produced 88% of SM yield, and it achieved the land equivalent ratio of 1.7. These results suggest that by maintaining the appropriate planting distances between maize and soybean we can improve the competitiveness and yield of intercrop species in relay‐intercropping system.
HIV testing uptake among pregnant women attending private midwife clinics: challenges of scaling up universal HIV testing at the private sectors in Indonesia
Authors: Wulandari Luh Putu Lila , Lubis Dinar S.M. , Widarini Putu , Widyanthini Desak Nyoman , Wirawan I. Made Ady , Wirawan Dewa Nyoman
Published: May 2019

Introduction

Being ranked seventh among countries with the highest number of new pediatric HIV infection, around 3% of new pediatric HIV infection worldwide occurs in Indonesia. UNAIDS has set a goal of elimination of mother‐to‐child HIV transmission, and private sector plays a critical role in achieving this goal. More than half of pregnant women in Indonesia seek antenatal care (ANC) services at private sectors, particularly at private midwife clinics. However, no published data is available on the rates of HIV testing uptake among pregnant women at these clinics, reflecting important gap on prevention of mother to child HIV transmission programmatic data.

Purpose

A longitudinal study was conducted to examine the rates of HIV testing uptake among pregnant women attending private midwife clinics in Bali and were referred to Voluntary HIV counselling and testing (VCT) clinics for a HIV test.

Methods

Seventy midwives from private clinics were asked to suggest women, who were deemed to be at risk of HIV, to seek HIV testing at the nominated VCT clinics and to provide the women with a referral. Data were then analyzed to identify the percentage of women who took HIV testing at the VCT clinics among those referred by the midwives.

Results

The midwives referred 619 women to VCT clinics. Of the referred women, only 321 (52%; 95% CI, 47.8%‐55.9%) took a HIV test at the appointed clinics. Among these who tested, three (0.9%) were HIV positive. This study identified a challenge in scaling up HIV testing coverage among women seeking ANC services at private sectors. Implications and recommendations are discussed.
β‐Elemene suppresses the proliferation of human airway granulation fibroblasts via attenuation of TGF‐β/Smad signaling pathway
Authors: Xue Cheng , Lin Xiao‐Ping , Zhang Jia‐Min , Zeng Yi‐Ming , Chen Xiao‐Yang
Published: May 2019

Background

Benign airway stenosis is easily to recur as a result of hyperplastic airway granulation tissues. Our previous study proved that a Chinese drug, β‐elemene, could inhibit the proliferation of fibroblasts cultured from these tissues, which could decrease the recurrence rate of this disease.

Methods

To find out the mechanism for this effect, we first cultured normal human airway fibroblasts and human airway granulation fibroblasts with different concentrations of β‐elemene for the same time or the same dose of β‐elemene for different times to explore the dose/time‐effect relationship between the drug and these cells. Then we used gene microarray to screen out the most important pathway by which the drug influenced human airway granulation fibroblasts. At last, we assessed the condition of this pathway in human airway granulation fibroblasts and verified the effect of this drug on this pathway.

Results

β‐Elemene inhibited the proliferation of human airway granulation fibroblasts in a dose but no time‐dependent manner and did not affect normal human airway fibroblasts. Affecting the expression of transforming growth factor β (TGF‐β)/Smad pathway may be the key mechanism for this effect. This pathway was activated in human airway granulation fibroblasts and β‐elemene inhibited it in a dose‐dependent manner. This effect was similar to the pathway inhibitor, SB431542, and exogenous TGF‐β could attenuate this effect.

Conclusion

These results indicated that suppressing TGF‐β/Smad pathway was possibly the key mechanism by which β‐elemene inhibits the proliferation of human airway granulation fibroblasts. This pathway may be a promising target to treat benign airway stenosis.
Lentiviral‐mediated silencing of mast cell‐expressed membrane protein 1 promotes angiogenesis of rats with cerebral ischemic stroke
Authors: Jian Rui , Yang Min , Xu Fangyuan
Published: May 2019

Cerebral ischemic stroke is a devastating neurological disease with high rates of morbidity, disability, and mortality. Lentiviral‐mediated mast cell‐expressed membrane protein 1 (MCEMP1) has been shown to function in ischemic stroke. Hence, this study aims to explore the function of MCEMP1 specifically in angiogenesis, neuronal proliferation, and apoptosis in rats with cerebral ischemic stroke. Initially, stroke‐related genes were obtained through microarray‐based gene expression analysis, followed by the construction of a lentiviral vector for MCEMP1 shRNA and establishment of the middle cerebral artery occlusion model. After rats were transfected with MCEMP1 shRNA lentivirus, microvessel density (MVD), expression of MCEMP1, caspase‐3, and vascular endothelial growth factor (VEGF), and neuronal proliferation and apoptosis were measured to explore the role of MCEMP1 in cerebral ischemic stroke. MCEMP1 was found to be highly expressed in rats with cerebral ischemic stroke. Silencing of MCEMP1 led to upregulation of VEGF, while downregulation of caspase‐3, and resulted in the promotion of MVD in rats with ischemic stroke. Moreover, MCEMP1 silencing could increase Ki67 positive cells and reduce terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling positive cells in the marginal zone of cortical infarction in rats. Our study provides evidence that silenced MCEMP1 could enhance angiogenesis and suppress neuronal apoptosis in rats with cerebral ischemic stroke, highlighting that MCEMP1 silencing could serve as a therapeutic target for cerebral ischemic stroke treatment.
Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate‐induced colitis
Authors: Chen Xiaoxing , Pan Huaqin , Li Jin , Zhang Guqin , Cheng Shizhe , Zuo Na , Zhao Qiu , Peng Zhiyong
Published: May 2019

Myeloid differentiation 1 (MD‐1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD‐2 and forms a complex with radioprotective 105 (RP105). RP105/MD‐1 complex negatively regulates toll‐like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD‐1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD‐1 in IBD, we inhibited MD‐1 in colon with antisense oligonucleotide (AS‐ODN) and assessed the effect of MD‐1 inhibition on dextran sodium sulfate (DSS)‐induced colitis. We discovered that MD‐1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS‐induced colitis. For the first time, we showed that oral administration of MD‐1 AS‐ODN to mice significantly suppressed the MD‐1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD‐1 AS‐ODN treated mice were more susceptible to DSS‐induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD‐1 inhibition also significantly enhanced inflammatory cytokines production such as IL‐6 and IL‐1β in colons. Finally, mice treated with MD‐1 AS‐ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)‐κB activation compared with the control. Taken together, specifically suppression of MD‐1 in colon tissues with AS‐ODN exacerbates DSS‐induced experimental colitis in mice, which is possibly related to activation of TLR4/NF‐κB signaling.
ELK1‐induced upregulation of lncRNA TRPM2‐AS promotes tumor progression in gastric cancer by regulating miR‐195/ HMGA1 axis
Authors: Huang Bo , Chang Cheng , Wang Bai‐lin , Li Huiwen
Published: May 2019

Long noncoding RNAs (lncRNAs) have been confirmed to be aberrantly expressed in various diseases including tumors. Recently, a new tumor‐related lncRNA, lncRNA TRPM2 antisense RNA (TRPM2‐AS), was shown to be involved in many tumors, such as lung cancer and breast cancer. However, the expression and role of TRPM2‐AS in the development of gastric cancer (GC) have not been elucidated. In the current study, we provided evidence that the expression levels of TRPM2‐AS were increased in both GC tissues and cell lines. We also showed that overexpression of TRPM2‐AS was modulated by ELK1, a transcription factor. The results of clinical assays showed that higher expressions of TRPM2‐AS were significantly related with invasion depth, TNM stage, lymphatic metastasis, and shorter overall survival. Further clinical assays using multivariate analysis suggested that TRPM2‐AS expression was an independent prognostic factor in patients with GC. Functional experiments illustrated that depression of TRPM2‐AS suppressed proliferation, migration, and invasion in GC cells. In terms of mechanism, we found that TRPM2‐AS directly inhibited miR‐195, which targeted the 3′‐untranslated region of high‐mobility group AT‐hook 1 (HMGA1) messenger RNA. Overall, these findings revealed that ELK1‐induced overexpression of TRPM2‐AS promoted the development and progression of GC in part through miR‐195/HMGA1 signaling axis, and established its candidacy as a new cancer biomarker for GC patients.
RETRACTED: Propofol‐induced miR‐219‐5p inhibits growth and invasion of hepatocellular carcinoma through suppression of GPC3‐mediated Wnt/β‐catenin signalling activation
Authors: Gong Ting , Ning Xue , Deng Zhiya , Liu Mingyu , Zhou Beixian , Chen Xijun , Huang Shisi , Xu Yan , Chen Zhongqing , Luo Rongcheng
Published: May 2019

Propofol is one of the most extensively used intravenous anaesthetic agents, which has been found to improve the surgical intervention outcome of several types of cancer, including hepatocellular carcinoma (HCC). Additionally, in vitro and in vivo experiments have also indicated that propofol affects the biological behaviour of HCC. However, the underlying mechanisms of the surgical resection of HCC with propofol have not been fully understood. In the present study, we aimed to investigate the underlying mechanism of propofol inhibition of the growth and invasion of HCC cells. Our results showed that treatment with propofol suppressed the proliferation, invasion and migration of HCC in vitro. The subcutaneous xenograft tumour and orthotopic xenograft tumour experiments in nude mice showed that propofol significantly decreased tumour volumes, growth rates and the liver orthotopic xenograft tumour in vivo. Furthermore, the underlying mechanism investigations of the suppressive effects of propofol on HCC cells revealed that propofol treatment upregulated the expression levels of the candidate tumour suppressor miR‐219‐5p. Silencing of propofol‐induced miR‐219‐5p using anti‐miR‐219‐5p abrogated the inhibitory effects on the proliferation, migration and invasion of HCC cells exerted by propofol treatment. Additionally, we demonstrated that propofol reversed the epithelial‐mesenchymal transition of Huh7 and SMMC7721 cells via miR‐219‐5p induction. The molecular mechanism behind these findings is that propofol‐induced miR‐219‐5p inhibits HCC cell progression by targeting glypican‐3 and subsequently results in the inhibition of Wnt/β‐catenin signalling. Taken together, our study provides new insights into the advantages of the surgical intervention of HCC with propofol anaesthetization.
Upregulation of IGF‐IIRα intensifies doxorubicin‐induced cardiac damage
Authors: Pandey Sudhir , Kuo Wei‐Wen , Ho Tsung‐Jung , Yeh Yu‐Lan , Shen Chia‐Yao , Chen Ray‐Jade , Chang Ruey‐Lin , Pai Pei‐Ying , Padma V. Vijaya , Huang Chih‐Yang , Huang Chih‐Yang
Published: May 2019

Cardiotoxicity by doxorubicin hampers its therapeutic potential as an anticancer drug, but mechanisms leading to cardiotoxicity remain contentious. Through this study, the functional contribution of insulin‐like growth factor receptor type II α (IGF‐IIRα) which is a novel stress‐inducible protein was explored in doxorubicin‐induced cardiac stress. Employing both in vitro H9c2 cells and in vivo transgenic rat models (SD‐TG [IGF‐IIRα]) overexpressing IGF‐IIRα specifically in heart, we found that IGF‐IIRα leads to cardiac structural abnormalities and functional perturbations that were severely aggravated by doxorubicin‐induced cardiac stress. Overexpression of IGF‐IIRα leads to cumulative elevation of stress associated cardiac hypertrophy and apoptosis factors. There was a significant reduction of survival associated proteins p‐Akt and estrogen receptor β/α, and abnormal elevation of cardiac hypertrophy markers such as atrial natriuretic peptide, cardiac troponin‐I, and apoptosis‐inducing agents such as p53, Bax, and cytochrome C, respectively. IGF‐IIRα also altered the expressions of AT1R, ERK1/2, and p38 proteins. Besides, IGF‐IIRα also increased the reactive oxygen species production in H9c2 cells which were markedly aggravated by doxorubicin treatment. Together, we showed that IGF‐IIRα is a novel stress‐induced protein that perturbed cardiac homeostasis and cumulatively exacerbated the doxorubicin‐induced cardiac injury that perturbed heart functions and ensuing cardiomyopathy.
An integrative bioinformatics pipeline to demonstrate the alteration of the interaction between the ALDH2*2 allele with NAD+ and Disulfiram
Authors: J Christy Priyadharshini , D Thirumal Kumar , P Sneha , R Siva , W Charles Emmanuel Jebaraj , C George Priya Doss , Zayed Hatem
Published: May 2019

Alcohol use disorder (AUD) is a multifactorial psychiatric behavior disorder. Disulfiram is the first approved drug by the Food and Drug Administration for alcohol‐dependent patients, which targets the ALDH2 enzyme. Several genes are known to be involved in alcohol metabolism; mutations in any of these genes are known to be associated with AUD. The E504K mutation in the ALDH2 of the precursor protein or the E487K of the mature protein (E504K/E487K; ALDH2*2 allele) is carried by approximately 8% of the world population. In this study, we aimed to test the known inactive allele ALDH2*2, to validate the use of our extensive computational pipeline (in silico tools, molecular modeling, and molecular docking) for testing the interaction between the ALDH2*2 allele, NAD+, and Disulfiram. In silico predictions showed that the E504K variant of ALDH2 to be pathogenic and destabilizing with the maximum number of prediction in silico tools. Consequently, we studied the effect of this mutation mainly on the interaction between NAD+‐E504K and Disulfiram‐E504K complexes using molecular docking technique, and molecular dynamics (MD) analysis. From the molecular docking analysis with NAD+, we observed that the interaction affinity of the NAD+ decreases with the impact of E504K variant. On the other hand, the drug Disulfiram showed similar interaction in both the native and mutant ALDH2 proteins. Further, the comprehensive MD analysis predicted that the E504K destabilizes the protein and influences the NAD+ and Disulfiram interactions. Our findings reveal that the interaction of NAD+ to the protein is disturbed by the E504K/E487K variant whereas the drug Disulfiram has a similar effect as both native ALDH2 and ALDH2 bearing E504K/E487K variant. This study provides a platform to understand the effect of E504K/E487K on the molecular interaction with NAD+ and Disulfiram.
miR‐148‐3p and miR‐152‐3p synergistically regulate prostate cancer progression via repressing KLF4
Authors: Feng Feng , Liu Hui , Chen Aiping , Xia Qinghua , Zhao Yong , Jin Xunbo , Huang Jianjun
Published: May 2019

Background

miR‐148‐3p and miR‐152‐3p as the tumor suppressors have been reported in various cancer types. Our study is aimed to discuss the synergistic effect of miR‐148‐3p and miR‐152‐3p in prostate cancer (PCa).

Methods

Bioinformatics algorithm and luciferase reporter assays were used to verify whether miR‐148‐3p and 152‐3p could bind with the 3′‐untranslated region (3′‐UTR) of Kruppel‐like factor 4 (KLF4). PCa cell growth in vivo was analyzed using the mouse xenograft tumor model.

Results

miR‐148‐3p and miR‐152‐3p were reduced in PCa tumor tissues. Moreover, the protein expression of KLF4 was increased in PCa tissues. The 3′‐UTR of KLF4 contained the conserved binding sites with miR‐148‐3p and miR‐152‐3p. The mimics or inhibitors of miR‐148‐3p and/or miR‐152‐3p could downregulated or upregulated KLF4 expression, respectively. miR‐148‐3p and miR‐152‐3p‐induced PCa cell growth inhibition were observed both in vivo and in vitro. KLF4 overexpression had the ability to neutralize the antitumor effect of miR‐148‐3p/152‐3p in vivo and in vitro.

Conclusion

miR‐148‐3p/152‐3p family could serve as tumor suppressors in PCa via repressing KLF4.
Retracted: Long noncoding RNA LINC00052 inhibits colorectal cancer metastasis by sponging microRNA‐574‐5p to modulate CALCOCO1 expression
Authors: Yu Gangfeng , Xiong Dongmei , Liu Zhengshu , Li Yongguo , Chen Ke , Tang Hua
Published: May 2019

The dysregulation of long‐chain noncoding ribonucleic acid (lncRNA) is a common phenomenon in many human cancers. Some studies on the biological function of long intergenic non‐protein‐coding RNA 52 (LINC00052) in cancer indicate that this gene can act as either oncogene or tumor suppressor in some kinds of cancers, such as breast cancer, gastric cancer, liver cancer, and lung cancer. However, the biological function of LINC00052 in colorectal cancer (CRC) has not been studied. Quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) and Western blot (WB) techniques were applied to detect the expression levels of LINC00052, miR‐574‐5p, and calcium‐binding and coiled‐coil domain 1 (CALCOCO1) in CRC cells and tissues. We authenticated the biological function of LINC00052 and miR‐574‐5p in CRC, and find some target genes for LINC00052 and miR‐574‐5p via bioinformatics methods. Dual‐luciferase reporter gene assay was performed to identify the interaction between LINC00052 and miR‐574‐5p or CALCOCO1 and miR‐574‐5p. The results demonstrated that LINC00052 was downregulated in CRC tissues compared with their adjacent tissues. And LINC00052 could suppress CRC cells metastasis both in vivo and in vitro. Beyond that, miR‐574‐5p was upregulated in CRC tissues, and as an oncogene, it accelerated CRC cell migration and invasion. More importantly, the results of our research demonstrated that LINC00052 could regulate the expression of CALCOCO1 via sponging miR‐574‐5p in CRC. Overall, our study illuminated the lncRNA‐miRNA functional networks in CRC, and these results might provide a new research direction for the diagnosis and treatment of CRC.
LXRα‐mediated downregulation of EGFR suppress colorectal cancer cell proliferation
Authors: Liang Xiaolong , Cao Yi , Xiang Song , Xiang Zheng
Published: May 2019

Liver X receptors (LXRs) are members of the nuclear receptor family, including the LXRα (NR1H3) and LXRβ (NR1H2) subtypes, which are related to the metabolism of glucose and cholesterol and possess anti‐inflammatory functions. Mounting evidence has linked LXRs to the inhibition of cell proliferation in a variety of cancers. We revealed a differential distribution for NR1H3, but not for NR1H2, in colorectal cancer and adjacent normal tissues. We found that NR1H3 enhanced the inhibitory action of GW3965, an agonist of LXRs, on the proliferation of colorectal cancer cells. Upregulation of NR1H3 enhanced the inhibition of cell proliferation by GW3965 while silencing of NR1H3 attenuated the inhibitory effect of GW3965 on cell proliferation. Bioinformatic prediction and luciferase assays showed that NR1H3 was able to inhibit the activity of the epidermal growth factor receptor (EGFR) promoter. Moreover, we demonstrated that activation of NR1H3 inhibited the growth of transplanted tumors in an animal experiment, with the inhibition accompanied by downregulation of EGFR. Our findings suggest that NR1H3 controls cell proliferation by affecting EGFR promoter activity. The high expression of EGFR was due to the downregulation of NR1H3 which is a novel molecular mechanism in the development of colorectal cancer.
Experimental study of influence of composition on radiopacity of fiber post materials
Authors: Erik Ayşe Aydoğmuş , Erik Cevat Emre , Yıldırım Derya
Published: May 2019

This experimental study aims to evaluate the radiopacity of various fiber post materials and to determine the effects of material composition as analyzed by energy‐dispersive X‐ray spectrophotometry (EDS; EDAX Team Software; EDAX, Inc., Mahwah, NJ) on radiopacity. Five specimens of seven fiber post materials with 2‐mm thickness were prepared and digital radiographs were taken with an aluminum stepwedge (SW) and 2‐mm‐thick tooth slice. The mean gray values (MGVs) of specimens were measured using the histogram function of a computer graphics program (Adobe Photoshop CS6; Adobe System, Inc., San Jose, CA). The MGVs of fiber post materials were compared with an aluminum SW and dentin of equal thickness. The fiber post specimens were examined by scanning electron microscopy and EDS analysis performed for the elementary analysis of material composition. The MGVs of fiber posts ranged between 83.67 ± 3.64 and 57.80 ± 7.08 pixels. Materials were sorted in descending order of MGV as follows: Reforpost, Carbopost, D.T. Light‐Post, Easypost, Glassix Radiopaque, Dentolic Glass Fiber Post, and RelyX Fiber Post. All fiber posts demonstrated significantly higher radiopacity values than 2‐mm‐thick aluminum (p < .05). EDS analysis results indicated that the evaluated fiber posts included various elements for radiopacity in different ratios. All tested fiber post materials showed radiopacity values above the minimum recommendations of the International Organization for Standardization. EDS analysis results indicated that each manufacturer used different compositions of elements like zirconium, barium, titanium, and iron for achieving radiopacity in materials.
Ultrasound Features of Ankle Retinacula: Normal Appearance and Pathologic Findings
Authors: Bianchi Stefano , Becciolini Marco
Published: May 2019

Disorders of retinacula are frequent in acute and repetitive microtrauma of the ankle. Ultrasound (US), thanks to its spatial resolution and dynamic capabilities, is routinely used in the evaluation of the posttraumatic ankle for accurate delineation of ligaments and tendons. In addition, US can provide a depiction of normal retinacula and a detailed assessment of their pathologic changes. An accurate US assessment of ankle retinacula is helpful in choosing the proper treatment. In this pictorial essay, we briefly review the normal anatomy of ankle retinacula, describe their normal US appearance, and present a wide range of US pathologic abnormalities.
Colonoscopy technologies for diagnostics and drug delivery
Authors: Ahmed Rajib , Santhirakumar Krieshshanthan , Butt Haider , Yetisen Ali K.
Published: May 2019

With a global increase of colorectal cancer, inflammatory bowel disease and other colon‐related illnesses, advanced technologies are needed for imaging of the colon and localized drug delivery. Optical colonoscopy is the gold standard for imaging of the colon. However, existing colonoscopy approaches have a high adenoma misdiagnosis rate, which can be lethal for patients. This article reviews the emergence of virtual colonoscopy, dye‐based chromoendoscopy, electronic chromoendoscopy and capsule endoscopy in diagnosis. Flexible spectral imaging colour enhancement, the use of second‐generation capsule endoscopy and i‐scan were described. Moreover, a drug delivery system using capsule endoscopy was discussed. Finally, this review includes market analyses of commercial products, clinical trials and future prospects of colonoscopy devices.
Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair
Authors: Schreurs Michaël , Suttorp C. Maarten , Mutsaers Henricus A.M , Kuijpers‐Jagtman Anne Marie , Von den Hoff Johannes W. , Ongkosuwito Edwin M. , Carvajal Monroy Paola L. , Wagener Frank A.D.T.G.
Published: May 2019

Cleft lip with or without cleft palate is a congenital deformity that occurs in about 1 of 700 newborns, affecting the dentition, bone, skin, muscles and mucosa in the orofacial region. A cleft can give rise to problems with maxillofacial growth, dental development, speech, and eating, and can also cause hearing impairment. Surgical repair of the lip may lead to impaired regeneration of muscle and skin, fibrosis, and scar formation. This may result in hampered facial growth and dental development affecting oral function and lip and nose esthetics. Therefore, secondary surgery to correct the scar is often indicated. We will discuss the molecular and cellular pathways involved in facial and lip myogenesis, muscle anatomy in the normal and cleft lip, and complications following surgery. The aim of this review is to outline a novel molecular and cellular strategy to improve musculature and skin regeneration and to reduce scar formation following cleft repair. Orofacial clefting can be diagnosed in the fetus through prenatal ultrasound screening and allows planning for the harvesting of umbilical cord blood stem cells upon birth. Tissue engineering techniques using these cord blood stem cells and molecular targeting of inflammation and fibrosis during surgery may promote tissue regeneration. We expect that this novel strategy improves both muscle and skin regeneration, resulting in better function and esthetics after cleft repair.
Quality‐based compositing of weather radar derived precipitation
Authors: Jurczyk Anna , Szturc Jan , Ośródka Katarzyna
Published: May 2019

The paper is focused on the problem of weather radar precipitation compositing and aims to produce the data for the whole measurement domain in a way that ensures the quality of the composite is as high as possible. This is achieved by employing information about the data quality in the form of a quality index (QI) map. Different techniques that take the QI values as the compositing criterion are investigated; they apply the maximum or the weighted mean from particular radars. The proposed method employs a combination of the QI value and the distance from the radar site as a criterion in a weighted mean approach. Different versions of the quality‐based techniques are compared with standard techniques that are based on the maximum of estimated precipitation and distance from the nearest radar site. Verification of the techniques was performed employing statistical metrics by comparison against rain gauge observations. Moreover qualitative verification with assessment of seamlessness and the presence of contamination was carried out on long‐term accumulations of the composites generated by means of different methods. The proposed method based on QI value and distance from the radar site was found to be the most suitable for radar precipitation compositing.
Somatic mosaicism by a de novo MLH1 mutation as a cause of Lynch syndrome
Authors: Geurts‐Giele Willemina R. , Rosenberg Efraim H. , Rens Anja van , Leerdam Monique E. van , Dinjens Winand N. , Bleeker Fonnet E.
Published: May 2019

Background

Lynch syndrome (LS) is caused by germline mismatch repair (MMR) gene mutations. De novo MMR gene mutations are rare, and somatic mosaicism in LS is thought to be infrequent. We describe the first case of somatic mosaicism by a de novo MLH1 mutation for a patient diagnosed with a rectosigmoid adenocarcinoma at age 31.

Methods

Twelve years after initial colorectal cancer diagnosis, tumor tissue of the patient was tested with sensitive next generation sequencing (NGS) analysis for the presence of somatic MMR mutations.

Results

In tumor tissue, an inactivating MLH1 mutation (c.518_519del; p.(Tyr173Trpfs*18)) was detected, which was also present at low level in the blood of the patient. In both parents, as well as the patient's sisters, the mutation was not present.

Conclusion

We show that low‐level mosaicism can be detected by using high‐coverage targeted NGS panels on constitutional and/or tumor DNA. This report illustrates that by using sensitive sequencing techniques, more cases of genetic diseases driven by mosaic mutations may be identified, with important clinical consequences for patients and family members.
New asymptotic estimates of solutions for generalized Rosenau equations
Authors: Michihisa Hironori
Published: May 2019

This paper presents new methods widely applicable to expand solutions for wave equations with damping terms such as Rosenau‐type equations. Some of them have the diffusion structure that appears strongly in the low‐frequency region, and some detailed analysis on diffusion waves is seen in this report. In the high‐frequency region, difficulties arising from the regularity‐loss type are overcome by a new discovery of suitable asymptotic profiles and expanding techniques of solutions even if regularity assumptions on the initial data are not imposed. It is also shown that stronger regularity assumptions on the initial data give better asymptotic estimates.
Families of patients in ICU: A Scoping review of their needs and satisfaction with care
Authors: Scott Pamela , Thomson Patricia , Shepherd Ashley
Published: May 2019

Aim

To describe published literature on the needs and experiences of family members of adults admitted to intensive care and interventions to improve family satisfaction and psychological well‐being and health.

Design

Scoping review.

Methods

Several selective databases were searched. English‐language articles were retrieved, and data extracted on study design, sample size, sample characteristics and outcomes measured.

Results

From 469 references, 43 studies were identified for inclusion. Four key themes were identified: (a) Different perspectives on meeting family needs; (b) Family satisfaction with care in intensive care; (c) Factors having an impact on family health and well‐being and their capacity to cope; and (d) Psychosocial interventions. Unmet informational and assurance needs have an impact on family satisfaction and mental health. Structured written and oral information shows some effect in improving satisfaction and reducing psychological burden. Future research might include family in the design of interventions, provide details of the implementation process and have clearly identified outcomes.
Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma
Authors: Cheng Hoyee H. , Kamarck Thomas W. , Gianaros Peter J. , Roecklein Kathryn A. , Vanegas Yanet , Tsung Allan , Geller David A. , Marsh James W. , Ahmed Nadia S. , Steel Jennifer L.
Published: May 2019

Objective

To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC).

Methods

A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES‐D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex. Descriptive statistics, Mann‐Whitney U, Kruskal‐Wallis, linear regression, and Bonferroni corrections were performed to test the hypotheses.

Results

Of the 266 patients, 24% reported depressive symptoms in the clinical range (CES‐D ≥ 22). Females had higher CES‐D score than males (Mann‐Whitney U = 7135, P = .014, Padj = .028). Being unemployed/disabled (Kruskal‐Wallis = 14.732, P = .001, Padj = .005) was found to be associated with higher depressive symptoms in males but not in females. Serum level of IL‐2 (Kruskal‐Wallis = 17.261, P = .001, Padj = .005) were found to be negatively associated with education level. Gender (β = .177, P = .035), income (β = −.252, P = .004), whether the patient's income met their basic needs (β = .180, P = .035), and IL‐1β (β = −.165, P = .045) independently predicted depressive symptoms and together explained 19.4% of variance associated with depressive symptoms.

Conclusions

Sociodemographic and socioeconomic factors were predictive of inflammation and depressive symptoms. Recommendations include the development of gender‐targeted interventions for patients diagnosed with HCC who have low socioeconomic status (SES) and may suffer from depressive symptoms.
Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy
Authors: Wu Xiaoning , Scott Helen , Carlsson Sigrid V. , Sjoberg Daniel D. , Cerundolo Lucia , Lilja Hans , Prevo Remko , Rieunier Guillaume , Macaulay Valentine , Higgins Geoffrey S. , Verrill Clare L. , Lamb Alastair D. , Cunliffe Vincent T. , Bountra Chas , Hamdy Freddie C. , Bryant Richard J.
Published: May 2019

Background

Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance.

Methods

EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and γH2AX assays following UNC1999 chemical probe‐mediated EZH2 inhibition.

Results

While there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri‐methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999‐mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased γH2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999‐mediated EZH2 inhibition vs controls.

Conclusions

Taken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance.
IL‐8 protects prostate cancer cells from GSK‐3β‐induced oxidative stress by activating the mTOR signaling pathway
Authors: Sun Yi , Ai Jian‐Zhong , Jin Xi , Liu Liang‐Ren , Lin Tian‐Hai , Xu Hang , Wei Qiang , Yang Lu
Published: May 2019

Introduction

Both oxidative stress and inflammation play important roles in prostate cancer cell apoptosis or proliferation; however, the mechanisms underlying these processes remain unclear. Thus, we selected interleukin‐8 (IL‐8) as the bridge between inflammation and cancer cell oxidative stress‐induced death and aimed to confirm its connection with mTOR and Glycogen synthase kinase‐3 beta (GSK‐3β).

Methods

We overexpressed GSK‐3β and observed its effect on reactive oxygen species (ROS) and oxidative stress‐induced cell death. IL‐8 was then upregulated or downregulated to determine its impact on preventing cell damage due to GSK‐3β‐induced oxidative stress. In addition, we overexpressed or knocked down mTOR to confirm its role in this process. Real‐time PCR, Western blotting, transcription, Cell Counting Kit 8 (CCK‐8), and flow cytometry analyses were performed in addition to the use of other techniques.

Results

IL‐8 promotes prostate cancer cell proliferation and decreases apoptosis, whereas GSK‐3β activates the caspase‐3 signaling pathway by increasing ROS and thereby induces oxidative stress‐mediated cell death. In addition, mTOR can also decrease activation of the caspase‐3 signaling pathway by inhibiting GSK‐3 and thus decreasing ROS production. Moreover, the inhibitory effect of IL‐8 on GSK‐3β occurs through the regulation of mTOR.

Conclusion

The results of this study highlight the importance of GSK‐3β, which increases the production of ROS and thereby induces oxidative stress in tumor cells, whereas IL‐8 and mTOR attenuate oxidative stress to protect prostate cancer cells through inhibition of GSK‐3β.
Multiple fungus balls in a patient with chronic pulmonary aspergillosis
Authors: Nakamoto Keitaro , Sasaki Yuka , Uchiyama Takashi , Ohta Ken
Published: May 2019

Key message

Typically, radiological examination in chronic pulmonary aspergillosis reveals cavities with fungus balls within the upper lobes. This case showed that multiple fungus balls can also be present in the lower lobes.
Effects of bed slope on the flow field of vertical slot fishways
Authors: Quaranta Emanuele , Katopodis Christos , Comoglio Claudio
Published: May 2019

Vertical slot fishways (VSFs) are the most efficient and least selective typology of technical fish passage, due to their ability to remain effective even when significant upstream and/or downstream water level fluctuations occur. Fishway construction costs can be reduced by increasing its bed slope, but this affects the flow field inside the pools, with higher head drops between the basins, as well as turbulence levels and flow velocities, which may affect fish passage. In light of this, a VSF was investigated by 3D numerical simulations to identify the possible effects of the bed slope (using values from 1.67% to 10%) on the flow field and subsequent implications for fish passage. A particular focus was devoted to cyprinind species, but the results can be extended to other species of similar swimming abilities and, therefore, be applicable to multispecies rivers. Flow velocity and turbulence values such as turbulent kinetic energy and Reynolds stresses were analysed from a fish passage perspective in relation to threshold values derived from previous studies. Pool areas where turbulence values are compatible with fish ability and behaviour were quantified. Maps of the location of fish‐friendly zones in the VSF pools were produced and can constitute a reference for practical applications in fishway design. The flow field generated with bed slopes lower than 6.67% is more compatible with fish swimming capabilities, because it exhibits a predominantly 2D behaviour and more suitable hydraulic conditions, whereas at higher slopes, turbulence levels in the pools increase.
Teaching Bilingual Learners: Effects of a Language‐Based Reading Intervention on Academic Language and Reading Comprehension in Grades 4 and 5
Authors: Proctor C. Patrick , Silverman Rebecca D. , Harring Jeffrey R. , Jones Renata Love , Hartranft Anna M.
Published: May 2019

Students are expected to comprehend and produce increasingly complex texts in upper elementary school, and academic language and literacy skills are considered critical to meeting these expectations. Notions of academic language are also controversial and require careful deliberation when applied to traditionally minoritized populations, including bilingual learners who negotiate more than one language in their daily lives and have varied linguistic repertoires. In the present study, the authors report on a quasi‐experimental field trial of a theoretically grounded and language‐based reading intervention framed around language components (semantics, syntax, and morphology), language functions, discussion, and reading comprehension. A sample of 239 Portuguese–English and Spanish–English bilingual students in grades 4 and 5 worked in small instructional groups to explore language, apply reading strategies, and discuss and write about big ideas in text. Half of the students were assigned to the intervention group (n = 119) and the other half (n = 120) to a business‐as‐usual control group. Classroom teachers (n = 12) and specialists (n = 10) implemented the intervention with small groups of four to six students. Results showed practically meaningful effects of the intervention on standardized measures of both academic language (Hedges’sg = 0.248) and reading comprehension (Hedges’sg = 0.166), with implications for theory, research, and classroom practice.
Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome
Authors: Mazzini Letizia , Gelati Maurizio , Profico Daniela Celeste , Sorarù Gianni , Ferrari Daniela , Copetti Massimiliano , Muzi Gianmarco , Ricciolini Claudia , Carletti Sandro , Giorgi Cesare , Spera Cristina , Frondizi Domenico , Masiero Stefano , Stecco Alessandro , Cisari Carlo , Bersano Enrica , De Marchi Fabiola , Sarnelli Maria Francesca , Querin Giorgia , Cantello Roberto , Petruzzelli Francesco , Maglione Annamaria , Zalfa Cristina , Binda Elena , Visioli Alberto , Trombetta Domenico , Torres Barbara , Bernardini Laura , Gaiani Alessandra , Massara Maurilio , Paolucci Silvia , Boulis Nicholas M. , Vescovi Angelo L. ,   on behalf of the ALS-NSCs Trial Study Group
Published: May 2019

The main objective of this phase I trial was to assess the feasibility and safety of microtransplanting human neural stem cell (hNSC) lines into the spinal cord of patients with amyotrophic lateral sclerosis (ALS). Eighteen patients with a definite diagnosis of ALS received microinjections of hNSCs into the gray matter tracts of the lumbar or cervical spinal cord. Patients were monitored before and after transplantation by clinical, psychological, neuroradiological, and neurophysiological assessment. For up to 60 months after surgery, none of the patients manifested severe adverse effects or increased disease progression because of the treatment. Eleven patients died, and two underwent tracheotomy as a result of the natural history of the disease. We detected a transitory decrease in progression of ALS Functional Rating Scale Revised, starting within the first month after surgery and up to 4 months after transplantation. Our results show that transplantation of hNSC is a safe procedure that causes no major deleterious effects over the short or long term. This study is the first example of medical transplantation of a highly standardized cell drug product, which can be reproducibly and stably expanded ex vivo, comprising hNSC that are not immortalized, and are derived from the forebrain of the same two donors throughout this entire study as well as across future trials. Our experimental design provides benefits in terms of enhancing both intra- and interstudy reproducibility and homogeneity. Given the potential therapeutic effects of the hNSCs, our observations support undertaking future phase II clinical studies in which increased cell dosages are studied in larger cohorts of patients. Stem Cells Translational Medicine  2019;8:887–897