bluuebunny/crossref_metadata_2025 huggingface dataset:
Combination therapy with KRAS siRNA and EGFR inhibitor AZD8931 suppresses lung cancer cell growth in vitro
Authors: Zarredar Habib , Pashapour Shadi , Ansarin Khalil , Khalili Majid , Baghban Roghayyeh , Farajnia Safar
Published: August 2018

Lung cancer is a leading cause of cancer‐related deaths worldwide, with less than a 5‐year survival rate for both men and women. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma oncogene (KRAS) signaling pathways play a critical role in the proliferation and progression of various cancers, including lung cancer. Genetic studies have shown that amplification, over‐expression, or mutation of EGFR is an early and major molecular event in many human tumors. KRAS mutation is a negative factor in various cancer, including non‐small‐cell lung cancer, and complicates therapeutic approaches with adjuvant chemotherapy and anti‐EGFR directed therapies. This article is dedicated to evaluating the synergistic effect of a novel EGFR inhibitor AZD8931 and KRAS small interfering RNA (siRNA) on the proliferation and apoptosis of lung adenocarcinoma cancer cells. A549 lung cancer cells were treated with KRAS siRNA and the EGFR inhibitor alone or in combination. The cytotoxic effects of KRAS siRNA and te EGFR inhibitor were determined usingMTT assay, and induction of apoptosis was determined by FACS analysis. Suppression of KRAS, Her‐2, and EGFR expression by treatments was measured by qRT‐PCR and western blotting. KRAS siRNA and the EGFR inhibitor significantly reduced the proliferation of A549 cells as well as KRAS and EGFR mRNA levels 24 hr after treatment. The results also indicated that the silencing of KRAS and EGFR has synergistic effects on the induction of apoptosis on the A549 cells. These results indicated that KRAS and EGFR might play important roles in the progression of lung cancer and could be potential therapeutic targets for treatment of lung cancer.
Intratumor lactate levels reflect HER2 addiction status in HER2‐positive breast cancer
Authors: Castagnoli Lorenzo , Iorio Egidio , Dugo Matteo , Koschorke Ada , Faraci Simona , Canese Rossella , Casalini Patrizia , Nanni Patrizia , Vernieri Claudio , Di Nicola Massimo , Morelli Daniele , Tagliabue Elda , Pupa Serenella M.
Published: August 2018

Despite different molecular tumor profiles indicate that human epidermal growth factor receptor 2 (HER2) messenger RNA (mRNA) levels mirror HER2 addiction and trastuzumab benefit in HER2‐positive breast cancer (BC), the identification of noninvasive clinical predictors of trastuzumab sensitivity remains an unmet clinical need. In the current study, we investigated whether intratumor lactate levels reflect HER2 addiction and, in turn, trastuzumab susceptibility. Accordingly, the gene expression profiles of transgenic murine BC cell lines expressing the human d16HER2 variant (HER2‐addicted) or human full‐length HER2 (WTHER2; HER2‐nonaddicted) revealed a significant enrichment of glycolysis‐related gene pathways in HER2‐addicted cells. We studied the metabolic content of 22 human HER2‐positive BC by quantitative nuclear magnetic resonance spectroscopy and found that those cases with higher lactate levels were characterized by higher HER2 transcript levels. Moreover, gene expression analyses of HER2‐positive BC samples from a TCGA data set revealed a significant enrichment in glycolysis‐related pathways in high/HER2‐addicted tumors. These data were confirmed by metabolic analyses of human HER2‐positive BC cell lines with high or low HER2 transcript levels, which revealed significantly more active glycolytic metabolism in high HER2 transcript than in low HER2 transcript cells. Overall, our results provide evidence for noninvasive intratumor lactate detection as a potential metabolic biomarker of HER2 addiction and trastuzumab response suggesting the possibility to use in vivo imaging to assess lactate levels and, in turn, select HER2‐positive BC patients who are more likely to benefit from anti‐HER2 treatments.
HPV16 E7‐induced upregulation of KDM2A promotes cervical cancer progression by regulating miR‐132–radixin pathway
Authors: Ou Rongying , Zhu Linyu , Zhao Liang , Li Wenfeng , Tao Fengxing , Lu Yiyi , He Qin , Li Jianrong , Ren Yi , Xu Yunsheng
Published: August 2018

Background

Human papillomavirus (HPV) infection and viral proteins expression cause a number of epigenetic alterations leading to cervical carcinogenesis. The recent discovery of a large amount of histone methylation modifiers reveals important roles of these enzymes in regulating tumor progression.

Methods

The changes in expression of 48 histone methylation modifiers were assessed following knockdown of HPV16 E7 in CaSki cells. Lysine‐specific demethylase 2A (KDM2A)‐regulated microRNAs (miRNAs) in cervical cancer pathogenesis were disclosed using quantitative real‐time polymerase chain reaction. The function of KDM2A–miRNAs on cervical cancer was investigated in vitro and in vivo.

Results

Upregulation of KDM2A induced by HPV16 E7 promotes cervical cancer cell proliferation and invasion and is correlated with poor prognosis in patients with cervical cancer. KDM2A physically interacts with the promoter of miR‐132 and suppresses its expression by removing the mono or dimethyl group from H3K36 at the miR‐132 locus. Functionally, miR‐132 represses cancer cell proliferation and invasion by inhibiting radixin (RDX). Upregulated KDM2A promotes cervical cancer progression by repressing miR‐132, which results in a derepression of RDX. Therefore, KDM2A functions as a tumor activator in cervical cancer pathogenesis by binding miR‐132 promoter and abrogating its tumor suppressive function.

Conclusion

Our results suggest a function for KDM2A in cervical cancer progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of cervical cancer.
An allogenic therapeutic strategy for canine spinal cord injury using mesenchymal stem cells
Authors: Bhat Irfan A. , T. B. Sivanarayanan , Somal Anjali , Pandey Sriti , Bharti Mukesh K. , Panda Bibhudatta S. K. , B. Indu , Verma Megha , J. Anand , Sonwane Arvind , Kumar G. Sai , Amarpal  , Chandra Vikash , Sharma G. Taru
Published: August 2018

This study was conducted to characterize canine bone marrow‐derived mesenchymal stem cells (BMSCs); in vivo tracking in mice, and therapeutic evaluation in canine clinical paraplegia cases. Canine BMSCs were isolated, cultured, and characterized in vitro as per International Society for Cellular Therapy criteria, and successfully differentiated to chondrogenic, osteogenic, and adipogenic lineages. To demonstrate the homing property, the pGL4.51 vector that contained luciferase reporter gene was used to transfect BMSCs. Successfully transfected cells were injected around the skin wound in mice and in vivo imaging was done at 6, 12 and 24 hr post MSCs delivery. In vivo imaging revealed that transfected BMSCs migrated and concentrated predominantly toward the center of the wound. BMSCs were further evaluated for allogenic therapeutic potential in 44 clinical cases of spinal cord injuries (SCI) and compared with conventional therapy (control). Therapeutic potential as evaluated by different body reflexes and recovery score depicted significantly better results in stem cell‐treated group compared to control group. In conclusion, allogenic canine BMSCs can serve as potent therapeutic candidate in cell‐based therapies, especially for diseases like SCI, where the conventional medication is not so promising.
LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR‐128/CD151 pathway in hepatocellular carcinoma
Authors: Zhang Peng‐Fei , Wang Fei , Wu Jing , Wu Yin , Huang Wei , Liu Dong , Huang Xiao‐Yong , Zhang Xue‐Mei , Ke Ai‐Wu
Published: August 2018

Dysregulation of long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and tumor progression, including hepatocellular carcinoma (HCC). Small nucleolar RNA host gene 3 (SNHG3) has been considered as an lncRNA to be associated with a poor prognosis in patients with HCC. Here, we reported that SNHG3 expression was significantly higher in the highly metastatic HCC (HCCLM3) cells compared with the lowly metastatic HCC cells (Hep3B and PLC/PRF/5). Furthermore, forced expression of SNHG3 promoted cell invasion, epithelial‐mesenchymal transition (EMT), and sorafenib resistance in HCC. Moreover, SNHG3 overexpression induced HCC cells EMT via miR‐128/CD151 cascade activation. Clinically, our data revealed that increased SNHG3 expression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.
Antitumor activity of cell‐penetrant kinin B1 receptor antagonists in human triple‐negative breast cancer cells
Authors: Dubuc Céléna , Savard Martin , Bovenzi Veronica , Lessard Andrée , Côté Jérôme , Neugebauer Witold , Geha Sameh , Chemtob Sylvain , Gobeil Fernand
Published: August 2018

High nuclear expression of G protein‐coupled receptors, including kinin B1 receptors (B1R), has been observed in several human cancers, but the clinical significance of this is unknown. We put forward the hypothesis that these “nuclearized” kinin B1R contribute to tumorigenicity and can be a new target in anticancer strategies. Our initial immunostaining and ultrastructural electron microscopy analyses demonstrated high B1R expression predominantly located at internal/nuclear compartments in the MDA‐MB‐231 triple‐negative breast cancer (TNBC) cell line as well as in clinical samples of patients with TNBC. On the basis of these findings, in the present study, we evaluated the anticancer therapeutic potential of newly identified, cell‐permeable B1R antagonists in MDA‐MB‐231 cells (ligand–receptor binding/activity assays and LC‐MS/MS analyses). We found that these compounds (SSR240612, NG67, and N2000) were more toxic to MDA‐MB‐231 cells in comparison with low‐ or non‐B1R expressing MCF‐10A normal human mammary epithelial cells and COS‐1 cells, respectively (clonogenic, MTT proliferative/cytocidal assays, and fluorescence‐activated cell‐sorting (FACS)‐based apoptosis analyses). By comparison, the peptide B1R antagonist R954 unable to cross cell membrane failed to produce anticancer effects. Furthermore, the putative mechanisms underlying the anticancer activities of cell‐penetrant B1R antagonists were assessed by analyzing cell cycle regulation and signaling molecules related to cell survival and apoptosis (FACS and western blot). Finally, drug combination experiments showed that cell‐penetrant B1R antagonists can cooperate with suboptimal doses of chemotherapeutic agents (doxorubicin and paclitaxel) to promote TNBC death. This study provides evidence on the potential value of internally acting kinin B1R antagonists in averting growth of breast cancer.
RETRACTED: CP‐31398 inhibits the progression of cervical cancer through reversing the epithelial mesenchymal transition via the downregulation of PAX2s
Authors: Liu Ling , Yu Tan‐Tan , Ren Chen‐Chen , Yang Li , Cui Shi‐Hong , Zhang Xiao‐An
Published: August 2018

CP‐31398, a styrylquinazoline, emerges from a screen for therapeutic agents that restore the wild‐type DNA‐binding conformation of mutant p53 to suppress tumors in vivo, but its effects on cervical cancer (CC) remain unknown. Hence, this study aimed to explore the effects CP‐31398 has on the CC cells and to investigate whether it is associated with paired box 2 (PAX2) expression. CC cells were treated with different concentrations of CP‐31398 (1, 2, 4, 6, 8, and 10 μg/ml) to determine the optimum concentration using fluorometric microculture cytotoxicity assay. After constructing the sh‐PAX2 vector, CC cells were transfected with sh‐PAX2 or treated with CP‐31398. The effects of CP‐31398 or PAX2 silencing on CC cell proliferation, apoptosis, invasion, and migration were evaluated. Epithelial mesenchymal transition (EMT)‐related genes such as E‐cadherin, vimentin, N‐cadherin, snail, and twist in CC cells were detected. Tumor formation experiment in nude mice was performed to observe tumor growth. The optimum concentration of CP‐31398 was 2 μg/ml. PAX2 was overexpressed in CC cells. CC cells treated with CP‐31398 or treated with sh‐PAX2 inhibited proliferation, invasion, and migration but promoted apoptosis with decreased PAX2 expression. The EMT process in CC cells was also reversed after treatment with CP‐31398 or sh‐PAX2. Moreover, the tumor formation experiment in nude mice revealed the inhibitory activity of CP‐31398 in CC tumor in nude mice by suppressing PAX2. Our results provide evidence that CP‐31398 could inhibit EMT and promote apoptosis of CC cells to curb CC tumor growth by downregulating PAX2.
CircRBMS3 promotes gastric cancer tumorigenesis by regulating miR‐153–SNAI1 axis
Authors: Li Guangyan , Xue Minghui , Yang Fang , Jin Yuhong , Fan Yingying , Li Wei
Published: August 2018

Gastric cancer (GC) is one of the leading causes of cancer‐related death worldwide. Mounting evidence showed that circular RNAs (circRNAs) play critical roles in human malignancy. However, the knowledge about circRNAs in GC is still unclear. In the current study, high throughput microarray assay showed that circRBMS3 was upregulated in GC tissues, which was further confirmed by quantitative reverse transcription polymerase chain reaction. Correlation analysis revealed that high circRBMS3 expression was associated with advanced TNM stage, depth of invasion, and lymph‐node metastasis. Kaplan–Meier analysis indicated that GC patients with high circRBMS3 expression have a poor overall survival (OS). Function assays showed that circRBMS3 silencing reduced GC cells proliferation and invasion in vitro, and inhibited the tumor growth in vivo. Mechanistically, we found that miR‐153 could act as a target of circRBMS3. Subsequently, we showed that circRBMS3 promoted snail family zinc finger 1 (SNAI1) expression via inhibiting miR‐153 in GC cells. Collectively, these results suggested that circRBMS3 promoted GC cells proliferation and invasion via regulating miR‐153/SNAI1 axis.
Reversine promotes browning of white adipocytes by suppressing miR‐133a
Authors: Kim Saetbyul , Park Jong Woo , Lee Min Gyu , Nam Ki Hong , Park Jee Hun , Oh Hwamok , Lee Jieun , Han Jihoon , Yi Sang Ah , Han Jeung‐Whan
Published: August 2018

Brown adipocytes are characterized by a high number of uncoupling protein 1 (UCP1)‐positive mitochondrial content and increased thermogenic capacity. As UCP1‐enriched cells can consume lipids by generating heat, browning of white adipocytes is now highlighted as a promising approach for the prevention of obesity and obesity‐associated metabolic diseases. Upon cold exposure or β‐adrenergic stimuli, downregulation of microRNA‐133 (miR‐133) elevates the expression levels of PR domain containing 16 (Prdm16), which has been shown to be a brown adipose determination factor, in brown adipose tissue and subcutaneous white adipose tissues (WAT). Here, we show that treatment of reversine to white adipocytes induces browning via suppression of miR‐133a. Reversine treatment promoted the expression of brown adipocyte marker genes, such as Prdm16 and UCP1, increasing the mitochondrial content, while decreasing the levels of miR‐133a and white adipocyte marker genes. Ectopic expression of miR‐133a mimic reversed the browning effects of the reversine treatment. Moreover, intraperitoneal administration of reversine in mice upregulated thermogenesis and resulted in resistance to high‐fat diet‐mediated weight gain as well as browning of subcutaneous and epididymal WAT. Taken together, we found a novel way to promote browning of white adipocytes through downregulation of miR‐133a followed by activation of Prdm16, with a synthetic chemical, reversine.
Identification of a five‐gene signature with prognostic value in colorectal cancer
Authors: Sun Guangwei , Li Yalun , Peng Yangjie , Lu Dapeng , Zhang Fuqiang , Cui Xueyang , Zhang Qingyue , Li Zhuang
Published: August 2018

Colorectal cancer (CRC) ranks as one of the most commonly diagnosed malignancies worldwide. Although mortality rates have been decreasing, the prognosis of CRC patients is still highly dependent on the individual. Therefore, identifying and understanding novel biomarkers for CRC prognosis remains crucial. The gene expression profiles of five‐gene expression omnibus (GEO) data sets of CRC were first downloaded. A total of 352 consistent differentially expressed genes (DEGs) were identified for CRC and paired with normal tissues. Functional analysis including gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment revealed that these DEGs were related to metabolic pathways, tight junctions, and the cell cycle. Ten hub DEGs were identified based on the search tool for the retrieval of interacting genes database and protein–protein interaction networks. By using univariate Cox proportional hazard regression analysis, we found 11 survival‐related genes among these DEGs. We finally established a five‐gene signature (kinesin family member 15, N‐acetyltransferase 2, glutathione peroxidase 3, secretogranin II, and chloride channel accessory 1) with prognostic value in CRC by step multivariate Cox regression analysis. Based on this risk scoring system, patients in the high‐risk group had significantly poorer survival results compared with those in the low‐risk group (log‐rank test, p < 0.0001). Finally, we validated our gene signature scoring system in two independent GEO cohorts (GSE17536 and GSE33113). We found all five of the signature genes to be DEGs in The Cancer Genome Atlas database. In conclusion, our findings suggest that our five DEG‐based signature can provide a novel biomarker with useful applications in CRC prognosis.
Decrease of MiR‐31 induced by TNF‐α inhibitor activates SATB2/RUNX2 pathway and promotes osteogenic differentiation in ethanol‐induced osteonecrosis
Authors: Yu Lingjia , Xu Yisheng , Qu Hao , Yu Yifeng , Li Wenjing , Zhao Yu , Qiu Guixing
Published: August 2018

Purpose

Suppressed osteogenic differentiation is considered a main cause of ethanol‐induced osteonecrosis. Tumor necrosis factor α (TNF‐α) and miR‐31 have been reported to be involved in the osteogenic induction. This study aimed to explore a possible molecular mechanism regulating osteogenic differentiation in ethanol‐induced osteonecrosis bone marrow stromal stem cells (BMSCs).

Methods

Alizarin red staining was used to examine the level of mineralization in osteogenic differentiation process. Alkaline phosphatase assay was applied to the validation of ALP level which was essential to bone mineralization. The level of osteogenesis markers was determined by western blot assay, whereas the fluctuations of messenger RNA levels were tested by quantitative real‐time polymerase chain reaction. Microarray analysis was conducted to identify differentially expressed genes, because the possible target relationship was predicted and validated by miRBase and luciferase reporter assay, respectively. Colony forming unit of fibroblast assay was used to observe the proliferation of BMSCs.

Results

BMSCs from patients with ethanol‐induced osteonecrosis exhibited weaker osteogenic differentiation and proliferation abilities. TNF‐α inhibitor added in the osteogenic medium significantly enhanced the osteogenic differentiation ability and BMSCs proliferation ability. TNF‐α by regulating miR‐31 downregulated the expressions of RUNX2 and SATB2, two contributors of osteoblast differentiation, further suppressed osteogenic differentiation. On the contrary, TNF‐α inhibitor could promote osteogenic differentiation in BMSCs from patients with ethanol‐induced osteonecrosis.

Conclusion

TNF‐α inhibitor could downregulate miR‐31 expressions, which directly promoted SATB2 and RUNX2 expressions and enhanced osteogenic differentiation of BMSCs from patients with ethanol‐induced osteonecrosis.
Recent trends in the occurrence of bleeding gastric and duodenal ulcers under the Japanese evidence‐based clinical practice guideline for peptic ulcer disease
Authors: Nagashima Kazunori , Tominaga Keiichi , Fukushi Koh , Kanamori Akira , Sasai Takako , Hiraishi Hideyuki
Published: August 2018

Background

Gastrointestinal hemorrhage occurs frequently. We reviewed the tendency of occurrence of bleeding gastric and duodenal ulcers and their association with antithrombotic therapy before and after the widespread use of Evidence‐Based Clinical Practice Guidelines for Peptic Ulcer 2009 (1st edition), which was published to improve treatment outcomes and prevent peptic ulcers.

Methods

The study enrolled 1105 patients with bleeding gastric and duodenal ulcers treated at our hospital between January 2000 and March 2016. They were divided into the preguideline group (807 patients treated between January 2000 and December 2010) and the postguideline group (298 patients treated between January 2011 and March 2016). The use of medications, severity, the incidence of Helicobacter pylori infection, the presence of any underlying disease, and other factors were compared between the pre‐ and postguideline groups.

Results

The number of patients receiving antithrombotic therapy was slightly higher in the postguideline group without a significant difference (P = 0.50). The incidence of H. pylori infection was significantly lower in the postguideline group (P < 0.001). The rate of premedication with a proton pump inhibitor (PPI) and the rate of severe ulcers were significantly higher in the postguideline group (P = 0.001 and P < 0.001, respectively). The rebleeding rate showed no significant difference, whereas the recurrence rate was significantly higher in the postguideline group (P = 0.041).

Conclusions

The major cause of hemorrhagic gastroduodenal ulcers seems to be shifting from H. pylori infection to the administration of drugs with gastrointestinal risk. Antithrombotic therapy tends to be associated with severe ulcers but without statistical significance.
Minimal conditioning in Fanconi anemia promotes multi‐lineage marrow engraftment at 10‐fold lower cell doses
Authors: Haworth Kevin G. , Ironside Christina , Ramirez Megan A. , Weitz Sarah , Beard Brian C. , Schwartz Jonathan D. , Adair Jennifer E. , Kiem Hans‐Peter
Published: August 2018

Background

Gene therapy approaches for the treatment of Fanconi anemia (FA) hold promise for patients without a suitably matched donor for an allogeneic bone marrow transplant. However, significant limitations include the collection of sufficient stem cell numbers from patients, the fragility of these cells during ex vivo manipulation, and clinically meaningful engraftment following transplantation. With these challenges in mind, we were interested in determining (i) whether gene‐corrected cells at progressively lower numbers can successfully engraft in FA; (ii) whether low‐dose conditioning facilitates this engraftment; and (iii) whether these cells can be selected for post‐transplant.

Methods

Utilizing a well characterized mouse model of FA, we infused donor bone marrow from healthy heterozygote littermates that are unaffected carriers of the FANCA mutation to mimic a gene‐corrected product, after administering low‐dose conditioning. Once baseline engraftment was observed, we administered a second, very‐low selective dose to determine whether gene‐corrected cells could be selected for in vivo.

Results

We demonstrate that upfront low‐dose conditioning greatly increases successful engraftment of hematopoietic corrected cells in a pre‐clinical animal model of FA. Additionally, without conditioning, cells can still engraft and demonstrate a selective advantage in vivo over time following transplantation, and these corrected cells can be directly selected for in vivo after engraftment.

Conclusions

Minimal conditioning prior to bone marrow transplant in Fanconi anemia promotes the multi‐lineage engraftment of 10‐fold fewer cells compared to nonconditioned controls. These data provide important insights into the potential of minimally toxic conditioning protocols for FA gene therapy applications.
Unhinging the machinery of sepsis: An unexpected role for vascular smooth muscle
Authors: Englert Joshua A , Christman John W , Ballinger Megan N
Published: August 2018

Discussion on the important role of cellular interaction in the design of potential sepsis therapeutics.
Follicular regulatory T cell in atherosclerosis
Authors: Baptista Daniela , Mach François , Brandt Karim J
Published: August 2018

Atherosclerosis is a chronic inflammatory disease involving the infiltration of immune cells, such as monocytes/macrophages, neutrophils, T cells, and B cells, into the inner layer of vessel walls. T and B cell functions in the process of atherogenesis, as well as their mutual regulation, have been investigated but several aspects remain to be clarified. In the present review, we give a brief overview of the functions of follicular regulatory T cell (Tfr) on follicular T (Tfh) and B cell regulation related to atherosclerosis pathogenesis, including their influence on lymphangiogenesis and lipoprotein metabolism. We will also discuss their potential therapeutics properties in the resolution of established atherosclerotic lesions.

Tfr cells are key regulators of atherosclerosis through regulation of Tfh cell population, inducing expansion of atheroprotective Breg cell population and stimulating lymphangiogenesis.
Nitrogen and sulfur co‐doped carbon nanodots toward bovine hemoglobin: A fluorescence quenching mechanism investigation
Authors: Wang Jiajun , Xiang Xueqing , Milcovich Gesmi , Chen Jingru , Chen Chao , Feng Jiuju , Hudson Sarah P. , Weng Xuexiang , Ruan Yongming
Published: August 2018

A deep understanding of the molecular interactions of carbon nanodots with biomacromolecules is essential for wider applications of carbon nanodots both in vitro and in vivo. Herein, nitrogen and sulfur co‐doped carbon dots (N,S‐CDs) with a quantum yield of 16% were synthesized by a 1‐step hydrothermal method. The N,S‐CDs exhibited a good dispersion, with a graphite‐like structure, along with the fluorescence lifetime of approximately 7.50 ns. Findings showed that the fluorescence of the N,S‐CDs was effectively quenched by bovine hemoglobin as a result of the static fluorescence quenching. The mentioned quenching mechanism was investigated by the Stern‐Volmer equation, temperature‐dependent quenching, and fluorescence lifetime measurements. The binding constants, number of binding sites, and the binding average distance between the energy donor N,S‐CDs and acceptor bovine hemoglobin were calculated as well. These findings will provide for valuable insights on the future bioapplications of N,S‐CDs.
Respiratory syncytial virus–associated illness in adults with advanced chronic obstructive pulmonary disease and/or congestive heart failure
Authors: Falsey Ann R , Walsh Edward E , Esser Mark T , Shoemaker Kathryn , Yu Li , Griffin M Pam
Published: August 2018

Background

Respiratory syncytial virus (RSV) is recognized as a serious pathogen in people with chronic cardiopulmonary conditions. Immunoprophylaxis might be considered for adults at high‐risk for frequent and severe RSV infection. Thus, we studied the incidence of RSV‐related medically attended acute respiratory illness (MARI) in adults with severe chronic obstructive pulmonary disease (COPD) and/or congestive heart failure (CHF).

Methods

Subjects ≥50 years of age with Gold Class III/IV COPD and/or American Heart Association class III/IV CHF and exposure to children ≥once per month were recruited. Subjects were evaluated over 1.5 to 2.5 years for RSV‐associated MARI, defined as polymerase chain reaction (PCR) and/or seroresponse.

Results

Four hundred forty‐five subjects were enrolled between October 2011 and May 2012. Overall, 99 RSV infections were documented by PCR or serology for a cumulative incidence of 22.2%. Of these, 42 (9.4%) subjects had protocol‐specified RSV‐MARI for an incidence of 4.68/100 patient‐seasons. All‐cause MARI was common (63.85/100 patient‐seasons) with rhinovirus most commonly identified.

Conclusion

RSV infection was common in adults with severe COPD and/or advanced CHF. Given the severity of underlying cardiopulmonary diseases in the study population, most illnesses were surprisingly mild. Thus, active immunization rather than passive immunoprophylaxis with monoclonal antibodies may be a more cost‐effective strategy.
High prevalence and autochtonous transmission of human pegivirus (HPgV‐1) in blood donors in the extreme southern of Brazil
Authors: Da Mota Luísa D. , Finger‐Jardim Fabiana , Silva Cláudio M. , Germano Fabiana N. , Nader Maiba M. , Gonçalves Carla Vitola , Da Hora Vanusa P. , Silveira Jussara , Basso Rossana P. , Soares Marcelo A. , Martínez Ana M.B.
Published: August 2018

Recent studies have suggested that human pegivirus 1 (HPgV‐1) may have some pathogenic potential. In the southernmost region of Brazil, studies on HPgV‐1 are scarce, and circulating genotypes have not yet been identified. The current study aimed to evaluate the prevalence of HPgV‐1 among blood donors from the southernmost region of Brazil and identify the genotypes involved with associated factors. A cross‐sectional study was conducted with 281 blood donors, who had their plasma subjected to RNA extraction, complementary DNA synthesis, HPgV‐1 detection by nested polymerase chain reaction, and subsequent genotyping. The observed prevalence of HPgV‐1‐RNA was 21.7%. The only variable that was significantly associated with virus infection was the relationship status of the donor. Single or no fixed partner blood donors were twice as likely to have HPgV‐1 (95% CI, 1.12 to 4.56; P = 0.02). Genotype 2—subtypes 2b (69%) and 2a (29%)—was the most prevalent. In the absence of risk factors for parenteral transmission, it is likely that sexual transmission was the route of infection in the individuals studied. Further work will be needed to determine whether this virus is inert in the population, or if there are potential deleterious effects in infected individuals.
The implication of CRISPR/Cas9 genome editing technology in combating human oncoviruses
Authors: Gilani Usman , Shaukat Memoona , Rasheed Arisha , Shahid Mehak , Tasneem Fareeda , Arshad Muhammad , Rashid Naeem , Shahzad Naveed
Published: August 2018

It is evidenced that 20% of all tumors in humans are caused by oncoviruses, including human papilloma viruses, Epstein‐Barr virus, Kaposi sarcoma virus, human polyomaviruses, human T‐lymphotrophic virus‐1, and hepatitis B and C viruses. Human immunodeficiency virus is also involved in carcinogenesis, although not directly, but by facilitating the infection of many oncoviruses through compromising the immune system. Being intracellular parasites with the property of establishing latency and integrating into the host genome, these viruses are a therapeutic challenge for biomedical researchers. Therefore, strategies able to target nucleotide sequences within episomal or integrated viral genomes are of prime importance in antiviral or anticancerous armamentarium. Recently, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) has emerged as a powerful genome editing tool. Standing out as a precise and efficient oncoviruses method, it has been extensively applied in recent experimental ventures in the field of molecular medicine, particularly in combating infections including tumor inducing viruses. This review is aimed at collating the experimental and clinical advances in CRISPR/Cas9 technology in terms of its applications against oncoviruses. Primarily, it will focus on the application of CRISPR/Cas9 in combating tumor viruses, types of mechanisms targeted, and the significant outcomes till date. The technical pitfalls of the CRISPR/Cas9 and the comparative approaches in evaluating this technique with respect to other available alternatives are also described briefly. Furthermore, the review also discussed the clinical aspects and the ethical, legal, and social issues associated with the use of CRISPR/Cas9.
Proactive career behaviors and subjective career success: The moderating role of national culture
Authors: Smale Adam , Bagdadli Silvia , Cotton Rick , Dello Russo Silvia , Dickmann Michael , Dysvik Anders , Gianecchini Martina , Kaše Robert , Lazarova Mila , Reichel Astrid , Rozo Paula , Verbruggen Marijke ,   Cross‐Cultural Collaboration on Contemporary Careers (5C) research collaborative
Published: August 2018

Although career proactivity has positive consequences for an individual's career success, studies mostly examine objective measures of success within single countries. This raises important questions about whether proactivity is equally beneficial for different aspects of subjective career success, and the extent to which these benefits extend across cultures. Drawing on Social Information Processing theory, we examined the relationship between proactive career behaviors and two aspects of subjective career success—financial success and work‐life balance—and the moderating role of national culture. We tested our hypotheses using multilevel analyses on a large‐scale sample of 11,892 employees from 22 countries covering nine of GLOBE's 10 cultural clusters. Although we found that proactive career behaviors were positively related to subjective financial success, this relationship was not significant for work‐life balance. Furthermore, career proactivity was relatively more important for subjective financial success in cultures with high in‐group collectivism, high power distance, and low uncertainty avoidance. For work‐life balance, career proactivity was relatively more important in cultures characterized by high in‐group collectivism and humane orientation. Our findings underline the need to treat subjective career success as a multidimensional construct and highlight the complex role of national culture in shaping the outcomes of career proactivity.
Coupled model fidelity in capturing atmospheric internal processes during organization and intensification of boreal summer intra‐seasonal oscillation
Authors: Sarkar Sahadat , Mukhopadhyay Parthasarathi , Phani Murali Krishna Ravuri , Dutta Somenath
Published: August 2018

The study investigates the Climate Forecast System version 2 (CFSv2) model fidelity in capturing large‐scale dynamical field and the energy conversion processes during organization and intensification of Boreal Summer Intra‐Seasonal Oscillation (BSISO). Experiment is carried out to make 10‐year free run to evaluate the model. Based on rainfall analyses, two types of events are defined one strong and other with weaker intensity. The result reveals that model over estimates the BSISO intensity starting from the initial phase. Strong events based on MERRA data show a persistent increasing lower‐level moisture convergence with respect to convection centre (CC) and a collocated vertical velocity with CC. However, model moisture convergence and vertical velocity are slightly stronger than observation at the initial phase but it is not persisting in the subsequent lags. The analysis of eddy kinetic energy (EKE) budget equation shows that the model intra‐seasonal EKE is very weak at 850 hPa level. The vertical structure of EKE has shown that a positive EKE at the lower to middle troposphere increases in the subsequent lags but it is very weak for model. The analysis of each term of EKE budget has shown that the barotropic energy conversion (ΔCK) and convergence of eddy geopotential fluxes (ΔFG) are the dominant contributors for positive EKE tendency in the ERA analysis and both the terms increase as the BSISO approaches towards its organized and intense phase. However for model, the above terms are very weak. The EKE advection through large‐scale background flow (ΔAM) and synoptic‐scale eddy (ΔAE) adds negatively to the EKE tendency for strong events. However for model, the magnitudes of the above terms are higher than that of the observation for both strong and weak events. Thus, the model has deficiency in capturing the dynamical processes and the energy conversion processes properly.
Crop production losses associated with anthropogenic climate change for 1981–2010 compared with preindustrial levels
Authors: Iizumi Toshichika , Shiogama Hideo , Imada Yukiko , Hanasaki Naota , Takikawa Hiroki , Nishimori Motoki
Published: August 2018

The accumulated evidence indicates that agricultural production is being affected by climate change. However, most of the available evidence at a global scale is based on statistical regressions. Corroboration using independent methods, specifically process‐based modelling, is important for improving our confidence in the evidence. Here, we estimate the impacts of climate change on the global average yields of maize, rice, wheat and soybeans for 1981–2010, relative to the preindustrial climate. We use the results of factual and non‐warming counterfactual climate simulations performed with an atmospheric general circulation model that do and do not include anthropogenic forcings to climate systems, respectively, as inputs into a global gridded crop model. The results of a 100‐member ensemble climate and crop simulation suggest that climate change has decreased the global mean yields of maize, wheat and soybeans by 4.1, 1.8 and 4.5%, respectively, relative to the counterfactual simulation (preindustrial climate), even when carbon dioxide (CO2) fertilization and agronomic adjustments are considered. For rice, no significant impacts (−1.8%) are detected. The uncertainties in estimated yield impacts represented by the 90% probability interval that are derived from the ensemble members are −8.5 to +0.5% for maize, −8.4 to −0.5% for soybeans, −9.6 to +12.4% for rice and − 7.5 to +4.3% for wheat. Based on the yield impacts, the estimates of average annual production losses throughout the world for the most recent years of the study (2005–2009) account for 22.3 billion USD (B$) for maize, 6.5 B$ for soybeans, 0.8 B$ for rice and 13.6 B$ for wheat. Our assessment confirms that climate change has modulated recent yields and led to production losses, and our adaptations to date have not been sufficient to offset the negative impacts of climate change, particularly at lower latitudes.
Systematic reviews and tech mining: A methodological comparison with case study
Authors: Anderson Patricia F. , Shannon Carol , Bickett Skye , Doucette Joanne , Herring Pamela , Kepsel Andrea , Lyons Tierney , McLachlan Scott , Wu Lin
Published: August 2018

When the Medical Library Association identified questions critical for the future of the profession, it assigned groups to use systematic reviews to find the answers to these questions. Group 6, whose question was on emerging technologies, recognized early on that the systematic review process would not work well for this question, which looks forward to predict future trends, whereas the systematic review process looks back in time. We searched for new methodologies that were more appropriate to our question, developing a process that combined systematic review, text mining, and visualization techniques. We then discovered tech mining, which is very similar to the process we had created.

In this paper, we describe our research design and compare tech mining and systematic review methodologies. There are similarities and differences in each process: Both use a defined research question, deliberate database selection, careful and iterative search strategy development, broad data collection, and thoughtful data analysis. However, the focus of the research differs significantly, with systematic reviews looking to the past and tech mining mainly to the future.

Our comparison demonstrates that each process can be enhanced from a purposeful consideration of the procedures of the other. Tech mining would benefit from the inclusion of a librarian on their research team and a greater attention to standards and collaboration in the research project. Systematic reviews would gain from the use of tech mining tools to enrich their data analysis and corporate management communication techniques to promote the adoption of their findings.
Comparing the long‐term outcomes among patients with stomach and small intestine gastrointestinal stromal tumors: An analysis of the National Cancer Database
Authors: Giuliano Katherine , Ejaz Aslam , Reames Bradley N. , Choi WonSeok , Sham Jonathan , Gage Michele , Johnston Fabian M. , Ahuja Nita
Published: August 2018

Background and Objectives

Gastrointestinal stromal tumors (GIST) are the most common sarcoma arising from the gastrointestinal tract. Data regrading long‐term prognosis based on tumor location (stomach vs small intestine) are mixed, so we aimed to analyze their outcomes using a large national oncology database.

Methods

The National Cancer Database was queried for cases of stomach and small intestine GIST between the years 2004 and 2014. Survival analysis was performed using the Kaplan‐Meier method, and factors related to survival were compared using the Cox proportional hazards model.

Results

Of 18 900 total patients, those with small intestine GIST had larger median tumor size (6.2 cm; interquartile range [IQR], 3.8 to 10.0 vs stomach: 5.0 cm; IQR, 3.0 to 9.0; P < 0.001) and a higher incidence of tumors with ≥5 mitoses/50 HPF (29.3% vs stomach: 24.2%; P < 0.001). Unadjusted median overall survival (OS) was longer for patients with stomach GIST (10.3 years) as compared to small intestine GIST (9.4 years) (P = 0.01). After controlling for patient and tumor‐related factors, however, OS did not differ between stomach and small intestine GIST (hazard ratio, 1.19; 95% confidence interval, 0.88 to 1.61; P = 0.26).

Conclusions

Patients with small intestine GIST more commonly have larger, high mitotic rate tumors, but despite these worse prognostic features, tumor location did not independently impact OS.
Value of MRI morphologic features with pT1‐2 rectal cancer in determining lymph node metastasis
Authors: Tang Yibo , Rao Shengxiang , Yang Chun , Hu Yabin , Sheng Ruofan , Zeng Mengsu
Published: August 2018

Background and objectives

To investigate the different features between metastatic lymph node and nonmetastatic lymph node on magnetic resonance imaging (MRI) and the relationship between the rectal lesion and lymph node metastasis (LNM).

Methods

Eighty‐two patients with retrospectively consecutive pT1‐2 stage rectal cancer in 2016 were divided into lymph node metastasis (LNM+) and lymph node nonmetastasis (LNM−) group based on their histopathologic examinations. We evaluated the following features of lymph nodes: number, shape, signal heterogeneity, border, and diameter of the largest lymph node on T2‐weight images. We also calculated tumor apparent diffusion coefficient ratio and tumor percent enhancement. Fisher’s exact test was applied for inspecting lymph node numbers on MRI and logistic regression analysis in examining risk factors for LNM.

Results

The MR‐LN number was significantly different between the LNM+ and LNM− group (median: 4 vs 1, P = 0.001). Multivariate logistic regression analysis exhibited that the diameter of the largest lymph node and the tumor percent enhancement of the arterial phase were independent risk factors of LNM (P = 0.005 vs 0.021, respectively).

Conclusions

The largest lymph node’s diameter and the tumor percent enhancement of arterial phase on MRI were helpful in determining LNM in pT1‐2 rectal cancer.
Lymph node transplantation for the treatment of lymphedema
Authors: Gould Daniel J , Mehrara Babak J , Neligan Peter , Cheng Ming‐Huei , Patel Ketan M
Published: August 2018

Lymphedema is a complex disease process with deranged lymphatic transport, fluid accumulation and secondary lipedema and fibrosis. This is a challenging disease to treat with a surgical focus on debulking and physiologic strategies. One strategy is the use of vascularized lymph node transplant (VLNT) to improve physiologic lymph clearance. In this article, VLNT is discussed in detail, including mechanisms, combined strategies, and outcomes.
Prognostic value of 18F‐FDG PET/CT parameters in patients who undergo salvage treatments for recurrent squamous cell carcinoma of the larynx and hypopharynx
Authors: Lee Jae Ryung , Almuhaimid Turki M. , Roh Jong‐Lyel , Oh Jungsu S. , Kim Soo‐Jong , Kim Jae Seung , Choi Seung‐Ho , Nam Soon Yuhl , Kim Sang Yoon
Published: August 2018

Background

Recurrent laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC) is commonly associated with poor survival outcomes. We evaluated the prognostic role of 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (18F‐FDG PET/CT) parameters quantitatively measured in patients who underwent salvage treatments for recurrent LHSCC.

Methods

This study involved 100 consecutive LHSCC patients who underwent 18F‐FDG PET/CT for recurrent staging and subsequent salvage treatments. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using 18F‐FDG PET/CT. Cox proportional hazards regression analyses were used to assess the associations between quantitative 18F‐FDG PET/CT parameters and other clinicopathological factors with progression‐free survival (PFS) and overall survival (OS).

Results

Two‐year postsalvage PFS and OS rates were 67.9% and 74.3%, respectively. All 18F‐FDG PET parameters of SUVmax, MTV, and TLG were significantly associated with poor PFS and OS outcomes after salvage treatment (all P < 0.05). Multivariate analyses revealed that recurrence site, MTV (>6.5 mL), and TLG (>17.1 g) were independent variables predictive of PFS. Karnofsky score, SUVmax (>4.0), and TLG (>17.1 g) were the independent prognostic factors for OS.

Conclusions

18F‐FDG PET/CT can be useful in predicting postsalvage recurrence and survival in patients with recurrent LHSCC.
Preparative separation of phloridzin from apple leaves using macroporous resins followed by preparative high‐performance liquid chromatography
Authors: Li Hongjuan , Hou Guige , Li Yuanyuan , Zhao Feng , Cong Wei , Wang Chunhua
Published: August 2018

Phloridzin is one of the major phenolic compounds in apple and has been widely used in medicine for a long time due to its significant biomedical activities. In this article, macroporous resin was used for purification of phloridzin from apple leaves. The HPD‐300 resin was selected for the enrichement of phloridzin according to its high adsorption and desorption capacities. The adsorption kinetics and isotherms were constructed on the HPD‐300 resin and fitted well to the pseudo‐second‐order kinetic model and Langmuir model, respectively. Dynamic adsorption and desorption tests were performed on the column packed with HPD‐300 resin to optimize the operating parameters. After one round treatment with HPD‐300 resin, the purity of phloridzin in the product increased from 11.4 to 50.1% with a recovery yield of 79.3%. Subsequently, preparative high‐performance liquid chromatography was employed for the purification of phloridzin. The purity of phloridzin could reach above 98% after further recrystallization with a recovery yield of 75.8%.
Applications of polydopamine modifications in capillary electrophoretic analysis
Authors: Zhang Hao , Yang Feng‐Qing
Published: August 2018

Mussel‐inspired polydopamine has been widely used in capillary electrophoresis as a facile and universal tool for the surface modification of capillary, mainly due to its versatility, stability, strong adhesiveness, and biocompatibility properties. In this review, the recent development of mussel‐inspired surface chemistry with rapid deposition of polydopamine was introduced, and the recent applications of polydopamine in capillary electrophoresis (2011–July 2018) were summarized into four main aspects, namely, sample pretreatments, functional coatings, codeposition coatings, and intermediate coatings. Further study may be focused on clarifying the mechanisms of polydopamine formation and polydopamine‐assisted codeposition, and expanding coatings methods to plant polyphenols.