bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumption of sugar‐sweetened and artificially sweetened soft drinks and risk of cancers not related to obesity
Authors: Bassett Julie K. , Milne Roger L. , English Dallas R. , Giles Graham G. , Hodge Allison M.
Published: November 2019

Consumption of sugary drinks increases the risk of obesity. Previously, we reported a positive association between sugar‐sweetened soft drink consumption and obesity‐related cancer, but this association was not fully explained by obesity; in contrast, we found no association for consumption of artificially sweetened soft drinks. Our aim was to determine whether the consumption of sugar‐sweetened or artificially sweetened soft drinks was associated with cancers other than those currently identified as being related to obesity. We used data from the Melbourne Collaborative Cohort Study. Participants completed a 121‐item food‐frequency questionnaire at baseline including separate questions about the number of times in the past year they had consumed sugar‐sweetened and artificially sweetened soft drinks. Cox regression models were fitted to estimate hazard ratios and 95% confidence intervals for the risk of cancers not related to obesity. During 19 years of follow‐up, there were 35,109 eligible participants who developed 4,789 cancers not related to obesity. There was no association between frequency of consuming sugar‐sweetened soft drinks and the risk of these cancers, but an unexpected positive association was observed for consumption of artificially sweetened soft drinks. Although, we did not find an association with sugar‐sweetened soft drinks, we previously reported a positive association with obesity‐related cancers, not fully explained by obesity. These findings leave unresolved the question of whether consumption of sugar‐sweetened soft drinks influences cancer risk independently of their influence on body size.
On the impact of exchange rate uncertainty on private investment in Ghana
Authors: Mensah Emmanuel Kwasi , Asamoah Lawrence Adu , Ahiadorme Johnson Worlanyo
Published: November 2019

High levels of private investment are correlated with higher economic growth and development across countries, but questions remain whether this relationship is sustainable given the high levels of exchange rate uncertainty in developing economies albeit other macroeconomic instabilities. This paper examines empirically the impact of real exchange rate uncertainty on private investment in Ghana. We, thus, apply the accelerator theory to investigate the contributing effect of real exchange rate uncertainty on the movement of private investment from the economic standpoint of an import‐dependent economy such as Ghana. The study employs annual time series data from 1980 to 2016. Moreover, we adopt the autoregressive distributed lag model of cointegration where we find evidence of a long‐run positive relationship between positive private investment and real exchange rate uncertainty as well as trade openness. The short‐run evidence provides a confirmation of the impact of inflation, trade, and real exchange rate uncertainty on private investment. Specifically, our results show that there is a positive pass‐through effect from real exchange rate uncertainty to private investment decision in resource allocation. Shocks from lending rate and terms of trade were found to exhibit negative effects on private investment in the short and long run. As a matter of policy, it is imperative for policymakers in developing economies to consider the effect of exchange rate and terms of trade associated with bilateral trade and investment‐related agreements to minimize the effects of contemporaneous shocks from uncertainties.
Effects of Intermittent Administration of Parathyroid Hormone and Parathyroid Hormone‐Related Protein on Fracture Healing: A Narrative Review of Animal and Human Studies
Authors: Yamashita Junro , McCauley Laurie K
Published: November 2019

Intermittent administration of parathyroid hormone (PTH) stimulates skeletal remodeling and is a potent anabolic agent in bone. PTH‐related protein (PTHrP) is anabolic acting on the same PTH1 receptor and is in therapeutic use for osteoporosis. The body of literature for PTH actions in fracture healing is emerging with promising yet not entirely consistent results. The objective of this review was to perform a literature analysis to extract up‐to‐date knowledge on the effects of intermittent PTH and PTHrP therapy in bone fracture healing. A literature search of the PubMed database was performed. Clinical case studies and articles related to “regeneration,” “implant,” and “distraction osteogenesis” were excluded. A narrative review was performed to deliberate the therapeutic potential of intermittent PTH administration on fracture healing. A smaller number of studies centered on the use of PTHrP or a PTHrP analog were also reviewed. Animal studies clearly show that intermittent PTH therapy promotes fracture healing and revealed the strong therapeutic potential of PTH. Human subject studies were fewer and not as consistent as the animal studies yet provide insight into the potential of intermittent PTH administration on fracture healing. Differences in outcomes for animal and human studies appear to be attributed partly to variable doses, fracture sites, age, remodeling patterns, and bone architectures, although other factors are involved. Future studies to examine the dose, timing, and duration of PTH administration will be necessary to further delineate the therapeutic potential of PTH for fracture healing in humans. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health
Authors: Silagi Elizabeth S , Novais Emanuel J , Bisetto Sara , Telonis Aristeidis G , Snuggs Joseph , Le Maitre Christine L , Qiu Yunping , Kurland Irwin J , Shapiro Irving M , Philp Nancy J , Risbud Makarand V
Published: November 2019

Maintenance of glycolytic metabolism is postulated to be required for health of the spinal column. In the hypoxic tissues of the intervertebral disc and glycolytic cells of vertebral bone, glucose is metabolized into pyruvate for ATP generation and reduced to lactate to sustain redox balance. The rise in intracellular H+/lactate concentrations are balanced by plasma-membrane monocarboxylate transporters (MCTs). Using MCT4 null mice and human tissue samples, complemented with genetic and metabolic approaches, we determine that H+/lactate efflux is critical for maintenance of disc and vertebral bone health. Mechanistically, MCT4 maintains glycolytic and tricarboxylic acid (TCA) cycle flux and intracellular pH homeostasis in the nucleus pulposus compartment of the disc, where hypoxia-inducible factor 1α (HIF-1α) directly activates an intronic enhancer in SLC16A3. Ultimately, our results provide support for research into lactate as a diagnostic biomarker for chronic, painful, disc degeneration. © 2019 American Society for Bone and Mineral Research.
Back Pain-Inducing Test, a Novel and Sensitive Screening Test for Painful Osteoporotic Vertebral Fractures: A Prospective Clinical Study
Authors: Jin Huaijian , Ma Xiaoyuan , Liu Yaoyao , Yin Xiang , Zhu Jun , Wang Zhong , Fan Weili , Jin Yufei , Pu Jungang , Zhao Jianhua , Liu Mingyong , Liu Peng
Published: November 2019

To detect painful vertebral fractures (VFs) in back pain populations at risk of osteoporosis, we designed a physical examination test (the Back Pain-Inducing Test [BPIT]) that included three movements: lying supine, rolling over, and sitting up. If back pain is induced during any of these movements, the result is defined as positive, thereby establishing a presumptive diagnosis of painful VFs. Pain severity is quantified using a self-reported numerical rating scale (NRS). The presence or absence of painful VFs is verified by whole-spine magnetic resonance imaging (MRI), the gold standard for final diagnosis. According to the standards for reporting diagnostic accuracy, a real-world, prospective, and observational study was performed on 510 back pain patients (enrolled from a single institute) at risk of osteoporosis. The sensitivity, specificity, and accuracy of the BPIT for identifying painful VFs were 99.1% (95% CI, 97.5% to 99.8%), 67.9% (95% CI, 60.4% to 74.5%), and 89.0%, respectively. The positive and negative predictive values were 86.6% (95% CI, 82.9% to 89.6%) and 97.4% (95% CI, 92.6% to 99.3%), respectively. Cutoff NRS scores for lying supine, rolling over, and sitting up were 3, 0, and 2, respectively. The corresponding area under the receiver operating characteristic curves (AUROCs) of each movement was 0.898 (95% CI, 0.868 to 0.922), 0.884 (95% CI, 0.854 to 0.911), and 0.910 (95% CI, 0.882 to 0.933), respectively. Although the high prevalence of VFs in the enrolled cohort partially limits the external validity of the predictive value in the general population, we conclude that the BPIT is potentially effective for detecting painful VFs in back pain populations at risk of osteoporosis. This test may be used as a stratification tool in decision-making on subsequent imaging procedures: a negative BPIT rules out painful VFs and indicates that an MRI should be spared, whereas a positive BPIT means that an MRI is necessary and is likely to identify painful VFs. © 2019 American Society for Bone and Mineral Research.
SNHG1/miR‐556‐5p/TCF12 feedback loop enhances the tumorigenesis of meningioma through Wnt signaling pathway
Authors: Zhang Yubing , Yu Runze , Li Qingsong , Li Yong , Xuan Tao , Cao Shen , Zheng Jun
Published: November 2019

Meningioma, as a sort of the malignantly intracranial tumors, has captured public attention for its second‐highest morbidity all over the world. Long noncoding RNAs (lncRNAs), including lncRNA SNHG1, have been well known as essential players in the development of diverse cancers. However, the biological effect and regulatory mechanism of SNHG1 have not been mentioned in meningioma. In this work, it was discovered that SNHG1 was overexpressed in meningioma cell lines. SNHG1 deficiency restrained cell growth as well as accelerated apoptosis. Then mechanism experiments demonstrated that SNHG1 functioned as the role of sponging miR‐556‐5p and negatively regulated miR‐556‐5p expression. Moreover, it was verified that TCF12 is the direct downstream target of miR‐556‐5p. Furthermore, SNHG1/miR‐556‐5p/TCF12 axis promoted cell proliferation and suppressed cell apoptosis in meningioma via activating the Wnt signaling pathway. In the end, it was confirmed that TCF12 expression was positively regulated by SNHG1, and TCF12 could promote transcription of SNHG1 through binding with the promoter region of SNHG1. In conclusion, the SNHG1/miR‐556‐5p/TCF12 feedback loop promotes the tumorigenesis of meningioma through the Wnt signaling pathway.
NR2F1‐AS1 regulated miR‐423‐5p/SOX12 to promote proliferation and invasion of papillary thyroid carcinoma
Authors: Yang Chuanjia , Liu Zhen , Chang Xiaoying , Xu Weixue , Gong Jian , Chai Fang , Cui Dongxu
Published: November 2019

Papillary thyroid carcinoma (PTC) is an aggressive histological subtype of thyroid carcinoma (THCA), whose occurrence rate is high. The participation of long noncoding RNAs in the pathologies of cancers has attracted significant attention during the past decades. The purpose of the current study is to investigate the role of NR2F1 antisense RNA 1 (NR2F1‐AS1) in PTC. The expression of NR2F1 in THCA samples was analyzed by bioinformatics tool gene expression profiling interactive analysis. Levels of NR2F1‐AS1, microRNA‐423‐5p (miR‐423‐5p), and SRY‐box 12 (SOX12) were evaluated by a quantitative reverse transcription‐polymerase chain reaction and Western blot. The impact of NR2F1‐AS1 on PTC cell proliferation and invasion was assessed by Cell Counting Kit‐8, EdU, and Transwell invasion assays. The interactions among NR2F1‐AS1, miR‐423‐5p, and SOX12 were determined by RNA immunoprecipitation and luciferase reporter assays. Consequently, we found that NR2F1‐AS1 and SOX12 levels were elevated in PTC, whereas miR‐423‐5p was downregulated in PTC cells. Functionally, NR2F1‐AS1 silence led to reduced proliferation and invasion of PTC cells. Mechanistically, NR2F1‐AS1 interacted with miR‐423‐5p to induce SOX12 expression in PTC cells. In conclusion, the present study firstly stated that NR2F1‐AS1 regulated miR‐423‐5p/SOX12 to promote proliferation and invasion of PTC, indicating NR2F1‐AS1 as a potential novel target for the molecular‐targeted therapy of PTC.
FOXO3 gene polymorphisms influence the risk of acute lymphoblastic leukemia in Chinese children
Authors: Yang Xu , Wu Xuedong , Fang Na , Liu Xiaoping , Liu Xiaodan , Yang Lihua , Huang Ke , Luo Ailing , Cai Mansi , Wu Fan , Jiang Hua , Xu Ling
Published: November 2019

Acute lymphoblastic leukemia (ALL) is the most frequently diagnosed cancer in children and single‐nucleotide polymorphisms (SNPs) in certain genes influence risk of ALL. Although FOXO3 had been demonstrated to be involved leukemia, the role of FOXO3 polymorphisms was still not clear. In the present study, we explored the association of FOXO3 SNPs with ALL risk in Chinese children. We genotyped four polymorphisms (rs17069665 A>G, rs4945816 T>C, rs4946936 C>T, and rs9400241 A>C) of FOXO3 in 425 ALL cases and 1339 health controls. The associations were estimated by odds ratios (ORs) with their 95% confidence intervals (CIs). Further analyses were performed to explore associations of rs17069665 and rs9400241 with ALL susceptibility in terms of age, gender, immunophenotype, minimal residual disease (MRD), and other clinical characteristics. We found rs17069665 related to the increased ALL risk (OR = 1.76; 95% CI = 1.02‐3.04), rs9400241 related to decreased ALL risk (OR = 0.80; 95% CI = 0.64‐0.99). The effects of rs17069665 on ALL risk were more predominant in males and children < 10 years, and patients with lower rates of platelet or neutrophil. As for rs9400241, the effects were more predominant in children < 10 years, and in patients with pre B ALL, positive MRD, anemia, or hepatomegaly. In conclusion, FOXO3 gene polymorphisms influence the risk of ALL in children and might be a potential biomarker for ALL susceptibility.
lncRNA GAS5‐promoted apoptosis in triple‐negative breast cancer by targeting miR‐378a‐5p/SUFU signaling
Authors: Zheng Shipeng , Li Mengquan , Miao Keke , Xu Han
Published: November 2019

Purpose

Long‐chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth‐stasis specific transcript 5 (GAS5) on triple‐negative breast cancer (TNBC).

Methods

Quantitative real‐time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a‐5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo.

Results

In this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum‐free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR‐378 could directly bind to each other. Moreover, the miR‐378a‐5p target of SUFU could promote lncRNA GAS5‐induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA‐231R could enhance the sensitivity of TNBC to PTX.

Conclusion

The above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR‐378a‐5p/SUFU signaling.
Molecular chaperone HspB2 inhibited pancreatic cancer cell proliferation via activating p53 downstream gene RPRM, BAI1, and TSAP6
Authors: Yu Ze , Wang Hao , Fang Yilin , Lu Liangliang , Li Minghao , Yan Bingru , Nie Yuzhe , Teng Chunbo
Published: November 2019

Heat shock proteins (HSPs) were known as the molecular chaperones, which play a pivotal role in the protein quality control system, ensuring correct folding of proteins, and facilitating the correct refolding of damaged proteins via the transient interaction with their substrate proteins. They also practice in the regulation of cell cycles and are involved in apoptosis. We found that HspB2 was almost completely silent in pancreatic cancer and few studies investigated the role of HspB2 in cancer cells, particularly in pancreatic cancer. Here, we reported that HspB2 effectively inhibited cell proliferation in Panc‐1 cells. Specifically, we demonstrated that HspB2 could combine mut‐p53 and change the DNA binding site of mutant p53, subsequently upregulated the expression of RPRM, BAI‐1, and TSAP6 which were the downstream genes of wt‐p53, participate in mediating downstream responses to p53, including inhibiting cell proliferation and angiogenesis. The main aim of this study is to investigate the relationship between HspB2 and p53, and provide a novel treatment strategy for pancreatic cancer.
DNA methylation and gene expression profiles characterize epigenetic regulation of lncRNAs in colon adenocarcinoma
Authors: Li Zhijin , Tan Hua , Yu Hai , Deng Zhong , Zhou Xiaobo , Wang Maode
Published: November 2019

The long noncoding RNAs (lncRNAs) are associated with tumorigenesis and progression of cancer. While DNA methylation is a common epigenetic regulator of gene expression, the methylation of lncRNAs was rarely studied. To address this gap, we integrated DNA methylation and RNA‐seq data to characterize the landscape of lncRNA methylation in colon adenocarcinoma (COAD). We collected and analyzed the lncRNA expression and methylation data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia to identify the epigenetically regulated lncRNAs. We further investigated the biological and clinical relevance of the identified lncRNAs via bioinformatics analysis. We identified 20 epigenetically upregulated lncRNAs in COAD, including several well‐studied lncRNAs whose methylation regulation were poorly investigated, such as PVT1 and UCA1. We also revealed several novel tumor‐associated lncRNAs in COAD, including GATA2‐As1 and CYTOR. Next, we explored their biology function using gene set enrichment analysis and competitive endogenous RNA analysis. We characterized the methylation landscape of lncRNA in COAD and identified 20 epigenetically upregulated lncRNAs. Our findings will shed new light on the epigenetic regulation of lncRNA expression by DNA methylation.
FASTKD2 promotes cancer cell progression through upregulating Myc expression in pancreatic ductal adenocarcinoma
Authors: Fang Rui , Zhang Bin , Lu Xiaoming , Jin Xin , Liu Tao
Published: November 2019

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers of the digestive system. Despite the development of novel therapeutic methods, including chemotherapy, radiotherapy, and molecular targeted therapy, the incidence rate of PDAC is almost equal to the mortality rate with 5‐year overall survival rate less than 5%. Kras mutation is found in 95% of patient with PDAC specimens, but targeting Kras mutation do not benefit patients with pancreatic cancer in preclinical trials. c‐Myc is one of the main effector molecules of the Kras signaling pathway. In this study, we found that dysregulation of FAST kinase–domain‐containing protein 2 (FASTKD2) resulted in the poor prognosis of patients with PDAC. Then, we showed that FASTKD2 promoted pancreatic cancer cell proliferation and invasion. Importantly, we demonstrated that c‐Myc was transcriptionally increased by FASTKD2/BRD4 axis and responsible for FASTKD2‐mediated tumor growth and invasion in pancreatic cancer cells. Collectively, this study uncovered that FASTKD2 promoted cancer cell progression through upregulating Myc expression in pancreatic cancer. FASTKD2 might be a potential target for pancreatic cancer therapy.
LINC00958 facilitates cervical cancer cell proliferation and metastasis by sponging miR‐625‐5p to upregulate LRRC8E expression
Authors: Wang Lifeng , Zhong Yanbo , Yang Baohua , Zhu Yunheng , Zhu Xiuxiang , Xia Ziyin , Xu Jun , Xu Ling
Published: November 2019

Accepted as a malignant tumor worldwide, cervical cancer (CC) has attracted much attention for its high incidence and mortality rates. Previous studies have elucidated the critical regulatory function that long noncoding RNAs (lncRNAs) exert on the tumorigenesis and progression of diverse tumors. Although multiple investigations have depicted that LINC00958 has a great impact on the complex biological process of many cancers, knowledge concerning the regulatory role of LINC00958 in CC remains limited and needs to be further explored. In our study, LINC00958 expression was evidently overexpressed in CC tissues and cells. Besides this, LINC00958 negatively regulated miR‐625‐5p expression and was verified to bind with miR‐625‐5p in CC. Subsequently, it was testified by a series of experiments that LINC00958 promotes CC cell proliferation and metastasis by sponging miR‐625‐5p. Furthermore, the leucine‐rich repeat containing the eight family member E (LRRC8E) could bind with miR‐625‐5p, and its expression was negatively modulated by miR‐625‐5p, whereas positively regulated by LINC00958 in CC. Final rescue assays verified the effects of LINC0095/LRRC8E interaction and miR‐625‐5p/LRRC8E interaction on CC cell proliferation and metastasis. Collectively, LINC00958 facilitates CC cell proliferation and metastasis via the miR‐625‐5p/LRRC8E axis.
BTN3A2 serves as a prognostic marker and favors immune infiltration in triple‐negative breast cancer
Authors: Cai Peian , Lu Zhenhui , Wu Jianjun , Qin Xiong , Wang Zetao , Zhang Zhi , Zheng Li , Zhao Jinmin
Published: November 2019

Immune infiltration is reported to be highly associated with tumor progress. Since butyrophilin subfamily 3 member A2 (BTN3A2) serves as a crucial mediator in immune activation, we aimed to investigate the correlation of BTN3A2 in immune infiltration and tumor prognosis via extensive‐cancer analysis. The levels of BTN3A2 expression in extensive cancers were analyzed with Oncomine and TIMER databases. Univariate cox and multivariate cox regression analyses were conducted to assess the associations of BTN3A2 to prognosis of various cancers. The correlations of BTN3A2 with immune infiltration were assessed by TIMER database. It suggested that BTN3A2 was a potential prognosis signature for breast cancer (BRCA) and ovarian cancer (OV). However, immune infiltrations were highly correlated with BTN3A2 in triple‐negative breast cancer (TNBC), compared with OV and other subtypes of BRCA. Multivariate cox regression analysis revealed that BTN3A2 was an independently prognostic signature of TNBC, as well as weighted correlation network analysis suggested BTN3A2 was only correlated with TNBC, rather than other subtypes of BRCA. Immune cell subtypes correlation analysis showed that BTN3A2 was highly correlated with general T, CD8+ T, T helper type 1, exhausted T cells, and dendritic cells in TNBC. And the coexpression geneset of BTN3A2 was mainly involved in T‐cell receptor interaction and the nuclear factor‐κB (NF‐κB) signaling pathway. Collectively, BTN3A2 that was positively associated with better prognosis could be served as a special diagnostic and independently prognostic marker for TNBC by regulating the T‐cell receptor interaction and NF‐κB signaling pathways.
Targeting BAX ubiquitin‐binding sites reveals that BAX activation is essential for its ubiquitin‐dependent degradation
Authors: Peng Rui , Zhu Jialin , Deng Shujin , Shi Hui , Xu Shutao , Wu Hongjuan , Zou Fangdong
Published: November 2019

BAX is an important proapoptotic protein of the BCL‐2 family, and its stability is essential for the regulation of the mitochondrial apoptotic pathway. A previous study revealed that BAX could undergo degradation through the ubiquitin‐proteasome pathway. In this study, we identified two lysine sites, K21 and K123, that were critical ubiquitin‐binding sites in BAX. Mutation of these two sites prolonged the half‐life of BAX and also affected its proapoptotic ability. Intriguingly, we found that ABT‐737, a BCL‐2 inhibitor, significantly enhanced TRAIL‐induced BAX degradation in HCT116 cells and increased TRAIL‐induced apoptosis in the HCT116 only with the BAX K21R/K123R mutant, not other BAX mutants. In addition, overexpression of PARKIN, an E3 ubiquitin ligase targeting BAX, dramatically decreased BAX protein level when only treated with ABT‐737 in HCT116 cells. Therefore, we speculated that BAX activation is essential for its ubiquitin‐dependent degradation.
KRAS mutation and abnormal expression of Cripto‐1 as two potential candidate biomarkers for detection of colorectal cancer development
Authors: Igder Somayeh , Mohammadiasl Javad , Azadpour Shima , Mansouri Esrafil , Ashktorab Hassan , Mokarram Pooneh
Published: November 2019

Colorectal cancer (CRC), regardless of standard procedures of treatment and screening, is still considered one of the deadliest cancers in the Western world, and in economically developed Asian countries, especially Iran. The current study was undertaken to investigate whether changes in the level of Cripto‐1 (CR‐1) expression and KRAS mutations have a cumulative effect on the onset and progression of CRC. Fifty colorectal tissue samples, including 35 colorectal carcinomas with matching adjacent mucosa, and 15 colorectal adenomas, were chosen for analysis. Twenty‐five CRC biopsies and 15 adenoma were analyzed for KRAS mutations by DNA sequencing (Sanger sequencing), and all 50 patients (35 CRCs and 15 adenomas) were evaluated by immunohistochemistry for the CR‐1 protein expression. The inducible somatic KRAS mutation (G12D) was observed in nine (36%) of CRC patients, and in two (13.3%) of adenoma patients. The CR‐1 expression level in both adenomas (P < .05) and carcinomas (P < .001), were significantly different, compared with the matching adjacent mucosa. The intensity of CR‐1 staining in adenomas was less than the intensity of staining, detected in the CRCs (P < .001). The G12D KRAS mutation and CR‐1 abnormalities are significantly associated as two signature biomarkers with potential clinical characteristics for the detection of CRC development.
Nano CuO–Ag‐catalyzed synthesis of some novel pyrano[2,3‐d] pyrimidine derivatives and evaluation of their bioactivity
Authors: Poola Sreelakshmi , Shaik Mahammad S. , Sudileti Murali , Yakkate Subbarao , Nalluri Vedasree , Chippada Apparao , Cirandur Suresh R.
Published: November 2019

A simple, highly efficient, and green method is developed for the synthesis of pyrano[2,3‐d] pyrimidine derivatives via Knoevenagel and Michael addition in the presence of nano CuO–Ag as a catalyst. The structures of synthesized target compounds 5a–l were confirmed by spectral and elemental analysis and were screened for their antioxidant activity by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH), H2O2, and NO methods. Their antibacterial activity against Gram‐negative bacteria Pseudomonas aeruginosa and Escherichia coli, against Gram‐positive bacteria such as Bacillus subtilis and Staphylococcus aureus, and antifungal activity against Candida albicans and Candida glabrata was also evaluated. The compounds showed higher bacterial activity than the standard used. Compounds 5b, 5d, 5g, 5h, and 5i exhibited higher free radical scavenging activity than the standard butylated hydroxy toluene (BHT). Compounds 5b, 5d, and 5h showed higher activity on Gram‐positive bacteria, and compounds 5b, 5d, 5h, and 5i showed higher activity on Gram‐negative bacteria than that of standard tetracycline. Compounds 5b, 5j, and 5l showed much higher antifungal activity against Candida globrata and C. albicans than that of standard Griseofulvin.
Evaluation of the clinical performance of the HISCL‐5000 analyzer in the detection of Krebs von den Lungen‐6 antigen and its diagnostic value in interstitial lung disease
Authors: Wang Jingxian , Huang Zhifeng , Xue Mingshan , Huang Huimin , Zheng Xiaomao , Zhong Nanshan , Sun Baoqing
Published: November 2019

Background

The sputum saccharide chain antigen (Krebs von den Lungen‐6 [KL‐6]) is a serum biomarker of lung injury. We aimed to evaluate the clinical performance of the automated immunoassay analyzer HISCL‐5000 in detecting KL‐6 by comparing it with LUMIPULSE G1200 and determine the diagnostic value of KL‐6 in interstitial lung disease (ILD).

Methods

A total of 145 serum samples from patients were tested using the two automated immunoassay analyzers in parallel.

Results

With a cutoff level of 500 U/mL, comparing the two systems, the agreement, sensitivity, specificity, and kappa value were 99.20%, 100%, 98.63%, and 0.984 (95% CI, 0.952‐1.000), respectively. Spearman's correlation and ICC showed that there was a strong correlation between serum KL‐6 levels measured by the two systems (rS = .991 [95% CI, 0.981‐0.995], ICC = 0.984 [95% CI, 0.978‐0.989], P < .01). The clinical diagnosis agreement rate in both systems was >80%. The kappa value was 0.707 (95% CI, 0.582‐0.832; SYSTEM B) and 0.707 (95% CI, 0.588‐0.826; SYSTEM A). The KL‐6 level in the ILD group (1339.5, 662.5‐2363) was significantly higher than that in the non‐ILD groups (252, 158.5‐353; Mann‐Whitney U = 381.5, P < .01), and the KL‐6 level (1558, 726‐2772.5) in the ILD group detected by SYSTEM A was significantly higher than that in the lung cancer group (339, 207‐424), other respiratory disease group (249, 194‐366), and control group (198, 131.5‐297; Kruskal‐Wallis H = 63.19, P < .01).

Conclusions

HISCL‐5000 showed well‐concordant results with those of HISCL‐5000 in the KL‐6 tests. In patients with ILD, KL‐6 showed a good diagnostic performance.
Clinical significance of serum bilirubin in primary Sjögren syndrome patients
Authors: Zhang Zunni , Su Qisheng , Zhang Liqian , Yang Zheng , Qiu Yuling , Mo Wuning
Published: November 2019

Objective

The purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS).

Patients and methods

A total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed.

Results

Serum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = −.406, P < .001; r = −.206, P = .026; r = −.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR.

Conclusions

This study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow‐up visits of the patients with pSS.
Posttranscriptional regulation of MMP‐9 by HuR contributes to IL‐1β‐induced pterygium fibroblast migration and invasion
Authors: Cui Yu‐Hong , Feng Qing‐Yang , Liu Qun , Li Hong‐Yang , Song Xi‐Ling , Hu Zi‐Xuan , Xu Zhi‐Yi , Li Jia‐Hui , Li Mei‐Jun , Zheng Wen‐Lin , Li Zhi‐Jie , Pan Hong‐Wei
Published: November 2019

Inflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase‐9 (MMP‐9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The influence of interleukin‐1β (IL‐1β) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP‐9 production was determined with qRT‐PCR and gelatin zymography. The interaction between HuR and MMP‐9 was investigated with RNP immunoprecipitation (IP) followed by RT‐PCR and messenger RNA (mRNA) stability analysis. HuR and MMP‐9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL‐1β could increase the expression and nucleus–cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL‐1β on PTF migration and MMP‐9 production. HuR bound to MMP‐9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP‐9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL‐1β on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.
Guess Who Buys Cheap? The Effect of Consumers’ Goal Orientation on Product Preference
Authors: Choi Woo Jin , Sun Haoying , Liu Yan (Lucy) , Chen Haipeng (Allan)
Published: November 2019

The current research examines how goal orientation affects consumer preference among products with different prices. We argue that a less expensive product may have not only lower perceived quality but also greater perceived quality variability. This greater perceived variability provides the opportunity for optimistic, promotion‐oriented consumers to overestimate the quality of the less expensive product. This effect is weaker, however, for a more expensive product that consumers perceive to have less quality variability and which thus provides less room for quality overestimation. As a result, we hypothesize that promotion‐oriented consumers, as compared to prevention‐oriented consumers, will demonstrate a stronger preference for a less expensive product. In a field study and two laboratory experiments, we obtain empirical support both for the hypothesized effect of consumers’ goal orientation on their product preference and for its underlying process. We conclude with a discussion of the theoretical and practical implications of our results.
The relationship between the BMI‐adjusted weight loss grading system and quality of life in patients with incurable cancer
Authors: Daly Louise , Dolan Ross , Power Derek , Ní Bhuachalla Éadaoin , Sim Wei , Fallon Marie , Cushen Samantha , Simmons Claribel , McMillan Donald C. , Laird Barry J. , Ryan Aoife
Published: November 2019

Background

Weight loss (WL) has long been recognized as an important factor associated with reduced quality of life (QoL) and reduced survival in patients with cancer. The body mass index (BMI)‐adjusted weight loss grading system (WLGS) has been shown to be associated with reduced survival. However, its impact on QoL has not been established. The aim of this study was to assess the relationship between this WLGS and QoL in patients with advanced cancer.

Methods

A biobank analysis was undertaken of adult patients with advanced cancer. Data collected included patient demographics, Eastern Cooperative Oncology Group performance status, and anthropometric parameters (BMI and %WL). Patients were categorized according to the BMI‐adjusted WLGS into one of five distinct WL grades (grades 0–4). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐C30. The Kruskal–Wallis test and multivariate logistic regression analyses were used to assess the relationship between the WLGS and QoL scores. Overall survival was assessed using Kaplan–Meier curve and Cox proportional hazard models.

Results

A total of 1027 patients were assessed (51% male, median age: 66 years). Gastrointestinal cancer was most prevalent (40%), and 87% of patients had metastatic disease. Half (58%) of patients had a WL grade of 0–1, while 12%, 20%, and 10% had WL grades of 2, 3, and 4, respectively. Increasing WL grades were significantly associated with poorer QoL functioning and symptoms scales (all P < 0.05). Physical, role, and emotional functioning decreased by a median of >20 points between WL grade 0 and WL grade 4, while appetite loss, pain, dyspnoea, and fatigue increased by a median score >20 points, indicative of a large clinical significant difference. Increasing WL grades were associated with deteriorating QoL summary score. WL grades 2, 3, and 4 were independently associated with a QoL summary score below the median (<77.7) [odds ratio (OR) 1.69, P = 0.034; OR 2.06, P = 0.001; OR 4.29, P < 0.001, respectively]. WL grades 3 and 4 were independently associated with reduced overall survival [hazard ratio 1.54 (95% confidence interval: 1.22–1.93), P < 0.001 and hazard ratio 1.87 (95% confidence interval: 1.42–2.45), P < 0.001, respectively].

Conclusions

Our findings support that the WLGS is useful in identifying patients at risk of poor QoL that deteriorates with increasing WL grades. WL grade 4 is independently associated with a particularly worse prognosis and increased symptom burden. Identification and early referral to palliative care services may benefit these patients.
Reactive oxygen species‐induced heterogeneous photocatalytic degradation of organic pollutant Rhodamine B by copper and zinc aluminate spinels
Authors: Vieira Yasmin , Leichtweis Jandira , Foletto Edson Luiz , Silvestri Siara
Published: November 2019

BACKGROUND

The importance of potable water is immeasurable and its contamination by pollutants is a serious environmental problem. Rhodamine B (RhB), one such pollutant, is highly toxic to various organisms and may cause long‐term undesirable effects when improperly disposed of. Thus, development of an efficient treatment technique is necessary. Among the new oxidation methods, heterogeneous photocatalysis is an emerging pollutant destructive technology.

RESULTS

The photocatalytic activities of copper (Cu) and zinc (Zn) aluminate spinels (CuAl2O4 and ZnAl2O4) was evaluated. Chemical and physical properties were considered, and ZnAl2O4 showed higher RhB degradation efficiency (73.90% in only 10 min) than CuAl2O4 (51.95% in 10 min), reaching up to 100% in 30 min. According to results, a further RhB catalytic degradation pathway by ZnAl2O4 was monitored by UV‐visible spectrometry and ultra‐high performance liquid chromatography coupled to diode array detection (UHPLC‐DAD) analysis. When applied to wastewater from gemstone beneficiation, containing elevated RhB concentration, the ZnAl2O4 caused 88% color removal in 120 min and its pollutant removal rate was 18 times greater than the commonly used ZnO.

CONCLUSION

The superior performance of ZnAl2O4 can be attributed to better pore properties, responsible for providing more active sites. These identified reactive oxygen species (ROS)‐induced interactions and the species demonstrated that degradation occurs due to generation of O2•‐ and h+. Thus, ZnAl2O4 proved to be an efficient photocatalyst for quick RhB pollutant degradation with promising potential for real wastewater treatment applications. © 2019 Society of Chemical Industry
Methyl lactate production from levoglucosan by using Sn‐Beta and H‐Beta catalysts
Authors: Luo Dan , Liu Shengnan , Yin Wang , Xia Shuqian
Published: November 2019

BACKGROUND

Fast pyrolysis of lignocellulosics has provided an abundant sugar source for production of value‐added chemicals, and levoglucosan is the most representative sugar in pyrolysis liquid (bio oil). This paper explored the potential for producing methyl lactate from levoglucosan by employing the mixed catalysts of zeolite tin beta (Sn‐Beta) and zeolite hydrogen beta (H‐Beta).

RESULTS

Under the optimal conditions (at 200 °C and mixed catalysts with H‐Beta:Sn‐Beta ratio of 1:5), the yield of methyl lactate obtained from levoglucosan conversion was as high as 35%. And the yield was comparable to that of methyl lactate obtained from glucose conversion under the similar conditions (at 200 °C and pure Sn‐Beta). In order to investigate the reason, a contrasting experiment with glucose as substrate also was carried out with the mixed catalysts. The results indicated that during the levoglucosan conversion process, ‘the methanolysis of levoglucosan’ was likely to compete with ‘the dehydration of glucose’ for the Brønsted acid sites of H‐Beta. In addition, the catalytic functions of H‐Beta and Sn‐Beta, and the reaction pathway were deeply investigated through tracking and comparing the conversion of levoglucosan over mixed H‐Beta/Sn‐Beta and over pure Sn‐Beta catalysts, respectively.

CONCLUSION

The appropriately lower ratio of H‐Beta:Sn‐Beta and relatively higher temperature were favorable for the reaction. H‐Beta containing Brønsted acid could remarkably accelerate the conversion of levoglucosan and methyl‐glucosides to glucose. Sn‐Beta containing Lewis acid mainly promoted the retro‐aldol condensation of glucose and formation of methyl lactate. © 2019 Society of Chemical Industry
Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men
Authors: Shieh Eugenie , Marzinke Mark A , Fuchs Edward J , Hamlin Allyson , Bakshi Rahul , Aung Wutyi , Breakey Jennifer , Poteat Tonia , Brown Todd , Bumpus Namandjé N , Hendrix Craig W
Published: November 2019

Introduction

Oral HIV Pre‐Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender‐affirming hormone treatment (GAHT), TDF/FTC‐oestrogen interactions may negatively affect HIV prevention or gender‐affirming goals. Our aim was to evaluate any pharmacokinetic drug‐drug interaction between GAHT and TDF/FTC.

Methods

We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV‐DP) and FTC triphosphate (FTC‐TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre‐dose, one, two, four, six, eight and twenty‐four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non‐parametric tests. Blood and colon tissue were also obtained to assess kinase expression.

Results

Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24‐hr area under the concentration‐time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration‐time curve) were all correlated.

Conclusions

GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.
Differentiated HIV care in South Africa: the effect of fast‐track treatment initiation counselling on ART initiation and viral suppression as partial results of an impact evaluation on the impact of a package of services to improve HIV treatment adherence
Authors: Pascoe Sophie JS , Fox Matthew P , Huber Amy N , Murphy Joshua , Phokojoe Mokgadi , Gorgens Marelize , Rosen Sydney , Wilson David , Pillay Yogan , Fraser‐Hurt Nicole
Published: November 2019

Introduction

In response to suboptimal adherence and retention, South Africa’s National Department of Health developed and implemented National Adherence Guidelines for Chronic Diseases. We evaluated the effect of a package of adherence interventions beginning in January 2016 and report on the impact of Fast‐Track Treatment Initiation Counselling (FTIC) on ART initiation, adherence and retention.

Methods

We conducted a cluster‐randomized mixed‐methods evaluation in 4 provinces at 12 intervention sites which implemented FTIC and 12 control facilities providing standard of care. Follow‐up was by passive surveillance using clinical records. We included data on subjects eligible for FTIC between 08 Jan 2016 and 07 December 2016. We adjusted for pre‐intervention differences using difference‐in‐differences (DiD) analyses controlling for site‐level clustering.

Results

We enrolled 362 intervention and 368 control arm patients. Thirty‐day ART initiation was 83% in the intervention and 82% in the control arm (RD 0.5%; 95% CI: −5.0% to 6.0%). After adjusting for baseline ART initiation differences and covariates using DiD we found a 6% increase in ART initiation associated with FTIC (RD 6.3%; 95% CI: −0.6% to 13.3%). We found a small decrease in viral suppression within 18 months (RD −2.8%; 95% CI: −9.8% to 4.2%) with no difference after adjustment (RD: −1.9%; 95% CI: −9.1% to 5.4%) or when considering only those with a viral load recorded (84% intervention vs. 86% control). We found reduced crude 6‐month retention in intervention sites (RD −7.2%; 95% CI: −14.0% to −0.4%). However, differences attenuated by 12 months (RD: −3.6%; 95% CI: −11.1% to 3.9%). Qualitative data showed FTIC counselling was perceived as beneficial by patients and providers.

Conclusions

We saw a short‐term ART‐initiation benefit to FTIC (particularly in districts where initiation prior to intervention was lower), with no reductions but also no improvement in longer‐term retention and viral suppression. This may be due to lack of fidelity to implementation and delivery of those components that support retention and adherence. FTIC must continue to be implemented alongside other interventions to achieve the 90‐90‐90 cascade and fidelity to post‐initiation counselling sessions must be monitored to determine impact on longer‐term outcomes. Understanding the cost‐benefit and role of FTIC may then be warranted.