bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA circFOXO3 regulates KDM2A by targeting miR‐214 to promote tumor growth and metastasis in oral squamous cell carcinoma
Authors: Ai Yilong , Wu Siyuan , Zou Chen , Wei Haigang 
Published: June 2021

AbstractOral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR‐214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor‐side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR‐214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR‐214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR‐214 to up‐regulate the expression of KDM2A, thus promotes tumor progression in OSCC.
MMP‐7 affects peritoneal ultrafiltration associated with elevated aquaporin‐1 expression via MAPK/ERK pathway in peritoneal mesothelial cells
Authors: Yin Yue , Zhang Fen , Zheng Zhuojun , Xiao Zhiwen , Yang Qiaomu , Gong Nirong , Zhou Jia , Zuo Daming , Ai Jun 
Published: June 2021

AbstractPeritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long‐term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP‐7 levels markedly increased in the patients with PD, and the elevated MMP‐7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP‐7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP‐7 activated mitogen‐activated protein kinases (MAPKs)‐extracellular signal‐regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin‐1 (AQP‐1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP‐7‐mediating AQP‐1 up‐regulation and cellular homeostasis. In summary, all the findings indicate that MMP‐7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP‐7 might be a non‐invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.
PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer
Authors: Chen Yongxia , Jia Yunlu , Mao Misha , Gu Yifeng , Xu Chenpu , Yang Jingjing , Hu Wenxian , Shen Jun , Hu Dengdi , Chen Cong , Li Zhaoqing , Chen Lini , Ruan Jian , Shen Peng , Zhou Jichun , Wei Qun , Wang Linbo 
Published: June 2021

AbstractAdriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours. Here, we found higher PLAC8 expression was correlated with worse outcome and aggressive phenotype in breast cancer. Breast cancer patients with higher PLAC8 expression showed potential ADM resistance. In vitro experiments further confirmed that PLAC8 inhibited by siRNA or enforced overexpression by infecting pcDNA3.1(C)‐PLAC8 plasmid correspondingly decreased or increased ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF‐7/ADMR cell blocked the accumulation of the autophagy‐associated protein LC3 and resulted in cellular accumulation of p62. Rapamycin‐triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3‐MA enhanced ADM resistance. 3‐MA and PLAC8 could synergistically cause ADM resistance via blocking the autophagy process. Additionally, the down‐regulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Thus, our findings suggest that PLAC8, through the participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62 pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.
The increased expression and aberrant methylation of SHC1 in non–small cell lung cancer: Integrative analysis of clinical and bioinformatics databases
Authors: Liang Yicheng , Lei Yangyang , Du Minjun , Liang Mei , Liu Zixu , Li Xingkai , Gao Yushun 
Published: June 2021

AbstractDespite the previous evidence showing that SHC adaptor protein 1 (SHC1) could encode three distinct isoforms (p46SHC, p52SHC and p66SHC) that function in different activities such as regulating life span and Ras activation, the precise underlying role of SHC1 in lung cancer also remains obscure. In this study, we firstly found that SHC1 expression was up‐regulated both in lung adenocarcinoma (LUAD) and in lung squamous cell carcinoma (LUSC) tissues. Furthermore, compared to patients with lower SHC1 expression, LUAD patients with higher expression of SHC1 had poorer overall survival (OS). Moreover, higher expression of SHC1 was also associated with worse OS in patients with stages 1 and 2 but not stage 3 lung cancer. Significantly, the analysis showed that SHC1 methylation level was associated with OS in lung cancer patients. It seemed that the methylation level at specific probes within SHC1 showed negative correlations with SHC1 expression both in LUAD and in LUSC tissues. The LUAD and LUSC patients with hypermethylated SHC1 at cg12473916 and cg19356022 probes had a longer OS. Therefore, it is reasonable to conclude that SHC1 has a potential clinical significance in LUAD and LUSC patients.
Evidence of a gabapentinoid and diuretic prescribing cascade among older adults with lower back pain
Authors: Read Stephanie H. , Giannakeas Vasily , Pop Paula , Bronskill Susan E. , Herrmann Nathan , Chen Simon , Luke Miles J. , Wu Wei , McCarthy Lisa M. , Austin Peter C. , Normand Sharon‐Lise , Gurwitz Jerry H. , Stall Nathan M. , Savage Rachel D. , Rochon Paula 
Published: June 2021

AbstractBackground/ObjectivesGabapentinoids are commonly prescribed to relieve pain. The development of edema, an established adverse effect of gabapentinoids, may lead to a potentially harmful prescribing cascade whereby individuals are subsequently prescribed diuretics and exposed to diuretic‐induced adverse events. The frequency of this prescribing cascade is unknown. Our objective was to measure the association between new dispensing of a gabapentinoid and the subsequent dispensing of a diuretic in older adults with new low back pain.DesignPopulation‐based cohort study.SettingOntario, Canada.ParticipantsA total of 260,344 community‐dwelling adults aged 66 years or older, newly diagnosed with low back pain between April 1, 2011, and March 31, 2019.MeasurementsExposure status was assigned using dispensed medications in the 1 week after low back pain diagnosis. Older adults newly dispensed a gabapentinoid (N = 7867) were compared with older adults who were not newly dispensed a gabapentinoid (N = 252,477). Hazard ratios (HRs) with 95% confidence intervals (CIs) for dispensing of a diuretic within 90 days of follow‐up among older adults prescribed gabapentin relative to those who were not.ResultsOlder adults newly dispensed a gabapentinoid had a higher risk of being subsequently dispensed a diuretic within 90 days compared with older adults who were not prescribed a gabapentinoid (2.0% vs. 1.3%). After covariate adjustment, new gabapentinoid users had a higher rate of being dispensed a diuretic compared with those not prescribed a gabapentinoid (HR: 1.44, 95% CI: 1.23, 1.70). The rate of diuretic prescription among new gabapentinoid users increased with increasing gabapentinoid dosages.ConclusionsWe have demonstrated the presence of a potentially inappropriate and harmful prescribing cascade. Given the widespread use of gabapentinoids, the population‐based scale of this problem may be substantial. Increased awareness of this prescribing cascade is required to reduce the unnecessary use of diuretics and the exposure of patients to additional adverse drug events.
What matters to older adults? Exploring person‐centred care during and after transitions between hospital and home
Authors: Nilsen Elin Rogn , Hollister Brooke , Söderhamn Ulrika , Dale Bjørg 
Published: June 2021

AbstractAims and objectivesTo explore person‐centred care provided to a group of older adults (65+) by understanding their experiences of care received, their participation in care and what matters to them during and after the transition process between hospital and home.BackgroundAlthough facilitating person‐centred care (PCC) has gained increasing importance globally over the last few decades, its practical implementation has been challenging. This has caused difficulties in determining its core elements and best practices. Person‐centred care aims to deliver healthcare services based on individuals' preferences. Several approaches have been developed to better implement person‐centred care practices. The Norwegian transitional and follow‐up model, ‘Holistic Continuity of Patient Care’, chooses the ‘What Matters to You?’ approach. Other approaches include ‘Shared Decision Making’ and ‘Continuity of Care’.DesignThis study employed a qualitative design.MethodsIndividual repeated interviews were conducted among eight participants. A hermeneutic exploratory research method was chosen. The COREQ checklist was followed.ResultsThree main themes related to person‐centred care emerged: what matters in meetings with the individual healthcare worker, mobilising health‐promoting capabilities and resources and what matters when being in the organisational healthcare system.ConclusionTo participate in their own health issues, older people need to be empowered and better informed about the importance and scope of person‐centred care. ‘What Matters to You?’ is a good focus for the direction of care but can lead to a simplified understanding of individuals' preferences. Increased focus on how care recipients' capabilities and resources affect their responding is needed.Relevance to clinical practiceEnsuring that person‐centred aspects are incorporated into the entire healthcare system requires better methods of engaging and empowering older adults in healthcare settings; more focus on PCC competence and skills of healthcare professionals as well as better integration of PCC practices into healthcare administration and policies.
Global value chain engagement and air pollution: Evidence from Chinese firms
Authors: Hua Yue , Lu Yue , Zhao Ruili 
Published: June 2021

AbstractThis paper studies the environmental consequences of firm's participation in the global value chain, based on a unique firm‐level data set from 2000 to 2007 by combining several large and representative databases in China. We propose a novel global value chain (GVC) engagement index that properly characterizes Chinese firm's importing patterns. By estimating fixed‐effects models with a rich set of firm‐level and industry‐level controls, our results robustly show that firm's engagement in GVC leads to decreased SO2 emission. The identified effects are stronger for firms with domestic ownership, firms of higher pollution intensity, and firms exposed to more stringent place‐based environmental regulation. We further demonstrate that the pollution reduction effects induced by firm's GVC engagement is attributable to lower SO2 intensity, which is likely to be achieved via the attenuated use of fossil fuels and the increased adoption of abatement devices.
Risk for hepatic and extra‐hepatic outcomes in nonalcoholic fatty liver disease
Authors: Hagström Hannes , Kechagias Stergios , Ekstedt Mattias 
Published: June 2021

AbstractNonalcoholic fatty liver disease (NAFLD) is defined by presence of steatosis in more than 5% of liver cells. The gold standard for diagnosis is liver biopsy, but this is seldom achieved due to costs and risk for side effects, and that is why the diagnosis is mostly made based on a combination of radiology and exclusion of other liver diseases. Disease severity staging can be noninvasively achieved with radiological exams such as elastography or blood‐based markers that usually have lower sensitivity and specificity. NAFLD is today the most common chronic liver disease globally with a prevalence estimated to be 25%. Fortunately, for many persons NAFLD is an incidental finding with a good prognosis. Whilst a major focus has been on liver‐related outcomes in NAFLD, there has recently been an increased interest in extrahepatic consequences of NAFLD. The most commonly studied outcomes include cardiovascular disease and cancer. The risk of adverse outcomes generally differs according to the baseline fibrosis stage. There is a five‐time higher risk of liver‐related events in NAFLD patients with fibrosis stage 3 as compared to those with no or little fibrosis. Meanwhile, the presence of nonalcoholic steatohepatitis (NASH) does not seem to influence prognosis in addition to fibrosis stage. Patients with NAFLD clearly have a higher risk for cardiovascular outcomes compared to the general population, with a recent meta‐analysis indicating a 37% increased hazard for cardiovascular events as opposed to individuals without NAFLD. The risk of liver cancer is increased, which is mostly driven by presence of cirrhosis, but the increased risk is present also in patients without cirrhosis, and to a greater extent than for other chronic liver disease. Around one‐third of patients with NAFLD and liver cancer do not have cirrhosis. Additionally, the risk of extrahepatic malignancies is thought to be moderately increased, with most evidence for a link between NAFLD and colorectal cancer where the risk is approximately 50% higher compared to patients without NAFLD. A particularly salient point is if NAFLD can be considered an independent risk factor for outcomes. Many studies have not been able to adjust for key confounders, or suffer from different forms of bias. The clinical problem is nevertheless to identify persons with an increased risk for adverse hepatic and extrahepatic outcomes. We here discuss the evidence linking NAFLD to severe hepatic and extrahepatic outcomes.
Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers
Authors: Grant Leilah K. , St Hilaire Melissa A. , Brainard George C. , Czeisler Charles A. , Lockley Steven W. , Rahman Shadab A. 
Published: June 2021

AbstractShiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near‐identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue‐enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue‐enriched white light. In the delay protocols, the cholesterol rhythm shifted later by −3.7 hours and −4.2 hours, respectively, compared to −6.6 hours and −4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.
Nicotinic acid supplementation at a supraphysiological dose increases the bioavailability of NAD+ precursors in mares
Authors: Pollard Charley‐Lea , Gibb Zamira , Swegen Aleona , Lawson Edwina F. , Grupen Christopher G. 
Published: June 2021

AbstractNAD+ deficiency has recently been linked with increased occurrences of congenital abnormalities and embryonic death in human and animal subjects. Early embryonic death is a major component of pregnancy loss in mares and very little is known regarding the requirement for NAD+ in horses. The aim of this study was to quantify NAD+ and its metabolites in the plasma and urine of mares after orally administering an acute dose of nicotinic acid and determine the absorption, metabolism and excretion of this essential precursor for NAD+ biosynthesis. Nicotinic acid (5 g per os) was administered to four mares via a dosing syringe. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6 and 22 h, and urine samples were collected at 0, 3, 6 and 22 h. The samples were processed and analysed by mass spectrometry. A general additive model was applied to all metabolite concentration values followed by a post‐hoc multiple comparisons test. Nicotinic acid was rapidly absorbed into peripheral blood within 15 min of administration and the concentrations of nicotinic acid, nicotinamide (NAM), nicotinuric acid, nicotinic acid mononucleotide and nicotinic acid adenine dinucleotide (NaAD) increased significantly in plasma at 30 min. The concentrations of NAM, nicotinic acid riboside and NaAD increased significantly in urine at 3 h. The levels of NAM and NaAD remained significantly elevated in plasma at 22 h, sixfold and ninefold greater, respectively, than the basal levels at 0 h. While the extracellular levels of NAD+ in the samples remained undetected, the large, sustained elevation of NaAD levels in plasma indicates that the NAD+ levels were boosted within the cellular compartments. The results show that nicotinic acid supplementation increases the bioavailability of NAD+ precursors in mares, which is proposed to be beneficial during periods of peak NAD+ demand, such as during early embryo development.
Pancreatic enzyme activity in the bile of healthy cats and its association with biliary morphology
Authors: Fujimoto Shinsuke , Torisu Shidow , Kaneko Yasuyuki , Mizutani Shinya , Yamamoto Shushi , Naganobu Kiyokazu , Nakamura Kensuke 
Published: June 2021

AbstractBackgroundIn human medicine, congenital maljunction of the common bile duct (CBD) and main pancreatic duct (MPD), or pancreatobiliary maljunction (PBM), is a known cause of cholecystitis.ObjectivePancreatic enzyme activity in the bile (a diagnostic marker for PBM) of healthy cats was measured to determine normal values and evaluate its relationship with biliary morphology.AnimalsFifty‐two healthy cats.MethodsCross‐sectional study of the biliary tracts of healthy cats during laparoscopic ovariohysterectomy and measurement of pancreatic enzyme activity in bile. The cats were divided into groups A and B based on the ratio of the diameter of the cystic duct (CD) to the CBD. The normal ratio was 3.4. Pancreatic enzyme activity in bile was compared between the groups.ResultsThe CBDs were straight in all cases, whereas the CDs were variably tortuous or dilated. Amylase activity in the bile (median, <100 U/L; range, <100‐591 U/L) was lower than in serum in all cases, and group B, which had a CD/CBD ratio >3.4, had significantly higher amylase activity (median, 109 U/L; range, <100‐591 U/L) in the bile than did group A (median, <100 U/L; range, <100‐238 U/L), which had a CD/CBD ratio <3.4 (P = .0009).Conclusions and Clinical ImportanceThe results suggest that a dilated CD is associated with reflux of pancreatic juice. In the future, it will be necessary to examine the clinical usefulness of these findings by measuring pancreatic enzyme activity in the bile of cats with cholangitis.
Habitat‐mediated reef fish assemblages in coral reef tidal pools
Authors: dos Santos Crislaine Morais , Santana Virginia , Bastos Alice , Teixeira Jessyca Luana , Gama Mateus Alexander Campeche , Kennedy Sara Buttrose , Félix‐Hackradt Fabiana Cézar , Hackradt Carlos Werner 
Published: June 2021

AbstractTide pools are important environments for several fish species, as they offer essential resources such as shelter and food. Thus, understanding the relationships of the ichthyofauna with the habitat structural characteristics in tide pools is important to understand the distribution patterns of fish assemblages in shallow environments. This study investigated how the habitat structure in tide pools influences the reef fish assemblages in Southwestern Atlantic (Bahia, Brazil). During 17 months, tidal pools were evaluated through visual censuses aiming to sampling the ichthyofauna, and additionally, variables of the structural characteristics of the pools (depth, area, volume, rugosity, etc.) were measured. By using multiple statistical modeling approaches, we found that there were significant differences in diversity, abundance, and species richness at the interaction between time and space factors, with higher averages of the three variables during the warmer months across all reef banks. Moreover, at local spatial scale, greater coral‐dominated and complex pools harbored higher fish species and diversity, while algae cover was most important in shaping fish numbers. The most important variables in the structuring of the fish assemblages were the pool volume, distance from the edge of the reef, and habitat complexity, confirming our hypothesis. Resident fish species were found in pools near the out reef edge, while occasional and transient species were found in pools closer to the inland sea. Our study highlights the multi‐scale role of habitat characteristics as predictors of the fish assemblage structure in these extremely variable environments and emphasizes the need to protect these fragile and overexploited tidal pools.