bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR‐182 enhances radioresistance in non‐small cell lung cancer cells by regulating FOXO3
Authors: Chen Gang , Yu Lina , Dong Hui , Liu Zhihao , Sun Yahong 
Published: October 2018

SummaryUpregulated in lung cancer, miRNA‐182 was found to be related to cancer proliferation and chemoresistance. However, there is no report on the role of miR‐182 in radioresistance, which is a main obstacle of radiotherapy. In this study, we aim to depict the effect of miR‐182 inhibition on cellular sensitivity to ionizing radiation. Our data confirm that miR‐182 is upregulated in lung cancers and tissues and that miR‐182 is responsive to irradiation. We also show that miR‐182 knockdown suppresses cell proliferation and increases cell apoptosis after irradiation. DNA damage remains unrepaired in miR‐182 knockdown cells, which results in cell cycle arrest. Finally, we find that FOXO3 is a direct target of miR‐182 and that overexpression of FOXO3 enhances radiation resistance in miR‐182 knockdown cells. In conclusion, our data suggest that miR‐182 might account for radioresistance in lung cancer and that miR‐182‐FOXO3 provides a novel radiosensitizing target.
Insight into the sulfur metabolism of Desulfurella amilsii by differential proteomics
Authors: Florentino Anna P. , Pereira Inês A. C. , Boeren Sjef , van den Born Michael , Stams Alfons J. M. , Sánchez‐Andrea Irene 
Published: October 2018

SummaryMany questions regarding proteins involved in microbial sulfur metabolism remain unsolved. For sulfur respiration at low pH, the terminal electron acceptor is still unclear. Desulfurella amilsii is a sulfur‐reducing bacterium that respires elemental sulfur (S0) or thiosulfate, and grows by S0 disproportionation. Due to its versatility, comparative studies on D. amilsii may shed light on microbial sulfur metabolism. Requirement of physical contact between cells and S0 was analyzed. Sulfide production decreased by around 50% when S0 was trapped in dialysis membranes, suggesting that contact between cells and S0 is beneficial, but not strictly needed. Proteome analysis was performed under the aforementioned conditions. A Mo‐oxidoreductase suggested from genome analysis to act as sulfur reductase was not detected in any growth condition. Thiosulfate and sulfite reductases showed increased abundance in thiosulfate‐reducing cultures, while rhodanese‐like sulfurtransferases were highly abundant in all conditions. DsrE and DsrL were abundantly detected during thiosulfate reduction, suggesting a modified mechanism of sulfite reduction. Proteogenomics suggest a different disproportionation pathway from what has been reported. This work points to an important role of rhodaneses in sulfur processes and these proteins should be considered in searches for sulfur metabolism in broader fields like meta‐omics.
NaCl promotes antibiotic resistance by reducing redox states in Vibrio alginolyticus
Authors: Yang Jun , Zeng Zao‐Hai , Yang Man‐Jun , Cheng Zhi‐Xue , Peng Xuan‐Xian , Li Hui 
Published: October 2018

SummaryThe development of antibiotic resistance in Vibrio alginolyticus represents a threat to human health and fish farming. Environmental NaCl regulation of bacterial physiology is well documented, but whether the regulation contributes to antibiotic resistance remains unknown. To explore this, we compared minimum inhibitory concentration (MIC) of V. alginolyticus cultured in different media with 0.5%–10% NaCl, and found that the MIC increased as the NaCl concentration increased, especially for aminoglycoside antibiotics. Consistent with this finding, internal NaCl also increased, while intracellular gentamicin level decreased. GC–MS‐based metabolomics showed different distributions of pyruvate cycle intermediates among 0.5%, 4% and 10% NaCl. Differential activity of enzymes in the pyruvate cycle and altered expression of Na(+)‐NQR led to a reducing redox state, characterized by decreased levels of NADH, proton motive force (PMF) and ATP. Meanwhile, NaCl negatively regulated PMF as a consequence of the reducing redox state. These together are responsible for the decreased intracellular gentamicin level with the increased external level of NaCl. Our study reveals a previously unknown redox state‐dependent mechanism regulated by NaCl in V. alginolyticus that impacts antibiotic resistance.
A novel citrate synthase isoform contributes infection and stress resistance of the stripe rust fungus
Authors: Li Dan , Pang Lijing , Yuan Pu , Zheng Peijing , Huai Baoyu , Yao Mohan , Kang Zhensheng , Liu Jie 
Published: October 2018

SummaryThe early development of a rust fungus is dependent on the endogenous lipids stored in the urediniospores. After it establishes a parasitic relationship with the host, sugars absorbed from the host cells by haustoria become the primary nutrients. The tricarboxylic acid (TCA) cycle is essential to oxidize these nutrients. However, few studies have addressed the role of citrate synthase (CS), a rate‐limiting enzyme of the TCA cycle, during the infection process of rust fungi. In this study, a CS gene fromPuccinia striiformisf. sp.tritici(Pst),PsCS1, was cloned and characterized. Transcripts ofPsCS1and the enzyme activity of the CS were increased in the earlyPstinfection stage. Biochemical features and subcellular localization revealed thatPsCS1encoded a mitochondrial CS. Size exclusion chromatography, yeast two‐hybrid and bimolecular fluorescence complementation experiments confirmed that PsCS1 could form a functional homo‐octamer. The overexpression ofPsCS1enhanced the resistance ofEscherichia colito salt stress. The knockdown ofPsCS1using a host‐induced gene silencing (HIGS) system blockedPstgrowth in wheat. These results indicate that PsCS1 is required for nutrient metabolism inPstand contributes toPstinfection by regulating ATP production and the supply of carbon sources.
Mobilising evidence in public policy: The contribution of the evidence provider
Authors: Thornthwaite Louise , O'Neill Sharron 
Published: October 2018

AbstractThis article contributes to the conceptualisation of evidence‐based policy through providing a framework of the key factors that influence research utilisation, including those that shape the quality of evidence provided. We apply this framework to an analysis of public policy to regulate the remuneration of freight truck drivers to improve workplace safety in their industry. Recent policymaking concerning the regulation of truck drivers’ remuneration in Australia provides an opportunity to examine the quality and utilisation of research evidence by external evidence providers in opposing political contexts. This article suggests the need for informed and vigilant scrutiny of the contributions of evidence providers to government policymaking, particularly in the case of wicked policy problems about which there are sustained ideological differences that underpin problematisation, research interpretation, and conceivable policy solutions.
The patient‐centered dental home: A standardized definition for quality assessment, improvement, and integration
Authors: Damiano Peter , Reynolds Julie , Herndon Jill Boylston , McKernan Susan , Kuthy Raymond 
Published: October 2018

ObjectiveTo develop the first standardized definition of the patient‐centered dental home (PCDH).Data Sources/Study SettingPrimary data from a 55‐member national expert panel and public comments.Study DesignWe used a modified Delphi process with three rounds of surveys to collect panelists’ ratings of PCDH characteristics and open‐ended comments. The process was supplemented with a 1‐month public comment period.Data Collection/Extraction MethodsWe calculated median ratings, analyzed consensus using the interpercentile range adjusted for symmetry, and qualitatively evaluated comments.Principal FindingsForty‐nine experts (89%) completed three rounds and identified eight essential PCDH characteristics, resulting in the following definition: “The patient‐centered dental home is a model of care that is accessible, comprehensive, continuous, coordinated, patient‐ and family‐centered, and focused on quality and safety as an integrated part of a health home for people throughout the life span.”ConclusionsThis PCDH definition provides the foundation for developing measures for research, care improvement, and accreditation and is aligned with the patient‐centered medical home. Consensus among a broad national expert panel—including provider, payer, and accreditation stakeholder organizations and experts in medicine, dentistry, and quality measurement—supports the definition's usability and its potential to facilitate medical‐dental primary care integration.
Partisanship and Popular Politics in a Cornish ‘Pocket’ Borough, 1660–1714†
Authors: Harris James 
Published: October 2018

AbstractHistorians have rarely considered the political views of electorates in small constituencies with strong proprietorial interests, or ‘pocket’ boroughs. However, through a detailed case study of the Cornish borough of Mitchell, this article reveals a rural settlement with a multifaceted and divided community, which experienced a high degree of partisan conflict during the later Stuart period as its inhabitants engaged in an ongoing struggle over the nature of the franchise. A group of often‐disenfranchised inhabitants launched a sustained and independent assault on the lord of the borough's limited franchise, in favour of an inhabitant‐based vote; they were opposed by a group which oscillated between loyalty to the borough's patron and attempts to secure its own influence. Party allegiances and political ideologies can occasionally be identified on both sides, but the franchise dispute did not always align with these divisions. The article argues that while partisan conflict occurred in ‘pocket’ boroughs, it took extraordinary circumstances for this to boil over and facilitate change – in Mitchell's case, these circumstances were the frequent elections to the Exclusion Parliaments, and the patron's self‐imposed exile in France. Yet even once a popular inhabitant‐based vote was established, the widened electorate still found it difficult to determine the outcome of elections, as the borough's patron and local gentry families soon reasserted their authority. Therefore, while the electorates of boroughs such as Mitchell were not supine or monolithic, their ability to actively participate in the electoral process was ultimately fragile.
Inhibition of miR‐24 suppresses malignancy of human non‐small cell lung cancer cells by targeting WWOX in vitro and in vivo
Authors: Wang Xue‐hai , Gan Chong‐zhi , Xie Jia‐yong 
Published: October 2018

BackgroundWe investigated the effect of micro‐RNA 24 (miR‐24) and WWOX on non‐small cell lung cancer (NSCLC) cell proliferation and migration in vitro and in vivo.MethodsWe performed bioinformatics analysis and 3′ untranslated region luciferase assay to investigate the direct target of miR‐24. Proliferation, apoptosis, and transwell invasion assays were employed to evaluate the effect of WWOX overexpression with pcDNA3‐WWOX and knocking down miR‐24 with miR‐24 small interfering RNA. Quantitative real‐time PCR, Western blot, and immunohistochemistry were also used to investigate miR‐24 and c‐Kit expression, and apoptosis and invasion‐related proteins. Finally, we constructed a tumor xenograft model in nude mice to confirm the effect of miR‐24 on NSCLC cell proliferation in vivo.ResultsAccording to our experimental data, miR‐24 inhibition could induce apoptosis by activating caspase 3 and suppress the viability and proliferation of NSCLC cells in vitro and in vivo. MiR‐24 downregulation could reduce the invasive ability of NSCLC cells by downregulating MMP9. WWOX was identified as a functional target of miR‐24. WWOX overexpression generated the same effect with antagonizing miR‐24, while blocking WWOX counteracted the tumor suppressive effect caused by miR‐24 inhibition. MiR‐24 may function as an oncogene and play an important role in the cell growth and migration of NSCLC.ConclusionsOur findings enhance understanding of the miR‐24 regulatory network and the molecular mechanism that underlies the oncogenesis and development of NSCLC. Suppressing the effect of miR‐24 on cancer cells using a miR‐24 inhibitor may be an attractive therapeutic strategy against NSCLC.
Cannabidiol affects circadian clock core complex and its regulation in microglia cells
Authors: Lafaye Geneviève , Desterke Christophe , Marulaz Laurent , Benyamina Amine 
Published: October 2018

AbstractCannabis is often used by consumers for sleep disorders. Studies show that circadian rhythm could be affected by a misuse of cannabis. Recent research has connected the role of microglial cells with psychiatric disorders such as substance abuse. The aim was to show the effect of two major components of cannabis on circadian genes regulation in microglial cells. In BV‐2 microglial cells, cannabidiol (CBD) induces a deregulation of circadian genes with (P‐value = 0.039) or without (P‐value = 0.0015) lipopolisaccharides stimulation. CBD up regulated Arntl (P = 9.72E‐5) and down regulated Clock (P = 0.0034) in BV‐2 cells. Temporal expression of Arntl (light and dark P = 0.0054) and Clock (light and dark P = 0.047) was confirmed to have 24 hours light and dark rhythmic regulation in dissected suprachiasmatic nucleus as well as of Cb1 cannabinoid receptor (light and dark P = 0.019). In BV‐2 microglia cells, CBD also up regulated CRY2 (P = 0.0473) and PER1 (P = 0.0131). Other nuclear molecules show a deregulation of circadian rhythm in microglial cells by CBD, such as RORA, RevErbα, RORB, CREBBP, AFT4, AFT5 and NFIL3. Our study suggests that circadian rhythm in microglial cells is deregulated by CBD but not by THC. It is consistent with clinical observations of the use of therapeutic cannabis to treat insomnia.
HPA axis stress reactivity and hair cortisol concentrations in recently detoxified alcoholics and healthy controls with and without childhood maltreatment
Authors: Muehlhan Markus , Höcker Anja , Miller Robert , Trautmann Sebastian , Wiedemann Klaus , Lotzin Annett , Barnow Sven , Schäfer Ingo 
Published: October 2018

AbstractChildhood maltreatment (CM) is a strong risk factor for alcohol dependence (AD) and is associated with a more severe course of the disease. Alterations of the hypothalamic‐pituitary‐adrenal (HPA) axis may play an important role in this relationship. The aim of the present study was to systematically investigate potential alterations in HPA functioning associated with AD diagnosis and CM. Four study groups were recruited: AD patients with (n = 29; 10♀) and without (n = 33; 8♀) CM and healthy controls with (n = 30; 20♀) and without (n = 38; 15♀) CM. Cumulative cortisol secretion was measured by hair cortisol concentration (HCC). To measure HPA axis response to the Trier social stress test (TSST), saliva and blood samples were analysed for adrenocorticotropic hormone (ACTH) and cortisol. In the AD groups, the period of hair growth covered acute alcohol consumption and withdrawal. The TSST was scheduled after completion of withdrawal. Irrespective of CM, higher HCCs and reduced ACTH and cortisol levels before and after TSST were observed in AD patients. The analyses did not reveal any differences between AD patients with and without CM. Healthy controls with CM had lower plasma cortisol levels compared with those without CM. The results suggest that AD is strongly related to HPA axis functioning, which may superimpose possible differences between AD patients with and without CM. Future studies should investigate whether biologically different subtypes of AD with and without CM can be identified in earlier stages or before the development of AD.
Gender‐ and cholesterol‐specific predictive value of body mass index in renal cell carcinoma: A multicenter study
Authors: Jeong Hyun Cheol , Bashraheel Fahad K. , Byun Seok‐Soo , Kwak Cheol , Hwang Eu Chang , Kang Seok Ho , Chung Jinsoo , Kim Tae‐Hwan , Kim Yong‐June , Hong Sung‐Hoo 
Published: October 2018

AbstractAimRecently, there have been some reports on preoperative body mass index (BMI) and total cholesterol (TC) as a prognostic predictor for patients with renal cell carcinoma (RCC) but the topic is controversial and still poorly understood. So we analyzed the effects of BMI and TC on the prognosis of RCC.MethodsRetrospective data from 1988 to 2015 were collected from eight centers with a total of 7,271 patients surgically treated for nonmetastatic RCC. Receiver operating characteristic curve analysis was analyzed and the highest Youden index was shown at 163.5 mg/dL. According to the Asian BMI criteria, patients were divided into normal BMI < 25 kg/m2 and high BMI ≥ 25 kg/m2. Kaplan‐Meier analysis, multivariate Cox regression model were performed to identify the overall survival (OS) and the recurrence‐free survival (RFS).ResultsNormal BMI and low TC group was associated with the shortest OS and RFS as compared to the other groups significantly. In the male patients, the results showed similar to the whole sample. But in the female, BMI had no effect on both OS and RFS. On multivariate Cox regression analysis, low TC was an independent predictor for OS in both genders. However, normal BMI was a significant prognostic factor in the males only.ConclusionPreoperative BMI and TC are good predictive factors for both OS and RFS significantly in RCC patients. Also, TC was an independent predictor for OS in all RCC patients; however, BMI was a significant predictor in males only.
Monitoring excess unplanned return to theatre following colorectal cancer surgery
Authors: Rasmussen Michael , Platell Cameron , Jones Mark 
Published: October 2018

BackgroundTo develop a risk‐adjustment model for unplanned return to theatre (URTT) outcomes following colorectal surgeries in Australia and New Zealand hospitals and apply top‐down and bottom‐up statistical process control methods for fair comparison of hospitals and surgeons’ URTT rates.MethodsWe analysed URTT outcomes from hospitals contributing data to the Bi‐National Colorectal Cancer Audit clinical registry between 2007 and 2016. Preoperative and intraoperative covariates were considered for risk adjustment. A risk‐adjusted rate funnel plot was prepared for between‐hospital comparisons and identification of outlying hospitals with unusually high rates of URTT. Cumulative observed‐minus‐expected charts with cumulative sum signals were then presented for surgeons within an outlying hospital.ResultsThe study included 15 134 patients and 166 surgeons across 70 hospitals. The weighted average URTT rate was 5.2%. The risk‐adjustment model identified 12 preoperative and intraoperative variables that significantly raise the risk of URTT: male sex, American Society of Anesthesiologists score, emergency admissions, conversion entry, left hemicolectomy, total colectomy, proctocolectomy, lower anterior resection, ultra‐low anterior resection, abdominoperineal resection, organ resection and excess lymph nodes harvested. Right hemicolectomy significantly reduced risk of URTT. URTT rates were not found to significantly vary across seniority of operator; however, comparisons were limited by lack of data on junior operators. The funnel plot identified five hospitals as ‘possible outliers’ and hospital T was identified as a ‘definite outlier’. The cumulative observed‐minus‐expected charts with cumulative sum signals showed that within hospital T, one surgeon among three had a particularly bad run of URTTs.ConclusionFeedback from aggregated URTT outcomes using a risk‐adjusted rate funnel plot is enhanced when follow‐up examination of outlying hospitals is conducted with concurrent application of cumulative observed‐minus‐expected charts with cumulative sum signals.
Predicting post‐operative pancreatic fistulae using preoperative pancreatic imaging: a systematic review
Authors: Barreto Savio G. , Dirkzwager Ilse , Windsor John A. , Pandanaboyana Sanjay 
Published: October 2018

BackgroundPost‐operative pancreatic fistulae (POPF) remain a major contributor to morbidity and mortality following pancreatic resection. Evidence for preoperative prediction of POPF based on cross‐sectional imaging has not been systemically reviewed. This review aimed to determine whether preoperative imaging modalities can accurately predict the development of POPF.MethodsA systematic review of major reference databases was undertaken, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines, up to May 2018.ResultsThere were 18 studies (2150 patients), seven used magnetic resonance imaging (MRI), five used computed tomography (CT) scans, four used transabdominal ultrasonography and one study each used MRI and CT and endoscopic ultrasonography elastography. All were retrospective, single‐centre studies. Intensity of the pancreas signal relative to the spleen, liver or muscle was commonly used. Other studies compared signal intensity between unenhanced and post‐contrast‐enhanced pancreas, apparent diffusion coefficient values comparing normal parenchyma to fibrosis, perfusion fraction (f) of intravoxel incoherent motion diffusion‐weighted imaging, or utilized a muscle‐normalized signal intensity curve with signal intensity ratio or directly assessed pancreatic volume and duct width. Shear wave velocity measurement on transabdominal ultrasonography may reflect pancreas tissue fibrosis or stiffness and predict POPF. Most parameters used to predict the development of POPF were based on identifying imaging features of a fatty or fibrotic pancreas and main pancreatic duct diameter.ConclusionA number of different and highly promising parameters have been used for preoperative prediction of POPF using ultrasound, MRI, CT or both. Large multicentre prospective studies are needed to determine which parameters most accurately predict POPF, using standardized definitions and methodology.
Age at diagnosis and the surgical management of small renal carcinomas: findings from a cross‐sectional population‐based study
Authors: White Victoria M. , Marco David J.T. , Bolton Damien , Papa Nathan , Neale Rachel E. , Coory Michael , Davis Ian D. , Wood Simon , Giles Graham G. , Jordan Susan J. 
Published: October 2018

ObjectivesTo describe the use of partial nephrectomy (PN) for patients with stage T1a renal cell carcinoma (RCC) by age group (<65 and ≥65 years) in two Australian states.Materials and MethodsAll adults diagnosed with RCC in 2012 and 2013 were identified through population‐based cancer registries in the Australian states of Queensland and Victoria. For each patient, research assistants extracted patient, tumour and treatment data from medical records. Percentages of patients treated by PN were determined for the two age groups. Multivariable logistic regression analyses examined factors associated with PN. Clinicians treating RCC were sent surveys to assess attitudes towards PN.ResultsData were collected on 956 patients (Victoria: n = 548; Queensland: n = 404) with stage T1a RCC. Of those undergoing surgery (n = 865), PN was more common for those aged <65 years (61%) than for those aged ≥65 years (44%), with this difference significant after adjusting for patient, tumour (odds ratio 0.50, 95% confidence interval 0.36–0.70). There were significant interactions between age and treatment centre volume (P < 0.05) and residential state (P < 0.05). PN was less likely for younger patients treated at lower‐volume hospitals (<24 patients a year) but hospital volume was not associated with PN for older patients. PN was less likely for older patients in Queensland than Victoria. In multivariable analyses, age was not related to laparoscopic surgery. Queensland clinicians were less likely than those from Victoria to agree that PN was the treatment of choice for most T1aN0M0 tumours (P < 0.001).ConclusionsIn Australia, patients aged > 65 years with small renal cancers were less likely to be treated by PN than younger patients. The variation in the surgical procedure used to treat older T1a RCC patients by state and hospital volume indicates that better evidence is needed to direct practice in this area.