Erratum to: Conformational changes and translocation of tissue-transglutaminase to the plasma membranes: role in cancer cell migration

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Key factors of scanning a plant virus with AFM in air and aqueous solution

Abstract

For tobacco mosaic virus (TMV) as a model virus, this article shows typical issues of scanning soft biological matter by atomic force microscopy (AFM). TMV adsorbed on chemically different flat surfaces, gold, mica, and APDMES-functionalized silicon, is studied in air and aqueous environment. In air, the TMV particles arrangement shows some variety, depending on the substrate. The height of TMV is reduced to 13.7, 15.8, and 15.6 nm, for gold, APDMES, and mica, respectively while the width is about ∼30 nm due to the influence of the tip radius. In aqueous solution, the surface charges of the virus and the solid support play an important role in the virus adsorption process. While deposition on negatively charged mica is favored only at low pH values, it is shown that positively charged APDMES functionalized silicon can be a suitable substrate to work with at neutral pHs. The effects of cantilever oscillation's free amplitude (A₀) and the amplitude set-point (A) are also assessed here. While high A₀ prompt reversible deformation of TMV in measurements performed in air, irreversible damage of the virus in liquid conditions (water) is observed using stiff cantilevers (0.35 N m⁻¹) and high A₀ (81 nm), leading to a 6 nm reduction in the height of TMV after the first scan. Finally, low values of the amplitude set-point (A/A₀ = 0.3), which means applying higher forces to the sample, also brings the damage of TMV virus assemblies, reducing its monolayer roughness to 0.3 nm.

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Effects of QMix and ethylenediaminetetraacetic acid on decalcification and erosion of root canal dentin

Abstract

The aim of this study was to evaluate the effect of initial NaOCl on the decalcification and erosion ability of EDTA and QMix. Sixty-maxillary-incisors were bisected longitudinally and the tooth-halves were used. The experiment was conducted in two-sets. In set-I, 80-tooth halves were treated in the presence or absence of initial NaOCl and EDTA. In set-II, 40-tooth halves were immersed in NaOCl and QMix. After each treatment, calcium-ion release was determined with flame photometry. The erosion was imaged using SEM. Initial NaOCl led to concentration- and time-dependent increase in calcium removal effect of 17% EDTA (p < .05). The rate of calcium removal and root canal wall erosion was considerably more severe with the use of 5% NaOCl for 3 min (p < .05). QMix as a final solution showed less decalcification and erosion than 17% EDTA when used 5% NaOCl as an initial irrigant (p < .05). Optimizing the concentration and application time of NaOCl can decrease the decalcification effect of chelating agents.

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Cancer cell survival without glucose illucidated

The main goal of a tumour cell is, above all, to survive, even at the cost of damaging the health of the organism to which it belongs. To do this, it is equipped with skills that healthy cells do not have, including the ability to continue surviving when...

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Study identifies novel treatment resistance mechanism in BRAF-mutant melanoma

A Massachusetts General Hospital (MGH) research team has identified an additional mechanism for resistance to targeted treatment for BRAF-mutant melanoma. Their paper, receiving advance online publication in Nature Medicine, reports that inactivating...

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Compound shows promise as next-generation prostate cancer therapy

In the search for new ways to attack recurrent prostate cancer, researchers at Duke Health report that a novel compound appears to have a unique way of blocking testosterone from fuelling the tumours in mice. The potential foundation for a...

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Rare case of gallbladder agenesis presenting with pancreatitis

Gallbladder agenesis (GA) is a rare congenital abnormality with an incidence of 0.01–0.09%. Majority of GA exist alone although it can be associated with other systemic malformations involving the gastrointestinal, genitourinary, cardiovascular and skeletal systems. It is thought that biliary and pancreatic pathologies coexist and this is the second case reported in the literature of GA presenting with pancreatitis.

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Cerebral venous thrombosis associated with thyrotoxicosis, the use of desmopressin and elevated factor VIII/von Willebrand factor

Cerebral venous thrombosis (CVT) is an uncommon disorder associated with diverse processes. We report a patient who, while receiving desmopressin and contraceptive pills (OCP), developed straight sinus thrombosis. Clinical assessment and laboratory investigations revealed untreated hyperthyroidism and a hypercoagulable state, characterised by high levels of von Willebrand factor, factor VIII coagulant activity and IgM cardiolipin antibody. The clinical picture improved with anticoagulation, treatment of hyperthyroidism and discontinuation of OCP and desmopressin. To the best of our knowledge, the association between the use of oral desmopressin and CVT has not been described. The multiple risk factors present in our case were probably additive in increasing the risk of CVT. Although this case represents a rare occurrence, practitioners should be alerted to the possible associations of desmopressin, oral contraceptives and Graves' disease with venous thrombosis.

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Successful treatment of recurrent pleural and pericardial effusions with tocilizumab in a patient with systemic lupus erythematous

A 22-year-old Caucasian man presented to hospital with pleuritic chest pain. He had had a history of a sun-sensitive rash a year prior. Workup revealed normal cardiac enzymes and chest X-ray. However, electrocardiogram revealed ST elevation and PR depression, and echocardiogram revealed a slight pericardial effusion without other findings. A diagnosis of pericarditis was made. Subsequently, he was found to be positive for antinuclear antibodies (ANAs), as well as antibodies to SSA, SSB and double-stranded DNA; C3 was low, and C4 was undetectable. A diagnosis of systemic lupus erythematosus was made. The patient initially responded to high-dose ibuprofen. One month later, he developed a new pericardial effusion, this time with concomitant massive left-sided pleural effusion, requiring three separate thoracenteses draining a total of 6 L of pleural fluid. The recurrent effusion failed to respond to high-dose corticosteroid treatment. Owing to the severity and rapidity of the recurrence of pleural and pericardial effusion, intravenous tocilizumab was administered. The patient had excellent clinical and radiographic improvement. This case shows that tocilizumab may have a role in the treatment of intractable pleuropericardial effusion and other forms of lupus-associated serositis.

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More than 60 per cent of coral reef in Maldives hit by bleaching

High sea temperatures have caused a mass bleaching of coral reefs in Maldives in the Indian Ocean, affecting 60 per of its reefs – and more in places

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Zika Virus 6 Months Later

In this Viewpoint, CDC Director Thomas Frieden and colleagues provide a mid-2016 update on Zika virus infection, including advances in understanding the epidemiology, clinical manifestations, diagnosis, prevention, and public health control of the infection.

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Simulator evaluation of a prototype device to reduce medication errors in anaesthesia

Summary

We undertook a randomised control led trial to evaluate the effect of a prototype device which attaches to the intravenous drug administration port, and allows injection of intravenous drugs only after the user scans the barcode on the syringe label. This requires two steps: first, that the correct drug label is generated; and second, that the syringe-with-label is scanned before administration. Ten anaesthetists, who were unaware of the primary outcome being measured, administered general anaesthesia for two simulated standardised cases each without and with our prototype (control and intervention, respectively). The primary outcome measured was compliance with a safe drug administration procedure (defined as a two-step procedure where, step one is scanning a drug ampoule to print a label for a syringe and step two is scanning of the labelled syringe before administering it intravenously). A total of 182 intravenous drug administrations occurred in the study (91 in each group). We found that the use of our prototype increased safe drug administration behaviour in experienced anaesthetists; 33 (36.3% [95% CI 26–47%]) vs. 91 (100% [95% CI 96–100%]) in the control and intervention groups, respectively (p = 0.0001).

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Validation of a point-of-care prothrombin time test after cardiopulmonary bypass in cardiac surgery

Summary

Point-of-care coagulation monitoring can be used for the guidance of haemostasis management. However, the influence of time on point-of-care prothrombin time testing following protamine administration after cardiopulmonary bypass has not been investigated. Bland–Altman and error grid analysis were used to analyse the level of agreement between prothrombin time measurements from point-of-care and laboratory tests before cardiopulmonary bypass, and then 3 min, 6 min and 10 min after protamine administration. Prothrombin times were expressed as International Normalised Ratios. While the point-of-care and laboratory prothrombin time measurements showed a high level of agreement before bypass, this agreement deteriorated following protamine administration to a mean (SD) bias of −0.22 (0.13) [limits of agreement 0.48–0.04]. Error grid analysis revealed that 35 (70%) of the paired values showed a clinically relevant discrepancy in international normalised ratio. At 3 min, 6 min and 10 min after cardiopulmonary bypass there is a clinical unacceptable discrepancy between the point-of-care and laboratory measurement of prothrombin time.

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Cognitive decline in the elderly after surgery and anaesthesia: results from the Oxford Project to Investigate Memory and Ageing (OPTIMA) cohort

Summary

Concerns have been raised about the effects on cognition of anaesthesia for surgery, especially in elderly people. We recorded cognitive decline in a cohort of 394 people (198 women) with median (IQR) age at recruitment of 72.6 (66.6–77.8) years, of whom 109 had moderate or major surgery during a median (IQR) follow-up of 4.1 (2.0–7.6) years. Cognitive decline was more rapid in people who on recruitment were: older, p = 0.0003; male, p = 0.027; had worse cognition, p < 0.0001; or carried the ε4 allele of apoliprotein E (APOEε4), p = 0.008; and after an operation if cognitive impairment was already diagnosed, p = 0.0001. Cognitive decline appears to accelerate after surgery in elderly patients diagnosed with cognitive impairment, but not other elderly patients.

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Digital palpation of the pilot balloon vs. continuous manometry for controlling the intracuff pressure in laryngeal mask airways

Summary

This study compared two methods of controlling the intracuff pressure in laryngeal mask airways. One hundred and eighty patients were randomly assigned into two groups. In the first group (n = 90), after training, the intracuff pressure was controlled using digital palpation of the pilot balloon. In the second group (n = 90), continuous manometry was used to control the intracuff pressure. An upper pressure limit of 60 cmH₂O was set. The median (IQR [range]) intracuff pressure in the palpation group was 130 (125–130 [120–130]) cmH₂O compared with 29 (20–39 [5–60]) cmH₂O in the manometry group (p < 0.001). In the palpation group, 37% of patients experienced pharyngolaryngeal complications vs. 12% in the manometry group (p < 0.001). We conclude that the digital palpation technique is not a suitable alternative to manometry in controlling the intracuff pressure in laryngeal mask airways.

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Standardising anaesthesia for hip fracture surgery

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Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma

ABSTRACT

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non-Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV-infected patients with diffuse large B-cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV-infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004-May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon-based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% v 72%; p=0.07) and upper gastrointestinal (GI; 42% v 24%; p=0.004) involvement. Cases never given AVT had DLBCL more refractory to first-line chemotherapy than that in the controls (33% v 17%; p=0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% v 32%; p=0.09) or cases given AVT (50% v 27%; p=0.06). Cases never given AVT had worse 5-year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01-5.3]; p=0.04). Furthermore, AVT improved 5-year OS rates among cases in both univariate (median [Interquartile range]: 39 [26-56] v 16 [6-41] months, p=0.02) and multivariate analyses (HR=0.21 [95% CI, 0.06-0.69]; p=0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5-year OS. This article is protected by copyright. All rights reserved.

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Anti-tumor Activity of the ATR Inhibitor AZD6738 in HER2 positive Breast Cancer Cells

ABSTRACT

Ataxia telangiectasia and Rad3-related (ATR) proteins are sensors of DNA damage, which induces homologous recombination (HR)-dependent repair. ATR is a master regulator of DNA damage repair (DDR), signaling to control DNA replication, DNA repair, and apoptosis. Therefore, the ATR pathway might be an attractive target for developing new drugs. This study was designed to investigate the antitumor effects of the ATR inhibitor, AZD6738 and its underlying mechanism in human breast cancer cells. Growth inhibitory effects of AZD6738 against human breast cancer cell lines were studied using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (methyl thiazolyl tetrazolium, MTT) assay. Cell cycle analysis, Western blotting, immunofluorescence, and comet assays were also performed to elucidate underlying mechanisms of AZD6738 action. Anti-proliferative and DDR inhibitory effects of AZD6738 were demonstrated in human breast cancer cell lines. Among 13 cell lines, the IC₅₀ values of 9 cell lines were less than 1 μmol/L using MTT assay. Two cell lines, SK-BR-3 and BT-474, were chosen for further evaluation focused on human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. Sensitive SK-BR-3 but not the less sensitive BT-474 breast cancer cells showed increased level of apoptosis and S phase arrest and reduced expression levels of phosphorylated check-point kinase 1 (CHK1) and other repair markers. Decreased functional CHK1 expression induced DNA damage accumulation due to HR inactivation. AZD6738 showed synergistic activity with cisplatin. Understanding the antitumor activity and mechanisms of AZD6738 in HER2-positive breast cancer cells creates the possibility for future clinical trials targeting DDR in HER2-positive breast cancer treatment. This article is protected by copyright. All rights reserved.

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Downregulation of nucleophosmin expression inhibited proliferation and induced apoptosis in salivary gland adenoid cystic carcinoma

Background

This study aimed to explore the relationship between nucleophosmin (NPM1) and patient clinical characteristics. Moreover, we investigated the effect of NPM1 in tumor proliferation and apoptosis of salivary gland adenoid cystic carcinoma (SACC).

Materials and methods

NPM1 expression was examined in 74 specimens of SACC and 31 non-cancerous epithelium adjacent to carcinoma (NCEAC) by immunohistochemistry (IHC). RNA interference technology was used to silence NPM1 expression in SACC cells. We used transwell culture assay, cell counting kit-8 tests, and colony formation assay to test the proliferation, cisplatin resistance, migration, and invasiveness of SACC cells.

Results

The nuclear and cytoplasmic expression of NPM1 in SACC tissue was overexpressed and was tightly linked to perineural invasion and lymph node metastasis. The downregulation of NPM1 inhibited proliferation and induced apoptosis in SACC cells. Knockdown of NPM1 expression had no effect on chemoresistance migration, or invasiveness.

Conclusions

NPM1 may play an important role in tumor progress in SACC and is a potential biomarker for SACC.

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More than 60 per cent of coral reef in Maldives hit by bleaching

High sea temperatures have caused a mass bleaching of coral reefs in Maldives in the Indian Ocean, affecting 60 per of its reefs – and more in places

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Nearly half of US pediatric trials are unfinished or unpublished, study finds

Nearly half of the pediatric randomized clinical trials registered on the US trial registry ClinicalTrials.gov were not completed or their results were not published, a study has found.1In the study,...

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Negative control of TRAIL-R1 signaling by transforming growth factor β1 in pancreatic tumor cells involves Smad-dependent down regulation of TRAIL-R1

Publication date: November 2016
Source:Cellular Signalling, Volume 28, Issue 11
Author(s): David I. Radke, Hendrik Ungefroren, Ole Helm, Susann Voigt, Gökhan Alp, Hendrik Braun, Sebastian Hübner, Janine Dilchert, Susanne Sebens, Dieter Adam, Holger Kalthoff, Anna Trauzold
Pancreatic ductal adenocarcinoma (PDAC) is characterized by both, overexpression of transforming growth factor (TGF)β and resistance of the tumor cells to many apoptosis-inducing stimuli. The latter negatively impacts the outcome of therapeutic efforts and represents one important mechanism which tumor cells utilize to escape the immune surveillance. Since TGFβ acts as a tumor promoter in advanced tumor stages and suppression of apoptosis is a known driver of tumor progression, it is possible that TGFβ functions as a crucial determinant of tumor cell sensitivity to apoptosis in PDAC. Here, we have studied the impact of TGFβ on TNF-related apoptosis inducing ligand (TRAIL)-induced signaling in PDAC cells.In TGFβ-responsive Panc1 and Colo357 cells, TGFβ1 reduced total and plasma membrane-associated levels of TRAIL-R1 but not those of TRAIL-R2. Consistent with the known predominant role of TRAIL-R1 in TRAIL-mediated signaling in PDAC, TGFβ1 inhibited TRAIL-induced DISC formation and apoptosis as well as phosphorylation of MAPKs and IκBα. Similarly, it also reduced signaling of TRAIL-R1 following its specific activation with an agonistic antibody. In contrast, specific TRAIL-R2 signaling remained unchanged. The TGFβ1 effect on TRAIL-R1 expression was mimicked by ectopic expression of a kinase-active version of the TGFβ type I receptor ALK5 (ALK5-T204D) but not by ALK5 double mutant lacking the ability to phosphorylate Smad proteins (RImL45-T204D). Moreover, TGFβ regulation of TRAIL-R1 was absent in two PDAC cell lines lacking the Smad4 gene DPC4 and siRNA-mediated silencing of Smad4 in Smad4-positive Panc1 cells abolished the TGFβ-mediated decrease in TRAIL-R1 expression, together showing that ALK5/Smad4 signaling is crucial for TGFβ regulation of TRAIL-R1 expression. Our results suggest a novel tumor-promoting function of TGFβ1. By downregulating TRAIL-R1, TGFβ1 may not only promote tumor escape from immune surveillance but also negatively impact on TRAIL- or TRAIL-R1-based therapy regimens for treatment of PDAC.



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Growth differentiation factor 8 induces SKOV3 ovarian cancer cell migration and E-cadherin down-regulation

Publication date: November 2016
Source:Cellular Signalling, Volume 28, Issue 11
Author(s): Jianfang Zhao, Christian Klausen, Siyuan Xiong, Jung-Chien Cheng, Hsun-Ming Chang, Peter C.K. Leung
Epithelial ovarian cancer is the most lethal gynecological malignancy because most women present with late stage disseminated disease. Epithelial-mesenchymal transition (EMT) is characterized by the down-regulation of E-cadherin and up-regulation of N-cadherin, and is a crucial event in the pathogenesis of ovarian cancer. Transforming growth factor-β (TGF-β) is a major regulator of EMT in many normal and neoplastic cell types. Growth differentiation factor 8 (GDF8), which also activates TGF-β-like SMAD2/3 signaling, is best known for negatively regulating muscle growth. Though recent studies suggest that GDF8 enhances placental trophoblast cell migration, little is known about the role of GDF8 in EMT and cancer metastasis. We hypothesized that GDF8 could enhance ovarian cancer cell migration by inducing EMT. Here we demonstrate for the first time that GDF8 down-regulates E-cadherin but does not alter N-cadherin in SKOV3 ovarian cancer cells. This effect is abolished by the activin receptor-like kinase (ALK)4/5/7 inhibitor SB431542 or siRNA-mediated knockdown of ALK5, whereas knockdown of ALK4 is only partially inhibitory. GDF8 treatment increases the phosphorylation of SMAD2/3 and up-regulates the E-cadherin transcriptional repressors Snail and Slug; and these effects are abolished by pre-treatment with SB431542. Knockdown of common SMAD4 fully reverses the effects of GDF8 on E-cadherin and partially attenuates its effects on Snail and Slug. Importantly, GDF8 treatment increases SKOV3 cell migration and this effect is blocked by SB431542. Our study suggests that GDF8 promotes ovarian cancer cell migration via ALK4/5-SMAD2/3-E-cadherin signaling.



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Current perspective on actinic keratosis: a review

Summary

Actinic keratoses (AKs) are common, with prevalence in the U.S.A. estimated at almost 40 million in 2004 and annual costs of > $1 billion (U.S.D.). However, there is no universally accepted definition of AK and thus it is difficult to identify reliably. AKs are lesions of epidermal keratinocytic dysplasia that result from chronic sun exposure and have the ability to progress to invasive squamous cell carcinoma (SCC), but clinicians disagree about whether AKs are premalignant lesions, superficial SCCin situ or epiphenomena of chronically sun-damaged skin. Yearly AK to SCC progression rates of 0·6% were reported in an elderly population with multiple prior keratinocyte carcinomas (KCs); and rates of spontaneous AK regression have been reported to be > 50%, but regressed lesions often reappear. As AKs have both cosmetic consequences and potential for malignant transformation, there are multiple reasons for treatment. There is no current agreement on the most efficacious treatment, but 5-fluorouracil has been shown to both prevent and treat AKs, and imiquimod and photodynamic therapy may have the best cosmetic outcomes. AKs may be treated to improve appearance and relieve symptoms, but the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, may be what actually threatens patient health. Thus, treatments should aim to decrease the risk of KC or facilitate KC diagnosis by reducing the potential for misidentification created when a KC appears in a field of AKs. Improved agreement among clinicians on AK definition may improve management.

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Paediatric primary cutaneous marginal zone B-cell lymphoma: Does it differ from the adult counterpart?

Summary

Background

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) has rarely been reported in patients younger than 20 years.

Objectives

To report our experience with PCMZL in the paediatric/adolescent age group.

Methods

Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the United States and Israel in 1992-2015 were reviewed.

Results

The study group included 11 patients (6 girls) of median age 16 years (range 6–19.5); 10 had generalized/multifocal (T3) and 1 had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in 6; 2 had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included non-radiation modalities: 1 patient with localized disease received intralesional steroids; 6 patients with multifocal disease received the following: 3 - topical/intralesional steroids, 2 - excision, 1 - “watch and wait”. No extracutaneous progression was noted during a median follow-up of 5.5 years (mean 7.5, range 0.5-14). At present, 5/11 patients are in complete remission.

Conclusions

Based on our data (largest series in the literature with the longest follow up); the clinico-pathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration.

This article is protected by copyright. All rights reserved.

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Is there an association between study size and reporting of study quality in dermatological clinical trials? A meta-epidemiological review

Abstract

Clinicians engaged in evidence-based medicine often have to base treatment decisions on randomised clinical trials (RCTs) with small sizes.¹ The choice of sample size is influenced by a number of factors including power, magnitude of difference anticipated, alpha, study design and whether the objective of the trial is equivalence or superiority. Based on our experience of reviewing hundreds of dermatological clinical trials, we hypothesized that sample size could be a crude surrogate of study quality in that larger studies are of generally better quality than smaller ones.

This article is protected by copyright. All rights reserved.

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Rosacea and gastrointestinal disorders – a population-based cohort study

Abstract

Background

Rosacea is a common inflammatory facial skin condition. Recent genetic and epidemiologic studies have suggested pathogenic links between rosacea and gastrointestinal disorders, but data are limited.

Objectives

The objective was to investigate the association between rosacea and celiac disease (CeD), Crohn's disease (CD), ulcerative colitis (UC), Helicobactor pylori (HP) infection, small intestinal bacterial overgrowth (SIBO), and irritable bowel syndrome (IBS), respectively.

Methods

We performed a nationwide cohort study. A total of 49,475 patients with rosacea, and 4,312,213 general population controls were identified using nationwide administrative registers. We established the prevalence of the aforementioned disorders, and used Cox regression to obtain hazard ratios (HRs) of the risk of new-onset CeD, CD, UC, HP infection, SIBO, and IBS, respectively, in patients with rosacea.

Results

The prevalence of CeD, CD, UC, HP infection, SIBO, and IBS, respectively, was higher among patients with rosacea when compared to the control subjects. Adjusted HRs revealed significant associations between rosacea and CeD (HR 1.46, 1.11-1.93), CD (HR 1.45, 1.19-1.77), UC (HR 1.19, 1.02-1.39), and IBS (HR 1.34, 1.19-1.50) respectively, but not HP infection (HR 1.04, 0.96-1.13) or SIBO (HR 0.71, 0.18-1.86).

Conclusions

Rosacea is associated with certain gastrointestinal diseases, but the possible pathogenic link is unknown. Gastrointestinal complaints in patients with rosacea should warrant clinical suspicion of disease.

This article is protected by copyright. All rights reserved.

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Shape Analysis of DNA–Au Hybrid Particles by Analytical Ultracentrifugation

ACS Nano

DOI: 10.1021/acsnano.6b01377

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Compatibilization of All-Conjugated Polymer Blends for Organic Photovoltaics

ACS Nano

DOI: 10.1021/acsnano.6b04244

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All-Dielectric Colored Metasurfaces with Silicon Mie Resonators

ACS Nano

DOI: 10.1021/acsnano.6b03207

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What predicts a positive response to acupuncture? A secondary analysis of three randomised controlled trials of insomnia

Objective

Few studies have investigated the predictors of the specific and non-specific effects of acupuncture. The aim of this secondary analysis was to determine patient characteristics that may predict a better treatment response to acupuncture for insomnia.

Methods

We pooled the data of three randomised, double-blind, placebo-controlled trials of acupuncture for insomnia to examine sociodemographic variables, clinical characteristics, baseline sleep-wake variables, and treatment expectancy in relation to acupuncture response. Subjects with an improvement in insomnia severity index (ISI) scores of ≥8 points from baseline to 1 week post-treatment were classified as responders. Factors were compared between responders and non-responders, and also by univariate and multivariate logistic regression analysis.

Results

A total of 116 subjects who received traditional needle acupuncture were included, of which 37 (31.9%) were classified as responders. Acupuncture responders had a higher educational level (p<0.01) and higher baseline ISI score (p<0.05), compared to non-responders. In the multivariate logistic regression analysis, only the number of years spent in full-time education remained significant as a predictor of treatment response (OR 1.21, 95% CI 1.06 to 1.38, p<0.01).

Conclusions

Consistent with previous studies, our data suggest that the response to acupuncture is difficult to predict. Although the predictive power of educational level is weak overall, our findings provide potentially valuable information that could be built upon in further research (including a larger sample size), and may help to inform patient selection for the treatment of chronic insomnia with acupuncture in the future.

Trial registration number

ClinicalTrials.gov: #NCT00839592; Results, #NCT00838994; Results, and #NCT01707706; Results.

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Can these tech tools fight gender bias and increase workplace diversity?

New software programs aim to do what unconscious bias training has not yet accomplished: Create blind hiring processes and diversify tech workplaces.

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Comparison of methods using paraffin-embedded tissues and exfoliated cervical cells to evaluate HPV genotype attribution

Summary

Monitoring the attribution of human papillomavirus (HPV) genotypes to cervical precancerous lesions is essential in assessing the efficacy of HPV vaccines. To resolve the lack of studies comparing the HPV genotyping procedures used to estimate HPV genotype attribution, we performed a retrospective cross-sectional study to determine the appropriate genotyping procedures for evaluating the potential efficacy of HPV vaccines. Three procedures, including two different genotyping methods, Clinichip^® HPV test (Chip) and modified GP5+/6+ PCR coupled to fluorescent bead sorter detection (MGP), and in exfoliated cervical cells (C-Chip and C-MGP, respectively) or formalin-fixed paraffin-embedded tissues (F-MGP), were compared. The overall agreement in detecting high-risk HPV was 88.5%–92.1% among the three procedures, and genotype-specific agreement was 83.9%–100% for all pairwise comparisons. In cervical intraepithelial neoplasia grade 2/3 specimens, HPV16/18 attribution estimated with the hierarchical attribution method was consistent among the procedures: 52.3% (45/86) for C-Chip, 54.7% (47/86) for C-MGP, and 52.3% (45/86) for F-MGP (p = 0.81). HPV16/18/31/33/45/52/58 hierarchical attribution was 88.4% (76/86) with C-Chip, 86.0% (74/86) with C-MGP, and 83.7% (72/86) with F-MGP (p = 0.49). In CIN3 specimens, the corresponding hierarchical attribution was 96.4% (53/55) with C-Chip, 89.1% (49/55) with C-MGP, and 94.5% (52/55) with F-MGP (p = 0.27). Although F-MGP is theoretically a reliable method for determining HPV genotype attribution, it is acceptable to use C-Chip or C-MGP, coupled to the hierarchical attribution formula to correct the bias of multiple infections. These approaches using exfoliated cervical cells are practical for monitoring the efficacy of HPV vaccines.

This article is protected by copyright. All rights reserved.

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Peperomin E reactivates silenced tumor suppressor genes in lung cancer cells via inhibition of DNA methyltransferase

Summary

Advanced lung cancer has poor prognosis owing to its low sensitivity to current chemotherapy agents. Therefore, discovery of new therapeutic agents is urgently needed. In this study, we investigated the antitumor effects of peperomin E, a secolignan isolated from Peperomia dindygulensis, a frequently used Chinese folk medicine for lung cancer treatment. The results indicate that peperomin E exhibits antiproliferative effects, promoting apoptosis and cell-cycle arrest in non-small cell lung cancer (NSCLC) cell lines in a dose-dependent manner, while demonstrating lower toxicity against normal human lung epidermal cells. Peperomin E inhibited tumor growth in A549 xenograft BALB/c nude mice without significant secondary adverse effects, indicating that it may be safely used to treat NSCLC. Furthermore, the mechanisms underlying the anticancer effects of peperomin E have been investigated. Using an in silico target fishing method, we observed that peperomin E directly interacts with the active domain of DNA methyltransferase 1 (DNMT1), potentially affecting its genome methylation activity. Subsequent experiments verified that peperomin E decreased DNMT1 activity and expression, thereby decreasing global methylation and reactivating the epigenetically silenced tumor suppressor genes (TSGs) including RASSF1A, APC, RUNX3 and p16INK4, which in turn activates their mediated pro-apoptotic and cell-cycle regulate signaling pathways in lung cancer cells. The observations herein report for the first time that peperomin E is a potential chemotherapeutic agent for NSCLC. The anticancer effects of peperomin E may be partly attributable to its ability to demethylate and reactivate methylation-silenced TSGs through direct inhibition of the activity and expression of DNMT1.

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Preparation and Performance of Asphalt Compound Modified with Waste Crumb Rubber and Waste Polyethylene

Three kinds of modified asphalt were prepared by adding waste crumb rubber (WCR), waste polyethylene (WPE), and WCR/WPE to base asphalt, respectively. The influence of different doses on the performance of modified asphalt, such as 25°C penetration, softening point, 5°C ductility, and 135°C, 165°C viscosity, was studied, and the modification mechanism of modified asphalt was discussed through the fluorescence microscope. As the waterproofing materials, the waterproofness of WCR/WPE compound modified asphalt was tested. The results show that the WPE modified asphalt has excellent resistance to high temperature and WCR modified asphalt has good low temperature resistance. The resistance to deformation ability of WPE modified asphalt is better than that of the WCR modified asphalt. The 135°C viscosity of compound modified asphalt is better than that of WPE and WCR modified asphalt. In addition, the waterproofness of compound modified asphalt using waterproofing materials is better than that of common waterproofing materials.

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Suppressing Syndecan-1 Shedding Ameliorates Intestinal Epithelial Inflammation through Inhibiting NF-κB Pathway and TNF-α

Syndecan-1 (SDC1), with a long variable ectodomain carrying heparan sulfate chains, participates in many steps of inflammatory responses. But reports about the efforts of SDC1’s unshedding ectodomain on intestinal epithelial inflammation and the precise underlying mechanism are limited. In our study, unshedding SDC1 from intestinal epithelial cell models was established by transfecting with unshedding SDC1 plasmid into the cell, respectively. And the role of unshedding SDC1 in intestinal inflammation was further investigated. We found that components of NF-κB pathway, including P65 and IκBα, and secretion of TNF-α were upregulated upon LPS stimulation in intestinal epithelial cells. SDC1, especially through its unshed ectodomain, significantly lessened the upregulation extent. It also functioned in inhibiting migration of neutrophils by downregulating secretion of CXCL-1. Taken together, we conclude that suppressing SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation by inactivating NF-κB pathway and downregulating TNF-α expression. These results indicate that the ectodomain of SDC1 might be the optional therapy for intestinal inflammation.

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Influence of Freeze-Thaw Damage on the Steel Corrosion and Bond-Slip Behavior in the Reinforced Concrete

This paper mainly studies the behavior of steel corrosion in various reinforced concrete under freeze-thaw environment. The influence of thickness of concrete cover is also discussed. Additionally, the bond-slip behavior of the reinforced concrete after suffering the freeze-thaw damage and steel corrosion has also be presented. The results show that the freeze-thaw damage aggravates the steel corrosion in concrete, and the results become more obvious in the concrete after suffering serious freeze-thaw damage. Compared with the ordinary concrete, both air entrained concrete and waterproofing concrete possess better resistance to steel corrosion under the same freeze-thaw environment. Moreover, increasing the thicknesses of concrete cover is also an effective method of improving the resistance to steel corrosion. The bond-slip behavior of reinforced concrete with corroded steel decreases with the increase of freeze-thaw damage, especially for the concrete that suffered high freeze-thaw cycles. Moreover, there exists a good correlation between the parameters of bond-slip and freeze-thaw cycles. The steel corrosion and bond-slip behavior of reinforced concrete should be considered serious under freeze-thaw cycles environment, which significantly impact the durability and safety of concrete structure.

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Nanoporous Glasses for Nuclear Waste Containment

Research is in progress to incorporate nuclear waste in new matrices with high structural stability, resistance to thermal shock, and high chemical durability. Interactions with water are important for materials used as a containment matrix for the radio nuclides. It is indispensable to improve their chemical durability to limit the possible release of radioactive chemical species, if the glass structure is attacked by corrosion. By associating high structural stability and high chemical durability, silica glass optimizes the properties of a suitable host matrix. According to an easy sintering stage, nanoporous glasses such as xerogels, aerogels, and composite gels are alternative ways to synthesize silica glass at relatively low temperatures (≈1,000–1,200°C). Nuclear wastes exist as aqueous salt solutions and we propose using the open pore structure of the nanoporous glass to enable migration of the solution throughout the solid volume. The loaded material is then sintered, thereby trapping the radioactive chemical species. The structure of the sintered materials (glass ceramics) is that of nanocomposites: actinide phases (~100 nm) embedded in a vitreous silica matrix. Our results showed a large improvement in the chemical durability of glass ceramic over conventional nuclear glass.

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An Expert PI Controller with Dead Time Compensation of Monitor AGC in Hot Strip Mill

Hot strip rolling production is a high-speed process which requires high-speed control and communication system, but because of the long distance between the delivery stand of the finishing mill and the gauge meter, dead time occurs when strip is transported from the site of the actuator to another location where the gauge meter takes its reading, which seriously affects the thickness control effect. According to the process model which is developed based on the measured data, a filtered Smith predictor is applied to predict the thickness deviation of the finishing mill. At the same time, an expert PI controller based on feature information is proposed for the strip thinning during looper rising and coiler biting period and the strip thickening during the tension loss period of the strip tail end. As a result, the thickness accuracy has been improved by about 1.06% at a steady rolling speed and about 1.23% in acceleration and deceleration.

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A Feature Selection Approach Based on Interclass and Intraclass Relative Contributions of Terms

Feature selection plays a critical role in text categorization. During feature selecting, high-frequency terms and the interclass and intraclass relative contributions of terms all have significant effects on classification results. So we put forward a feature selection approach, IIRCT, based on interclass and intraclass relative contributions of terms in the paper. In our proposed algorithm, three critical factors, which are term frequency and the interclass relative contribution and the intraclass relative contribution of terms, are all considered synthetically. Finally, experiments are made with the help of kNN classifier. And the corresponding results on 20 NewsGroup and SougouCS corpora show that IIRCT algorithm achieves better performance than DF, -Test, and CMFS algorithms.

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Hepatitis B, HIV, and Syphilis Seroprevalence in Pregnant Women and Blood Donors in Cameroon

Objectives. We estimated seroprevalence and correlates of selected infections in pregnant women and blood donors in a resource-limited setting. Methods. We performed a cross-sectional analysis of laboratory seroprevalence data from pregnant women and voluntary blood donors from facilities in Cameroon in 2014. Rapid tests were performed to detect hepatitis B surface antigen, syphilis treponemal antibodies, and HIV-1/2 antibodies. Blood donations were also tested for hepatitis C and malaria. Results. The seroprevalence rates and ranges among 7069 pregnant women were hepatitis B 4.4% (1.1–9.6%), HIV 6% (3.0–10.2%), and syphilis 1.7% (1.3–3.8%) with significant variability among the sites. Correlates of infection in pregnancy in adjusted regression models included urban residence for hepatitis B (aOR 2.9, CI 1.6–5.4) and HIV (aOR 3.5, CI 1.9–6.7). Blood donor seroprevalence rates and ranges were hepatitis B 6.8% (5.0–8.8%), HIV 2.2% (1.4–2.8%), syphilis 4% (3.3–4.5%), malaria 1.9%, and hepatitis C 1.7% (0.5–2.5%). Conclusions. Hepatitis B, HIV, and syphilis infections are common among pregnant women and blood donors in Cameroon with higher rates in urban areas. Future interventions to reduce vertical transmission should include universal screening for these infections early in pregnancy and provision of effective prevention tools including the birth dose of univalent hepatitis B vaccine.

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Time-Shift Correlation Algorithm for P300 Event Related Potential Brain-Computer Interface Implementation

A high efficient time-shift correlation algorithm was proposed to deal with the peak time uncertainty of P300 evoked potential for a P300-based brain-computer interface (BCI). The time-shift correlation series data were collected as the input nodes of an artificial neural network (ANN), and the classification of four LED visual stimuli was selected as the output node. Two operating modes, including fast-recognition mode (FM) and accuracy-recognition mode (AM), were realized. The proposed BCI system was implemented on an embedded system for commanding an adult-size humanoid robot to evaluate the performance from investigating the ground truth trajectories of the humanoid robot. When the humanoid robot walked in a spacious area, the FM was used to control the robot with a higher information transfer rate (ITR). When the robot walked in a crowded area, the AM was used for high accuracy of recognition to reduce the risk of collision. The experimental results showed that, in 100 trials, the accuracy rate of FM was 87.8% and the average ITR was 52.73 bits/min. In addition, the accuracy rate was improved to 92% for the AM, and the average ITR decreased to 31.27 bits/min. due to strict recognition constraints.

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Anger Management among Medical Undergraduate Students and Its Impact on Their Mental Health and Curricular Activities

Background. This study was intended to determine the practice of students in good anger management skills and to what extent their anger can affect their studies, work, and social interactions. In this study the relationship between anger management and the effects on the mental health of medical students was evaluated. A survey was also done to determine duration of the feeling of anger which lasts among medical students and its consequences. Materials and Methods. A newly developed questionnaire was utilized which included a simplified version of the Novaco Anger Scale and Provocation Inventory and the modified Patient Health Questionnaire 9 (to measure the mental health). Results. The data suggests that although students with high anger tendencies display poor mental health, there is no lowering of the mental health/PHQ-9 score as the anger management technique’s effectiveness rises. “Friends” was cited as the major triggering factor for anger, whereby the feelings can last for up to a day and somewhat affect their concentration on normal activities. Conclusion. When anger is suppressed and not let out, it can be an underlying factor for anxiety and depression. Therefore, more emphasis needs to be placed on educating students on how to manage their anger especially in a stressful environment away from home.

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Urethral Solitary Fibrous Tumor: A Rare Pathologic Diagnosis of a Periurethral Mass

Solitary fibrous tumors (SFTs) may occur at any site in the body. SFTs can only be conclusively diagnosed based on histopathologic and immunohistochemical characteristics of the tumor. The presence of SFTs in the abdomen and pelvis is extremely rare. To our knowledge no cases of urethral solitary fibrous tumor in the literature have been reported so far. We present a case of a solitary fibrous tumor arising from the urethra in a twenty-three-year-old female presenting with vaginal mass.

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Neural Modulation in Aversive Emotion Processing: An Independent Component Analysis Study

Emotional processing has an important role in social interaction. We report the findings about the Independent Component Analysis carried out on a fMRI set obtained with a paradigm of face emotional processing. The results showed that an independent component, mainly cerebellar-medial-frontal, had a positive modulation associated with fear processing. Also, another independent component, mainly parahippocampal-prefrontal, showed a negative modulation that could be associated with implicit reappraisal of emotional stimuli. Independent Component Analysis could serve as a method to understand complex cognitive processes and their underlying neural dynamics.

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Tumor Regression in HCC Patient with Portal Vein Tumor Thrombosis after Intraportal Radiofrequency Thermal Ablation

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Portal vein tumor thrombosis (PVTT) is a frequent entity in HCC, which strictly limits the gold standard treatment options such as surgical resection and transarterial chemoembolization. Therefore, the prognosis of patients with PVTT is extremely poor and an emergence of seeking an alternative option for intervention is inevitable. We present a case of a 60-year-old male patient with HCC induced PVTT who was subjected to the intraportal RFA and stenting-VesOpen procedure. No additional medical intervention was performed. The repeated CT performed 5 months after the VesOpen procedure revealed significant decrease of the tumor size, patent right, and main portal vein and a recanalization of the left portal vein, which was not processed. At this time point, liver functional tests, appetite, and general condition of the patient were improved evidently. This report designates the RFA as an instrumental option of therapeutic intervention for HCC patients with PVTT.

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Array Mutual Coupling Reduction Using L-Loading E-Shaped Electromagnetic Band Gap Structures

A mutual coupling reduction method between microstrip antenna array elements is proposed by using periodic L-loading E-shaped electromagnetic band gap structures. Two identical microstrip patch antennas at 2.55 GHz are settled together and used to analyze the performance of the designed two-element antenna array. The two antenna elements are settled with a distance of about . To reduce the mutual coupling, the L-loading E-shaped electromagnetic band gap structures are used between these antenna elements. The simulated and measured results show that the isolation of the antenna array reaches 38 dB, which has a mutual coupling reduction of 26 dB in comparison with the antenna array without the decoupling structures.

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Insurance status and disparities in disease presentation, treatment, and outcomes for men with germ cell tumors

BACKGROUND

People aged 26 to 34 years represent the greatest proportion of the uninsured, and they have the highest incidence of testicular cancers. The aim of this study was to investigate the association between insurance status and cancer outcomes in men diagnosed with germ cell tumors.

METHODS

The Surveillance, Epidemiology, and End Results database was used to identify 10,211 men diagnosed with germ cell gonadal neoplasms from 2007 to 2011. Associations between insurance status and characteristics at diagnosis and receipt of treatment were examined with log-binomial regression. The association between insurance status and mortality was assessed with Cox proportional hazards regression.

RESULTS

Uninsured patients had an increased risk of metastatic disease at diagnosis (relative risk [RR], 1.26; 95% confidence interval [CI], 1.15-1.38) in comparison with insured patients, as did Medicaid patients (RR, 1.62; 95% CI, 1.51-1.74). Among men with metastatic disease, uninsured and Medicaid patients were more likely to be diagnosed with intermediate/poor-risk disease (RR for uninsured patients, 1.22; 95% CI, 1.04-1.44; RR for Medicaid patients, 1.39; 95% CI, 1.23-1.57) and were less likely to undergo lymph node dissection (RR for uninsured patients, 0.74; 95% CI, 0.57-0.94; RR for Medicaid patients, 0.76; 95% CI, 0.63-0.92) in comparison with insured patients. Men without insurance were more likely to die of their disease (hazard ratio [HR], 1.88; 95% CI, 1.29-2.75) in comparison with insured men, as were those with Medicaid (HR, 1.58; 95% CI, 1.16-2.15).

CONCLUSIONS

Patients without insurance and patients with Medicaid have an increased risk of presenting with advanced disease and dying of the disease in comparison with those who have insurance. Future studies should examine whether implementation of the Patient Protection and Affordable Care Act reduces these disparities. Cancer 2016. © 2016 American Cancer Society.

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Insurance status, health equity, and the cancer care continuum

As illustrated in two studies published in this issue of Cancer, an individual's sociodemographic characteristics including type of health insurance can decrease access to receiving high-quality and timely cancer care and result in adverse outcomes. Understanding the factors that create cancer health care disparities can help researchers, clinicians, and policy makers develop strategies and interventions to reduce them. See also pages.

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Influence of insurance status on survival of adults with glioblastoma multiforme: A population-based study

BACKGROUND

To the authors' knowledge, the impact of insurance status on the survival time of patients with glioblastoma multiforme (GBM) has not been fully understood. The objective of the current study was to clarify the association between insurance status and survival of patients with GBM by analyzing population-based data.

METHODS

The authors performed a cohort study using data from the Surveillance, Epidemiology, and End Results program. They included adult patients (aged ≥18 years) with GBM as their primary diagnosis from the years 2007 to 2012. Patients without information regarding insurance status were excluded. A survival analysis between insurance status and GBM-related death was performed using an accelerated failure time model. Demographic and clinical variables were included to adjust for confounding effects.

RESULTS

Among the 13,665 adult patients in the study cohort, 558 (4.1%) were uninsured, 1516 (11.1%) had Medicaid coverage, and 11,591 (84.8%) had non-Medicaid insurance. Compared with patients who were uninsured, insured patients were more likely to be older, female, white, married, and with a smaller tumor size at diagnosis. Accelerated failure time analysis demonstrated that older age (hazard ratio [HR], 1.04; P<.001), male sex (HR, 1.08; P<.001), large tumor size at the time of diagnosis (HR, 1.26; P<.001), uninsured status (HR, 1.14; P =.018), and Medicaid insurance (HR, 1.10; P =.006) were independent risk factors for shorter survival among patients with GBM, whereas radiotherapy (HR, 0.40; P<.001) and married status (HR, 0.86; P<.001) indicated a better outcome. The authors discovered an overall yearly progressive improvement in survival in patients with non-Medicaid insurance who were diagnosed from 2007 through 2011 (P =.015), but not in uninsured or Medicaid-insured patients.

CONCLUSIONS

Variations existed in insurance status within the GBM population. Uninsured status and Medicaid insurance suggested shorter survival compared with non-Medicaid insurance among a population of patients with GBM. Cancer 2016. © 2016 American Cancer Society.

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