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While the world is battling COVID-19 pandemic and its variants; netizens are combating Infodemic – "Proliferation of fake news online". Spread of fake news during this global pandemic COVID-19 has dangerous consequences. Precise automated fake news detection is the need of the hour. This is the driving force behind this study. Intrinsic quality of news data: precision and objectivity can be studied to detect the credibility. However, to gain the knowledge or inference from it further it is a challenge. To address this challenge, this work proposes derivation of features into two categories: intrinsic word level features (Fine-grained) and sentence level features (Coarse- grained).For experimentation, fine-grained features are learned from word vector representation of the news articles. Psycho-linguistic and sentiment level word level features are derived using Empath library. Coarse-grained features (sentence-level) comprise of vectors generated by Text summarization and DOC2Vec. Taking the advantages of existing approaches, this paper proposes a new framework Granularity based Fake news Detection (GRAFED) that explores fusion of fine and coarse-grained features. The fusion of feature set is more powerful than individual fine or coarse-grained feature sets as they can capture complex interdependence of words in the sentence along with the semantics. Exhaustive experimentation using traditional classifiers with hybrid granular feature vector of GRAFED outperformed the existing approaches for publicly available state-of-art LIAR dataset. Experimental results show that the hybrid feature set is superior to individual feature set and the results are promising when compared to the existing state-of-art approaches as analyzed in the comparative analysis section. [ABSTRACT FROM AUTHOR]

To determine the prevalence of non-use and limited use of cochlear implants. To find out the reasons for the same. This study was carried out among the paediatric patients who underwent cochlear implantation under the SHP* scheme in Civil Hospital, Ahmedabad between 2013 and 2020. Study Design: Retrospective cross-sectional study. Study Setting: Civil Hospital Ahmedabad. Sample Size: 150 paediatric patients. Patients were selected based on a random number generator. The data was collected through a telephonic interview based upon a preformed questionnaire. The study indicates that out of a total 150 participants, 109 (72.7%) used their cochlear implant regularly while 41 (27.3%) did not. Major issue faced by the participants was in the external device -damage to the device and monetary issues for its repair. The participants who have dropped the usage of their implants faced issues mostly after 2 years of usage. The age group of less than 3 years showed 15.6% of non-usage, while the age group of 3–6 years showed an increase to 34.5% of non-users. The age group of more than 6 years showed an even higher proportion (41.3%) of non-users. It is recommended that the government ensures the follow-up of the patients undergoing cochlear implantation for at least 2 years after the surgery. The proportion of non-users in the consecutive increasing age groups saw a rise in number. Therefore, it is recommended to divert the resources towards lower age groups to facilitate a better outcome. [ABSTRACT FROM AUTHOR]

Background: Endoscopic papillectomy (EP) offers a safe and effective method for resection of ampullary adenomas. Data regarding the long-term resolution of adenoma following EP are limited. The aim of this study therefore was to examine the timing of recurrence after EP of ampullary adenomas. Methods: This was a single-center retrospective study including patients who received EP for ampullary adenomas from 8/2000 to 1/2018. Patients with confirmed complete eradication of adenoma were included in the recurrence analysis with recurrence defined as finding adenomatous histology after 1 negative surveillance endoscopy. Kaplan–Meier estimates were calculated to determine recurrence rates. Results: Of the 165 patients who underwent EP, 136 patients (mean age 61.9, 51.5% female) had adenomatous histology with a mean lesion size of 21.2 mm. A total of 124 (91.2%) achieved complete eradication with a follow-up of 345.8 person-years. Recurrence occurred in 20 (16.1%) patients at a mean of 3.2 (± 3) years (range 0.5–9.75 years) for a recurrence rate of 5.8 (95% CI 3.6–8.8) per 100 person-years. Nine (45%) recurrences occurred after the 1st 2 years of surveillance. Recurrence rate did not differ by baseline pathology [low-grade dysplasia: 5.2 (95% CI 3.0–9.0), high-grade dysplasia: 6.9 (95% CI 2.3–15.5), adenocarcinoma: 7.7 (95% CI 0.9–25.1)]. Conclusion: Recurrence remains a significant concern after EP. Given the timing of recurrence, long surveillance periods may be necessary. Larger multicenter studies are needed, however, to determine appropriate surveillance intervals. [ABSTRACT FROM AUTHOR]

Background: The development of guidelines by gastroenterology societies increasingly stresses evidence-based endoscopic practice. Aims: We performed a systematic assessment to determine whether endoscopic video teaching platforms incorporate evidence-based educational strategies and methods in order to disseminate guideline-based endoscopic management strategies. Methods: Platforms with a video component were systematically identified using the Google search engine, Apple and Android application stores, and searching four major gastroenterology society websites and three known platforms, to identify all relevant platforms. Two video samples from each teaching platform were reviewed independently by two authors and assessed for use of a priori defined principles of evidence-based medicine, as determined by consensus agreement and for the use of simulation. Results: Fourteen platforms were included in the final analysis, and two videos from each were analyzed. One of the 14 platforms used simulation and incorporated evidence-based medicine principles consistently. Nine of the 14 platforms were not transparent in regard to citation. None of the platforms consistently cited the certainty of evidence or explained how evidence was selected. Conclusions: Education of guideline-based endoscopic management strategies using principles of evidence-based medicine is under-utilized in endoscopic videos. In addition, the use of cognitive simulation is absent in this arena. There is a paucity of evidence-based cognitive endoscopy simulators designed for fellows that incorporate systematic evaluation, and efforts should be made to create this platform. [ABSTRACT FROM AUTHOR]

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583) [ABSTRACT FROM AUTHOR]

Background: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking.Objective: Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people.Design: Prospective cohort study.Setting: Primary care (Australia and USA).Participants: 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100.Measurements: Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition.Results: At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications.Limitations: Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible.Conclusions: High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people. [ABSTRACT FROM AUTHOR]

Background: Biliary stricture evaluation with brush cytology and intraductal forceps biopsy carries a low sensitivity, but the combination of newer modalities may improve sensitivity. Aim: To determine whether the addition of advanced modalities increases diagnostic yield of ERCP-based sampling. Methods: This single-center retrospective study evaluates patients with biliary strictures sampled using brush cytology. Operating characteristics were calculated for individual and combinations of modalities including cholangioscopy, fluoroscopy- and cholangioscopy-directed intraductal biopsy, fluorescence in situ hybridization (FISH), and confocal laser endomicroscopy. Analyses under Standard Criteria (SC) included malignant results as "positive" and Expanded Criteria (EC) included "suspicious" and "high-grade dysplasia" results as "positive." Results: A total of 614 patients were included, and 354 (57.8%) received brush cytology alone, which had a sensitivity of 38.5% (SC) to 40.3% (EC) and a specificity of 97.8% (EC) to 99.3% (SC). Combining brush cytology with fluoroscopy-guided biopsy (n = 259, 42.2%) had a sensitivity of 62.5% (SC) to 67.9% (EC) and specificity of 90.2% (EC) to 96.7% (SC). Adding FISH to brush cytology had a sensitivity of 84.2% (SC) to 87.5% (EC) and specificity of 54.1% (SC and EC), while cholangioscopy visualization addition resulted in a sensitivity of 80.4% (SC) to 92.2% (EC) and specificity of 67.3% (EC) to 89.1% (SC). There were no significant differences in sensitivity and specificity using SC and EC. Conclusions: Brush cytology has a low sensitivity, but the addition of other modalities increases sensitivity. There was no difference in specificity between the SC and the EC, supporting the inclusion of "suspicious" impressions with malignant results at our center. [ABSTRACT FROM AUTHOR]

Background: Despite the growing trend of obesity, the utilization of anti-obesity therapeutic interventions is not robust in the USA. We aimed to analyze the trends of anti-obesity pharmacotherapy using a population level database. Methods: We used an electronic health record-derived database (Explorys, IBM Watson Health) to identify adults with obesity (body mass index ≥ 30 kg/m2), 2010–2019. Annual rates of anti-obesity pharmacotherapy were analyzed. To assess post-bariatric utilization of these medications, the trend of adults with morbid obesity (BMI ≥ 40 kg/m 2) who were newly started on anti-obesity medications after sleeve gastrectomy was also analyzed. Results: Among 11,195,020 adults with obesity, 274,160 (2.4%) were prescribed anti-obesity medications during the study period with an increase from 1.1% in 2010 to 2.9% in 2019 (p < 0.0001). A total of 900 (3.5%) of those with morbid obesity were started on weight loss medications within 5 years of sleeve gastrectomy. Women [odds ratio (OR) 3.57, 95% confidence interval (CI) 3.51–3.58], individuals under 50 years (OR 1.59, CI 1.57–1.60), non-Hispanics (OR 1.12, 1.10–1.14, p < 0.0001), African Americans (OR 1.18, CI 1.16–1.19), Medicaid (OR 1.70, CI 1.67–1.73), and commercial insurance holders (OR 2.46, 2.43–2.49) were more likely to receive anti-obesity pharmacotherapy, p < 0.001 for all comparisons. Conclusion: There has been a modest increase in the prevalence of anti-obesity medications in the last 10 years, but they remain significantly underutilized. Further studies addressing the barriers to anti-obesity pharmacotherapy might help in increasing the utilization of these medications among adults with obesity. [ABSTRACT FROM AUTHOR]

This paper presents a design methodology for a single-gate single-electron transistor (SG-SET) for room temperature operation of SET and hybrid SETMOS circuits. Initially, the SET electrostatics is analytically modeled using a free-energy equation. Tunneling probability is determined by modifying the Mahapatra–Ionescu–Banerjee model. The SET is designed systematically so as to achieve process and supply voltage compatibility with 22-nm CMOS technology. A Si–Al–Si SG-SET with 3-nm ultra-thin SiO 2 tunnel barriers is proposed and simulated with drift-diffusion, Philips unified mobility, and Schenk direct tunneling models. A 1D Schrodinger equation was solved in the critical region that covered two tunnel barriers and a conductive island. The current-voltage characteristic of the SG-SET is plotted to observe a Coulomb blockade of ± 0.8 V at room temperature. The tunnel resistance and total island capacitance of the proposed SET for circuit simulations are extracted as 20 M Ω and 0.193 aF, and they are in very close agreement with the analytical values. The tunnel resistance extracted from TCAD simulations is used in the MIB model for validation of SET functionality. Further, we propose the use of this SET in hybrid SETMOS logic implementation at room temperature with ultra-low power consumption. [ABSTRACT FROM AUTHOR]

A novel hybrid silicon Single Electron Transistor Metal Oxide Semiconductor (SETMOS) logic is evaluated for its functionality and usability. Emphasis is given on obtaining functionality at ambient temperature with low power consumption and significant drive. Performance is evaluated with respect to 22 nm Complementary Metal Oxide Semiconductor (CMOS) technology and other popular hybrid SETMOS topologies. The results produced here not only comprehend performance of various SET-CMOS based logic architectures, but they are also closer to real values as they consider effect of parasitic in respective topologies. Proposed work is power efficient, scalable, accurate and process compatible logic design, which uses less hardware and operates at room temperature. It relies on CMOS compatible fabrication of Silicon SET and P-Type Metal Oxide Semiconductor (PMOS) on same chip footprint. When compared with contemporary SETMOS hybrid circuits, it offers 90.29 % power improvement at the cost of 16.53 % reduction in speed. [ABSTRACT FROM AUTHOR]

Nanostructured iron–zirconium oxides (NIZOs), with Fe-to-Zr molar ratio of 1:1 and 1:2, have been found to show high adsorption efficiency toward Pb2+ from aqueous solution. The NIZO was synthesized by the co-precipitation method and characterized in terms of XRD, TEM, SEM–EDX, BET surface area analysis, TGA, FT-IR spectroscopy and zeta potential measurement. The data of adsorption of Pb2+ on the NIZO, under optimized condition of pH, Pb2+ concentration, adsorbent amount, time and temperature, were fitted in Langmuir, Freundlich and Temkin adsorption model, and the data showed the best agreement with Langmuir model with R2 = 0.990 and 0.994 for Fe/Zr molar ratio = 1:1 and 1:2, respectively. The thermodynamic studies showed that the adsorption of Pb2+ on the NIZO proceeds spontaneously and exothermically through the involvement of weak van der Waals forces. Further, the adsorption of Pb2+ on the NIZO was found to follow pseudo-second-order kinetics. [ABSTRACT FROM AUTHOR]

Nanostructured zirconium ferrite with improved surface area of 392 m2/g has been found to show high adsorption affinity for Co2+, Cu2+, and Zn2+. The adsorption was found to be greatly dependent on pH and the maximum adsorption was found at pH 6. The adsorption trends were found to be best fitted with Langmuir adsorption isotherm with regression coefficient (R2) value of 0.999, 0.998, and 0.999 for Co2+, Cu2+, and Zn2+, respectively, at 288 K. The values of Xm and KL were calculated and showed the maximum adsorption capacities towards Cu2+ and minimum adsorption of Co2+ under the optimized pH, contact time, concentration of adsorbate, adsorbent dose, and temperature. The values of thermodynamic parameters ΔH°, ΔS°, and ΔG° were calculated and showed that the adsorption of Co2+, Cu2+, and Zn2+ on ZFNPs takes place through weak van der Waals interaction. Further, the adsorption of Co2+, Cu2+, and Zn2+ on ZFNPs was found to follow the pseudo–second–order kinetics. [ABSTRACT FROM AUTHOR]

Background: Biliary-enteric anastomotic strictures (AS) in long-limb surgical biliary bypass (LLBB) require percutaneous transhepatic biliary drains (PTBD), enteroscopy-assisted ERCP (E-ERCP), or surgical revision.Aim: To compare E-ERCP and PTBD for AS treatment.Methods: E-ERCP stricturoplasty included dilation, cautery, and stent; PTBD included balloon dilation and serial drain upsizing events.Results: From May 2008 to October 2015, 71 patients (37 M, median age 52) had E-ERCP (n = 45) or PTBD (n = 26) for AS in Roux-en-Y hepaticojejunostomy: liver transplant (n = 28), cholecystectomy injury revision (n = 21), other (n = 13) or Whipple's resection (n = 9). Median follow-up is 11 months (range 1-56) in 67 (94%) patients. Technical success, clinical improvement, and adverse events between E-ERCP and PTBD were similar (76% vs. 77%, p = 0.89; 82% vs. 85%, p = 0.80, and 6% vs. 5%, p = 0.60, respectively). However, E-ERCP had fewer post-procedural hospitalization days (0.2 ± 0.65 vs. 4.5±10, p = 0.0001), mean procedures (4.4 ± 6.3 vs. 9.5 ± 8, p = 0.006), and median months of treatment to resolve AS (1, range 1-22 vs. 7, range 3-23; p = 0.003). Two patients in PTBD group required surgery.Conclusions: (1) Technical success and clinical improvement are seen in the majority of LLBB patients with biliary-enteric AS undergoing E-ERCP or PTBD. (2) E-ERCP is associated with fewer procedures, post-procedure hospitalization days, and months to resolve AS. When expertise is available, E-ERCP to identify and treat AS should be considered as an alternative to PTBD. [ABSTRACT FROM AUTHOR]

Pure, 3 mol% and 5 mol% Sr-doped cerium oxide nanoparticles were synthesized by facile aqueous co-precipitation method using cerium nitrate hexahydrate and strontium chloride hexahydrate as the precursors without using any capping agent. The synthesized material was characterized by XRD, SEM, EDX, TEM, Raman spectroscopy and UV–Vis spectroscopic techniques. SEM analysis showed agglomeration of the particles. The Debye–Scherrer analysis revealed fluorite structure of the synthesized material with crystallite size in 6–10 nm range. TEM confirmed the spherical morphology of the particles and particle size distribution in the range of 5–8 nm. UV–Vis spectroscopic study revealed that Sr-doping led to increase in the band gap from 3.2 to 3.7 eV and shifting of absorption edge to the lower wavelength. The blue shift in the band gap with the dopant concentration shows that the band gap of doped cerium oxide nanoparticles can be tuned with variation in the dopant concentration. [ABSTRACT FROM AUTHOR]

Background: Statin use has been frequently associated with depressive symptoms in an older population. However, the nature of this association is uncertain in the literature. In this study, we aimed to investigate the association of statin intake and the prevalence of depressive symptoms in healthy community-dwelling older adults living in Australia and the USA.Methods: We analysed baseline data from 19,114 participants, over 70 years of age (over 65 years of age, if from an ethnic minority). The association of self-reported statin use and prevalence of depressive symptoms, as measured by a validated depression scale [Center for Epidemiological Studies Depression Scale (CES-D 10)], was determined using logistic regression models. Multivariable logistic models were implemented to account for important demographics and other lifestyle and socioeconomic factors, such as sex, age, living status, education and smoking history.Results: A total of 5987 individuals were statin users. Of those, 633 (10.6%) had depressive symptoms (CES-D 10 cut-off ≥ 8), compared with 1246 (9.5%) of the non-statin users. In the unadjusted model, statin use was associated with an increase in prevalence of depressive symptoms (odds ratio 1.13, confidence interval 1.02-1.25, p = 0.02). However, after adjusting for important demographic and socioeconomic factors, the use of statins was not significantly associated with depressive symptoms (odds ratio 1.09, confidence interval 0.98-1.20, p = 0.11). In secondary analyses, only simvastatin was marginally associated with an increased prevalence of depressive symptoms. Statins were associated with a decreased prevalence of depressive symptoms in individuals with severe obesity (body mass index > 35 kg/m2) and an increased prevalence in participants between 75 and 84 years of age.Conclusion: This study in a large community-dwelling older population did not show any association of statins with late-life depressive symptoms, after accounting for important socioeconomic and demographic factors. Confounding by indication is an important issue to be addressed in future pharmacoepidemiologic studies of statins. [ABSTRACT FROM AUTHOR]

Purpose: To explore the relationship between sociodemographic and lifestyle variables with health-related quality of life (HRQoL) of a large cohort of 'healthy' older individuals.Methods: The sample included individuals aged 65+ years from Australia (N = 16,703) and the USA (N = 2411) enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) multicentre placebo-controlled trial study and free of cardiovascular disease, dementia, serious physical disabilities or 'fatal' illnesses. The associations with the physical (PCS) and mental component scores (MCS) of HRQoL (SF-12 questionnaire) were explored using multiple linear regression models from data collected at baseline (2010-2014).Results: The adjusted PCS mean was slightly higher in the USA (49.5 ± 9.1) than Australia (48.2 ± 11.6; p < 0.001), but MCS was similar in both samples (55.7 ± 7.5 and 55.7 ± 9.6, respectively; p = 0.603). Males, younger participants, better educated, more active individuals, or those currently drinking 1-2 alcoholic drinks/day showed a better HRQoL (results more evident for PCS than MCS), while current heavy smokers had the lowest physical HRQoL in both countries. Neither age, walking time, nor alcohol intake was associated with MCS in either cohort.Conclusions: Baseline HRQoL of ASPREE participants was higher than that reported in population-based studies of older individuals, but the associations between sociodemographic and lifestyle variables were consistent with the published literature. As the cohort ages and develops chronic diseases, ASPREE will be able to document HRQoL changes. [ABSTRACT FROM AUTHOR]

Purpose: Lung cancer early detection screening has been demonstrated to decrease lung cancer mortality among high-risk smokers. This study aimed to examine whether current screening guidelines may disproportionately exclude African American smokers who are at higher overall risk for lung cancer.Methods: Data from the 2014 Health and Retirement Study were analyzed. Older African Americans and Whites with a history of smoking were included in the analyses (n = 7,348). Eligibility criteria established by the U.S. Preventive Services Task Force (USPSTF) for LDCT lung cancer screening were used. Multivariate logistic regression analyses were conducted to examine racial differences in eligibility for LDCT lung cancer screening.Results: Overall, 21.1% of current and 10.5% of former smokers met USPSTF's eligibility criteria for LDCT screening. In multivariate logistic regression analyses, African American smokers were less likely to be eligible for LDCT lung cancer screening compared to Whites (odds ratio = 0.5; p < 0.001).Conclusion: African American smokers were less likely to meet established lung cancer screening eligibility criteria compared to Whites. Current lung cancer screening criteria may not adequately capture African Americans at risk and may widen the health disparities in African Americans. Further longitudinal studies are needed to evaluate the efficacy of current lung cancer screening guideline. [ABSTRACT FROM AUTHOR]

Considerable research has focused on patients with trinucleotide (CGG) repeat expansions in the fragile X mental retardation 1 ( FMR1) gene that fall within either the full mutation (>200 repeats) or premutation range (55-200 repeats). Recent interest in individuals with gray zone expansions (41-54 CGG repeats) has grown due to reported phenotypes that are similar to those observed in premutation carriers, including neurological, molecular, and cognitive signs. The purpose of this manuscript is to describe a series of adults with FMR1 alleles in the gray zone presenting with movement disorders or memory loss. Gray zone carriers ascertained in large FMR1 screening studies were identified and their clinical phenotypes studied. Thirty-one gray zone allele carriers were included, with mean age of symptom onset of 53 years in patients with movement disorders and 57 years in those with memory loss. Four patients were chosen for illustrative case reports and had the following diagnoses: early-onset Parkinson disease (PD), atypical parkinsonism, dementia, and atypical essential tremor. Some gray zone carriers presenting with parkinsonism had typical features, including bradykinesia, rigidity, and a positive response to dopaminergic medication. These patients had a higher prevalence of peripheral neuropathy and psychiatric complaints than would be expected. The patients seen in memory clinics had standard presentations of cognitive impairment with no apparent differences. Further studies are necessary to determine the associations between FMR1 expansions in the gray zone and various phenotypes of neurological dysfunction. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. Aim: To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. Methods: Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. Results: A total of 69 patients (22 male, aged 66.1 ± 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma ( n = 45), pancreatic cancer ( n = 19), gallbladder cancer ( n = 2), gastric cancer ( n = 1), and liver metastasis from colon cancer ( n = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation ( p < 0.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95 % 1.03-5.38)]. Seven patients (10 %) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46 months (6.2-25 months). Conclusion: Radiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival. [ABSTRACT FROM AUTHOR]

Metabotropic glutamate receptor 1 (mGluR1/Grm1) is a member of the G-protein-coupled receptor superfamily, which was once thought to only participate in synaptic transmission and neuronal excitability, but has more recently been implicated in non-neuronal tissue functions. We previously described the oncogenic properties of Grm1 in cultured melanocytes in vitro and in spontaneous melanoma development with 100 % penetrance in vivo. Aberrant mGluR1 expression was detected in 60-80 % of human melanoma cell lines and biopsy samples. As most human cancers are of epithelial origin, we utilized immortalized mouse mammary epithelial cells (iMMECs) as a model system to study the transformative properties of Grm1. We introduced Grm1 into iMMECs and isolated several stable mGluR1-expressing clones. Phenotypic alterations in mammary acinar architecture were assessed using three-dimensional morphogenesis assays. We found that mGluR1-expressing iMMECs exhibited delayed lumen formation in association with decreased central acinar cell death, disrupted cell polarity, and a dramatic increase in the activation of the mitogen-activated protein kinase pathway. Orthotopic implantation of mGluR1-expressing iMMEC clones into mammary fat pads of immunodeficient nude mice resulted in mammary tumor formation in vivo. Persistent mGluR1 expression was required for the maintenance of the tumorigenic phenotypes in vitro and in vivo, as demonstrated by an inducible Grm1-silencing RNA system. Furthermore, mGluR1 was found be expressed in human breast cancer cell lines and breast tumor biopsies. Elevated levels of extracellular glutamate were observed in mGluR1-expressing breast cancer cell lines and concurrent treatment of MCF7 xenografts with glutamate release inhibitor, riluzole, and an AKT inhibitor led to suppression of tumor progression. Our results are likely relevant to human breast cancer, highlighting a putative role of mGluR1 in the pathophysiology of breast cancer and the potential of mGluR1 as a novel therapeutic target. [ABSTRACT FROM AUTHOR]