1,721,307 research outputs found
The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years’ experience of association studies to understand the genetic architecture of pancreatic cancer
Full text linkPancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33
susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant
hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease.
Additionally, the inability to adequately power research questions prevents small monocentric studies from being
successful. Several consortia have been established to pursue a better understanding of the genetic architecture of
pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is
spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groupsAssociazione Italiana per la Ricerca sul Cancro (AIRC) under IG
2019—ID. 23672 project—P.I. Campa Daniele and IG 2021 ID – 26201
project P.IThe Czech Ministry of Health, NU21–07–00247 and from
Programme EXCELESID Project No. LX22NPO5102. Fondazione IRCCS
“Casa Sollievo della Sofferenza” Hospital, San Giovanni Rotondo (FG)Italian Minister of Health, Ricerca
Corrente program 2022–2024Cancer Research UK (C7690/A26881, C18616/A25153)
and Pancreatic Cancer UK. Sample accrual at the Amsterdam UMC was
supported by the AMC FoundationCOST Action TRANSPANCA21116COST (European
Cooperation in Science and Technology
Dispositivo microarray e procedimento per la rivelazione e identificazione di patogeni fungini
No full textExplainable machine learning identifies a polygenic risk score as a key predictor of pancreatic cancer risk in the UK Biobank
No full textBackground: Predicting the risk of developing pancreatic ductal adenocarcinoma (PDAC) is of paramount importance, given its high mortality rate. Current PDAC risk prediction models rely on a limited number of variables, do not include genetics, and have a modest accuracy. Aim: This study aimed to develop an interpretable PDAC risk prediction model, based on machine learning (ML). Methods: Five ML models (Adaptive Boosting, eXtreme Gradient Boosting, CatBoost, Deep Forest and Random Forest) built on 56 exposome variables and a polygenic risk score (PRS) were tested in 654 PDAC cases and 1,308 controls of the UK Biobank. Additionally, SHapley Additive exPlanation (SHAP) and Global model Interpretation via the Recursive Partitioning (Girp) were employed to explain the models. Results: All models provided similar performance, but based on recall the best was CatBoost (77.10 %). SHAP highlighted age and the PRS as primary contributors across all models. Girp developed rules to discern cases from controls, identifying age, PRS, and pancreatitis in most of the rules. Conclusion: The predictive models tested have exhibited good performance, indicating their potential application in the clinical field in the near future, with the PRS playing a key role in identifying high-risk individuals as demonstrated by the explainers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Could polymorphisms in ATP-binding cassette C3/multidrug resistance associated protein 3 (ABCC3/MRP3) modify colorectal cancer risk
No full textMultidrug resistance associated protein 3 (ABCC3/MRP3) mediates the efflux of bile salts and several conjugated organic anions out of cells and could be involved in protecting tissues from xenobiotic accumulation and resulting toxicity. In this report, we investigated the hypothesis that a functional missense variant, namely the Arg1297His, and a polymorphism in the promoter region, namely the -211 C > T of the ABCC3 gene, could be associated with colorectal cancer risk. We did not find any significant association between the two ABCC3 polymorphisms and colorectal cancer ris
Differential expression of secretory aspartyl proteinase genes (SAP1-10) in oral Candida albicans isolates with distinct karyotypes
Full text linkTwo karyotypes of oral Candida albicans isolates, named b and c, constituted >80% of a collection from healthy carriers (22 b and 16 c isolates) and oral candidiasis patients who were either infected (31 b and 16 c isolates) or uninfected (13 b and 38 c isolates) with human immunodeficiency virus (HIV). The prevalence of the b and c karyotypes within HIV-positive and HIV-negative patients, respectively, who were suffering from oral candidiasis (P < or = 0.0001) suggested that these two types possessed different virulence potentials. Since C. albicans proteinases (Saps) are virulence factors in oral candidiasis, we evaluated whether the b and c karyotypes secreted different levels of Saps and expressed different patterns of Sap-encoding genes (SAP1-10). We found that the mean value of Sap activity was significantly lower (P = 0.003) in the commensal type than in the infectious b karyotype, whereas Sap activity in the commensal c type was as high as that registered for the infectious c strains. Marked differences in SAP mRNA expression were observed in commensal strains under non-Sap-inducing conditions, with all SAP genes being expressed only by strains with the c karyotype; interestingly, none of the commensal b strains expressed SAP2. In addition, while all of the SAP1-10 genes were detectable under Sap-inducing conditions, the timing of their expression during growth differed significantly, with mRNAs of SAP1-10 genes detected at 8 and 24 h postinoculation in c and b commensal strains, respectively. This provides the first evidence that commensal oral C. albicans isolates with distinct karyotypes are characterized by different patterns of SAP1-10 gene expression and different levels of Sap secretion
Polymorphisms of dopamine receptor/transporter genes and risk of non-small cell lung cancer
No full textBackground: The dopaminergic pathway may be of interest in assessing risk of non-small cell lung cancer (NSCLC). Dopamine receptors are expressed in alveolar epithelial cells and human lung tumours, and dopamine inhibits both cell proliferation in vitro and growth of lung tumour xenografts in nude mice. Moreover, dopamine selectively inhibits the vascular permeability and angiogenic activity of vascular endothelial growth factor (VPF/VEGF). The bioavailability of dopamine is regulated by dopamine receptors D2 (DRD2), D4 (DRD4) and dopamine transporter 1 (DAT1/SLC6A3) genes. Methods: We have analysed 10 single nucleotide polymorphisms in DRD2, DRD4 and DAT1/SLC6A3 genes in relation to lung cancer risk in a case-control study of smoking subjects. The study subjects were 413 healthy individuals from general population and 335 NSCLC cases. Both cases and controls were Caucasians of Norwegian origin. Results: We demonstrate that DRD2 polymorphisms -141Cdel, 3208G > T, TaqIB; DRD4 -521C > T and DAT1/SLC6A3 -1476T > G are associated with a two- to five-fold increased NSCLC risk. The variant alleles of DRD2 1412A > G and 960C > G had protective effects. Conclusion: The dopamine receptor/transport gene polymorphisms are associated with the risk of NSCLC among smokers. The data show that the polymorphisms resulting in lower dopamine bioavailability were associated with increased risk of NSCLC
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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