Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of ...circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients.
During the recent restoration of two large‐dimension paintings by Murillo, entitled “Miracle of the loaves and fishes” and “Moses and the water from the rock of Horeb,” several studies about the ...materials employed for their execution were carried out. Macro X‐ray fluorescence scanning technique was performed on both works complemented by point X‐ray fluorescence and stratigraphic analyses, in order to characterize the different components of the paintings (i.e., ground layer, pigments, and binders). The results allowed us to better elucidate Murillo painting technique and his creative process. Ground layer was prepared in the usual fashion of the artist, using earths, calcium carbonate, iron oxide pigments, and white lead. The polichromy is composed of lead white mixed with various pigments, depending on the colour tone to be obtained in the pictorial composition: Red and yellow ochres, vermilion, azurite, smalt, and lead‐tin yellow were the main pigments identified during our study. Finally, the presence of previous conservation treatments was evidenced by detecting pigments (zinc white, Prussian blue, etc.) not coeval with the artist palette.
Francisco de Zurbarán was one of the greatest painters of the Spanish Golden Age, with artworks scattered all over the world. Unfortunately, there are hardly any exhaustive studies on the pigments ...that he used. In this work, four canvas paintings attributed to the Zurbarán Workshop were studied. Each of them presents the figure of a different saint in a particular isolation scene: Saint Bruno, Saint Francis of Assisi, Saint Dominic of Guzman, and Saint Peter Martyr. Nevertheless, the painting of Saint Peter Martyr shows superior quality in both technique and colours, so it is not clear whether this canvas was also made by the Workshop or by Zurbarán himself, as some art historians claim. Coinciding with conservation and restoration works, the paintings were initially analysed with non-invasive techniques such as ultraviolet photography (UV), infrared reflectography (IRR) and X-ray fluorescence (XRF) to determine the characterization of the pigments. Those studies were complemented by stratigraphic analysis of some extracted samples with optical microscopy (OM) and scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX). Among a number of results obtained, we found significant differences between the pigment palette used in Saint Peter Martyr and the other paintings, supporting the hypothesis that this painting was done by Zurbarán himself instead of his workshop. These results could also help to distinguish other authentic paintings by the master's hand from very similar paintings by his workshop or by other artists.
Hematopoietic stem cell transplantation (HSCT) involves the infusion of either bone marrow or blood cells preceded by toxic chemotherapy. However, there is little knowledge about the clinical ...benefits of parenteral nutrition (PN) in patients receiving high-dose chemotherapy during HSCT. We investigated the lipidomic profile of plasma and the targeted fatty acid profiles of plasma and erythrocytes in children after HSCT using PN with either a fish oil-based lipid emulsion or a classic soybean oil emulsion. An untargeted liquid chromatography high-resolution mass spectrometry platform connected with a novel in silico annotation algorithm was utilized to determine the most relevant chemical subclasses affected. In addition, we explored the interrelation between the lipidomics profile in plasma, the targeted fatty acid profile in plasma and erythrocytes, several biomarkers of inflammation, and antioxidant defense using an innovative data integration analysis based on Latent Components. We observed that the fish oil-based lipid emulsion had an impact in several lipid subclasses, mainly glycerophosphocholines (PC), glycerophosphoserines (PS), glycerophosphoethanolamines (PE), oxidized PE (O-PE), 1-alkyl,2-acyl PS, lysophosphatidylethanolamines (LPE), oxidized PS (O-PS) and dicarboxylic acids. In contrast, the classic soybean oil emulsion did not. Several connections across the different blocks of data were found and aid in interpreting the impact of the lipid emulsions on metabolic health.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common entity (30%-40%) and can significantly limit the quality of life of patients, especially those that persist for more than 6 months after ...treatment (chronic neuropathy). Studies have shown a possible association between the presence of genetic polymorphisms in ABCB1 and the development of acute CIPN, although this relationship with chronic CIPN remains unexplored. This is an analytical observational case-control study defined by the presence (cases) or absence (controls) of CIPN at 6 months after the end of the neurotoxic drug. Our aim is to demonstrate whether these ABCB1 polymorphisms also influence the chronification of this toxicity, as well as the clinical factors that can help us to predict it.
The study included 152 patients treated with tri-weekly oxaliplatin (O) or weekly paclitaxel (P); 86 cases and 66 controls. Clinical and analytical parameters were analysed including the study of ABCB1 genetic polymorphisms in a blood sample.
ABCB1 genetic polymorphisms C1236T (rs1128503) and C3435T (rs1045642) are associated with the development of chronic CIPN in patients treated with P. No differences were found in patients treated with O. Other predictive factors to be considered in the development of this toxicity are age >60 years, BMI ≥30, toxic habits and cardiovascular risk factors.
CIPN is a common and understudied toxicity, despite being a limiting factor in the quality of life of many patients. As described in acute CIPN, our study demonstrates the relationship between chronic neuropathy and being a carrier of specific polymorphisms (C1236T and C3435T) of the ABCB1 gene in patients treated with P. In addition, there are modifiable factors (obesity, smoking, or alcohol) that may influence its development. Further prospective studies are needed to investigate genetic and clinical modifiable factors predisposing to CIPPN to develop prevention and treatment strategies.
A multi-approach study has been designed to evaluate the mannerist-style masterpiece of the Christ of the Expiration (Museum Brotherhood, Seville, Spain), a polychrome wooden paste sculpture of the ...16th Century that was restored in the Andalusian Historical Heritage Institute (IAPH). During its intervention, a combination of two non-destructive prototypes were used to evaluate the different color in its feet regarding its legs and torso and its cause. A portable equipment that combined X-ray diffraction (XRD) and X-ray fluorescence (XRF) was employed to analyze chemical composition and mineralogical characterization of pigments. This equipment allowed obtaining simultaneously XRF and XRD at the same point without sampling. X-ray techniques identified cerussite, hydrocerussite and barite in different layers. The presence of zinc oxide from a recent restoration was also detected. Additionally, laser induced fluorescence (LIF) was employed to assess the presence of different fluorescent compounds on the surface. This technique showed the use of acrylic products in the feet, loincloth and torso of Christ from previous restoration and allowed to detect spectral difference on the feet and a high ration of the acrylic product on feet, both could be the cause of the differential degradation between the feet and torso. This multi-approach study based on portable and non-destructive techniques allowed restoration monitoring and helped restorers to take decisions without sampling.
Purpose
The standard treatment of rectal adenocarcinoma is total mesorectal excision (TME), in many cases requires a temporary or permanent stoma. TME is associated with high morbidity and ...genitourinary alterations. Transanal endoscopic microsurgery (TEM) allows access to tumors up to 20 cm from the anal verge, achieves minimal postoperative morbidity and mortality rates, and does not require an ostomy. The treatment of T2, N0, and M0 cancers remains controversial. Preoperative chemoradiotherapy (CRT) in association with TEM reduces local recurrence and increases survival. The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with TEM compared with TME.
Methods
Prospective, multicenter, randomized controlled non-inferiority trial includes patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size, staged as T2 or T3-superficial N0-M0. Patients will be randomized to two areas: CRT plus TEM or radical surgery (TME). Postoperative morbidity and mortality will be recorded and patients will complete the quality of life questionnaires before the start of treatment, after CRT in the CRT/TEM arm, and 6 months after surgery in both arms. The estimated sample size for the study is 173 patients. Patients will attend follow-up controls for local and systemic relapse.
Conclusions
This study aims to demonstrate the preservation of the rectum after preoperative CRT and TEM in rectal cancer stages T2–3s, N0, M0 and to determine the ability of this strategy to avoid the need for radical surgery (TME).
Trial registration
ClinicalTrials.gov
identifier: NCT01308190. Número de registro del Comité de Etica e Investigación Clínica (CEIC) del Hospital universitario Parc Taulí: TAU-TEM-2009-01.
Laser-induced fluorescence is a remote analysis tool, successfully applied to real-time diagnosis of historical artworks, allowing the observation of features invisible to naked eye, as traces of ...retouches or presence of modern consolidants. Aim of the present paper is to introduce an historical database of pigments with respective binders and consolidants, realized to support the remote identification and mapping of these materials onto a mural in the least invasive way. To this aim, a monochromatic ultraviolet laser source emitting at 266nm with remote scanning has been used in combination with reflectance. Wall painted models have been built with a secco technique according to traditional recipes of XVII century. Digital image analysis, principal component analysis and spectral angle mapping have been carried out on data to get the mapping of two selected pigments, blue smalt and red carmine, in a real mural painting (XVII century). This non-invasive technique allowed us to operate remotely, a distance up to 11 m from the artwork. Results are consistent with traditional microanalysis performed to identity major pigments.
The dissemination of research in cultural heritage preservation to the public is a task that needs new models and expressions, to capture the attention of the public and the assessment of results. ...With this purpose, a new educational experience in Parque de las Ciencias (Science Park of Granada, Spain) was developed. The science window titled Hidden Face of Cultural Heritage (ScW-CH) was an exhibition to show the risks (hazards + vulnerability) associated to different artworks and materials of our cultural heritage (CH). ScW-CH was led by the researchers themselves, in collaboration with museum specialists, in order to develop a new model that makes their research accessible to all demographics. An innovative methodology based into simulating a showcase, was designed to study hazards and vulnerability in CH. Therefore, the montage contained materials, equipment, information sheets, and guides to accompany visitors as storytellers. The aim of the exhibition, was for the visitors to understand the risks posed to our monuments and artworks from a scientific point of view, and to raise awareness about the care that we should give to our CH. The ScW-CH was held for 6 months and visited by 8226 visitors. During the exhibition, a survey about the opinion of visitors was carried out to study the impact of the designed new model and assess the results of the experience. The collected data was analysed by the Statistical Package for the Social Sciences (version 22.0). Visitors usually presented a medium–high initial interest about visiting this exhibition, and a medium–low level of knowledge of this subject. Thanks to ScW-CH, 92% of visitors showed a very high learning level after the experience. The ratio of interest and learning in the ScW-CH in relationship with the level of study showed that secondary school pupils had the highest degree of interest and learning.
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