[¹⁸F]FMCH PET/CT biomarkers and similarity analysis to refine the definition of oligometastatic prostate cancer

Background:The role of image-derived biomarkers in recurrent oligometastatic Prostate Cancer (PCa) is unexplored. This paper aimed to evaluate [18F]FMCH PET/CT radiomic analysis in patients with recurrent PCa after primary radical therapy. Specifically, we tested intra-patient lesions similarity in oligometastatic and plurimetastatic PCa, comparing the two most used definitions of oligometastatic disease.Methods:PCa patients eligible for [18F]FMCH PET/CT presenting biochemical failure after first-line curative treat-ments were invited to participate in this prospective observational trial. PET/CT images of 92 patients were visually and quantitatively analyzed. Each patient was classified as oligometastatic or plurimetastatic according to the total number of detected lesions (up to 3 and up to 5 or > 3 and > 5, respectively). Univariate and intra-patient lesions’ similarity analysis were performed.Results: [18F]FMCH PET/CT identified 370 lesions, anatomically classified as regional lymph nodes and distant metastases. Thirty-eight and 54 patients were designed oligometastatic and plurimetastatic, respectively, using a 3-lesion threshold. The number of oligometastic scaled up to 60 patients (thus 32 plurimetastatic patients) with a 5-lesion threshold. Similarity analysis showed high lesions’ heterogeneity. Grouping patients according to the number of metastases, patients with oligometastatic PCa defined with a 5-lesion threshold presented lesions heterogene-ity comparable to plurimetastic patients. Lesions within patients having a limited tumor burden as defined by three lesions were characterized by less heterogeneity.Conclusions:We found a comparable heterogeneity between patients with up to five lesions and plurimetastic patients, while patients with up to three lesions were less heterogeneous than plurimetastatic patients, featuring dif-ferent cells phenotypes in the two groups. Our results supported the use of a 3-lesion threshold to define oligometa-static PCa

Genesi, evoluzione e paleografia delle grotte costiere di marina di Camerota (parco nazionale del Cilento Vallo Di Diano, Italia Meridionale)

ItLa costa tra Marina di Camerota e P.to Infreschi (SA) presenta numerose grotte, già note per il loro valore preistorico. E’ stato condotto uno studio geomorfologico e stratigrafico, per delucidare la loro genesi ed evoluzione. Sono stati individuati 4 tipi di cavità: grotte sviluppate in depositi marini o continentali, grotte in substrato calcareo impostate su faglia o frattura, grotte associate all’emergenza di una falda in rete e relitti di cavità crollate. All’interno delle cavità sono stati riconosciuti diversi stazionamenti del livello del mare. Le grotte studiate contengono il registro delle oscillazioni eustatiche e climatiche tardo pleistoceniche, oltre che importanti tracce preistoriche. Esse possono dunque essere considerate geositi di rilevanza nazionale e come tali devono essere preservate e valorizzate in maniera adeguata.EnThe coastline between Marina di Camerota and the bay of Porto Infreschi (Province of Salerno) is characterized by several caves, known above all for their prehistoric records. We carried out a detailed study of these caves in order to better understand their genesis and evolution in function of the main middle and late Pleistocene eustatic sea level fluctuations.Along the coastal sector four different kind of cave have been identified. The first one includes caves developed into Pleistocene marine conglomerates or into slope breccias, located at altitude higher than the present see level and which are associated with ancient see level. The second one contains fault-guided or joint-guided caves developed into carbonate bedrock; some are active and some other are fossil. The third kind includes phreatic caves cut into carbonate bedrock. Generally, they are present in group and developed along front line(for example, the case of the bay of Porto Infreschi). The last one is represented by the remains of collapsed caves; which are visible for the presence of marine deposits, speleothems and remains of alluvial fan along the sea cliff (i. e. the case of the Riparo degli Infreschi cave). Into the caves the traces of at least three different high stands located at altitude of 8.5-8, 4.5, 3.5 m a.s.l. which can be referred to the Last Interglacial period have been observed (ESPOSITO et al., 2002). Moreover in the Porto Infreschi caves are clearly recorded moments of speleothems formations between the different phases of marine ingression.During the low stands of the isotopic stages 4 and 3 the most of the caves were abandoned by the sea and they became a safe refuge for the prehistoric man. The richness of their stratigraphical record, from a paleoclimatical and archaeological point of view, in addition to their prehistoric importance, allow many of these caves to be considered as important "geosites"

Supersymmetric Electroweak Corrections to Charged Higgs Boson Production in Association with a Top Quark at Hadron Colliders

We calculate the $O(\alpha_{ew}m_{t(b)}^{2}/m_{W}^{2})$ and $O(\alpha_{ew} m_{t(b)}^4/m_W^4)$ supersymmetric electroweak corrections to the cross section for the charged Higgs boson production in association with a top quark at the Tevatron and the LHC. These corrections arise from the quantum effects which are induced by potentially large Yukawa couplings from the Higgs sector and the chargino-top(bottom)-sbottom(stop) couplings, neutralino-top(bottom)-stop(sbottom) couplings and charged Higgs-stop-sbottom couplings. They can decrease or increase the cross section depending on $\tan\beta$ but are not very sensitive to the mass of the charged Higgs boson for high $\tan\beta$. At low $\tan\beta(=2)$ the corrections decrease the total cross sections significantly, which exceed -12% for $m_{H^{\pm}}$ below $300GeV$ at both the Tevatron and the LHC, but for $m_{H^{\pm}}>300GeV$ the corrections can become very small at the LHC. For high $\tan\beta(=10,30)$ these corrections can decrease or increase the total cross sections, and the magnitude of the corrections are at most a few percent at both the Tevatron and the LHC.Comment: 28 pages including 4 eps figure

Many-nodes/many-links spinfoam: the homogeneous and isotropic case

I compute the Lorentzian EPRL/FK/KKL spinfoam vertex amplitude for regular graphs, with an arbitrary number of links and nodes, and coherent states peaked on a homogeneous and isotropic geometry. This form of the amplitude can be applied for example to a dipole with an arbitrary number of links or to the 4-simplex given by the compete graph on 5 nodes. All the resulting amplitudes have the same support, independently of the graph used, in the large j (large volume) limit. This implies that they all yield the Friedmann equation: I show this in the presence of the cosmological constant. This result indicates that in the semiclassical limit quantum corrections in spinfoam cosmology do not come from just refining the graph, but rather from relaxing the large j limit.Comment: 8 pages, 4 figure

Coronary computed tomography: current role and future perspectives for cardiovascular risk stratification.

Atherosclerotic coronary artery disease (CAD) is a major cause of morbidity and mortality. The majority of cardiovascular events, more than 50% of CAD deaths, occur in previously asymptomatic individuals at intermediate cardiovascular risk, highlighting the relevance of accurate individual risk assessment to decrease cardiovascular events through more appropriate targeting of preventive measures. In the last decades, the development of non-invasive imaging techniques have prompted interest in imaging of atherosclerosis. Coronary computed tomography provides the opportunity to assess the deposition of calcium in the coronary tree and to non-invasively image coronary vessels. Both information are useful for risk stratification of asymptomatic subjects or of subjects with suspected CAD

Nab-paclitaxel/gemcitabine combination is more effective than gemcitabine alone in locally advanced, unresectable pancreatic cancer - A GISCAD phase II randomized trial

The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials

Label-free, atomic force microscopy-based mapping of DNA intrinsic curvature for the nanoscale comparative analysis of bent duplexes

We propose a method for the characterization of the local intrinsic curvature of adsorbed DNA molecules. It relies on a novel statistical chain descriptor, namely the ensemble averaged product of curvatures for two nanosized segments, symmetrically placed on the contour of atomic force microscopy imaged chains. We demonstrate by theoretical arguments and experimental investigation of representative samples that the fine mapping of the average product along the molecular backbone generates a characteristic pattern of variation that effectively highlights all pairs of DNA tracts with large intrinsic curvature. The centrosymmetric character of the chain descriptor enables targetting strands with unknown orientation. This overcomes a remarkable limitation of the current experimental strategies that estimate curvature maps solely from the trajectories of end-labeled molecules or palindromes. As a consequence our approach paves the way for a reliable, unbiased, label-free comparative analysis of bent duplexes, aimed to detect local conformational changes of physical or biological relevance in large sample numbers. Notably, such an assay is virtually inaccessible to the automated intrinsic curvature computation algorithms proposed so far. We foresee several challenging applications, including the validation of DNA adsorption and bending models by experiments and the discrimination of specimens for genetic screening purposes

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor