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The law for the refraction of a wave when the two fluids and the interface are moving with relativistic velocities is given in an exact form, at the same time correcting a first order error in a previous paper [Cavalieri and Tonni, Phys. Rev. E 57, 3478 (1998)]. The treatment is then extended to a generally moving fluid with variable refractive index, ready to be applied to the refraction of acoustic, electromagnetic, or magnetohydrodynamic waves in the atmosphere of rapidly rotating stars. In 'the particular case of a gas cloud receding because of the universe expansion, our result can be applied to predict observable micro- and mesolensings. The first order approximation of our exact result for the deviation due to refraction of the light coming from a further quasar has a relativistic dependence equal to the one obtained by Einsteins' linearized theory of gravitation. [ABSTRACT FROM AUTHOR]

The standard of care for advanced or metastatic urothelial carcinoma (mUC) was historically identified with platinum-based chemotherapy. Thanks to the advances in biological and genetic knowledge and technologies, new therapeutic agents have emerged in this setting recently: the immune checkpoint inhibitors and the fibroblast growth factor receptor inhibitors as the target therapy for patients harboring alterations in the fibroblast growth factor receptor (FGFR) pathway. However, chasing a tumor's tendency to recur and progress, a new class of agents has more recently entered the scene, with promising results. Antibody-drug conjugates (ADCs) are in fact the latest addition, with enfortumab vedotin being the first to receive accelerated approval by the U.S. Food and Drug Administration in December 2019, followed by sacituzumab govitecan. Many other ADCs are still under investigation. ADCs undoubtedly represent the new frontier, with the potential of transforming the management of mUC treatment in the future. Therefore, we reviewed the landscape of mUC treatment options, giving an insight into the molecular basis and mechanisms, and evaluating new therapeutic strategies in the perspective of more and more personalized treatments.

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.

Meat quality seems to be influenced by the dietary regimes applied for animal feeding. Several research studies are aimed at improving meat quality, preserving it from oxidative processes, by the incorporation of antioxidant components in animal feeding. The main part of these studies evaluates meat quality, determining different parameters directly on meat, while few research studies take into account what may happen after meat ingestion. To address this topic, in this study, an in vitro gastrointestinal digestion protocol was applied to two different pork muscles, longissimus dorsi and rectus femoris , obtained from pigs fed with different diets. In detail, two groups of 12 animals each were subjected to either a conventional diet or a supplemented diet with extruded linseeds as a source of omega-3 fatty acids and plant extracts as a source of phenolics antioxidant compounds. The digested meat was subjected to an untargeted metabolomics approach. Several metabolites deriving from lipid and protein digestion were detected. Our untargeted approach allowed for discriminating the two different meat cuts, based on their metabolomic profiles. Nonetheless, multivariate statistics allowed clearly discriminating between samples obtained from different animal diets. In particular, the inclusion of linseeds and polyphenols in the animal diet led to a decrease in metabolites generated from oxidative degradation reactions, in comparison to the conventional diet group. In the latter, fatty acyls, fatty aldehydes and oxylipins, as well as cholesterol and vitamin D3 precursors and derivatives, could be highlighted.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities for de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have modified the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road toward personalized treatment for de novo mHSPC is still long, considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that did not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as a predictive biomarker requires further validation, and it remains to be ascertained how the genomic variants detected in mHSPC, which are regarded as predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

Introduction: Since 2016, the progressive use of immune checkpoint inhibitors (ICIs) starting from second-line treatment has led to an improvement in overall survival in locally advanced and metastatic urothelial cancer (UC). Clinical trials are underway testing the role of ICIs since the first stages of the disease, alone or in combination with standard therapies., Areas Covered: This review summarizes the current updated evidence regarding the role of ICIs in the different stages of UC, the ongoing clinical trials exploring the potential benefit of immunotherapy alone or in combination with standard-of-care therapies, as well as the promising association of ICIs with antibody-drug conjugates (ADCs)., Expert Opinion: In the first-line setting, ICIs alone in platinum-unfit patients have shown unconvincing results; the ongoing EV-302 trial will probably suggest enfortumab vedotin plus pembrolizumab as a new effective option. The optimal duration of maintenance immunotherapy is still to be determined, finding a balance with the risk-benefit profile. The clinical benefit of ICIs as second-line treatment is limited to a subset of patients that cannot be definitively established yet. In the next 5 years, a lot of new ADCs will likely emerge for the treatment of UC.

In the conformal field theories given by the Ising and Dirac models, when the system is in the ground state, the moments of the reduced density matrix of two disjoint intervals and of its partial transpose have been written as partition functions on higher genus Riemann surfaces with Z_{n} symmetry. We show that these partition functions can be expressed as the grand canonical partition functions of the two-dimensional two component classical Coulomb gas on certain circular lattices at specific values of the coupling constant.

The law for the refraction of a wave when the two fluids and the interface are moving with relativistic velocities is given in an exact form, at the same time correcting a first order error in a previous paper [Cavalleri and Tonni, Phys. Rev. E 57, 3478 (1998)]. The treatment is then extended to a generally moving fluid with variable refractive index, ready to be applied to the refraction of acoustic, electromagnetic, or magnetohydrodynamic waves in the atmosphere of rapidly rotating stars. In the particular case of a gas cloud receding because of the universe expansion, our result can be applied to predict observable micro- and mesolensings. The first order approximation of our exact result for the deviation due to refraction of the light coming from a further quasar has a relativistic dependence equal to the one obtained by Einsteins' linearized theory of gravitation.

We develop a systematic method to extract the negativity in the ground state of a 1+1 dimensional relativistic quantum field theory, using a path integral formalism to construct the partial transpose ρ(A)(T(2) of the reduced density matrix of a subsystem [formula: see text], and introducing a replica approach to obtain its trace norm which gives the logarithmic negativity E=ln//ρ(A)(T(2))//. This is shown to reproduce standard results for a pure state. We then apply this method to conformal field theories, deriving the result E~(c/4)ln[ℓ(1)ℓ(2)/(ℓ(1)+ℓ(2))] for the case of two adjacent intervals of lengths ℓ(1), ℓ(2) in an infinite system, where c is the central charge. For two disjoint intervals it depends only on the harmonic ratio of the four end points and so is manifestly scale invariant. We check our findings against exact numerical results in the harmonic chain.

Our paper [Phys. Rev. E 58, 2505 (1998)] described experimental results that brought into agreement standard theory and experiment, in contrast to two previous experiments that claimed disagreement. The shape of our circuit was designed to improve knowledge of the electric flux lines. Such a shape required numerical calculations to predict the relevant force on the mobile part of the circuit.