Development and Validation of Prognostic Model for Metastatic Castration-Resistant Prostate Cancer Patients Treated With First-Line Abiraterone or Enzalutamide.

Introduction: Over the years, several prognostic models were developed in patients receiving chemotherapy for metastatic castration resistant prostate cancer (mCRPC), while data on androgen-receptor signaling inhibitors (ARSI) in a real-world setting are limited.

Patients And Methods: We compared a consecutive series of 565 mCRPC patients receiving first-line ARSI at 4 high-volume Italian Centers (development set) to an external series of 180 patients receiving the same treatment at another Italian high-volume Center (training set), between 2011 and 2022. Sixteen clinical and baseline laboratory variables were selected to develop a prognostic model.

Large-Area Intercalated Two-Dimensional Pb/Graphene Heterostructure as a Platform for Generating Spin-Orbit Torque.

A scalable platform to synthesize ultrathin heavy metals may enable high-efficiency charge-to-spin conversion for next-generation spintronics. Here, we report the synthesis of air-stable, epitaxially registered monolayer Pb underneath graphene on SiC (0001) by confinement heteroepitaxy (CHet). Diffraction, spectroscopy, and microscopy reveal that CHet-based Pb intercalation predominantly exhibits a mottled hexagonal superstructure due to an ordered network of Frenkel-Kontorova-like domain walls.

Identification of new correctors for traffic-defective ABCB4 variants by a high-content screening approach.

ABCB4 is located at the canalicular membrane of hepatocytes and is responsible for the secretion of phosphatidylcholine into bile. Genetic variations of this transporter are correlated with rare cholestatic liver diseases, the most severe being progressive familial intrahepatic cholestasis type 3 (PFIC3). PFIC3 patients most often require liver transplantation.

Prediction of a Novel Electromechanical Response in Polar Polymers with Rigid Backbones: Contrasting Furan-Derived Nanothreads to Poly(Vinylidene Fluoride).

furan nanothreads have all oxygen atoms arranged on one side of the thread backbone; these polar threads present intriguing opportunities in electromechanical response owing to their rigid ladder-like backbone. We retrained a C/H/O reactive force field to simulate their response to external electric field for both end-anchored individual threads and bulk nanothread crystals, contrasting the results to those for poly(vinylidene fluoride) (PVDF) polymer. Whereas the field induces a length-independent torque in PVDF through backbone rotation about σ bonds, furan-derived nanothreads generate a length-dependent torque by progressively twisting their rigid backbone.

Hormonal Agents in Localized and Advanced Prostate Cancer: Current Use and Future Perspectives.

Prostate cancer (PC) is generally a hormone-dependent tumor. Androgen deprivation therapy ( has been the standard of care in metastatic disease for more than 80 years. Subsequent studies have highlighted the efficacy of ADT even in earlier disease settings such as in localized disease or in the case of biochemical recurrence (BCR).

Emergence of inertia in the low-Reynolds regime of self-diffusiophoretic motion.

For isotropic swimming particles driven by self-diffusiophoresis at zero Reynolds number (where particle velocity responds instantaneously to applied force), the diffusive timescale of emitted solute can produce an emergent quasi-inertial behavior. These particles can orbit in a central potential and reorient under second-order dynamics, not the first-order dynamics of classical zero-Reynolds motion. They are described by a simple effective model that embeds their history-dependent behavior as an effective inertia, this being the most primitive expression of memory.

Strain-Induced 2H to 1T' Phase Transition in Suspended MoTe Using Electric Double Layer Gating.

MoTe can be converted from the semiconducting (2H) phase to the semimetallic (1T') phase by several stimuli including heat, electrochemical doping, and strain. This type of phase transition, if reversible and gate-controlled, could be useful for low-power memory and logic. In this work, a gate-controlled and fully reversible 2H to 1T' phase transition is demonstrated via strain in few-layer suspended MoTe field effect transistors.

Step engineering for nucleation and domain orientation control in WSe epitaxy on c-plane sapphire.

Epitaxial growth of two-dimensional transition metal dichalcogenides on sapphire has emerged as a promising route to wafer-scale single-crystal films. Steps on the sapphire act as sites for transition metal dichalcogenide nucleation and can impart a preferred domain orientation, resulting in a substantial reduction in mirror twins. Here we demonstrate control of both the nucleation site and unidirectional growth direction of WSe on c-plane sapphire by metal-organic chemical vapour deposition.

The Role of Germline Mutations in Thoracic Malignancies: Between Myth and Reality.

Considering the established contribution of environmental factors to the development of thoracic malignancies, the inherited susceptibility of these tumors has rarely been explored. However, the recent introduction of next-generation sequencing-based tumor molecular profiling in the real-word setting enabled us to deeply characterize the genomic background of patients with lung cancer with or without smoking-related history, increasing the likelihood of detecting germline mutations with potential prevention and treatment implications. Pathogenic germline variants have been detected in 2% to 3% of patients with NSCLC undergoing next-generation sequencing analysis, whereas the proportion of germline mutations associated with the development of pleural mesothelioma widely varies across different studies, ranging between 5% and 10%.

Computational and structural insights into the pre- and post-hydrolysis states of bovine multidrug resistance-associated protein 1.

ATP-binding cassette C-family drug membrane transporters play an important role in local pharmacokinetics, that is, drug concentration in cellular compartments. From the structural point of view, only the bovine ortholog of the multidrug resistance-associated protein 1 (bMRP1) has been resolved. We here used μs-scaled molecular dynamics simulations to investigate the structure and dynamics of the bovine multidrug resistance-associated protein 1 in pre- and post-hydrolysis functional states.

On the interplay between lipids and asymmetric dynamics of an NBS degenerate ABC transporter.

Multidrug resistance-associated proteins are ABC C-family exporters. They are crucial in pharmacology as they transport various substrates across membranes. However, the role of the degenerate nucleotide-binding site (NBS) remains unclear likewise the interplay with the surrounding lipid environment.

How to Improve the Quality of Life of Patients with Prostate Cancer Treated with Hormone Therapy?

Prostate cancer (PC) is a hormone-sensitive tumor. Androgen deprivation therapy (ADT) is the cornerstone of systemic therapy for patients with intermediate or high-risk localized, recurrent, and metastatic prostate cancer. Although generally well tolerated, ADT can lead to short- and long-term adverse events that can worsen the quality of life of patients with PC.

Three-dimensional topological magnetic monopoles and their interactions in a ferromagnetic meta-lattice.

Topological magnetic monopoles (TMMs), also known as hedgehogs or Bloch points, are three-dimensional (3D) non-local spin textures that are robust to thermal and quantum fluctuations due to the topology protection. Although TMMs have been observed in skyrmion lattices, spinor Bose-Einstein condensates, chiral magnets, vortex rings and vortex cores, it has been difficult to directly measure the 3D magnetization vector field of TMMs and probe their interactions at the nanoscale. Here we report the creation of 138 stable TMMs at the specific sites of a ferromagnetic meta-lattice at room temperature.

Nonstoichiometric Salt Intercalation as a Means to Stabilize Alkali Doping of 2D Materials.

Although doping with alkali atoms is a powerful technique for introducing charge carriers into physical systems, the resulting charge-transfer systems are generally not air stable. Here we describe computationally a strategy towards increasing the stability of alkali-doped materials that employs stoichiometrically unbalanced salt crystals with excess cations (which could be deposited during, e.g.

Photochemically Mediated Polymerization of Molecular Furan and Pyridine: Synthesis of Nanothreads at Reduced Pressures.

Nanothreads are emerging one-dimensional sp-hybridized materials with high predicted tensile strength and a tunable band gap. They can be synthesized by compressing aromatic or nonaromatic small molecules to pressures ranging from 15-30 GPa. Recently, new avenues are being sought that reduce the pressure required to afford nanothreads; the focus has been placed on the polymerization of molecules with reduced aromaticity, favorable stacking, and/or the use of higher reaction temperatures.

Theory of Borazine-Derived Nanothreads: Enumeration, Reaction Pathways, and Piezoelectricity.

Nanothreads are one-dimensional macromolecules formed by pressure-induced polymerization along stacks of multiply unsaturated (or highly strained) molecules such as benzene (or cubane). Borazine is isoelectronic to benzene yet with substantial bond polarity, thus motivating a theoretical examination of borazine-derived nanothreads with degrees of saturation of 2, 4, and 6 (defined as the number of four-coordinated boron and nitrogen atoms per borazine formula unit). The energy increases upon going from molecular borazine to degree-2 borazine-derived threads and then decreases for degree-4 and degree-6 nanothreads as more σ bonds are formed.

Confined Monolayer Ag As a Large Gap 2D Semiconductor and Its Momentum Resolved Excited States.

2D materials have intriguing quantum phenomena that are distinctively different from their bulk counterparts. Recently, epitaxially synthesized wafer-scale 2D metals, composed of elemental atoms, are attracting attention not only for their potential applications but also for exotic quantum effects such as superconductivity. By mapping momentum-resolved electronic states using time-resolved and angle-resolved photoemission spectroscopy (ARPES), we reveal that monolayer Ag confined between bilayer graphene and SiC is a large gap (>1 eV) 2D semiconductor, consistent with ab initio GW calculations.

Shape Entropy of a Reconfigurable Ising Surface.

Disclinations in a 2D sheet create regions of Gaussian curvature whose inversion produces a reconfigurable surface with many distinct metastable shapes, as shown by molecular dynamics of a disclinated graphene monolayer. This material has a near-Gaussian "density of shapes" and an effectively antiferromagnetic interaction between adjacent cones. A∼10  nm patch has hundreds of distinct metastable shapes with tunable stability and topography on the size scale of biomolecules.

Encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mutated metastatic colorectal cancer: real-life data from an Italian multicenter experience.

Background: Encorafenib plus cetuximab with or without binimetinib showed increased objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared with chemotherapy plus anti-EGFR in previously treated patients with BRAF V600E-mutated (mut) metastatic colorectal cancer (mCRC). Although no formal comparison was planned, addition of binimetinib to encorafenib plus cetuximab did not provide significant efficacy advantage.

Patients And Methods: This real-life study was aimed at evaluating safety, activity, and efficacy of encorafenib plus cetuximab with or without binimetinib in patients with BRAF V600E-mut mCRC treated at 21 Italian centers within a nominal use program launched in May 2019.

Metastatic Urothelial Carcinoma: Have We Take the Road to the Personalized Medicine?

Urothelial cancer is a lethal malignancy characterized by a wide diffusion in Western countries due to a larger exposure to known risk factors, such as aromatic amines, tobacco smoke and benzene [...

ZrTe/CrTe: an epitaxial van der Waals platform for spintronics.

The rapid discovery of two-dimensional (2D) van der Waals (vdW) quantum materials has led to heterostructures that integrate diverse quantum functionalities such as topological phases, magnetism, and superconductivity. In this context, the epitaxial synthesis of vdW heterostructures with well-controlled interfaces is an attractive route towards wafer-scale platforms for systematically exploring fundamental properties and fashioning proof-of-concept devices. Here, we use molecular beam epitaxy to synthesize a vdW heterostructure that interfaces two material systems of contemporary interest: a 2D ferromagnet (1T-CrTe) and a topological semimetal (ZrTe).

Mutual information and breakdown of the Perron-Frobenius scenario in zero-temperature triangular Ising antiferromagnets on cylinders.

A nominally two-dimensional spin model wrapped onto a cylinder can profitably be viewed, especially for long cylinders, as a one-dimensional chain. Each site of such a chain is a ring of spins with a complex state space. Traditional correlation functions are inadequate for the study of correlations in such a system and need to be replaced with something like mutual information.

Theoretical Studies of Furan and Thiophene Nanothreads: Structures, Cycloaddition Barriers, and Activation Volumes.

This theoretical study examines the formation, structure, and stability of two of the most ordered nanothreads produced yet, those derived from furan and thiophene. The energetic consequences and activation barriers of the first two steps of oligomerization via a Diels-Alder mechanism were examined. The ca.

Predicting Progression from Mild Cognitive Impairment to Alzheimer's Disease using MRI-based Cortical Features and a Two-State Markov Model.

Magnetic resonance imaging (MRI) has a potential for early diagnosis of individuals at risk for developing Alzheimer's disease (AD). Cognitive performance in healthy elderly people and in those with mild cognitive impairment (MCI) has been associated with measures of cortical gyrification [1] and thickness (CT) [2], yet the extent to which sulcal measures can help to predict AD conversion above and beyond CT measures is not known. Here, we analyzed 721 participants with MCI from phases 1 and 2 of the Alzheimer's Disease Neuroimaging Initiative, applying a two-state Markov model to study the conversion from MCI to AD condition.