PubMed Health⌕ Search

Biomedical subjects

Giulia Galli

Publications and source records attributed to Giulia Galli.

At least 19 recordsLinked to original sources
PubMed2026

Hyperprogression Upon Cemiplimab Alone or With Short Course Chemotherapy in PD-L1 ≥ 50% Non-small Cell Lung Cancer: A Biomarker Guided Multicenter International Phase 2 Trial-HYPERBOLIC Study.

BACKGROUND: Immune checkpoint inhibitor (ICI) monotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with PD-L1 ≥ 50%; however, up to 30% of patients experience early progression or death, including cases of hyperprogressive disease (HPD). High baseline levels (≥ 30.5%) of circulating CD10- low-density neutrophils (LDNs) have been associated with increased HPD occurrence. Emerging evidence suggests that combining ICI with platinum-based chemotherapy (PCT) may mitigate the risk of HPD. Currently, no prospective studies have addressed HPD prevention in this context. PATIENTS AND METHODS: HYPERBOLIC (NCT07274384) is a phase 2, randomized, open-label, multicenter, international trial evaluating whether adding 3 cycles of PCT to first-line cemiplimab reduces HPD rate in stage IV NSCLC with PD-L1 ≥ 50% and CD10- LDNs (identified by flow cytometry as CD15⁺CD11b⁺ within the PBMC fraction, with immature cells defined by loss of CD10) ≥ 30.5%. Seventy-four patients will be randomized (1:1 ratio) to receive cemiplimab alone or cemiplimab plus 3 PCT cycles, followed by cemiplimab maintenance. Randomization will be stratified by Lung Immune Prognostic Index. The first computed tomography scan at week 7 after treatment start will assess HPD occurrence, defined as RECIST v 1.1. disease progression with a delta tumor growth rate (ΔTGR) ≥ 50% and/or TGR ratio ≥ 2. The primary endpoint will be the combined rate of HPD and early death (death within 12 weeks with no radiological evaluation). Secondary endpoints will be HPD rate according to alternative definitions, overall survival, progression free survival, objective response rate, and safety. An extensive translational research platform will include spatial transcriptomics of tumor tissue, single-cell RNA sequencing of PBMCs, circulating-free DNA and plasma factors profiling, and saliva/stool microbiome genomics and metabolomics, to longitudinally explore tumor-host dynamic interactions during treatment. CONCLUSION: to our knowledge, HYPERBOLIC is the first prospective, biomarker-driven trial investigating early treatment escalation based on HPD risk in PD-L1-high NSCLC.

CD10↗
PubMed2004

Optical properties of silicon clusters in the presence of water: a first principles theoretical analysis.

We investigate the impact of water on the optical absorption of prototypical silicon clusters. Our clusters contain 5 silicon atoms, tetrahedrally coordinated and passivated with either hydrogen or oxygen. We approach this complex problem by assessing the contributions of three factors: chemical reactivity, thermal equilibration, and dielectric screening. We find that the silanone (Si=O) functional group is not chemically stable in the presence of water and exclude this as a source of significant red shift in absorption in aqueous environments. We perform first principles molecular dynamics simulations of the solvation of a chemically stable, oxygenated silicon cluster with explicit water molecules at 300 K. We find a systematic 0.7 eV red shift in the absorption gap of this cluster, which we attribute to thermally induced fluctuations in the molecular structure. Surprisingly, we find no observable screening impact of the solvent, in contrast with consistent blue shifts observed for similarly sized organic molecules in polar solvents. The predicted red shift is expected to be significantly smaller for larger Si quantum dots produced experimentally, guaranteeing that their vacuum optical properties are preserved even in aqueous environments.

Journal Article↗
PubMed2004

A quantum fluid of metallic hydrogen suggested by first-principles calculations.

It is generally assumed that solid hydrogen will transform into a metallic alkali-like crystal at sufficiently high pressure. However, some theoretical models have also suggested that compressed hydrogen may form an unusual two-component (protons and electrons) metallic fluid at low temperature, or possibly even a zero-temperature liquid ground state. The existence of these new states of matter is conditional on the presence of a maximum in the melting temperature versus pressure curve (the 'melt line'). Previous measurements of the hydrogen melt line up to pressures of 44 GPa have led to controversial conclusions regarding the existence of this maximum. Here we report ab initio calculations that establish the melt line up to 200 GPa. We predict that subtle changes in the intermolecular interactions lead to a decline of the melt line above 90 GPa. The implication is that as solid molecular hydrogen is compressed, it transforms into a low-temperature quantum fluid before becoming a monatomic crystal. The emerging low-temperature phase diagram of hydrogen and its isotopes bears analogies with the familiar phases of 3He and 4He (the only known zero-temperature liquids), but the long-range Coulomb interactions and the large component mass ratio present in hydrogen would result in dramatically different properties.

Journal Article↗
PubMed2004

Towards an assessment of the accuracy of density functional theory for first principles simulations of water. II.

A series of 20 ps ab initio molecular dynamics simulations of water at ambient density and temperatures ranging from 300 to 450 K are presented. Car-Parrinello (CP) and Born-Oppenheimer (BO) molecular dynamics techniques are compared for systems containing 54 and 64 water molecules. At 300 K, an excellent agreement is found between radial distribution functions (RDFs) obtained with BO and CP dynamics, provided an appropriately small value of the fictitious mass parameter is used in the CP simulation. However, we find that the diffusion coefficients computed from CP dynamics are approximately two times larger than those obtained with BO simulations for T>400 K, where statistically meaningful comparisons can be made. Overall, both BO and CP dynamics at 300 K yield overstructured RDFs and slow diffusion as compared to experiment. In order to understand these discrepancies, the effect of proton quantum motion is investigated with the use of empirical interaction potentials. We find that proton quantum effects may have a larger impact than previously thought on structure and diffusion of the liquid.

Journal Article↗
PubMed2004

Atomic control of water interaction with biocompatible surfaces: the case of SiC(001).

The interaction of water with Si- and C- terminated beta-SiC(001) surfaces was investigated by means of ab initio molecular dynamics simulations. Irrespective of coverage, varied from 1/4 to 1 monolayer, we found that water dissociates on the Si-terminated surface, substantially modifying the clean surface reconstruction, while the C-terminated surface is nonreactive and hydrophobic. Based on our results, we propose that STM images and photoemission experiments may detect specific changes induced by water on both the structural and electronic properties of SiC(001) surfaces.

Biocompatible Materials↗
PubMed2004

Optical properties of passivated silicon nanoclusters: the role of synthesis.

The effect of preparation conditions on the structural and optical properties of silicon nanoparticles is investigated. Nanoscale reconstructions, unique to curved nanosurfaces, are presented for silicon nanocrystals and shown to have lower energy and larger optical gaps than bulk-derived structures. We find that high-temperature synthesis processes can produce metastable noncrystalline nanostructures with different core structures than bulk-derived crystalline clusters. The type of core structure that forms from a given synthesis process may depend on the passivation mechanism and time scale. The effect of oxygen on the optical of different types of silicon structures is calculated. In contrast to the behavior of bulklike nanostructures, for noncrystalline and reconstructed crystalline structures surface oxygen atoms do not decrease the gap. In some cases, the presence of oxygen atoms at the nanocluster surface can significantly increase the optical absorption gap, due to decreased angular distortion of the silicon bonds. The relationship between strain and the optical gap in silicon nanoclusters is discussed.

Journal Article↗
PubMed2004

Early chemistry in hot and dense nitromethane: molecular dynamics simulations.

We report density functional molecular dynamic simulations to determine the early chemical events of hot (T=3000 K) and dense (rho=1.97 g/cm(3), V/V(0)=0.68) nitromethane (CH(3)NO(2)). The first step in the decomposition process is an intermolecular proton abstraction mechanism that leads to the formation of CH(3)NO(2)H(+) and the aci ion H(2)CNO(2) (-). This event is also confirmed to occur in a fast annealing simulation to a final temperature of 4000 K at rho=2.20 g/cm(3). An intramolecular hydrogen transfer that transforms nitromethane into the aci acid form, CH(2)NO(2)H, accompanies this event. To our knowledge, this is the first confirmation of chemical reactivity with bond selectivity for an energetic material near the Chapman-Jouget state of the fully reacted material. We also report the decomposition mechanism followed up to the formation of H(2)O as the first stable product. We note that similarities in the global features of reactants, intermediates, and products of the reacting fluid seem to indicate a threshold for similar chemistry in the range of high densities and temperatures reported herein.

Journal Article↗
PubMed2004

Self-healing of CdSe nanocrystals: first-principles calculations.

Ab initio calculations of the structural, electronic, and optical properties of CdSe nanoparticles are presented. The atomic structures of the clusters are relaxed both in vacuum and in the presence of surfactant ligands. In both cases, we predict significant geometrical rearrangements of the nanoparticle surface while the wurtzite core is maintained. These reconstructions lead to the opening of an optical gap without the aid of passivating ligands, thus "self-healing" the surface electronic structure. Our calculations also predict the existence of a midgap state responsible for recently observed subband emission.

Journal Article↗
PubMed2004

Ab initio calculations in a uniform magnetic field using periodic supercells.

We present a formulation of ab initio electronic structure calculations in a finite magnetic field, which retains the simplicity and efficiency of techniques widely used in first principles molecular dynamics simulations, based on plane-wave basis sets and Fourier transforms. In addition we discuss results obtained with this method for the energy spectrum of interacting electrons in quantum wells, and for the electronic properties of dense fluid deuterium in a uniform magnetic field.

Journal Article↗
PubMed2004

Insulator to metal transition in fluid deuterium.

We have investigated the insulator to metal transition in fluid deuterium using first principles simulations. Both density functional and quantum Monte Carlo calculations indicate that the electronic energy gap of the liquid vanishes at about ninefold compression and 3000 K. At these conditions the computed conductivity values are characteristic of a poor metal. These findings are consistent with those of recent shock wave experiments but the computed conductivity is larger than the measured value. From our ab initio results we conclude that the transition is driven by molecular dissociation rather than disorder and that both temperature and pressure play a key role in determining structural changes in the fluid.

Journal Article↗
PubMed2004

A first principles simulation of rigid water.

We present the results of Car-Parrinello (CP) simulations of water at ambient conditions and under pressure, using a rigid molecule approximation. Throughout our calculations, water molecules were maintained at a fixed intramolecular geometry corresponding to the average structure obtained in fully unconstrained simulations. This allows us to use larger time steps than those adopted in ordinary CP simulations of water, and thus to access longer time scales. In the absence of chemical reactions or dissociation effects, these calculations open the way to ab initio simulations of aqueous solutions that require time scales substantially longer than presently feasible (e.g., simulations of hydrophobic solvation). Our results show that structural properties and diffusion coefficients obtained with a rigid model are in better agreement with experiment than those determined with fully flexible simulations. Possible reasons responsible for this improved agreement are discussed.

Journal Article↗
PubMed2004

Towards an assessment of the accuracy of density functional theory for first principles simulations of water.

A series of Car-Parrinello (CP) molecular dynamics simulations of water are presented, aimed at assessing the accuracy of density functional theory in describing the structural and dynamical properties of water at ambient conditions. We found negligible differences in structural properties obtained using the Perdew-Burke-Ernzerhof or the Becke-Lee-Yang-Parr exchange and correlation energy functionals; we also found that size effects, although not fully negligible when using 32 molecule cells, are rather small. In addition, we identified a wide range of values of the fictitious electronic mass (micro) entering the CP Lagrangian for which the electronic ground state is accurately described, yielding trajectories and average properties that are independent of the value chosen. However, care must be exercised not to carry out simulations outside this range, where structural properties may artificially depend on micro. In the case of an accurate description of the electronic ground state, and in the absence of proton quantum effects, we obtained an oxygen-oxygen correlation function that is overstructured compared to experiment, and a diffusion coefficient which is approximately ten times smaller.

Journal Article↗
PubMed2003

Structure and bonding of dense liquid oxygen from first principles simulations.

Using first principles simulations we have investigated the structural and bonding properties of dense fluid oxygen up to 180 GPa. We have found that band gap closure occurs in the molecular liquid, with a "slow" transition from a semiconducting to a poor metallic state occurring over a wide pressure range. At approximately 80 GPa, molecular dissociation is observed in the metallic fluid. Spin fluctuations play a key role in determining the electronic structure of the low pressure fluid, while they are suppressed at high pressure.

Journal Article↗
PubMed2003

Optically activated functionalization reactions in Si quantum dots.

Using ab initio calculations, we have studied the influence of optical activation on functionalization reactions of silicon quantum dots with unsaturated hydrocarbons. We find that the energy barrier for the replacement of silicon-hydrogen with silicon-carbon bonds is dramatically reduced if the silicon dot is optically excited. These results provide an explanation for recent experiments on optically excited porous silicon. In addition, our calculations point at the existence of an intermediate spin-polarized state formed by the dot and an alkene or alkyne, upon relaxation after absorbing a photon. This state could be detected experimentally, by, for example, electron spin resonance measurements. Based on the results of our calculations as a function of the dot size, varied from 0.8 to 1.5 nm, we propose that light activated reactions could be used to functionalize and size select silicon quantum dots at the same time.

Journal Article↗
PubMed2003

Ultradispersity of diamond at the nanoscale.

Nanometre-sized diamond has been found in meteorites, protoplanetary nebulae and interstellar dusts, as well as in residues of detonation and in diamond films. Remarkably, the size distribution of diamond nanoparticles seems to be peaked around 2-5 nm, and to be largely independent of preparation conditions. We have carried out ab initio calculations of the stability of nanodiamond as a function of surface hydrogen coverage and of size. We have found that at about 3 nm, and for a broad range of pressures and temperatures, particles with bare, reconstructed surfaces become thermodynamically more stable than those with hydrogenated surfaces, thus preventing the formation of larger grains. Our findings provide an explanation of the size distribution of extraterrestrial and of terrestrial nanodiamond found in ultradispersed and ultracrystalline diamond films. They also provide an atomistic structural model of these films, based on the topology and structure of 2-3-nm dimond clusters consisting of a diamond core surrounded by a fullerene-like carbon network.

Computer Simulation↗
PubMed2003

Melting of lithium hydride under pressure.

We have computed the melting line of lithium hydride up to 200 GPa using the two-phase simulation technique coupled with first-principles molecular dynamics. Our predicted melting temperature at high pressures varies slowly with compression, ranging from 2000 to 2450 K at 50-200 GPa pressures. The compressed fluid close to the melting line retains the ionic character of the low pressure molten state, while at higher temperatures dynamical hydrogen clustering processes are observed, which are accompanied by changes in the electronic structure.

Journal Article↗
PubMed2003

Structural stability and optical properties of nanomaterials with reconstructed surfaces.

We present density functional and quantum Monte Carlo calculations of the stability and optical properties of semiconductor nanomaterials with reconstructed surfaces. We predict the relative stability of silicon nanostructures with reconstructed and unreconstructed surfaces, and we show that surface step geometries unique to highly curved surfaces dramatically reduce the optical gaps and decrease excitonic lifetimes. These predictions provide an explanation of both the variations in the photoluminescence spectra of colloidally synthesized nanoparticles and observed deep gap levels in porous silicon.

Journal Article↗