Theory of quasiballistic transport through nanocrystalline silicon dots

A model to describe the underlying physics of high-energy electron emission from a porous silicon diode is presented. The model is based on an atomistic tight-binding method combined with semiclassical Monte Carlo simulation. It well reproduces essential features of experimental findings. An initial acceleration region is shown to play a crucial role in generating quasiballistic electron emission

Identification of Burgers vectors along <111> in In-doped GaAs, by X-ray transmission topography andimage simulation.

International audienceLong dislocations with Burgers vectors along are unusual in f.c.c. lattices. X-ray topographs have beenobtained of as-grown GaAs crystals doped with 1020 atoms cm -3 of In, where the usual extinction criterion g.b = 0leads to this type of defect. However, for several g satisfying the condition g.b = 0 with b = a [111], the images of thesedislocations were still clearly visible. Comparison between experimental and computer-simulated X-ray topographicsections of these defects confirms the existence of Burgers vectors along

Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy

The quest for immunotherapy (IT) biomarkers is an element of highest clinical interest in both solid and hematologic tumors. In non-small-cell lung cancer (NSCLC) patients, besides PD-L1 expression evaluation with its intrinsic limitations, tissue and circulating parameters, likely portraying the tumor and its stromal/immune counterparts, have been proposed as potential predictors of IT responsiveness. STK11 mutations have been globally labeled as markers of IT resistance. After a thorough literature review, STK11 mutations condition the prognosis of NSCLC patients receiving ICI-containing regimens, implying a relevant biological and clinical significance. On the other hand, waiting for prospective and solid data, the putative negative predictive value of STK11 inactivation towards IT is sustained by less evidence. The physiologic regulation of multiple cellular pathways performed by STK11 likely explains the multifaceted modifications in tumor cells, stroma, and tumor immune microenvironment (TIME) observed in STK11 mutant lung cancer, particularly explored in the molecular subgroup of KRAS co-mutation. IT approaches available thus far in NSCLC, mainly represented by anti-PD-1/PD-L1 inhibitors, are not promising in the case of STK11 inactivation. Perceptive strategies aimed at modulating the TIME, regardless of STK11 status or specifically addressed to STK11-mutated cases, will hopefully provide valid therapeutic options to be adopted in the clinical practice

PD-L1 SNPs as biomarkers to define benefit in patients with advanced NSCLC treated with immune checkpoint inhibitors

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups. Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association (p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype (p = 0.05). Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required

Dynamic evaluation of circulating mirna profile in egfr‐ mutated nsclc patients treated with egfr‐tkis

Background: Resistance to EGFR‐TKIs constitutes a major challenge for the management of EGFR‐mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR‐21, miR‐27a and miR‐181a) as a surrogate for predicting EGFR‐TKI performance in EGFR‐mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR‐mutated NSCLC patients treated with EGFR‐TKIs were collected at different points in time and miRNA levels were assessed by RT‐PCR. Results: Higher basal values of miR‐21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR‐21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR‐TKI treatment showed that patients who experienced SD had an increase in miR‐21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR‐27a (FC = 3.1) and miR‐181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR‐21 levels in NSCLC cells that became resistant after exposure to EGFR‐TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR‐21, and their dynamic change over time in predicting EGFR‐TKI response in EGFR‐mutated NSCLC

Efficacy of the cdk4/6 dual inhibitor abemaciclib in egfr-mutated nsclc cell lines with different resistance mechanisms to osimertinib

Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 that inhibits the transition from the G1 to the S phase of the cell cycle by blocking downstream CDK4/6-mediated phosphorylation of Rb. The effects of abemaciclib alone or combined with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib were examined in a panel of PC9 and HCC827 osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines carrying EGFR-dependent or-independent mechanisms of intrinsic or acquired resistance. Differently from sensitive cells, all the resistant cell lines analyzed maintained p-Rb, which may be considered as a biomarker of osimertinib resistance and a potential target for therapeutic intervention. In these models, abemaciclib inhibited cell growth, spheroid formation, colony formation, and induced senes-cence, and its efficacy was not enhanced in the presence of osimertinib. Interestingly, in osimertinib sensitive PC9, PC9T790M, and H1975 cells the combination of abemaciclib with osimertinib significantly inhibited the onset of resistance in long-term experiments. Our findings provide a preclinical support for using abemaciclib to treat resistance in EGFR mutated NSCLC patients progressed to osimertinib either as single treatment or combined with osimertinib, and suggest the combination of osimertinib with abemaciclib as a potential approach to prevent or delay osimertinib resistance in first-line treatment

Invasive pulmonary aspergillosis in patients with decompensated cirrhosis: case series

BACKGROUND: Opportunistic invasive fungal infections are increasingly frequent in intensive care patients. Their clinical spectrum goes beyond the patients with malignancies, and for example invasive pulmonary aspergillosis has recently been described in critically ill patients without such condition. Liver failure has been suspected to be a risk factor for aspergillosis. CASE PRESENTATION: We describe three cases of adult respiratory distress syndrome with sepsis, shock and multiple organ failure in patients with severe liver failure among whom two had positive Aspergillus antigenemia and one had a positive Aspergillus serology. In all cases bronchoalveolar lavage fluid was positive for Aspergillus fumigatus. Outcome was fatal in all cases despite treatment with voriconazole and agressive symptomatic treatment. CONCLUSION: Invasive aspergillosis should be among rapidly raised hypothesis in cirrhotic patients developing acute respiratory symptoms and alveolar opacities