Search

The linear electromagnetic interaction between innovative hybrid metallo-dielectric nanostructured targets and laser in visible and IR range is investigated through numerical simulations. The obtained results rely on the optimization of a target based on metallic nanowires (NWs) to enhance light absorption in the visible range of the electromagnetic spectrum. The NWs are grown within the ordered nanoholes of an alumina substrate, thus, forming a plasmonic lattice with triangular symmetry. The remaining volume of the nanoholes on top of the NWs is sealed with a transparent layer of aluminum oxide that is suitable to be chemically modified for containing about 25% of deuterium atoms. The study presented here is carried out within the framework of a scientific program named PLANETA (Plasmonic Laser Absorption on Nano-Engineered Targets) aiming at investigating new laser–matter interaction schemes in the ns domain and for nuclear fusion purposes, involving especially the D–D reaction.

Abstract Background To compare the functional and anatomic outcomes at 24 months of eyes with a primary macular hole that failed to close after a prior surgery and were treated with either an autologous transplantation of internal limiting membrane (AT-ILM) or the retina expansion (RE) technique. Methods Retrospective, single center, comparative study of 28 eyes with a macular hole that failed to close after a prior vitrectomy. All eyes had a size of ≥ 500 μm. Participants were divided into two groups according to the type of intervention performed: AT-ILM group (n = 14) and RE group (n = 14). Main outcomes measured were the MH closure rate assessed by spectral-domain optical coherence tomography (SD-OCT) and the best-corrected visual acuity (BCVA) at 24 months after surgery. Results Patients in the AT-ILM group experienced a statistically significantly improved post-operative BCVA (median 49.50 letters, range 20–66 letters) over the pre-operative BCVA (median 39 letters, range 18–52 letters) (p-value = 0.006 Wilcoxon paired sample test). In contrast, patients in the RE group did not achieve a statistically significant improvement (p-value = 0.328, Wilcoxon paired sample test). The median pre-operative BCVA was 35 letters (range 18–52 letters), whereas the median post-operative BCVA was 39 letters (range 16–66 letters). At 24 months of follow-up, 85.7% of patients in the AT-ILM group achieved closure compared to 57.1% in the RE group (p-value = 0.209, Fisher’s exact test). Multivariate analysis showed that MH size and baseline BCVA were important determinants of post-operative BCVA. The baseline MH size was the only significant pre-operative factor that influenced MH closure. Conclusions This study demonstrates similar closure rates for both groups however better visual outcomes were obtained with the AT-ILM.

Blood tests play an essential role in everyday medicine and are used by doctors in several diagnostic procedures. Moreover, this data is multivariate – and often some diseases, such as COVID-19, could have different symptom manifestations and outcomes. This study proposes a method of extracting useful information from blood tests using UMAP technique - Uniform Manifold Approximation and Projection for Dimension Reduction combined with DBSCAN clustering and statistical approaches. The analysis performed here indicates several clusters of infection prevalence varying between 2%–37%, showing that our procedure is indeed capable of finding different patterns. A possible explanation is that COVID-19 is not just a respiratory infection but a systemic disease with critical hematological implications, primarily on white-cell fractions, as indicated by relevant statistical test p-values in the range of 0.03–0.1. The novel analysis procedure proposed could be adopted in other data-sets of different illnesses to help researchers to discover new patterns of data that could be used in various diseases and contexts.

We review recent achievements in the field of nanoscale nonlinear AlGaAs photonics based on all-dielectric optical antennas. After discussing the motivation and main technological challenges for the development of an AlGaAs monolithic platform for χ(2) nonlinear nanophotonics, we present numerical and experimental investigations of the second-order nonlinear response and physical reasons for high efficiency of second-order nonlinear interactions in the AlGaAs nano-antennas. In particular, we emphasize the role of the dipolar resonances at the fundamental frequency and the multipolar resonances at the second harmonic wavelength. We also discuss second-harmonic generation directionality and show possible strategies to engineer the radiation pattern of nonlinear antennas. [ABSTRACT FROM AUTHOR]

Background: As for squamous (Sq)-NSCLC, Checkmate-017 trial showed a significant overall survival (OS) improvement in favor of Nivolumab (Nivo) over Docetaxel in 2nd-line. We hypothesized that anticipating Nivo use, as early switch maintenance after 1st-line chemotherapy (CHT), might have improved survival as compared to delayed 2nd-line treatment., Methods: EDEN was an open-label, 2-arm, phase III study which randomized (1:1) stage IIIB/IV Sq-NSCLC pts non-progressive after 1st-line platinum-based CHT, to receive early Nivo as switch maintenance (Arm A) or standard best supportive care followed by 2nd-line Nivo at disease progression (Arm B). In both arms, Nivo was administered at the dose of 240 mg i.v. every 2 weeks until progressive disease, intolerable toxicity, or for a maximum of 2 years. The primary endpoint was OS., Results: From Sep 2017 to Aug 2020 125 patients (62 Arm A vs 63 Arm B) were randomized from 32 Italian centers. Accrual was stopped early, before the planned sample size (388 pts) was reached, because of registration of ICPIs in 1st-line. Most patients were male (79.2 %), current/former smokers (93.6 %), had stage IV (74.4 %), performance status 0-1 (98.4 %). mOS (95 % CI) was 14.9 (10.4-18.6) months in arm A vs 18.8 (14.4-21.1) months in arm B (HR 1.09, 95 %CI 0.74-1.62, p = 0.659)., Conclusions: In advanced Sq-NSCLC, the use of Nivo as switch maintenance after 1st-line CHT, does not improve OS compared to its use as 2nd-line. Although the optimal use of ICPIs remains in 1st-line, its role as maintenance has to be better investigated., Clinicaltrials: gov: registration number: NCT03542461., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Francesco Gelsomino has received honoraria or personal fees for the advisory role or consulting from Eli Lilly, Novartis, AstraZeneca, and Bristol-Myers Squibb. Marcello Tiseo has received institutional research grants from Astra-Zeneca, Boehringer Ingelheim and received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi. Diego Cortinovis has received speaker’s bureau/scientific advisor activity for BMS, MSD, AstraZeneca, Sanofi Genzyme, Novartis, Amgen, Takeda, Roche, Janssen. Andrea Ardizzoni has received research grants from Celgene, Bristol-Myers Squibb, Ipsen, and Roche; and honoraria for advisory roles from Bristol-Myers Squibb, Merck Sharp & Dohme, ROCHE, AstraZeneca, and Eli Lilly., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Measuring psychological traits with standardised questionnaires is an essential component of clinical practice and research; however, patients and participants risk fatigue from overly long and repetitive measures. When developing the short form of a questionnaire, the most widely used method for selecting an item subset uses factor analysis loadings to identify the items most closely related to the psychological construct being measured. However, this approach will tend to select highly correlated, homogeneous items and might therefore restrict the breadth of the construct examined. In this study, we will present Yarkoni's genetic algorithm for scale reduction and compare it with the classical scale reduction method. The algorithm will be applied to the shortening of three instruments for measuring self-compassion and social safeness (two unidimensional measures and a three-factor measure). We evaluated the shortened scales using correlation with long-form scores, internal reliability and the change in the correlations observed with other related constructs. Findings suggested that the classical method preserves internal reliability, but Yarkoni's genetic algorithm better maintained correlations with other constructs. An additional qualitative assessment of item content showed that the latter method led to a more heterogeneous selection of items, better preserving the full complexity of the constructs being measured., (© 2024 The Author(s). International Journal of Psychology published by John Wiley & Sons Ltd on behalf of International Union of Psychological Science.)

Introduction: Personalized medicine has revolutionized the clinical management of patients with solid tumors. However, the large volumes of molecular data derived from next-generation sequencing (NGS) and the lack of harmonized bioinformatics pipelines drastically impact the clinical management of patients with solid tumors. A possible solution to streamline the molecular interpretation and reporting of NGS data would be to adopt automated data analysis software. In this study, we tested the clinical efficiency of the Navify Mutation Profiler (nMP) software in improving the interpretation of NGS data analysis in diagnostic routine samples from patients with solid tumors., Methods: This study included one coordinating institution (Federico II University of Naples) and five other Italian institutions. Variant call format (VCF) files from reference standard samples previously tested by the coordinating institution and from n = 8 diagnostic routine samples (n = 2 from colorectal carcinoma; n = 2 from non-small cell lung cancer; n = 2 from advanced melanoma; and n = 2 from patients with gastrointestinal stromal tumors) and previously analyzed by each participating institution (n = 5) with standardized internal analysis workflows were uploaded onto the Navify ® Mutation Profiler (nMP) system (Roche Sequencing Solutions, Pleasanton, CA, USA) for automated analysis and interpretation of DNA and RNA molecular alterations analytical parameters, molecular profiling, and clinical interpretation were carried out by the nMP system and compared with the standard workflow data analyzed by the participating institutions., Results: Overall, all VCF files were successfully submitted and interpreted by the nMP system. A concordance agreement rate of 89.6% was observed between the automated and standard workflow systems. In particular, DNA and RNA molecular profiles obtained with the nMP system matched those obtained with standardized approaches in 44 out of 48 patients (91.7%) and in 11 out of 12 (91.7%) cases, respectively. In addition, the nMP system evidenced wild-type variants in 6 out of 7 (85.7%) cases., Conclusions: The nMP system represents a valid, easily manageable, and clinically useful system to interpret NGS data on diagnostic routine samples from patients with solid tumors., Competing Interests: Declarations. Conflict of Interest: Francesco Pepe has a relevant relationship (advisory fees, honoraria, travel accommodation and expenses, grants, and non-financial support) with Menarini and Roche that is unrelated to the current work. Luisella Righi reports personal fees (for speaker’s bureaus or acting as an advisor) from Roche, MSD, Boehringer Ingelheim, Eli Lilly, BMS, AstraZeneca, Amgen, and Bayer that are unrelated to the current work. Giancarlo Troncone reports personal fees (for speaker’s bureaus or acting as an advisor) from Roche, MSD, Pfizer, Boehringer Ingelheim, Eli Lilly, BMS, GSK, Menarini, AstraZeneca, Amgen, and Bayer that are unrelated to the current work. Umberto Malapelle has received personal fees (for acting as a consultant and/or speaker’s bureaus) from Boehringer Ingelheim, Roche, MSD, Amgen, Thermo Fisher Scientific, Eli Lilly, Diaceutics, GSK, Merck, AstraZeneca, Janssen, Diatech, Novartis, and Hedera that are unrelated to the current work. Umberto Malapelle is an editorial board member of Oncology and Therapy. Umberto Malapelle was not involved in the selection of peer reviewers for the manuscript nor in any of the subsequent editorial decisions. All other named authors confirm that they have no conflicts of interest to declare. Ethical Approval: Written informed consent was acquired from all patients involved in the study and documented in accordance with the general authorization for processing personal data for scientific research purposes from the Italian Data Protection Authority ( http://www.garanteprivacy.it/web/guest/home/docweb/-/docwebdisplay/export/2485392 ). All information regarding human material was managed using anonymous numerical codes, and all samples were handled in compliance with the Helsinki Declaration ( http://www.wma.net/en/30publications/10policies/b3/ )., (© 2024. The Author(s).)

Patients with health pathologies may exhibit psychological features in addition to medical symptomatology. A sample of 76 Italian women with an age range between 23 and 78 years old (mean = 50.22 ± 10.47 years) diagnosed with fibromyalgia (a disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, cognitive and mood issues) was examined to identify typical characteristics of their psychological profile. All patients were administered a series of questionnaires, to assess avoidance of physical touch by others; anxiety; depression; risk of developing psychotic disorders; self-criticism and perfectionism; acceptance of chronic pain; general impact of the pathology on their lives, and the predisposition to experience positive emotional states. The scores resulting from this assessment were evaluated against the normative data. Patients with fibromyalgia showed psychological dysfunction in most of the scales administered, with a significantly higher disposition to experience compassion towards others ( t = 5.94, df = 75, p < 0.001). A higher risk of psychosis was related with higher levels of depression ( B = 0.49, t = 0.20, p = 0.015), poor involvement in daily activities ( B = 0.41, t = 0.13, p = 0.002), touch avoidance (especially towards strangers, B = -0.20, t = 0.14, p = 0.01), and overall poor quality of life ( B = 0.40, t = 0.16, p = 0.01). This study may broaden the possibility to evaluate psychological features in this clinical population; it may contribute to tailoring psychological care and related treatments in the context of health services.

Competing Interests: There are no conflicts of interest.

Context: Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete., Objective: To identify pre- and posttreatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib., Design: Multicenter, retrospective, cohort study., Setting: 3 Italian thyroid cancer referral centers., Participants: 55 RR-DTC treated with lenvatinib., Main Outcome Measures: Progression-free survival (PFS) and overall survival (OS)., Results: Lenvatinib was the first-line kinase-inhibitor in 96.4% of subjects. Median follow-up was 48 months. Median PFS and OS were 26 [95% confidence interval (CI) 19.06-32.93] and 70 months (95% CI 36-111.99), respectively. Pretreatment setting: Eastern Cooperative Oncology Group (ECOG) performance status was independently related to PFS [P < .001; hazard ratio (HR) 18.82; 95% CI 3.65-97.08: score 0-1 as reference] and OS (P = .001; HR 6.20; 95% CI 2.11-18.20; score 0-1 as reference); radioactive iodine (RAI) avidity was independently related to PFS (P = .047; HR 3.74; 95% CI 1.01-13.76; avid disease as reference). Patients with good ECOG status (0-1) and RAI-avid disease obtained objective response in 100% of cases and achieved a median PFS of 45 months without any death upon a median follow-up of 81 months. Posttreatment setting: the best radiological response independently predicted PFS (P = .001; HR 4.6; 95% CI 1.89-11.18; partial/complete response as reference) and OS (P = .013; HR 2.94; 95% CI 1.25-6.89; partial/complete response as reference)., Conclusion: RR-DTC with good performance status and RAI-avid disease obtains the highest clinical benefit from lenvatinib. After treatment initiation, objective response was the only independent survival predictor., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

One-dimensional sub-wavelength gratings are versatile photonic platforms supporting diverse resonances, including symmetry-protected bound states in the continuum. However, practical access to these bound modes relies on their quasi-bound form, which necessitates the introduction of perturbations in either geometry or material properties. Despite having a large, finite quality factor, quasi-bound modes retain their characteristically strong field confinement. Gaining control over field localization and leakage of quasi-bound modes requires an investigation not limited to studying the degree of asymmetry and the incoming polarization. Here, we demonstrate that by carefully combining specific types of asymmetries and refractive index contrast between the grating and its surrounding environment, one can tailor field localization and Q-factor almost at will. Our findings reveal a strategic roadmap for optimizing quasi-bound mode implementation, dramatically improving their use in applications such as optical communication, sensing, and nonlinear optical processes.

Context: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS)., Objective: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature., Design: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up., Methods: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues., Results: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219)., Conclusions: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined., (© 2024. The Author(s).)

We demonstrate that AlGaAs thin films and metasurfaces generate a distinct intrinsic nonlinear geometric phase in their second harmonic signals, differing significantly from previous studies on nonlinear dielectric, plasmonic, or hybrid metasurfaces. Unlike conventional observations, our study reveals that the second harmonic phase remains unaffected by the linear optical response at both pump and harmonic wavelengths, introducing a novel realm of achievable phase functions yet to be explored. Furthermore, we explore the interplay between this intrinsic nonlinear geometric phase and the geometric phase induced by rotations of nanoresonators within metasurface arrangements. Our findings extend the capabilities of nonlinear wavefront shaping metasurfaces, exploiting phase manipulation to uncover unique phenomena exclusive to the nonlinear regime., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Nowadays, dielectric metasurfaces are a promising platform in many different research fields such as sensing, lasing, all-optical modulation and nonlinear optics. Among all the different kinds of such thin structures, asymmetric geometries are recently attracting increasing interest. In particular, nonlinear light-matter interaction in metasurfaces constitutes a valid approach for achieving miniaturized control over light. Here, we demonstrate nonlinear asymmetric generation of light in a dielectric metasurface via second harmonic generation. By inverting the illumination direction of the pump, the nonlinear emitted power is modulated by more than one order of magnitude. Moreover, we demonstrate how a properly designed metasurface can generate two completely different images at the second harmonic when the direction of illumination is reversed. Our results may pave the way to important opportunities for the realization of compact nanophotonic devices for imaging applications by densely integrating numerous nonlinear resonators.

All-optical modulation yields the promise of high-speed information processing. In this field, metasurfaces are rapidly gaining traction as ultrathin multifunctional platforms for light management. Among the featured functionalities, they enable light-wavefront manipulation and more recently demonstrated the ability to perform light-by-light manipulation through nonlinear optical processes. Here, by employing a nonlinear periodic metasurface, we demonstrate the all-optical routing of telecom photons upconverted to the visible range. This is achieved via the interference between two frequency-degenerate upconversion processes, namely, third-harmonic and sum-frequency generation, stemming from the interaction of a pump pulse with its frequency-doubled replica. By tuning the relative phase and polarization between these two pump beams, we route the upconverted signal among the diffraction orders of the metasurface with a modulation efficiency of up to 90%. This can be achieved by concurrently engineering the nonlinear emission of the individual elements (meta-atoms) of the metasurface along with its pitch. Owing to the phase control and ultrafast dynamics of the underlying nonlinear processes, free-space all-optical routing could be potentially performed at rates close to the employed optical frequencies divided by the quality factor of the optical resonances at play. Our approach adds a further twist to optical interferometry, which is a key enabling technique employed in a wide range of applications, such as homodyne detection, radar interferometry, light detection and ranging technology, gravitational-wave detection and molecular photometry. In particular, the nonlinear character of light upconversion combined with phase sensitivity is extremely appealing for enhanced imaging and biosensing., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

In this work, phytochemical analysis on different extracts of Roccella tinctoria DC. was reported using different techniques with respect to the past. Twenty volatile and three non-volatile compounds were identified, some of which were found in this species for the first time. The methanolic extracts and their non-volatile components were then evaluated for their antitumor effects in cancerous A549 and Mz-ChA-1 cells and for their tolerability in non-cancerous BEAS-2B and H69 cells, showing IC 50 values from 94.6 µg/mL to 416.4 µg/mL, in general. The same extracts and compounds were also tested for their antifungal effects in Candida albicans, with only compound 2 being active, with an MIC 50 value of 87 µg/mL. In addition, they were tested for their anti- Candida adhesion activity, anti- Candida biofilm formation, and anti- Candida mature biofilm inhibition, with efficacy percentages generally above 50% but not for all of them. Lastly, the DF3 extract and compounds 1 - 2 were tested in vivo according to the Galleria mellonella survival assay, showing positive mortality rates above 50% at different concentrations. All these biological assays were conducted on this species for the first time. Comparisons with other lichens and compounds were also presented and discussed.

Background: MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) exon 14 skipping mutation represents one of the most common MET alterations, accounting for approximately 1-3% of all mutations in advanced lung adenocarcinomas. While until 2020 no specific treatment was available for this subset of patients, as of today, three MET Tyrosine Kinase Inhibitors (TKIs) are currently approved in this setting, namely capmatinib, tepotinib and savolitinib., Objective: This article aims to provide an extensive overview of the current therapeutic standard of care for exon 14 skipped advanced Non-small Cell Lung Cancer (NSCLC) patients, alongside with mentions of the main future challenges and opportunities., Conclusion: FDA-approved MET-TKIs currently represent the best option for treating exon 14 skipped advanced NSCLC patients, thanks to their excellent efficacy profile, alongside their manageable safety and tolerability. However, we currently lack specific agents to treat patients progressing on capmatinib or tepotinib, due to a limited understanding of the mechanisms underlying both on- and off-target resistance. In this respect, on-target mutations presently constitute the most explored ones from a mechanistic point of view, and type II MET-TKIs are currently under investigation as the most promising agents capable of overcoming the acquired resistance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Metasurfaces, composed of artificial meta-atoms of subwavelength size, can support strong light-matter interaction based on multipolar resonances and plasmonics, hence offering the great capability of empowering nonlinear generation. Recently, owing to their ability to manipulate the amplitude and phase of the nonlinear emission in the subwavelength scale, metasurfaces have been recognized as ultra-compact, flat optical components for a vast range of applications, including nonlinear imaging, quantum light sources, and ultrasensitive sensing. This review focuses on the recent progress on nonlinear metasurfaces for those applications. The principles and advances of metasurfaces-based techniques for image generation, including image encoding, holography, and metalens, are investigated and presented. Additionally, the overview and development of spontaneous photon pair generation from metasurfaces are demonstrated and discussed, focusing on the aspects of photon pair generation rate and entanglement of photon pairs. The recent blossoming of the nonlinear metasurfaces field has triggered growing interest to explore its ability to efficiently up-convert infrared images of arbitrary objects to visible images and achieve spontaneous parametric down-conversion. This recently emerged direction holds promising potential for the next-generation technology in night-vision, quantum computing, and biosensing fields., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

In this paper, novel optimization methodologies of sub-relativistic guided interaction structures for dielectric laser particle acceleration (DLA) are presented. In particular, we focus on co-propagating geometries based on slot waveguides in continuous wave (CW) operation, where the particle flow and the direction of propagation of the accelerating field are co-linear. Since the velocity of sub-relativistic particles varies along the acceleration path, proper tapering of the waveguide geometry is required to achieve an extended acceleration region, and, thus a large energy gain. The design of an optimal taper ensuring particle-wave synchronicity and maximum energy gain is pursued through a physics-based approach, and these results are compared, for validation, with the outcomes of a downhill simplex method searching algorithm. Additionally, the application of a simplified 2D model of the accelerating slot waveguide is investigated and profitably used to get qualitative results useful for fast structure optimization. Indeed, this approach can hold significant potential for the development of novel accelerating structures, as it enables a thorough and fast exploration of the design space.

Taking into account the huge epidemiologic impact of lung cancer (in 2020, lung cancer accounted for 2,206,771 of the cases and for 1,796,144 of the cancer-related deaths, representing the second most common cancer in female patients, the most common cancer in male patients, and the second most common cancer in male and female patients) and the current lack of recommendations in terms of prognostic factors for patients selection and management, this article aims to provide an overview of the current landscape in terms of currently available immunotherapy treatments and the most promising assessed prognostic biomarkers, highlighting the current state-of-the-art and hinting at future challenges.

We investigate nonlinear THz generation from lithium niobate films and crystals of different thicknesses by optical rectification of near-infrared femtosecond pulses. A comparison between numerical studies and polarization-resolved measurements of the generated THz signal reveals a 2 orders of magnitude enhancement in the nonlinear response compared to optical frequencies. We show that this enhancement is due to optical phonon modes at 4.5 and 7.45 THz and is most pronounced for films thinner than 2 μm where optical-to-THz conversion is not limited by self-absorption. These results shed new light on the employment of thin film lithium niobate platforms for the development of new integrated broadband THz emitters and detectors. This may also open the door for further control (e.g., polarization, directivity, and spectral selectivity) of the process in nanophotonic structures, such as nanowires and metasurfaces, realized in the thin film platform. We illustrate this potential by numerically investigating optical-to-THz conversion driven by localized surface phonon-polariton resonances in sub-wavelength lithium niobate rods., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Vinca sardoa (Stearn) Pignatti, known as Sardinian periwinkle, is widely diffused in Sardinia (Italy). This species contains indole alkaloids, which are known to have a great variety of biological activities. This study investigated the antileukemic activity against a B lymphoblast cell line (SUP-B15) of V. sardoa alkaloid-rich extracts obtained from plants grown in Italy, in Iglesias (Sardinia) and Rome (Latium). All the extracts showed a good capacity to induce reductions in cell proliferation of up to 50% at the tested concentrations (1-15 µg/mL). Moreover, none of the extracts showed cytotoxicity on normal cells at all the studied concentrations.

Introduction: CTLA-4/PD-1/PD-L1- directed immune checkpoint inhibitors (ICIs) are one of the standard therapies for the treatment of advanced non-small cell lung cancer (NSCLC). However, some new classes of monoclonal antibodies are emerging as promising therapies for advanced NSCLC., Areas Covered: Therefore, this paper aims to provide a comprehensive review of the recently approved as well as emerging monoclonal antibody immune checkpoint inhibitors for the treatment of advanced NSCLC., Expert Opinion: Further and larger studies will be needed to explore the promising emerging data on new ICIs. Future phase III trials could allow us to properly assess the role of each immune checkpoints in the wider context of the tumor microenvironment and thus the best new ICIs to use, the best approach and the most effective subset of patients to select.

Somatic activating mutations of PIK3CA are associated with development of vascular malformations (VMs). Here, we describe a microfluidic model of PIK3CA -driven VMs consisting of human umbilical vein endothelial cells expressing PIK3CA activating mutations embedded in three-dimensional hydrogels. We observed enlarged, irregular vessel phenotypes and the formation of cyst-like structures consistent with clinical signatures and not previously observed in cell culture models. Pathologic morphologies occurred concomitant with up-regulation of Rac1/p21-activated kinase (PAK), mitogen-activated protein kinase cascades (MEK/ERK), and mammalian target of rapamycin (mTORC1/2) signaling networks. We observed differential effects between alpelisib, a PIK3CA inhibitor, and rapamycin, an mTORC1 inhibitor, in mitigating matrix degradation and network topology. While both were effective in preventing vessel enlargement, rapamycin failed to reduce MEK/ERK and mTORC2 activity and resulted in hyperbranching, while inhibiting PAK, MEK1/2, and mTORC1/2 mitigates abnormal growth and vascular dilation. Collectively, these findings demonstrate an in vitro platform for VMs and establish a role of dysregulated Rac1/PAK and mTORC1/2 signaling in PIK3CA -driven VMs.