New southernmost record of the European Brook Lamprey, Lampetra planeri (Bloch, 1784) (Agnatha, Petromyzontidae)

We report the occurrence of the European Brook Lamprey, Lampetra planeri (Bloch, 1784), in the Lao river in the Calabria region (southern Italy). This record extends the species’ known distribution limit southwards. Information regarding some morphometric and ecological data are provided and discussed

An updated checklist of chondrichthyans of Calabria (Central Mediterranean, southern Italy), with emphasis on rare species

In this contribution the checklist of chondrichthyans of Calabria (Central Mediterranean, southern Italy) is reported. Data presented is derived from twenty years of opportunistic and active surveys from 2000 to 2020. A total of 55 species of chondrichthyans is present in Calabrian seas: 33 sharks, 20 rays, and 2 chimaeras. These species represent approximately 62% of the total reported for the Mediterranean. Approximately 71% of Calabrian species have been reported in the Tyrrhenian Sea, 49% in the Ionian Sea, and 33% in the Strait of Messina. According to IUCN criteria, new records of Endangered and Critically Endangered species (i.e., Carcahrodon carcharias [Linnaeus, 1758], Lamna nasus [Bonnaterre, 1788], Cetorhinus maximus [Gunnerus, 1765], Mobula mobular [Bonnaterre, 1788], Sphyrna zygaena [Linnaeus, 1758]) are reported, together with the first record of Raya brachyura Lafont, 1873 for the Ionian coasts and probably third confirmed record of the rare chimaera Hydrolagus mirabilis (Collett, 1904) for the Mediterranean

Insights into the Complex Formed by Matrix Metalloproteinase-2 and Alloxan Inhibitors: Molecular Dynamics Simulations and Free Energy Calculations

Matrix metalloproteinases (MMP) are well-known biological targets implicated in tumour progression, homeostatic regulation, innate immunity, impaired delivery of pro-apoptotic ligands, and the release and cleavage of cell-surface receptors. Hence, the development of potent and selective inhibitors targeting these enzymes continues to be eagerly sought. In this paper, a number of alloxan-based compounds, initially conceived to bias other therapeutically relevant enzymes, were rationally modified and successfully repurposed to inhibit MMP-2 (also named gelatinase A) in the nanomolar range. Importantly, the alloxan core makes its debut as zinc binding group since it ensures a stable tetrahedral coordination of the catalytic zinc ion in concert with the three histidines of the HExxHxxGxxH metzincin signature motif, further stabilized by a hydrogen bond with the glutamate residue belonging to the same motif. The molecular decoration of the alloxan core with a biphenyl privileged structure allowed to sample the deep S1′ specificity pocket of MMP-2 and to relate the high affinity towards this enzyme with the chance of forming a hydrogen bond network with the backbone of Leu116 and Asn147 and the side chains of Tyr144, Thr145 and Arg149 at the bottom of the pocket. The effect of even slight structural changes in determining the interaction at the S1′ subsite of MMP-2 as well as the nature and strength of the binding is elucidated via molecular dynamics simulations and free energy calculations. Among the herein presented compounds, the highest affinity (pIC50 = 7.06) is found for BAM, a compound exhibiting also selectivity (>20) towards MMP-2, as compared to MMP-9, the other member of the gelatinases

Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking status and treatment modality was concordantly statistically significant with respect to ORR (p = 0.0074), PFS (p = 0.0001) and OS (p = 0.0020), confirming the significantly different impact of smoking status across the two cohorts. Conclusions: Among metastatic NSCLC patients with PD-L1 expression ≥50% receiving first-line pembrolizumab, current/former smokers experienced improved PFS and OS. On the contrary, worse outcomes were reported among current/former smokers receiving first-line chemotherapy

Some Novel Numerical Applications of Cosserat Continua

Cosserat continua demonstrated to have peculiar mechanical properties, with respect to classic Cauchy continua, due to the fact that they are able to more accurately model heterogeneous materials, as particle composites, masonry-like materials and others, taking into account, besides the disposition, the size and the orientation of the heterogeneities [1-3]. On the contrary, classical Cauchy elasticity fails in the modeling of problems in which the characteristic internal length is comparable with the structural length [4]. For this reason, many studies are devoted to the numerical implementation of the Cosserat model for practical engineering purposes. Due to the complexity of real physical systems, generally it is not convenient to use semi-analytical approaches for solving such problems, due to limitations related to the boundary conditions and constitutive material models. Thus, numerical approaches are considered as a better choice in these studies. In particular, the authors in the present paper are studying some reference benchmarks, well known from the literature of Cosserat continua, by comparing the solution provided by strong and weak formulations. On one hand, the high accuracy of the so-called Strong Formulation Finite Element Method (SFEM) [5-7] is compared to the numerical models provided by a Finite Element (FE) modeling given by COMSOL® Multiphysics. Convergence, stability and reliability of both modelling will be discussed. The aim is to investigate the more convenient numerical strategies for solving the Cosserat elastic problem. Moreover, differences between classical (Cauchy) and micropolar (Cosserat) model will be discussed in order to emphasize the capabilities of the Cosserat continua in modelling the aforementioned class of problems