Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. Oral presentation, abstracts, and posters presented at the American Society of Clinical Oncology (ASCO, Alexandria, VA, USA) 2020 and the European Society for Medical Oncology (ESMO, Lugano, Switzerland) 2020 annual meetings were retrieved for data on T-DXd. We also overview ongoing research and data of combination therapies currently under investigation, which will impact on future therapeutic strategies. Clinicaltrials.gov was searched to identify ongoing clinical trials of T-DXd alone or in combination in solid tumors.     

Polymerization of lactams, 95 Preparation of polyesteramides by the anionic polymerization of ε-caprolactam in the presence of poly(ε-caprolactone)

Preparation of polyesteramides-poly[(ε-caprolactam)-co-(ε-caprolactone)]s by anionic polymerization of ε-caprolactam in the presence of poly(ε-caprolactone) at 150 °C was studied in this paper. ε-Caprolactam magnesium bromide was used as an initiator of polymerization and polymeric materials containing 5-25 wt% ε-caprolactone units were obtained. Thermal methods (DSC and DMA) were employed for characterization of poly[(ε-caprolactam)-co-(ε-caprolactone)]s and their mechanical properties were also evaluated. By introducing the activator with N-acyllactam structure, the polymerization rate increased and it was possible to carry out the polymerization at 110 °C. Mechanical properties of polyesteramides were influenced by both the content of ε-caprolactone units incorporated into copolymer and polymerization temperature. The mechanism of incorporation of poly(ε-caprolactone) is discussed. The results show that it is not possible to restrict exchange transacylation reactions, progressing in the course of polymerization, by kinetic tools.     

Die antioxidativen Eigenschaften von Lecithin

Antioxidizing Properties of Lecithin In various storage trials with sunflower oil and lard the antioxidizing properties of crude soybean lecithin as well as of its alcohol soluble and alcohol insoluble fraction could be proved. The addition of a very small quantity of these phospholipids to the oil after the refining process (prior to this process crude oil contains approx. 2–3% lecithin) improves the stability of these oils. The antioxidizing properties of phospholipids depend on: 1. composition of phospholipids, 2. tocopherol content of the oil. In our trials the alcohol soluble fraction of soybean lecithin performed the best antioxidizing results in sunflower oil by adding not less than 1%. In lard the same effect could already be reached with 0.1% of this fraction. As shown before, lecithin with a special phospholipid composition has antioxidizing properties and its addition in small quantities is beneficial to increase the stability of oils and fats. In new Japanese literature soybean saponines are the most favoured antioxidizing agents. Our trials did not confirm the results of these publications.     

Discovering social structures of local influence by using tweetStimuli

Information diffusion in large-scale networks has been studied to identify the users influence. The influence has been targeted as a key feature either to reach large populations or influencing public opinion. Through the use of micro-blogs, such as Twitter, global influencers have been identified and ranked based on message propagation (retweets). In this paper, a new application is presented, which allows to find first and classify then the local influence on Twitter: who have influenced you and who have been influenced by you. Until now, social structures of tweets’ original authors that have been either retweeted or marked as favourites are unobservable. Throughout this application, these structures can be discovered and they reveal the existence of communities formed by users of similar profile (that are connected among them) interrelated with other similar profile users’ communities.     

Learning Read-Constant Polynomials of Constant Degree Modulo Composites

Boolean functions that have constant degree polynomial representation over a fixed finite ring form a natural and strict subclass of the complexity class ACC⁰. They are also precisely the functions computable efficiently by programs over fixed and finite nilpotent groups. This class is not known to be learnable in any reasonable learning model. In this paper, we provide a deterministic polynomial time algorithm for learning Boolean functions represented by polynomials of constant degree over arbitrary finite rings from membership queries, with the additional constraint that each variable in the target polynomial appears in a constant number of monomials. Our algorithm extends to superconstant but low degree polynomials and still runs in quasipolynomial time.     

Dynamic light scattering measurements on the polystyrene/ethyl acetate system at semi-dilute concentrations as a function of temperature

Summary Measurements of autocorrelation functions extending over a broad time range are reported for a sample of polystyrene in ethyl acetate as a function of temperature between –44°C (-temperature) and 70°C. The corresponding spectra of decay times are obtained by two mathematical methods. The existence of three dynamic processes is shown and their temperature and angular behaviour is studied.     

Microstructure of a nitrided steel previously decarburized

In this study the effects of a surface-controlled decarburization on the structure of a nitrided steel are analyzed. Samples of a quenched and tempered 42CrMo4 steel were decarburized by heating in air at different depths and submitted to gaseous nitriding. After decarburization and nitriding, the microstructure of surface layers was investigated by optical microscopy (OM) and scanning electron microscopy (SEM). The nitrogen and carbon profiles in the diffusion layers were determined by SEM equipped with a wavelength dispersive spectrometer (EPMA-WDS) and by glow discharge optical spectrometry (GDOS). The effect of nitriding was determined by microhardness measurements. Our results indicate that a previous decarburization only slightly affects the surface hardness, but reduces the conventional nitriding depth. The decarburization also favors the nitrogen take-up and produces increased nitrogen concentrations in the compound layer and in the narrow zone beneath it.     

Computing the Ramsey number R(4,3,3) using abstraction and symmetry breaking

The number R(4, 3, 3) is often presented as the unknown Ramsey number with the best chances of being found “soon”. Yet, its precise value has remained unknown for almost 50 years. This paper presents a methodology based on abstraction and symmetry breaking that applies to solve hard graph edge-coloring problems. The utility of this methodology is demonstrated by using it to compute the value R(4, 3, 3) = 30. Along the way it is required to first compute the previously unknown set \(\mathcal {R}(3,3,3;13)\) consisting of 78,892 Ramsey colorings.     

Coreference resolution: an empirical study based on SemEval-2010 shared Task 1

This paper presents an empirical evaluation of coreference resolution that covers several interrelated dimensions. The main goal is to complete the comparative analysis from the SemEval-2010 task on Coreference Resolution in Multiple Languages. To do so, the study restricts the number of languages and systems involved, but extends and deepens the analysis of the system outputs, including a more qualitative discussion. The paper compares three automatic coreference resolution systems for three languages (English, Catalan and Spanish) in four evaluation settings, and using four evaluation measures. Given that our main goal is not to provide a comparison between resolution algorithms, these are merely used as tools to shed light on the different conditions under which coreference resolution is evaluated. Although the dimensions are strongly interdependent, making it very difficult to extract general principles, the study reveals a series of interesting issues in relation to coreference resolution: the portability of systems across languages, the influence of the type and quality of input annotations, and the behavior of the scoring measures.     

Experimental characterization of electrostatically actuated in-plane bending of microcantilevers

Experimental validation of numerical models developed by the authors to predict the static behaviour of microelectrostatic actuators is described. Cantilever microbeams, currently used in connection with RF-MEMS and micro-scale material testing were analysed. A set of microcantilevers, bending in the plane of the wafer, i.e. in the same plane as the profiling system’s target, was tested. This differs from the popular case of out-of-plane microbeams, usually studied in the literature. Geometry nonlinearity caused by large deflection of the microbeam was investigated and nonlinear coupled formulation of electromechanical equilibrium was performed. Coupled-field analysis was implemented using the Finite Element Method (FEM), to predict displacements and pull-in voltage measured by Fogale Zoomsurf 3D, subsequently plotting the displacement-versus-voltage curve to complete model validation. FEM nonlinear analysis, based on iterative approach with mesh morphing, and FEM non-incremental approach, including a special element proposed by the authors, are compared to the linear solution and to experimental results. Geometry nonlinearity appears relevant in microbeam modelling and requires a nonlinear solution of the coupled problem. Investigative work, which compared the results of 2D and 3D models to experimental data, revealed that some three dimensional effects are significant in model validation, but the 2D approach may be effective in predicting static behaviour provided that at least a microbeam thickness equivalent is adopted.