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The reporting of lung neuroendocrine neoplasms (NENs) according to the 2021 World Health Organisation (WHO) is based on mitotic count per 2 mm2, necrosis assessment and a constellation of cytological and immunohistochemical details. Accordingly, typical carcinoid and atypical carcinoid are low‐ to intermediate‐grade neuroendocrine tumours (NETs), while large‐cell neuroendocrine carcinoma (NEC) and small‐cell lung carcinoma are high‐grade NECs. In small‐sized diagnostic material (cytology and biopsy), the noncommittal term of carcinoid tumour/NET not otherwise specified (NOS) and metastatic carcinoid NOS have been introduced with regard to primary and metastatic diagnostic settings, respectively. Ki‐67 antigen, a well‐known marker of cell proliferation, has been included in the WHO classification as a non‐essential but desirable criterion, especially to distinguish NETs from high‐grade NECs and to delineate the provisional category of carcinoid tumours/NETs with elevated mitotic counts (> 10 mitoses per mm2) and/or Ki‐67 proliferation index (≥ 30%). However, a wider use of this marker in the spectrum of lung NENs continues to be highly reported and debated, thus witnessing a never‐subsided attention. Therefore, the arguments for and against incorporating Ki‐67 in the classification and clinical practice of these neoplasms are discussed herein in detail. [ABSTRACT FROM AUTHOR]

A general approach for the synthesis of the optimal sequential network for use in sequentially rotated antenna (SRA) arrays with an arbitrary number of elements is presented. The performance of this class of antennas are strictly bound to the capacity of the feeding network to produce the nominal power distribution and phase progression. Despite the very high interest in the scientific community on SRA architectures, very few papers have addressed the problem of synthesizing a generic network, with an arbitrary number of outputs. In this paper we propose a novel approach based on closed formulas which solves the synthesis problem exactly, for a given frequency. The proposed approach is then validated with a set of simulations and with the fabrication and measurement of a prototype. Both the simulations and the experimental validation confirms the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Little is known as to whether there may be any pathogenetic link between pulmonary carcinoids and neuroendocrine carcinomas (NECs). A gene signature we previously found to cluster pulmonary carcinoids, large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), and which encompassed MEN1, MYC, MYCL1, RICTOR, RB1, SDHA, SRC and TP53 mutations or copy number variations (CNVs), was used to reclassify an independent cohort of 54 neuroendocrine neoplasms (NENs) [31 typical carcinoids (TC), 11 atypical carcinoids (AC) and 12 SCLC], by means of transcriptome and mutation data. Unsupervised clustering analysis identified two histology-independent clusters, namely CL1 and CL2, where 17/42 (40.5%) carcinoids and all the SCLC samples fell into the latter. CL2 carcinoids affected survival adversely, were enriched in T to G transversions or T > C/C > T transitions in the context of specific mutational signatures, presented with at least 1.5-fold change (FC) increase of gene mutations including TSC2 , SMARCA2 , SMARCA4 , ERBB4 and PTPRZ1 , differed for gene expression and showed epigenetic changes in charge of MYC and MTORC1 pathways, cellular senescence, inflammation, high-plasticity cell state and immune system exhaustion. Similar results were also found in two other independent validation sets comprising 101 lung NENs (24 carcinoids, 21 SCLC and 56 LCNEC) and 30 carcinoids, respectively. We herein confirmed an unexpected sharing of molecular traits along the spectrum of lung NENs, with a subset of genomically distinct aggressive carcinoids sharing molecular features of high-grade neuroendocrine neoplasms. [ABSTRACT FROM AUTHOR]

Transformation optics is a powerful tool allowing remapping a generic domain into another yet maintaining a correspondence of the solution of Maxwell's equations within the two domains. Transformation optics has been used in the past to conveniently solve for modes in a generic waveguide by transforming its cross‐section into a circular one. Such a transformation needs particular care in enforcing boundary conditions in the transformed, circular, domain. In this paper, a theoretical treatment of boundary conditions is presented, allowing for an accurate computation of all field components in a generic waveguide. [ABSTRACT FROM AUTHOR]

A synthesis method for the design of large planar array antennas with phase-only control is here presented. The synthesis is based on the use of Zernike polynomials, as global basis function for the phase, to reduce the number of optimization variables with respect to the number of elements of the array. Invasive weed optimization (IWO) is applied to polynomial coefficients’ optimization to circumvent nonlinearity and local trapping issues typical of phase-only problems. The periodicity of the array factor is exploited to reduce the optimization to a Voronoi cell of the grating-lobes’ lattice and nonuniform meshing is introduced to best adapt the control stations to the beam shape requirements. The technique is applied to the design of shaped beams for continental coverage from geostationary satellites. [ABSTRACT FROM AUTHOR]

Background: Over the last 2 decades, great progress has been made in the understanding of the clinical aspects and pathogenesis of lymphangioleiomyomatosis (LAM), leading to publication of guidelines and approval of an effective therapy. Objectives: Aim of our study was to describe how the management and the natural history of this rare disease have changed after the publication of the ERS and American Thoracic Society/Japanese Respiratory Society guidelines and the introduction of sirolimus. Methods: We examined 162 LAM patients followed at our center between 2001 and 2017, reporting clinical characteristics and diagnostic approach. Response to sirolimus in patients undergoing long-term treatment and mortality risk, estimated in terms of cumulative incidence taking into account organ transplantation as a competing cause of the event, were evaluated. The difference in the cumulative incidence between the patients admitted to the observation before 2011 and after 2011, year of the publication of the MILES trial for the efficacy of sirolimus, has also been estimated. Results: Sixty-one patients had a histological diagnosis (22 from 2010 onward). 101 patients received a radiological diagnosis according to the guidelines criteria. Pulmonary function tests remained stable over a 3-year treatment period in patients who received sirolimus for over 12 months. The cumulative incidence of mortality after 10 years in the whole population was 25.5%. The cumulative incidence of mortality after 5 years was significantly lower in patients who entered the study since 2011 (after publication of the MILES trial) than in patients who entered the study before. Conclusions: We provide the data supporting the long-term efficacy of sirolimus therapy in a large cohort of patients with functional impairment and other manifestations of the disease. Our results also suggest that the advent of sirolimus and the publication of international guidelines changed the natural history of the disease lowering the mortality and reducing the need of invasive diagnostic techniques. [ABSTRACT FROM AUTHOR]

This study introduces the conic section arc elements in 2D and 2.5D finite element method (FEM). Elements are obtained by deforming an edge in a standard triangular element through a coordinate transformation. This allows to completely eliminate the geometrical error in structures composed of circular, elliptical, hyperbolic and parabolic arcs. The element order is defined independently of the geometrical description of the boundary, allowing the use of simple meshers. Previously available FEM codes can be straightforwardly modified to introduce the conic section boundaries. [ABSTRACT FROM AUTHOR]

Acinar cell carcinoma (ACC) of the pancreas are known to be rare and difficult to be recognize because they mimic other unrelated tumors (neuroendocrine, solid pseudopapillary) with different clinical behavior. Especially in the setting of inoperable patients, fine needle aspiration cytology (FNAC), core needle biopsy (FNAB) and immunocyto/histochemistry (ICC/IHC) play a crucial role in the differential diagnosis. The biological material available for ICC tests obtained by minimal invasive procedures is usually limited. Aim of the current study was to evaluate diagnostic panel based on a limited number of ICC markers for typing preoperatively ACC of the pancreas. Of 1820 needle sampling procedures performed and related to pancreatic lesions, 21 cases were extracted with a confirmed diagnosis of ACC on histology. Of them,12 were pure ACC and 9 mixed acinar-neuroendocrine carcinoma (MANEC). Smears of ACC, MANEC and a control group composed of 34neuroendocrine, 7solid pseudopapillary, 50ductal and 4 adenosquamous carcinoma were assessed with an ICC panel made up of BCL10, trypsin, synaptophysin, chromograninA, β-catenin. On cytology, BCL10 sensitivity and specificity for ACC was 100%. Trypsin correctly recognized 90% of the cases. Synaptophysin was helpful to correctly identify all the cases with a mixed neuroendocrine component. No significant cross-reaction was observed between BCL10 and trypsin in any of the control group case. BCL10 is a determinant marker for the diagnosis of acinar cell carcinoma and mixed acinar neuroendocrine cell carcinoma of the pancreas in a pre-operative citologic/histologic setting. [ABSTRACT FROM AUTHOR]