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Abstract: Metastatic breast cancer is ultimately an incurable disease, although recent data have shown that its incidence is decreasing and that patients with metastatic breast cancer live longer. This improvement in survival seems to be linked with the introduction of new therapeutic agents, novel combinations of existing therapies and targeted therapies. Our increasing understanding of the molecular biology of metastatic disease has allowed the development of therapies aimed at specific molecular targets. Some of these have already been approved for the treatment of metastatic breast cancer in combination with cytotoxics, and others have shown promising results regarding disease-free survival, overall response rates and time to disease progression. Given the enormous amount of information about drug discovery in cancer, it is important to be familiar with the present state of the treatment of metastatic breast cancer. The purpose of this review is to provide an update on the development of some of the most promising novel agents and treatment strategies in metastatic breast cancer. [Copyright &y& Elsevier]

Condition monitoring of gear trains by classic techniques based on vibrations and/or extensometry measurements requires the preparation of the sensor contact surfaces and the cables installation. In the case of planetary gear trains, this task is more difficult due to their compactness and the complexity of the relative movements among their different elements. As an alternative, the authors studied the possibility of using acoustic measurements for the planetary gear-set characterisation, as well as for predictive maintenance of this mechanical system. In order to perform this study, a suitable measurement equipment was selected and a bespoke software was developed to control it, to process the data, as well as to represent the results. This informatic tool was used to perform the acoustic characterisation, in which acoustic pressure and intensity measurements were combined with advanced algorithms, such as sincronous-average technique. In this study, two different failures were experimentally recreated in a commercial gearbox, representing the results by frequency and order spectra and intensity maps. The obtained results were compared with those obtained in the box without defect. [ABSTRACT FROM AUTHOR]

To describe patient characteristics, effectiveness and safety in a real-world population treated with niraparib in the Spanish expanded-access programme. This retrospective observational study included women with platinum-sensitive recurrent high-grade serous ovarian cancer who received maintenance niraparib within the Spanish niraparib expanded-access programme. Eligible patients had received ≥2 previous lines of platinum-containing therapy, remained platinum-sensitive after the penultimate line of platinum and had responded to the most recent platinum-containing therapy. Niraparib dosing was at the treating physician's discretion (300 mg/day fixed starting dose or individualised starting dose [ISD] according to baseline body weight and platelet count). Safety, impact of dose adjustments, patient characteristics and effectiveness were analysed using data extracted from medical records. Among 316 eligible patients, 80% had BRCA wild-type tumours and 66% received an ISD. Median niraparib duration was 7.8 months. The most common adverse events typically occurred within 3 months of starting niraparib. Median progression-free survival was 8.6 (95% confidence interval [CI] 7.6–10.0) months. One- and 2-year overall survival rates were 86% (95% CI 81–89%) and 65% (95% CI 59–70%), respectively. Dose interruptions, dose reductions, haematological toxicities and asthenia/fatigue were less common with ISD than fixed starting dose niraparib, but progression-free survival was similar irrespective of dosing strategy. Subsequent therapy included platinum in 71% of patients who received further treatment. Outcomes in this large real-world dataset of niraparib-treated patients are consistent with phase III trials, providing reassuring evidence of the tolerability and activity of niraparib maintenance therapy for platinum-sensitive recurrent ovarian cancer. NCT04546373. • In this real-world study of maintenance niraparib, 80% had BRCA wt ovarian cancer. • Median progression-free survival was 8.6 (95% confidence interval 7.6–10.0) months. • Adverse events typically occurred within 3 months of starting niraparib. • Tolerability was improved with an individualised versus fixed niraparib starting dose. • Real-world data for niraparib are consistent with phase III results. [ABSTRACT FROM AUTHOR]

• Using rheology in a polymer-metallic spur gear system. • Simulating the viscoelastic behavior of nylon 6,6 using generalized Maxwell model. • Identifying parameters using parameter identification method Poel-zero formulation. • Deducing gear mesh stiffness of polymer-metallic gear for different temperatures. Polymer-metal gears become increasingly interesting to manufacturers and researchers for their advantages to combine the two material's efficiencies. Despite the variety of studies in the literature, there is a significant drop in the number of studies concerning the Gear Mesh Stiffness (GMS). The variation of the GMS by time has a major influence on the dynamic response of transmission. Therefore, this study proposes to take into consideration the viscoelastic behavior of polymer in order to model effectively the GMS of a gear system. The suggested rheological model is the Generalized Maxwell Model (GMM). It is first used to model the viscoelastic behavior of the plastic material of the pinion. Then, Pole Zero Formulation (PZF) is employed to identify parameters of the proposed model. A numerical simulation is then carried out to illustrate the results of this new approach adopted on a pure Nylon 6,6-steel pinions. The evolution of the GMS is illustrated to highlight the viscoelastic behavior's model presented in this paper. Finally, the influence of the change in the temperature is investigated. [ABSTRACT FROM AUTHOR]

Accurate diagnosis of invasive breast lesions, when analyzed by Core Needle Biopsy, may suppose a major challenge for the pathologist. Various markers of invasiveness such as laminin, S-100 protein, P63 or calponin have been described; however, none of them is completely reliable. The use of a specific marker of the infiltrating tumor microenvironment seems vital to support the diagnosis of invasive against in situ lesions. At this point, Collagen, type XI, alpha 1 (COL11A1), might be helpful since it has been described to be associated to cancer associated fibroblasts in other tumors such as lung, pancreas or colorectal. This paper aims to analyze the role of COL11A1 as a marker of invasiveness in breast tumor lesions. Two hundred and one breast Core Needle Biopsy samples were analyzed by immunohistochemistry against pro-COL11A1. The results show a significant difference ( p < 0.0001) when comparing the expression in infiltrative tumors (93%) versus immunostaining of non-invasive lesions (4%). Forty cases of underestimated DCIS were also stained for COL11A1, presenting a sensitivity of 90% when compared with p63 and calponin which not tagged invasion. In conclusion, pro-COL11A1 expression is a promising marker of invasive breast lesions, and may be included in immunohistochemical panels aiming at identifying infiltration in problematic breast lesions. [ABSTRACT FROM AUTHOR]

Background We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. Methods In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4 mg every 28 days) from the baseline visit. Results 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3 months ( P < 0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214–20.839; P = 0.0259]) and at 3 months (3.41 [95% CI: 1.367–8.498; P = 0.0085]). HRs > 2 were found for increased baseline and 3-month levels of NTX and CTC ( P < 0.05). Only increased baseline BSAP levels were associated with DP (HR = 2.25 [95% CI: 1.391–3.626; P = 0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3 months of NTX and BSAP were significantly associated with mortality (HRs = 3.59 [95% CI: 1.375–9.382; P = 0.0091] and 3.25 [95% CI: 1.293–8.189; P = 0.0120], respectively). CTC and BSAP were correlated during all study timepoints ( P < 0.05). Conclusions Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value. [ABSTRACT FROM AUTHOR]