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Background Breast cancer is a chronic disease with a large growth in its treatments, prognosis, improvements, side effects and rehabilitation therapies research. These advances have also highlighted the need to use physical exercise as a countermeasure to reduce the cardiotoxicity of pharmacological treatments, increase patients' strength and quality of life and improve body composition, physical condition and mental health. However, new investigations show the need for a closed exercise individualisation to produce higher physiological, physical and psychological benefits in remote exercise programs. To this end, the present study will use, in a novel way in this population, heart rate variability (HRV) as a measure for prescribing high-intensity training. Thus, the primary objective of this randomised clinical trial is to analyse the effects of a high-intensity exercise program daily guided by HRV, a preplanned moderate to high-intensity exercise intervention and a usual care group, in breast cancer patients after chemotherapy and radiotherapy treatments. Methods For this purpose, a 16-week intervention will be carried out with 90 breast cancer patients distributed in 3 groups (a control group, a moderate to high-intensity preplanned exercise group and a high-intensity exercise group guided by HRV). Both physical exercise interventions will be developed remotely and supervised including strength and cardiovascular exercises. Physiological variables, such as cardiotoxicity, biomarkers, lipid profile, glucose, heart rate and blood pressure; physical measures like cardiorespiratory capacity, strength, flexibility, agility, balance and body composition; and psychosocial variables, as health-related quality of life, fatigue, functionality, self-esteem, movement fear, physical exercise level, anxiety and depression will be measure before, after the intervention and 3 and 6 months follow up. Discussion Personalized high-intensity exercise could be a promising exercise intervention in contrast to moderate-intensity or usual care in breast cancer patients to reach higher clinical, physical and mental effects. In addition, the novelty of controlling HRV measures daily may reflect exercise effects and patients' adaptation in the preplanned exercise group and a new opportunity to adjust intensity. Moreover, findings may support the effectiveness and security of physical exercise remotely supervised, although with high-intensity exercise, to reach cardiotoxicity improvements and increase physical and psychosocial variables after breast cancer treatments. Trial registration ClinicalTrials.gov nº NCT05040867 ( https://clinicaltrials.gov/ct2/show/record/NCT05040867 ).

According to the \"World Cancer Research Fund\" and the \"American Institute of Cancer Research\" (WCRF/AICR) one in four cancer cases could be prevented through a healthy diet, weight control and physical activity. To explore the association between the WCRF/AICR recommendations and risk of breast cancer. During the period 2006 to 2011 we recruited 973 incident cases of breast cancer and 973 controls from 17 Spanish Regions. We constructed a score based on 9 of the WCRF/AICR recommendations for cancer prevention:: 1)Maintain adequate body weight; 2)Be physically active; 3)Limit the intake of high density foods; 4)Eat mostly plant foods; 5)Limit the intake of animal foods; 6)Limit alcohol intake; 7)Limit salt and salt preserved food intake; 8)Meet nutritional needs through diet; S1)Breastfeed infants exclusively up to 6 months. We explored its association with BC by menopausal status and by intrinsic tumor subtypes (ER+/PR+ & HER2-; HER2+; ER&PR-&HER2-) using conditional and multinomial logistic models respectively. Our results point to a linear association between the degree of noncompliance and breast cancer risk. Taking women who met 6 or more recommendations as reference, those meeting less than 3 showed a three-fold excess risk (OR=2.98(CI95%:1.59-5.59)), especially for postmenopausal women (OR=3.60(CI95%:1.24;10.47)) and ER+/PR+&HER2- (OR=3.60(CI95%:1.84;7.05)) and HER2+ (OR=4.23(CI95%:1.66;10.78)) tumors. Noncompliance of recommendations regarding the consumption of foods and drinks that promote weight gain in premenopausal women (OR=2.24(CI95%:1.18;4.28); p for interaction=0.014) and triple negative tumors (OR=2.93(CI95%:1.12-7.63)); the intake of plant foods in postmenopausal women (OR=2.35(CI95%:1.24;4.44)) and triple negative tumors (OR=3.48(CI95%:1.46-8.31)); and the alcohol consumption in ER+/PR+&HER2- tumors (OR=1.52 (CI95%:1.06-2.19)) showed the strongest associations. Breast cancer prevention might be possible by following the \"World Cancer Research Fund\" and the \"American Institute of Cancer Research\" recommendations, even in settings like Spain, where a high percentage of women already comply with many of them.

Disruption of apoptosis may allow metastatic cell survival and confer resistance to chemotherapeutic drugs. We have analysed the molecular pathways that activate these survival genes in specific sites of metastasis. Estrogen receptor-negative breast cancer cell line MDA-MB435 and two metastatic sublines derived from lung (435L) and brain (435B) were analysed for the expression of members of the Bcl-2 family of apoptosis regulators. The levels of Bcl-2 were higher in the metastatic sublines than in parental cells, which correlated with the activation of Stat3, but not with the expression and/or activation of known bcl-2 transcription factors (CREB and WT1). In the brain subline, both expression of Bcl-2 and Stat3 activation were induced by epidermal growth factor and abrogated after treatment with kinase inhibitors specific for epidermal growth factor receptor or Jak2. Furthermore, transfection of 435B with a dominant-negative Stat3 markedly reduced the expression of Bcl-2 protein, whereas transient expression of a constitutively active Stat3 increased Bcl-2 in parental 435 cells. In addition, blockade of Stat3 activation by treatment with epidermal growth factor receptor and Jak2 kinase inhibitors or transfection with a dominant negative Stat3, sensitizes 435B cells to chemotherapy-induced apoptosis. Our data suggest that an increased activation of the Stat3-Bcl-2 pathway in estrogen receptor-negative metastatic breast cancer cell lines confer a survival advantage to these cells and contribute to their chemoresistance.

This study analyzes the association of excessive energy intake and caloric restriction with breast cancer (BC) risk taking into account the individual energy needs of Spanish women. We conducted a multicenter matched case-control study where 973 pairs completed lifestyle and food frequency questionnaires. Expected caloric intake was predicted from a linear regression model in controls, including calories consumed as dependent variable, basal metabolic rate as an offset and physical activity as explanatory. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. The association with BC risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. While premenopausal women that consumed few calories (>20% below predicted) had lower BC risk (OR = 0.36; 95% CI = 0.21–0.63), postmenopausal women with an excessive intake (≥40% above predicted) showed an increased risk (OR = 2.81; 95% CI = 1.65–4.79). For every 20% increase in relative (observed/predicted) caloric intake the risk of hormone receptor positive (p-trend < 0.001) and HER2+ (p-trend = 0.015) tumours increased 13%, being this figure 7% for triple negative tumours. While high energy intake increases BC risk, caloric restriction could be protective. Moderate caloric restriction, in combination with regular physical activity, could be a good strategy for BC prevention.

The great majority of thyroid cancers are of the non-medullary type. Here we report findings from a genome-wide association study of non-medullary thyroid cancer, including in total 3,001 patients and 287,550 controls from five study groups of European descent. Our results yield five novel loci (all with P combined <3 × 10 −8 ): 1q42.2 (rs12129938 in PCNXL2 ), 3q26.2 (rs6793295 a missense mutation in LRCC34 near TERC ), 5q22.1 (rs73227498 between NREP and EPB41L4A ), 10q24.33 (rs7902587 near OBFC1 ), and two independently associated variants at 15q22.33 (rs2289261 and rs56062135; both in SMAD3 ). We also confirm recently published association results from a Chinese study of a variant on 5p15.33 (rs2736100 near the TERT gene) and present a stronger association result for a moderately correlated variant (rs10069690; OR=1.20, P=3.2 × 10 −7 ) based on our study of individuals of European ancestry. In combination, these results raise several opportunities for future studies of the pathogenesis of thyroid cancer. Non-medullary thyroid cancers include papillary and follicular subtypes, and are the most common type of thyroid cancer. Here, the authors extend previous work by performing a large genome-wide association study and find five novel loci associated with this disease.

To evaluate the feasibility of acute and chronic toxicity in patients suitable for accelerated partial breast irradiation (APBI) in a single 18 Gy fraction with multicatheter high-dose-rate (HDR) brachytherapy, as well as cosmetic and oncological outcomes. Between September 2014 and March 2016, twenty consecutive patients with low-risk invasive and ductal carcinoma in situ were treated with interstitial multicatheter HDR brachytherapy in a single 18 Gy fraction. Median age was 63.5 years (range, 51-79). Acute toxicity was observed in seven patients, while the pain during following days and hematoma were seen in four patients. With a median follow-up of 24 months, late toxicity was found in one patient with fat necrosis g2 and fibrosis g2 in another patient. The overall survival (OS) and locoregional control (LC) was 100%. Disease-free survival (DFS) and distant control was 95%. Good to excellent cosmetic outcomes were noted in 80% of patients and fair in 4 patients (20%). This is the first report in the medical literature that focuses on feasibility and acute and chronic toxicity, with a median follow-up of 24 months (range, 20-40). The protocol is viable and convenient. However, a longer follow-up is needed to know chronic toxicity and oncologic outcomes.

The main dimensional errors in stamped parts are caused by the springback phenomenon. Those errors usually lead to assembly difficulties and/or the malfunction of those parts. The objective of this contribution is to give a comprehensive and detailed view of the sheet metal-forming process of an actual industrial part, with the focus on the setup adjustment of the blank-holder force (BHF), using the springback as the determining factor of the manufacturing quality. The complete cycle of the simulation will be detailed from the experimental determination of the model parameters to the correlation with experimental results of the simulated values. Many studies use simple geometries with limited practical application, failing to provide a quantitative understanding of actual springback in industrial processes. This work aims to offer a realistic reference for springback in a real production part, combining numerical prediction during design using a well-established model and experimental measurements in the factory. The simulation, carried out using LS-DYNA, determines the influence of the BHF in the springback observed in the manufacturing process of a gas cooktop part made from non-stable austenitic 1.4301 steel. The material has been modeled using Barlat’s Yld2000, experimentally determining the strain rate-dependent hardening, yield locus and isotropic–kinematic hardening. To validate the model, an experimental campaign has been developed, testing the part with values of BHF within the range of 50 t to 200 t. The results show that the numerical model is able to represent the influence of the BHF on the springback, demonstrating the relation between them.

The prediction of the behavior of vibration isolators is essential for effective and efficient design of these devices, as well as for accurately characterizing the isolator behavior. In this work, an experimental study was performed to characterize the behavior of metal-mesh isolators. Although these elements’ performance is of great interest because of their usage in several applications, their characterization is complex due to their nonlinear nature, among other factors. This study’s aim was to obtain the quasi-static behavior of these isolators, although dynamic tests are required for their complete characterization. These quasi-static tests allowed for the highlighting of some characteristics in a simpler and faster manner and also provided a starting point for designing future dynamic tests. The quasi-static tests performed resulted in the calculation of the hysteresis cycle under different operating conditions and manufacturing parameters. The study of different insulator characteristics, such as the energy dissipation coefficient and stiffness, led to interesting conclusions about the isolator performance. From the results, it was observed that the relative density affected most the nonlinear behavior of the insulator. Moreover, to correctly characterize their behavior, not only the Coulomb’s damping but also the viscous damping had to be considered.

The aim of this study was to identify an easily reliable prognostic score that selects the subset of advanced soft tissue sarcoma (ASTS) patients with a higher benefit with trabectedin in terms of time to progression and overall survival. A retrospective series of 357 patients with ASTS treated with trabectedin as second- or further-line in 19 centers across Spain was analyzed. First, it was confirmed that patients with high growth modulation index (GMI > 1.33) were associated with the better clinical outcome. Univariate and multivariate analyses were performed to identify factors associated with a GMI > 1.33. Thus, GEISTRA score was based on metastasis free-interval (MFI ≤ 9.7 months), Karnofsky < 80%, Non L-sarcomas and better response in the previous systemic line. The median GMI was 0.82 (0–69), with 198 patients (55%) with a GMI < 1, 41 (11.5%) with a GMI 1–1.33 and 118 (33.1%) with a GMI > 1.33. The lowest GEISTRA score showed a median of time-to-progression (TTP) and overall survival (OS) of 5.7 and 19.5 months, respectively, whereas it was 1.8 and 3.1 months for TTP and OS, respectively, for the GEISTRA 4 score. This prognostic tool can contribute to better selecting candidates for trabectedin treatment in ASTS.

Background To determine the state of current practice and to reach a consensus on recommendations for the management of advanced ovarian cancer using a Delphi survey with a group of Spanish gynecologists and medical oncologists specially dedicated to gynecological tumors. Methods The questionnaire was developed by the byline authors. All questions but one were answered using a 9-item Likert-like scale with three types of answers: frequency, relevance and agreement. We performed two rounds between December 2018 and July 2019. A consensus was considered reached when at least 75% of the answers were located within three consecutive points of the Likert scale. Results In the first round, 32 oncologists and gynecologists were invited to participate, and 31 (96.9%) completed the online questionnaire. In the second round, 27 (87.1%) completed the online questionnaire. The results for the questions on first-line management of advanced disease, treatment of patients with recurrent disease for whom platinum might be the best option, and treatment of patients with recurrent disease for whom platinum might not be the best option are presented. Conclusions This survey shows a snapshot of current recommendations by this selected group of physicians. Although the majority of the agreements and recommendations are aligned with the recently published ESMO-ESGO consensus, there are some discrepancies that can be explained by differences in the interpretation of certain clinical trials, reimbursement or accessibility issues.