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iPSC clones, when differentiated along different non-mammary lineages in vitro, were also not able to exhibit either mammary ontogenesis or oncogenesis in vivo. Therefore, in vitro and in vivo regulation of differentiation is an important determinant of breast cancer oncogenesis.Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of a humanized anti-Trop-2 IgG antibody conjugated via a hydrolysable linker to SN-38, the topoisomerase I-inhibitory active component of irinotecan. We investigated whether Trop-2-expression and homologous recombination repair (HRR) of SN-38-mediated double-strand DNA (dsDNA) breaks play a role in the sensitivity of triple-negative breast cancer (TNBC) to SG. Activation of HRR pathways, as evidenced by Rad51 expression, was assessed in SG-sensitive cell lines with low and moderate Trop-2-expression (SK-MES-1 squamous cell lung carcinoma and HCC1806 TNBC, respectively), compared to a low Trop-2-expressing, less SG-sensitive TNBC cell line (MDA-MB-231). Further, two Trop-2-transfectants of MDA-MB-231, C13 and C39 (4- and 25-fold higher Trop-2, respectively), were treated in mice with SG to determine whether increasing Trop-2 expression improves SG efficacy. SG mediated &gt;2-fold increase in Rad51 in MDA-MB-231 but had no effect in SK-MES-1 or HCC1806, resulting in lower levels of dsDNA breaks in MDA-MB-231. SG and saline produced similar effects in parental MDA-MB-231 tumor-bearing mice (median survival time (MST) = 21d and 19.5d, respectively). However, in mice bearing higher Trop-2-expressing C13 and C39 tumors after Trop-2 transfection, SG provided a significant survival benefit, even compared to irinotecan (MST = 97d vs. 35d for C13, and 81d vs. 28d for C39, respectively; P less then 0.0007). These results suggest that SG could provide better clinical benefit than irinotecan in patients with HRR-proficient tumors expressing high levels of Trop-2, as well as to patients with HRR-deficient tumors expressing low/moderate levels of Trop-2.Access to information and intercultural approaches in the field of health are essential for the elimination of inequities in health access and care. Intercultural models such as traditional, complementary and integrative medicine (TCIM) are an important part of health care in most countries and often contribute to expanding access to primary health care. Despite legal recognition and policies to integrate TCIM into health systems, their contribution to health, well-being, and people-centered care to achieve universal health is still underestimated. This article presents the progress (2017-2020) achieved by the Virtual Health Library specialized in the TCIM (VHL TCIM Americas), an initiative created as a tool to reduce the gaps in the production and access to validated information on TCIM. Through collaborative network work, the VHL TCIM Americas contributes to the democratization of health, access to verified scientific data, visibility of non-conventional knowledge, strengthening of research capacities, and exchange of experiences for informed decision-making.Research on the topic of poor perinatal mental health in South America is scarce. Nevertheless, studies have shown that it is not uncommon, and that it is linked to women's experience of sexual and intimate partner violence and to inequality, poverty and low educational attainment. High-quality research in large samples with rigorous methodology is a priority, so that data from this region may be compared and analysed in systematic reviews. The links with intimate partner violence need to be explored. Risk and protective factors must be investigated with a strong intercultural perspective. Service integration needs to be implemented. This will require improvements in the availability, accessibility and quality of obstetric and mental health services. There is a need for targeted evidence-based interventions for women and children at risk that incorporate a strong gender and rights perspective.We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton-proton collisions at an energy of s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb - 1 . A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b b ¯ .Improving the delivery of existing treatment may often bring much greater benefits than developing new treatments and technologies. To achieve this, clinical teams and organisations need to build capacity for sustained and systematic improvement. Organisations can build improvement capacity and skills by developing permanent multidisciplinary centres to provide sustained inspiration, research, training and practical support for implementation and innovation. [https://www.selleckchem.com/products/etanercept.html Etanercept cell line] In the longer term, organisations need to build an infrastructure for quality improvement that includes an information system to track change and dedicated improvement leads across the organisation.The European Psychiatric Association (EPA), the main association in the field of mental health in Europe, has long been supporting the development of early career psychiatrists. The EPA Early Career Psychiatrists Committee (ECPC) and its core task forces promote research activities among young psychiatrists, contribute to their professional development through organising courses and other educational events, prepare online educational materials and publications, and actively collaborate with other organisations. The EPA ECPC is always open to fostering cooperation on new professional, educational or research initiatives with early career psychiatrists from different countries.This paper gives a narrative account of how the Oxford Healthcare Improvement Centre has embedded continuous quality improvement (CQI) across both mental health and community services in Oxford, UK. The aim of the centre is to develop capability across healthcare services, with frontline staff leading CQI independently. The paper discusses the various methods employed to achieve this aim, including the provision of training, mentoring and support to those undertaking improvement work, alongside developing the required governance for CQI.