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Gonadal fate in mammals is determined during embryogenesis and is actively maintained in adulthood. This study shows that E3-SUMO ligase activity of TRIM28 is required for ovarian identity maintenance and testicular-specific gene repression in mouse adult ovary; in its absence, ovarian granulosa cells transdifferentiate to Sertoli cells.

This article proposes a systematic review of the recent literature on the impacts of the deployment of autonomous vehicles through the lens of lifestyle changes that will modify our mobility practices. It discusses the main findings of the studies, analyzes their links with the foresight methods used by their authors, and identifies research gaps. Four components of lifestyles are considered: residential location, car ownership, activity patterns, and tourism. Particular attention is given to the diversity of the reviewed foresight approaches, to the way they complement one another in the construction of knowledge, and to their influence on the forecasts and the lessons learned. Our work shows a convergence of results across methods, especially for expected impacts on household location and car ownership, and the influence of the way autonomous vehicles are deployed. Our analysis also makes it possible to draw up a more comprehensive and nuanced picture of the anticipated changes in lifestyles, and the main sources of uncertainty. Finally, our work identifies several research gaps and avenues for future studies such as the impacts on job choices and tourism, the need for a better understanding of the links between the different deployment models for autonomous vehicles, and the need to explore more scenarios that are compatible with environmentally- and socially-oriented goals.

A net zero transition is likely to generate substantial and irreversible economic transformation. High-carbon industries and their related occupations will disappear, while new low-carbon industries and occupations will be created. In the aggregate, the impact of the transition on GDP and employment is commonly projected to be relatively moderate. However, such estimates hide drastic distributional issues that are sectorally and regionally concentrated. We use three sectorally detailed and regionally disaggregated macroeconomic models to explore the possible levels and impacts of structural change in a well below 2°C scenario. In addition to the expected decline in the carbon-intensive industries, we observe secondary impacts, particularly in the services sectors, that vary significantly between models. The risks entailed with structural change involve worsening economic disparity and societal division that could exacerbate existing socioeconomic and political polarisation. Impact assessments of decarbonisation should consider such distributional issues to avoid post-industrial decline and widening socioeconomic inequalities. [ABSTRACT FROM AUTHOR]

Abstract Background Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma. Methods GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles. For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4–6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4–10 weeks after surgery. Using a Simon’s two-stage design, up to 67 patients will be enrolled, including 23 in the first stage. Discussion Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes. Trial registration NCT04736485, registered February, 3, 2021.

We study the impact of socioeconomic factors on two key parameters of epidemic dynamics. Specifically, we investigate a parameter capturing the rate of deceleration at the very start of an epidemic, and a parameter that reflects the pre-peak and post-peak dynamics at the turning point of an epidemic like coronavirus disease 2019 (COVID-19). We find two important results. The policies to fight COVID-19 (such as social distancing and containment) have been effective in reducing the overall number of new infections, because they influence not only the epidemic peaks, but also the speed of spread of the disease in its early stages. The second important result of our research concerns the role of healthcare infrastructure. They are just as effective as anti-COVID policies, not only in preventing an epidemic from spreading too quickly at the outset, but also in creating the desired dynamic around peaks: slow spreading, then rapid disappearance. [ABSTRACT FROM AUTHOR]

Aquaculture has been recognised for achieving multiple United Nations Sustainable Development Goals; its further growth depends on understanding, and responding to, societal perceptions in a broader context. Thus, this study aims to understand societal perceptions of aquaculture through a scoping review and media analysis. A scoping review identified 151 academic studies for inclusion in our five identified research clusters: (1) social acceptability, (2) growth and development, (3) media coverage, (4) sustainable aquaculture, and (5) consumer perceptions. Further, newspaper articles (n = 100) were sampled from the United Kingdom, Denmark, France, Spain, Turkey, and China; elsewhere all articles identified were included (Poland, 79; Hungary, 29; India, 70). The findings suggest that scientific and newspaper articles tend to present sustainability aspects in a simplified form. Key stakeholder groups include fish farming enterprises, civil society, governmental officials, scientists, and business leaders both within aquaculture value chains (retailers/wholesalers, technology industry) and outside of them (fisheries, tourism). Also, other stakeholders included the public (indigenous groups, residents, consumers). The stakeholder groups perceived aquaculture differently and depending on the circumstances and context, their perceptions ranged from positive to negative. Many factors influenced their perceptions, including aquaculture's impact on multiple sustainability dimensions, knowledge, transparency, personal interests, types, and location of aquaculture practises, regulations, experience, and sociodemographic characteristics such as age, gender, education, and income. We recommend that aquaculture practitioners focus on context‐specific multifaceted strategies—prioritising transparency, communication, and accountability—and provide essential knowledge to ensure that societal perceptions of aquaculture are based on accurate, empirical information. [ABSTRACT FROM AUTHOR]

Global Integrated Assessment Models (IAMs) used to characterise mitigation pathways have very limited or no formal representation of lifestyles and lifestyle change. We demonstrate a novel approach to endogenously simulating low-carbon lifestyle heterogeneity and lifestyle change through soft-coupling with our new empirically-based LIFE model. Coupling LIFE to global IAMs enables dynamic simulation of distinctive lifestyle change contributions to targeted mitigation strategies. We set out the empirical basis of the LIFE model, the methodological steps for soft-coupling to a global IAM, and show results from a test application to the residential sector using the MESSAGEix-Buildings model. A first key insight is that coupling with the LIFE model introduces heterogeneous behaviour between ‘engaged’ types, who experience faster and higher reductions in final energy demand compared to ‘disengaged’ types. When we further simulate a widespread shift in normative values, this gap is closed. A second key insight is that drivers of lifestyle change, act differently across ‘Improve’ and ‘Avoid’ dimensions. The ‘disengaged’ types, characterised by lower incomes, are more highly responsive to energy saving ‘Avoid’ behaviours. Our approach demonstrates how improved understanding of lifestyle change dynamics and more realistic, empirically-based quantitative simulations in climate mitigation pathways enriches scientific and policy analysis of how to achieve Paris Climate Agreement goals.

Two main nonpharmaceutical policy strategies have been used in Europe in response to the COVID‐19 epidemic: one aimed at natural herd immunity and the other at avoiding saturation of hospital capacity by crushing the curve. The two strategies lead to different results in terms of the number of lives saved on the one hand and production loss on the other hand. Using a susceptible–infected–recovered–dead model, we investigate and compare these two strategies. As the results are sensitive to the initial reproduction number, we estimate the latter for 10 European countries for each wave from January 2020 till March 2021 using a double sigmoid statistical model and the Oxford COVID‐19 Government Response Tracker data set. Our results show that Denmark, which opted for crushing the curve, managed to minimize both economic and human losses. Natural herd immunity, sought by Sweden and the Netherlands does not appear to have been a particularly effective strategy, especially for Sweden, both in economic terms and in terms of lives saved. The results are more mixed for other countries, but with no evident trade‐off between deaths and production losses. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions Existing methods to evaluate skin care products suffer limitations. This is the case for ex vivo skin explants, a first‐choice 3D model. While essential to analyse mid‐ to long‐term biological effects, this classical model hinders assessing microrelief variations. To circumvent these limitations, we developed an ex vivo PERFused EXplant setup (Perfex) that maintains the outer skin surface in the open air, closely mirroring physiological conditions.A custom‐designed reservoir enables perfusing the dermal side of explants with buffered, temperature‐controlled medium, while the epidermis is subjected to “normal” conditions. Skin tension and characteristics of the stratum corneum, microrelief, histology and immunohistology (collagen types I and III, elastin and fibrillin‐1) were analysed and compared to those of explants maintained under conventional conditions or in vivo skin. The effects of skin care formulas intended to induce short‐ and/or mid‐ to long‐term effects were also assessed.Skin explants maintained with the Perfex setup exhibit characteristics (firmness, elasticity, hydration and barrier function) closer to those of in vivo skin than with conventional conditions. Moreover, Perfex‐maintained explants present no alteration in histology after 7 days and slight variation in the expression of key protein markers. Microrelief characteristics also remain mostly stable over 7 days. Formula applications corroborate that skin tensor‐containing products primarily induce short‐term changes in the microrelief, while those with biologically active ingredients mainly lead to mid‐ to long‐term effects on the histology and expression of molecular markers. Furthermore, maintaining skin explants with a physiologically relevant skin surface enabled analysing the relationship between microrelief and key markers, showing that fibrillin‐1 is the protein most correlated with microrelief characteristics.The Perfex setup allows for similar preservation of skin explant histology and key protein expression as the conventional system, yet it maintains a skin surface close to that of in vivo skin. Therefore, it is valuable to analyse both the short‐ and mid‐ to long‐term impacts of skin care formulas and better comprehend their effects. The Perfex system also offers a new tool for investigating fundamental questions, such as the link that can exist between dermal proteins and skin surface properties. [ABSTRACT FROM AUTHOR]