| 1. |
- Garcia-Alonso, L, et al.
(author)
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Single-cell roadmap of human gonadal development
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 607:7919, s. 540-
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Journal article (peer-reviewed)abstract
- Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries1. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal–mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15+ and TREM2+ fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.
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| 2. |
- Prusakov, Pavel, et al.
(author)
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A global point prevalence survey of antimicrobial use in neonatal intensive care units : The no-more-antibiotics and resistance (NO-MAS-R) study
- 2021
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 32
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Journal article (peer-reviewed)abstract
- Background: Global assessment of antimicrobial agents prescribed to infants in the neonatal intensive care unit (NICU) may inform antimicrobial stewardship efforts.Methods: We conducted a one-day global point prevalence study of all antimicrobials provided to NICU infants. Demographic, clinical, and microbiologic data were obtained including NICU level, census, birth weight, gestational/chronologic age, diagnoses, antimicrobial therapy (reason for use; length of therapy), antimicrobial stewardship program (ASP), and 30-day in-hospital mortality.Findings: On July 1, 2019, 26% of infants (580/2,265; range, 0-100%; median gestational age, 33 weeks; median birth weight, 1800 g) in 84 NICUs (51, high-income; 33, low-to-middle income) from 29 countries (14, high-income; 15, low-to-middle income) in five continents received >= 1 antimicrobial agent (92%, antibacterial; 19%, antifungal; 4%, antiviral). The most common reasons for antibiotic therapy were "rule-out" sepsis (32%) and "culture-negative" sepsis (16%) with ampicillin (40%), gentamicin (35%), amikacin (19%), vancomycin (15%), and meropenem (9%) used most frequently. For definitive treatment of presumed/confirmed infection, vancomycin (26%), amikacin (20%), and meropenem (16%) were the most prescribed agents. Length of therapy for culture-positive and "culture-negative" infections was 12 days (median; IQR, 8-14) and 7 days (median; IQR, 5-10), respectively. Mortality was 6% (42%, infection-related). An NICU ASP was associated with lower rate of antibiotic utilization (p = 0.02).Interpretation: Global NICU antibiotic use was frequent and prolonged regardless of culture results. NICU-specific ASPs were associated with lower antibiotic utilization rates, suggesting the need for their implementation worldwide.
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| 3. |
- Calderón-Contreras, Rafael, et al.
(author)
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A regional PECS node built from place-based social-ecological sustainability research in Latin America and the Caribbean
- 2022
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In: Ecosystems and People. - : Informa UK Limited. - 2639-5908 .- 2639-5916. ; 18:1, s. 1-14
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Journal article (peer-reviewed)abstract
- Sustainability requires a combination of meaningful co-production of locally relevant solutions, synthesis of insights gained across regions, and increased cooperation between science, policy and practice. The Programme for Ecosystem Change and Society (PECS) has been coordinating Place-Based Social-Ecological Sustainability Research (PBSESR) across the globe and emphasizes the need for regional scientific nodes from diverse biocultural regions to inform sustainability science and action. In this paper, we assess the strengths of the PBSESR communities in Latin America and the Caribbean (LAC). We provide an overview of PBSESR literature associated with this region and highlight the achievements of two prominent regional networks: The Social-Ecological Systems and Sustainability Research Network from Mexico (SocioEcoS) and the South American Institute for Resilience and Sustainability Studies from Uruguay (SARAS Institute). Finally, we identify the potential in these nodes to constitute a regional PECS node in Latin America and discuss the capacity needed to ensure such function. The results of the literature review show that while still loosely interconnected across the region, networks play key roles in connecting otherwise cloistered teams and we illustrate how the SocioEcoS network (focusing on transdisciplinary co-production of knowledge towards sustainability) and the SARAS Institute (focusing on innovative approaches for looking at complex social-ecological problems, rooted in slow science and arts) operate as key connectors in the region. We conclude that these organizations combined can embody a Latin American node for PECS, and would thereby not only contribute to regional but also global capacities to advance the sustainability agenda.
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| 4. |
- Elkadeem, M. R., et al.
(author)
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Geospatial-assisted multi-criterion analysis of solar and wind power geographical-technical-economic potential assessment
- 2022
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In: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 322
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Journal article (peer-reviewed)abstract
- Amid the increasing electricity demand, energy crisis and pollution, the transition to renewable energy (RE) is becoming a preoccupation and major global challenge due to the multidimensional and intricate problem of RE planning. In Egypt, about 90% of gross power generation comes from carbon-intensive power plants (natural gas and coal). Here, we propose a novel geospatial-decision-making model aimed at geographical-technical–economic potential mapping and assessment of solar photovoltaic (PV) and onshore wind turbine (WT) power plants at a high level of resolution (1 km2) in Egypt. We identify the locations suitable for PV and WT development considering sixteen restrictive and contradictory evaluation criteria. These locations have been further analyzed to estimate how much energy generation is available and at what energy cost. The analysis identifies Middle-Upper Egypt and Suez Canal as hosting the majority of highly suitable locations for PV and WT power plants, respectively. Our finding reveals that the proper planning on RE projects at the proposed optimum locations could support the country's energy mix with a sizable 32% share of the projected country's electricity consumption from PV and 50% share from WT, by 2030. Furthermore, we show that the investment opportunities of PV and WT generation are potentially attractive with affordable competitive prices estimated at 57.84 $/MWh and 32.36 $/MWh, respectively, against conventional generation for today and the future. We anticipate that our results will provide valuable support in realizing Egypt's vision for sustainable electricity generation and in keeping abreast of the global transformation in power systems being witnessed. Ultimately, the method's relevance extends beyond the geographical boundaries of the present territory; it features a strategic, clear and reproducible approach that may be applied to a larger area or continent, provided the necessary input data and criteria are introduced.
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| 5. |
- Garcia-Alonso, Luz, et al.
(author)
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Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:12, s. 1698-
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Journal article (peer-reviewed)abstract
- The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated dense single-cell and spatial reference maps of the human uterus and three-dimensional endometrial organoid cultures. We dissect the signaling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids reveals the pathways and cell states regulating differentiation of the secretory and ciliated lineages both in vivo and in vitro. In vitro downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. We utilize our cellular maps to deconvolute bulk data from endometrial cancers and endometriotic lesions, illuminating the cell types dominating in each of these disorders. These mechanistic insights provide a platform for future development of treatments for common conditions including endometriosis and endometrial carcinoma. Single-cell and spatial transcriptomic profiling of the human endometrium highlights pathways governing the proliferative and secretory phases of the menstrual cycle. Analyses of endometrial organoids show that WNT and NOTCH signaling modulate differentiation into the secretory and ciliated epithelial lineages, respectively.
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