| 1. |
- Pocas, Juliana, et al.
(författare)
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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:20
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Tidskriftsartikel (refereegranskat)abstract
- Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
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| 2. |
- Blaschikoff, Ludmilla, et al.
(författare)
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A multidisciplinary study of Iberian Chalcolithic dogs
- 2022
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Ingår i: Journal of Archaeological Science. - : Elsevier BV. - 2352-409X .- 2352-4103. ; 42
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Tidskriftsartikel (refereegranskat)abstract
- Domesticated dogs have been present in the Iberian Peninsula long before other domesticated species, back to the late Palaeolithic period. Their origin is still uncertain, but dogs were already well established during the Chalcolithic period (ca. 5000-4000 BP). This study employed a multidisciplinary approach comprising osteometric, radiographic and palaeogenomic analyses to characterize Chalcolithic Iberian Canis remains. Two Chalcolithic archaeological sites - Leceia, Oeiras, in Portugal, and El Caset ' on de la Era, Villalba de los Alcores, Valladolid, in Spain - were the main focus of this study. Osteometric and odontometric data from eleven other sites in Iberia were also included. Osteometric results show signs of phenotypic variability, likely the result of human-driven selective pressure. Dental radiographic and dental wear analyses allowed age at death estimation for four individuals (two juvenile and two adults). Three Chalcolithic Iberian dogs had their mitogenomes resequenced and the mitochondrial DNA analysis allowed to assign each individual to two of the major known haplogroups - A and C. Molecular sex infered by the chromosomeX/chromosome1 coverage ratio allowed to identify one female and two males. This study unveils some aspects of the Iberian Chalcolithic dogs: these dogs already exhibited various morphotypes whose profiles might be associated to the performance of certain tasks, as well as mitogenomes of two distinct lineages that help tracking the evolutionary paths of Iberian dogs.
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| 3. |
- Brandão, Andreia, et al.
(författare)
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The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
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| 4. |
- Colas, Kilian, et al.
(författare)
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Direct Addition of Grignard Reagents to Aliphatic Carboxylic Acids Enabled by Bulky turbo-Organomagnesium Anilides
- 2022
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 28:9
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of ketones through addition of organometallic reagents to aliphatic carboxylic acids is a straightforward strategy that is limited to organolithium reagents. More desirable Grignard reagents can be activated and controlled with a bulky aniline-derived turbo-Hauser base. This operationally simple procedure allows the straightforward preparation of a variety of aliphatic and perfluoroalkyl ketones alike from functionalized alkyl, aryl and heteroaryl Grignard reagents.
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| 5. |
- Costa, Raquel, et al.
(författare)
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Quality of maternal and newborn care around the time of childbirth for migrant versus nonmigrant women during the COVID-19 pandemic: Results of the IMAgiNE EURO study in 11 countries of the WHO European region.
- 2022
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 159:Suppl 1, s. 39-53
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Tidskriftsartikel (refereegranskat)abstract
- To describe the perception of quality of maternal and newborn care (QMNC) around the time of childbirth among migrant and nonmigrant women in Europe.Women who gave birth at a health facility in 11 countries of the WHO European Region from March 2020 to July 2021 were invited to answer an online questionnaire including demographics and childbirth experience. Data were analyzed and compared for 1781 migrant and 20653 nonmigrant women.Migrant women who experienced labor perceived slightly more difficulties in attending routine antenatal visits (41.2% vs 39.4%; P=0.001), more barriers in accessing facilities (32.9% vs 29.9%; P=0.001), lack of timely care (14.7% vs 13.0%; P=0.025), inadequate room comfort and equipment (9.2% vs 8.5%; P=0.004), inadequate number of women per room (9.4% vs 8.6%; P=0.039), being prevented from staying with their baby as they wished (7.8% vs 6.9%; P=0.011), or suffering abuse (14.5% vs 12.7%; P=0.022) compared with nonmigrant women. For women who had a prelabor cesarean, migrant women were more likely not to receive pain relief after birth (16.8% vs.13.5%; P=0.039) and less likely to provide informal payment (1.8% vs 4.4%; P=0.005) compared with nonmigrant women. Overall, the QMNC index was not significantly different for migrant compared with nonmigrant women.Gaps in overall QMNC were reported by both migrant and nonmigrant women, with improvements to healthcare necessary for all.
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| 6. |
- Costa, Raquel, et al.
(författare)
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Regional differences in the quality of maternal and neonatal care during the COVID-19 pandemic in Portugal : Results from the IMAgiNE EURO study
- 2022
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Ingår i: International Journal of Gynecology and Obstetrics. - : Wiley. - 0020-7292 .- 1879-3479. ; 159:S1, s. 137-153
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare women's perspectives on the quality of maternal and newborn care (QMNC) around the time of childbirth across Nomenclature of Territorial Units for Statistics 2 (NUTS-II) regions in Portugal during the COVID-19 pandemic. Methods: Women participating in the cross-sectional IMAgiNE EURO study who gave birth in Portugal from March 1, 2020, to October 28, 2021, completed a structured questionnaire with 40 key WHO standards-based quality measures. Four domains of QMNC were assessed: (1) provision of care; (2) experience of care; (3) availability of human and physical resources; and (4) reorganizational changes due to the COVID-19 pandemic. Frequencies for each quality measure within each QMNC domain were computed overall and by region. Results: Out of 1845 participants, one-third (33.7%) had a cesarean. Examples of high-quality care included: low frequencies of lack of early breastfeeding and rooming-in (8.0% and 7.7%, respectively) and informal payment (0.7%); adequate staff professionalism (94.6%); adequate room comfort and equipment (95.2%). However, substandard practices with large heterogeneity across regions were also reported. Among women who experienced labor, the percentage of instrumental vaginal births ranged from 22.3% in the Algarve to 33.5% in Center; among these, fundal pressure ranged from 34.8% in Lisbon to 66.7% in Center. Episiotomy was performed in 39.3% of noninstrumental vaginal births with variations between 31.8% in the North to 59.8% in Center. One in four women reported inadequate breastfeeding support (26.1%, ranging from 19.4% in Algarve to 31.5% in Lisbon). One in five reported no exclusive breastfeeding at discharge (22.1%; 19.5% in Lisbon to 28.2% in Algarve). Conclusion: Urgent actions are needed to harmonize QMNC and reduce inequities across regions in Portugal.
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| 7. |
- Gorasso, Vanessa, et al.
(författare)
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Burden of disease attributable to risk factors in European countries: a scoping literature review
- 2023
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Ingår i: Archives of Public Health. - 0778-7367 .- 2049-3258. ; 81:1
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Forskningsöversikt (refereegranskat)abstract
- Objectives: Within the framework of the burden of disease (BoD) approach, disease and injury burden estimates attributable to risk factors are a useful guide for policy formulation and priority setting in disease prevention. Considering the important differences in methods, and their impact on burden estimates, we conducted a scoping literature review to: (1) map the BoD assessments including risk factors performed across Europe; and (2) identify the methodological choices in comparative risk assessment (CRA) and risk assessment methods. Methods: We searched multiple literature databases, including grey literature websites and targeted public health agencies websites. Results: A total of 113 studies were included in the synthesis and further divided into independent BoD assessments (54 studies) and studies linked to the Global Burden of Disease (59 papers). Our results showed that the methods used to perform CRA varied substantially across independent European BoD studies. While there were some methodological choices that were more common than others, we did not observe patterns in terms of country, year or risk factor. Each methodological choice can affect the comparability of estimates between and within countries and/or risk factors, since they might significantly influence the quantification of the attributable burden. From our analysis we observed that the use of CRA was less common for some types of risk factors and outcomes. These included environmental and occupational risk factors, which are more likely to use bottom-up approaches for health outcomes where disease envelopes may not be available. Conclusions: Our review also highlighted misreporting, the lack of uncertainty analysis and the under-investigation of causal relationships in BoD studies. Development and use of guidelines for performing and reporting BoD studies will help understand differences, avoid misinterpretations thus improving comparability among estimates.
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| 8. |
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| 9. |
- Isca, Vera M. S., et al.
(författare)
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Molecular Docking Studies of Royleanone Diterpenoids from Plectranthus spp. as P-Glycoprotein Inhibitors
- 2020
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Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 11:5, s. 839-845
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Tidskriftsartikel (refereegranskat)abstract
- The development of multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. Several abietane diterpenes with antitumoral activities have been isolated from Plectranthus spp. such as 6,7-dehydroroyleanone (DHR, 1) and 7 alpha-acetoxy-6 beta-hydroxyroyleanone (AHR, 2). Several royleanone derivatives were prepared through hemisynthesis from natural compounds 1 and 2 to achieve a small library of products with enhanced anti-P-glycoprotein activity. Nonetheless, some derivatives tend to be unstable. Therefore, to reason such lack of stability, the electron density based local reactivity descriptors condensed Fukui functions and dual descriptor were calculated for several derivatives of DHR. Additionally, molecular docking and molecular dynamics studies were performed on several other derivatives to clarify the molecular mechanisms by which they may exert their inhibitory effect in P-gp activity. The analysis on local reactivity descriptors was important to understand possible degradation pathways and to guide further synthetic approaches toward new royleanone derivatives. A molecular docking study suggested that the presence of aromatic moieties increases the binding affinity of royleanone derivatives toward P-gp. It further suggests that one royleanone benzoylated derivative may act as a noncompetitive efflux modulator when bound to the M-site. The future generation of novel royleanone derivatives will involve (i) a selective modification of position C-12 with chemical moieties smaller than unsubstituted benzoyl rings and (ii) the modification of the substitution pattern of the benzoyloxy moiety at position C-6.
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| 10. |
- Lazzerini, Marzia, et al.
(författare)
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Quality of facility-based maternal and newborn care around the time of childbirth during the COVID-19 pandemic : online survey investigating maternal perspectives in 12 countries of the WHO European Region
- 2022
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Ingår i: The Lancet regional health. Europe. - : Elsevier BV. - 2666-7762. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multi-country studies assessing the quality of maternal and newborn care (QMNC) during the COVID-19 pandemic, as defined by WHO Standards, are lacking.Methods: Women who gave birth in 12 countries of the WHO European Region from March 1, 2020 - March 15, 2021 answered an online questionnaire, including 40 WHO Standard-based Quality Measures.Findings: 21,027 mothers were included in the analysis. Among those who experienced labour (N=18,063), 41·8% (26·1%- 63·5%) experienced difficulties in accessing antenatal care, 62% (12·6%-99·0%) were not allowed a companion of choice, 31·1% (16·5%-56·9%) received inadequate breastfeeding support, 34·4% (5·2%-64·8%) reported that health workers were not always using protective personal equipment, and 31·8% (17·8%-53·1%) rated the health workers' number as "insufficient". Episiotomy was performed in 20·1% (6·1%-66·0%) of spontaneous vaginal births and fundal pressure applied in 41·2% (11·5% -100%) of instrumental vaginal births. In addition, 23·9% women felt they were not treated with dignity (12·8%-59·8%), 12·5% (7·0%-23·4%) suffered abuse, and 2·4% (0·1%-26·2%) made informal payments. Most findings were significantly worse among women with prelabour caesarean birth (N=2,964). Multivariate analyses confirmed significant differences among countries, with Croatia, Romania, Serbia showing significant lower QMNC Indexes and Luxemburg showing a significantly higher QMNC Index than the total sample. Younger women and those with operative births also reported significantly lower QMNC Indexes.Interpretation: Mothers reports revealed large inequities in QMNC across countries of the WHO European Region. Quality improvement initiatives to reduce these inequities and promote evidence-based, patient-centred respectful care for all mothers and newborns during the COVID-19 pandemic and beyond are urgently needed.Funding: The study was financially supported by the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.Study registration: ClinicalTrials.gov Identifier: NCT04847336.
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