Breast DWI at 3 T: influence of the fat-suppression technique on image quality and diagnostic performance

Aim To evaluate two fat-suppression techniques: short tau inversion recovery (STIR) and spectral adiabatic inversion recovery (SPAIR) regarding image quality and diagnostic performance in diffusion-weighted imaging (DWI) of breast lesions at 3 T. Materials and methods Ninety-two women (mean age 48 ± 12.1 years; range 21–78 years) underwent breast MRI. Two DWI pulse sequences, with b-values (50 and 1000 s/mm2) were performed with STIR and SPAIR. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), suppression homogeneity, and apparent diffusion coefficient (ADC) values were quantitatively assessed for each technique. Values were compared between techniques and lesion type. Receiver operating characteristics (ROC) analysis was used to evaluate lesion discrimination. Results One hundred and fourteen lesions were analysed (40 benign and 74 malignant). SNR and CNR were significantly higher for DWI-SPAIR; fat-suppression uniformity was better for DWI-STIR (p < 1 × 10−4). ADC values for benign and malignant lesions and normal tissue were 1.92 × 10−3, 1.18 × 10−3, 1.86 × 10−3 s/mm2 for DWI-STIR and 1.80 × 10−3, 1.11 × 10−3, 1.79 × 10−3 s/mm2 for SPAIR, respectively. Comparison between fat-suppression techniques showed significant differences in mean ADC values for benign (p = 0.013) and malignant lesions (p = 0.001). DWI-STIR and -SPAIR ADC cut-offs were 1.42 × 10−3 and 1.46 × 10−3 s/mm2, respectively. Diagnostic performance for DWI-STIR versus SPAIR was: accuracy (81.6 versus 83.3%), area under curve (87.7 versus 89.2%), sensitivity (79.7 versus 85.1%), and specificity (85 versus 80%). Positive predictive value was similar. Conclusion The fat-saturation technique used in the present study may influence image quality and ADC quantification. Nevertheless, STIR and SPAIR techniques showed similar diagnostic performances, and therefore, both are suitable for use in clinical practice.info:eu-repo/semantics/publishedVersio

The silent extinction of freshwater mussels in Portugal

Freshwater mussels are one of the most threatened animal groups in the world. In the European Union, threatened and protected mussel species are not adequately monitored, while species considered to be common and widespread receive even less attention. This is particularly worrying in the Mediterranean region, where species endemism is high and freshwater habitats are severely affected by water scarcity. In the absence of hard data on population trends, we report here a long-term comparison of freshwater mussel assemblages at 132 sites covering 15 different hydrological basins in Portugal. This study reveals a widespread decline of 60 % in the number of sites and 67 % in the overall abundance of freshwater mussels across Portugal over the last 20 years, indicating that all species are rapidly declining and threatened with extinction. These results show that current legislation and conservation measures are largely ineffective and highlight the importance of updating the Habitats Directive to enforce standard monitoring protocols for threatened species in the European Union and to extend monitoring to other freshwater species thought to be common and widespread. Efficient water management, restrictions on irrigation expansion in important biodiversity areas, mitigation of hydrological changes and loss of aquatic habitat connectivity caused by physical alterations are urgently needed to reverse these declining population trends. For the severely endangered species Margaritifera margaritifera, Potomida littoralis, and Unio tumidiformis, where populations are now critically low, more urgent action is needed, such as ex-situ conservation, protection of remaining populations and large-scale habitat restoration.We would like to thank Jake Dimon, José Tourais, Filipe Rolo, and Elza Fonseca for their help in the surveys. This research was developed under the project EdgeOmics - Freshwater Bivalves at the edge: Adaptation genomics under climate-change scenarios (PTDC/CTA-AMB/3065/2020) funded by the Portuguese Foundation for Science and Technology (FCT) through national funds. FCT also funded MLL under contract 2020.03608.CEECIND, EF under contract CEECINST/00027/2021/CP2789/CT0003, AGS under the grants SFRH/BD/137935/2018 and COVID/DB/152933/2022, and JGN under the grant 2020.04637. BD. The baseline survey was funded by the project “Documentos Estruturantes” (POA 1.100021) of the Instituto da Conservaçã da Natureza

Rabbit derived VL single-domains as promising scaffolds to generate antibody–drug conjugates

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not found in the human or mouse. Thus, to develop a new generation of ADCs, we explored the potential of rabbit-derived VL-single-domain antibody scaffolds (sdAbs) to selectively conjugate a payload to Cys80. Hence, a rabbit sdAb library directed towards canine non-Hodgkin lymphoma (cNHL) was subjected to in vitro and in vivo phage display. This allowed the identification of several highly specific VL-sdAbs, including C5, which specifically target cNHL cells in vitro and present promising in vivo tumor uptake. C5 was selected for SN-38 site-selective payload conjugation through its exposed free Cys80 to generate a stable and homogenous C5-DAB-SN-38. C5-DAB-SN-38 exhibited potent cytotoxicity activity against cNHL cells while inhibiting DNA-TopoI activity. Overall, our strategy validates a platform to develop a novel class of ADCs that combines the benefits of rabbit VL-sdAb scaffolds and the canine lymphoma model as a powerful framework for clinically translation of novel therapeutics for cancer.This work was supported by the Portuguese Funding Agency, Fundação para a Ciência e Tecnologia, FCT IP (SAICT/2017/32085, PTDC/QUI-OUT/3989/2021 and Ph.D. fellowship SFRH/BD/131468/2017 to ASA and SFRH/BD/90514/2012 to JD). CIISA has provided support through Project UIDB/00276/2020, funded by FCT and LA/P/0059/2020-AL4AnimalS. Research Institute for Medicines (iMed.ULisboa) acknowledges the financial support of Fundação para a Ciência e Tecnologia (Projects: PTDC/QUI-OUT/3989/2021; UIDB/04138/2020 and UIDP/04138/2020). The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio

Relação entre deficiência de vitamina D, Síndrome Metabólico e obesidade em mulheres

[resumo][abstract

The role of anthropogenic habitats in freshwater mussel conservation

Anthropogenic freshwater habitats may provide undervalued prospects for long-term conservation as part of species conservation planning. This fundamental, but overlooked, issue requires attention considering the pace that humans have been altering natural freshwater ecosystems and the accelerated levels of biodiversity decline in recent decades. We compiled 709 records of freshwater mussels (Bivalvia, Unionida) inhabiting a broad variety of anthropogenic habitat types (from small ponds to large reservoirs and canals) and reviewed their importance as refuges for this faunal group. Most records came from Europe and North America, with a clear dominance of canals and reservoirs. The dataset covered 228 species, including 34 threatened species on the IUCN Red List. We discuss the conservation importance and provide guidance on how these anthropogenic habitats could be managed to provide optimal conservation value to freshwater mussels. This review also shows that some of these habitats may function as ecological traps owing to conflicting management practices or because they act as a sink for some populations. Therefore, anthropogenic habitats should not be seen as a panacea to resolve conservation problems. More information is necessary to better understand the trade-offs between human use and the conservation of freshwater mussels (and other biota) within anthropogenic habitats, given the low number of quantitative studies and the strong biogeographic knowledge bias that persists.This publication is based upon work from COST Action CA18239, supported by COST (European Cooperation in Science and Technology). A.M.L. was financed by the Institute of Environmental Sciences Jagiellonian University (N18/DBS/000003) and K.N. by the Aragón Government. The authors acknowledge Jarosław Andrzejewski, Bartosz Czader, Anna Fica, Marcin Horbacz, Tomasz Jonderko, Steinar Kålås, Tomasz Kapela, Bjørn Mejdell Larsen, Maciej Pabijan, Katarzyna Pawlik, Ilona Popławska, Joanna Przybylska, Tomasz Przybył, Mateusz Rybak, Kjell Sandaas, Jarosław Słowikowski, Tomasz Szczasny, Michał Zawadzki and Paweł Zowada for providing detailed information on specific examples concerning freshwater mussels in anthropogenic habitats. We thank the editor and two anonymous referees for the valuable suggestions made, which increased the clarity of our manuscript.info:eu-repo/semantics/publishedVersio

Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine

Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio

Participation of Candida albicans transcription factor Rlm1 in cell wall biogenesis and virulence

Candida albicans cell wall is important for growth and interaction with the environment. RLM1 is one of the putative transcription factors involved in the cell wall integrity pathway, which plays an important role in the maintenance of the cell wall integrity. In this work we investigated the involvement of RLM1 in the cell wall biogenesis and in virulence. Newly constructed C. albicans Δ/Δrlm1 mutants showed typical cell wall weakening phenotypes, such as hypersensitivity to Congo Red, Calcofluor White, and caspofungin (phenotype reverted in the presence of sorbitol), confirming the involvement of RLM1 in the cell wall integrity. Additionally, the cell wall of C. albicans Δ/Δrlm1 showed a significant increase in chitin (213%) and reduction in mannans (60%), in comparison with the wild-type, results that are consistent with cell wall remodelling. Microarray analysis in the absence of any stress showed that deletion of RLM1 in C. albicans significantly down-regulated genes involved in carbohydrate catabolism such as DAK2, GLK4, NHT1 and TPS1, up-regulated genes involved in the utilization of alternative carbon sources, like AGP2, SOU1, SAP6, CIT1 or GAL4, and genes involved in cell adhesion like ECE1, ALS1, ALS3, HWP1 or RBT1. In agreement with the microarray results adhesion assays showed an increased amount of adhering cells and total biomass in the mutant strain, in comparison with the wild-type. C. albicans mutant Δ/Δrlm1 strain was also found to be less virulent than the wild-type and complemented strains in the murine model of disseminated candidiasis. Overall, we showed that in the absence of RLM1 the modifications in the cell wall composition alter yeast interaction with the environment, with consequences in adhesion ability and virulence. The gene expression findings suggest that this gene participates in the cell wall biogenesis, with the mutant rearranging its metabolic pathways to allow the use of alternative carbon sources.This work was supported by CBMA (Centre of Molecular and Environmental Biology) through the FCT (Fundacao para a Ciencia e Tecnologia) project PEst-C/BIA/UI4050/2011. Yolanda Delgado-Silva was supported by an ALbAN scholarship (No E07D400922PE), and Alexandra Correia by SFRH/BD/31354/2006 fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Imigração e saúde: a (in)acessibilidade das mulheres imigrantes aos cuidados de saúde

A utilização dos serviços de saúde pelas populações imigrantes tem vindo a ser considerado um dos mais importantes indicadores da sua integração nas so- ciedades receptoras (Dias e col., 2009). No entanto, o conhecimento em torno da qualidade e da eficácia do acesso dos/as imigrantes aos cuidados de saúde, especialmente no que respeita às mulheres imigran- tes, é ainda escasso em Portugal (Fonseca e col., 2005). Embora os estudos nacionais tenham vindo, nas últimas décadas, a procurar traçar os diferentes perfis sociais das mulheres imigrantes em Portugal, sobretudo no que concerne às suas relações fami- liares ou laborais (Wall e col., 2005), a investigação no domínio da saúde é ainda parca e exclusora de uma análise centrada no género ou interseccional. Neste texto apresenta-se uma reflexão sobre os de- terminantes que condicionam a (in)acessibilidade das mulheres imigrantes aos cuidados de saúde, enfatizando-se os fatores que poderão estar a agir no sentido contrário à sua integração neste setor

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease